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Sonic hedgehog protein (SHH) (HHG-1) (Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains) (ShhNC) [Cleaved into: Sonic hedgehog protein N-product (ShhN) (Shh N-terminal processed signaling domains) (ShhNp)]

 SHH_HUMAN               Reviewed;         462 AA.
Q15465; A4D247; Q75MC9;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
22-NOV-2017, entry version 204.
RecName: Full=Sonic hedgehog protein;
Short=SHH;
AltName: Full=HHG-1;
AltName: Full=Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains {ECO:0000303|PubMed:24522195};
Short=ShhNC {ECO:0000303|PubMed:24522195};
Contains:
RecName: Full=Sonic hedgehog protein N-product;
Short=ShhN;
AltName: Full=Shh N-terminal processed signaling domains {ECO:0000303|PubMed:24522195};
Short=ShhNp {ECO:0000303|PubMed:24522195};
Flags: Precursor;
Name=SHH {ECO:0000312|HGNC:HGNC:10848};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Fetal lung;
PubMed=7590746; DOI=10.1006/geno.1995.1104;
Marigo V., Roberts D.J., Lee S.M.K., Tsukurov O., Levi T.,
Gastier J.M., Epstein D.J., Gilbert D.J., Copeland N.G., Seidman C.E.,
Jenkins N.A., Seidman J.G., McMahon A.P., Tabin C.;
"Cloning, expression, and chromosomal location of SHH and IHH: two
human homologues of the Drosophila segment polarity gene hedgehog.";
Genomics 28:44-51(1995).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tate G., Kishimoto K., Mitsuya T.;
"Expression of Sonic hedgehog and its receptor Patched/Smoothened in
human cancer cell lines and embryonic organs.";
J. Biochem. Mol. Biol. Biophys. 4:27-34(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NIEHS SNPs program;
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12690205; DOI=10.1126/science.1083423;
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
Mural R.J., Adams M.D., Tsui L.-C.;
"Human chromosome 7: DNA sequence and biology.";
Science 300:767-772(2003).
[6]
PROTEIN SEQUENCE OF 24-32, PALMITOYLATION AT CYS-24, CHOLESTERYLATION,
MUTAGENESIS OF CYS-24, AND MASS SPECTROMETRY.
PubMed=9593755; DOI=10.1074/jbc.273.22.14037;
Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P.,
Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R.,
Wang E.A., Galdes A.;
"Identification of a palmitic acid-modified form of human Sonic
hedgehog.";
J. Biol. Chem. 273:14037-14045(1998).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 119-167.
PubMed=7720571;
Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K.,
Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.;
"Products, genetic linkage and limb patterning activity of a murine
hedgehog gene.";
Development 120:3339-3353(1994).
[8]
INVOLVEMENT IN TPTPS, AND INVOLVEMENT IN PPD2.
PubMed=12837695; DOI=10.1093/hmg/ddg180;
Lettice L.A., Heaney S.J.H., Purdie L.A., Li L., de Beer P.,
Oostra B.A., Goode D., Elgar G., Hill R.E., de Graaff E.;
"A long-range Shh enhancer regulates expression in the developing limb
and fin and is associated with preaxial polydactyly.";
Hum. Mol. Genet. 12:1725-1735(2003).
[9]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278.
TISSUE=Plasma;
PubMed=16335952; DOI=10.1021/pr0502065;
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
Moore R.J., Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
[10]
INVOLVEMENT IN TPTPS.
PubMed=18417549; DOI=10.1136/jmg.2008.057646;
Sun M., Ma F., Zeng X., Liu Q., Zhao X.-L., Wu F.-X., Wu G.-P.,
Zhang Z.-F., Gu B., Zhao Y.-F., Tian S.-H., Lin B., Kong X.-Y.,
Zhang X.-L., Yang W., Lo W.H.-Y., Zhang X.;
"Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV
are caused by genomic duplications involving the long range, limb-
specific SHH enhancer.";
J. Med. Genet. 45:589-595(2008).
[11]
INVOLVEMENT IN THYP.
PubMed=19847792; DOI=10.1002/humu.21142;
Wieczorek D., Pawlik B., Li Y., Akarsu N.A., Caliebe A., May K.J.,
Schweiger B., Vargas F.R., Balci S., Gillessen-Kaesbach G.,
Wollnik B.;
"A specific mutation in the distant sonic hedgehog (SHH) cis-regulator
(ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS
duplications underlie Haas type polysyndactyly and preaxial
polydactyly (PPD) with or without triphalangeal thumb.";
Hum. Mutat. 31:81-89(2010).
[12]
INTERACTION WITH DISP1 AND SCUBE2, SUBUNIT, AND CAUTION.
PubMed=22902404; DOI=10.1016/j.celrep.2012.07.010;
Tukachinsky H., Kuzmickas R.P., Jao C.Y., Liu J., Salic A.;
"Dispatched and scube mediate the efficient secretion of the
cholesterol-modified hedgehog ligand.";
Cell Rep. 2:308-320(2012).
[13]
INTERACTION WITH SCUBE2, SUBUNIT, AND CAUTION.
PubMed=22677548; DOI=10.1101/gad.191866.112;
Creanga A., Glenn T.D., Mann R.K., Saunders A.M., Talbot W.S.,
Beachy P.A.;
"Scube/You activity mediates release of dually lipid-modified Hedgehog
signal in soluble form.";
Genes Dev. 26:1312-1325(2012).
[14]
PTM, AND DOMAIN.
PubMed=23118222; DOI=10.1074/jbc.M112.356667;
Ohlig S., Pickhinke U., Sirko S., Bandari S., Hoffmann D., Dreier R.,
Farshi P., Goetz M., Grobe K.;
"An emerging role of Sonic hedgehog shedding as a modulator of heparan
sulfate interactions.";
J. Biol. Chem. 287:43708-43719(2012).
[15]
REVIEW.
PubMed=23154980; DOI=10.1101/gad.207126.112;
Ingham P.W.;
"Zebrafish genetics gets the Scube on Hedgehog secretion.";
Genes Dev. 26:2468-2470(2012).
[16]
PTM, INTERACTION WITH SCUBE2, SUBUNIT, SUBCELLULAR LOCATION, FUNCTION,
AND CAUTION.
PubMed=24522195; DOI=10.1242/jcs.137695;
Jakobs P., Exner S., Schuermann S., Pickhinke U., Bandari S.,
Ortmann C., Kupich S., Schulz P., Hansen U., Seidler D.G., Grobe K.;
"Scube2 enhances proteolytic Shh processing from the surface of Shh-
producing cells.";
J. Cell Sci. 127:1726-1737(2014).
[17]
INVOLVEMENT IN LSS.
PubMed=24456159; DOI=10.1111/cge.12352;
Lohan S., Spielmann M., Doelken S.C., Floettmann R., Muhammad F.,
Baig S.M., Wajid M., Huelsemann W., Habenicht R., Kjaer K.W.,
Patil S.J., Girisha K.M., Abarca-Barriga H.H., Mundlos S.,
Klopocki E.;
"Microduplications encompassing the Sonic hedgehog limb enhancer ZRS
are associated with Haas-type polysyndactyly and Laurin-Sandrow
syndrome.";
Clin. Genet. 86:318-325(2014).
[18]
INVOLVEMENT IN THYP.
PubMed=24965254; DOI=10.1038/jhg.2014.50;
Norbnop P., Srichomthong C., Suphapeetiporn K., Shotelersuk V.;
"ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly
and triphalangeal first fingers.";
J. Hum. Genet. 59:467-470(2014).
[19]
REVIEW, AND FUNCTION.
PubMed=24863049; DOI=10.1002/dneu.22193;
Pal K., Mukhopadhyay S.;
"Primary cilium and sonic hedgehog signaling during neural tube
patterning: role of GPCRs and second messengers.";
Dev. Neurobiol. 75:337-348(2015).
[20]
REVIEW, CAUTION, SUBCELLULAR LOCATION, AND PTM.
PubMed=26875496; DOI=10.1016/j.ydbio.2016.02.009;
Xavier G.M., Seppala M., Barrell W., Birjandi A.A., Geoghegan F.,
Cobourne M.T.;
"Hedgehog receptor function during craniofacial development.";
Dev. Biol. 415:198-215(2016).
[21]
X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-197 IN COMPLEX WITH ZINC
IONS, FUNCTION, DOMAIN, AND SUBUNIT.
PubMed=10753901; DOI=10.1074/jbc.275.15.10995;
Pepinsky R.B., Rayhorn P., Day E.S., Dergay A., Williams K.P.,
Galdes A., Taylor F.R., Boriack-Sjodin P.A., Garber E.A.;
"Mapping sonic hedgehog-receptor interactions by steric
interference.";
J. Biol. Chem. 275:10995-11001(2000).
[22]
X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 29-197 IN COMPLEX WITH HHIP;
ZINC AND CALCIUM IONS, DOMAIN, INTERACTION WITH HHIP, AND SUBUNIT.
PubMed=19561609; DOI=10.1038/nsmb.1632;
Bosanac I., Maun H.R., Scales S.J., Wen X., Lingel A., Bazan J.F.,
de Sauvage F.J., Hymowitz S.G., Lazarus R.A.;
"The structure of SHH in complex with HHIP reveals a recognition role
for the Shh pseudo active site in signaling.";
Nat. Struct. Mol. Biol. 16:691-697(2009).
[23]
X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 29-197 IN COMPLEX WITH
MONOCLONAL ANTIBODY; ZINC AND CALCIUM IONS, AND DOMAIN.
PubMed=20504762; DOI=10.1074/jbc.M110.112284;
Maun H.R., Wen X., Lingel A., de Sauvage F.J., Lazarus R.A.,
Scales S.J., Hymowitz S.G.;
"Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active
site.";
J. Biol. Chem. 285:26570-26580(2010).
[24]
VARIANTS HPE3 ARG-31; GLY-117 AND ARG-117.
PubMed=8896572; DOI=10.1038/ng1196-357;
Roessler E., Belloni E., Gaudenz K., Jay P., Berta P., Scherer S.W.,
Tsui L.-C., Muenke M.;
"Mutations in the human Sonic hedgehog gene cause holoprosencephaly.";
Nat. Genet. 14:357-360(1996).
[25]
VARIANTS HPE3 ARG-31; GLY-117; ARG-117; GLU-224; THR-226 AND THR-383.
PubMed=9302262; DOI=10.1093/hmg/6.11.1847;
Roessler E., Belloni E., Gaudenz K., Vargas F., Scherer S.W.,
Tsui L.-C., Muenke M.;
"Mutations in the C-terminal domain of Sonic hedgehog cause
holoprosencephaly.";
Hum. Mol. Genet. 6:1847-1853(1997).
[26]
VARIANTS HPE3 HIS-100; GLN-188 AND ASN-222.
PubMed=10441331; DOI=10.1093/hmg/8.9.1683;
Odent S., Atti-Bitach T., Blayau M., Mathieu M., Aug J.,
Delezo de A.L., Gall J.Y., Le Marec B., Munnich A., David V.,
Vekemans M.;
"Expression of the Sonic hedgehog (SHH) gene during early human
development and phenotypic expression of new mutations causing
holoprosencephaly.";
Hum. Mol. Genet. 8:1683-1689(1999).
[27]
VARIANTS HPE3 VAL-88; LYS-115; ARG-236; 263-ARG--ALA-269 DEL; ASP-290;
ALA-424 AND LEU-436.
PubMed=10556296; DOI=10.1093/hmg/8.13.2479;
Nanni L., Ming J.E., Bocian M., Steinhaus K., Bianchi D.W.,
Die-Smulders C., Giannotti A., Imaizumi K., Jones K.L., Campo M.D.,
Martin R.A., Meinecke P., Pierpont M.E.M., Robin N.H., Young I.D.,
Roessler E., Muenke M.;
"The mutational spectrum of the sonic hedgehog gene in
holoprosencephaly: SHH mutations cause a significant proportion of
autosomal dominant holoprosencephaly.";
Hum. Mol. Genet. 8:2479-2488(1999).
[28]
VARIANT SMMCI PHE-111.
PubMed=11471164;
DOI=10.1002/1096-8628(20010722)102:1<1::AID-AJMG1336>3.0.CO;2-U;
Nanni L., Ming J.E., Du Y., Hall R.K., Aldred M., Bankier A.,
Muenke M.;
"SHH mutation is associated with solitary median maxillary central
incisor: a study of 13 patients and review of the literature.";
Am. J. Med. Genet. 102:1-10(2001).
[29]
VARIANTS HPE3 PRO-140 AND PHE-183.
PubMed=11479728; DOI=10.1007/s004390100537;
Orioli I.M., Castilla E.E., Ming J.E., Nazer J., Burle de Aguiar M.J.,
Llerena J.C., Muenke M.;
"Identification of novel mutations in SHH and ZIC2 in a South American
(ECLAMC) population with holoprosencephaly.";
Hum. Genet. 109:1-6(2001).
[30]
VARIANT MCOPCB5 401-SER--GLY-408 DEL.
PubMed=12503095; DOI=10.1002/ajmg.a.10884;
Schimmenti L.A., de la Cruz J., Lewis R.A., Karkera J.D.,
Manligas G.S., Roessler E., Muenke M.;
"Novel mutation in sonic hedgehog in non-syndromic colobomatous
microphthalmia.";
Am. J. Med. Genet. A 116:215-221(2003).
[31]
VARIANT SMMCI ALA-332.
PubMed=15103725; DOI=10.1002/ajmg.a.20685;
Garavelli L., Zanacca C., Caselli G., Banchini G., Dubourg C.,
David V., Odent S., Gurrieri F., Neri G.;
"Solitary median maxillary central incisor syndrome: clinical case
with a novel mutation of sonic hedgehog.";
Am. J. Med. Genet. A 127:93-95(2004).
[32]
VARIANTS HPE3 ALA-27; ILE-267 AND THR-373.
PubMed=15107988; DOI=10.1007/s00431-004-1459-0;
Hehr U., Gross C., Diebold U., Wahl D., Beudt U., Heidemann P.,
Hehr A., Mueller D.;
"Wide phenotypic variability in families with holoprosencephaly and a
sonic hedgehog mutation.";
Eur. J. Pediatr. 163:347-352(2004).
[33]
VARIANTS HPE3 THR-6; HIS-100; 106-LEU-ASN-107 DEL; ASP-110; ARG-150;
176-GLU--LYS-178 DEL; GLN-188; ASN-222; PRO-271; ALA-332; GLN-347;
THR-354 AND PRO-381.
PubMed=15221788; DOI=10.1002/humu.20056;
Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M.,
Le Duff F., Durou M.-R., Odent S., David V.;
"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients
with features of holoprosencephaly spectrum: mutation review and
genotype-phenotype correlations.";
Hum. Mutat. 24:43-51(2004).
[34]
VARIANT HPE3 ASN-111.
PubMed=15942952; DOI=10.1002/ajmg.a.30624;
El-Jaick K.B., Brunoni D., Castilla E.E., Moreira M.A., Orioli I.M.;
"SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose
mother had only a solitary median maxillary incisor.";
Am. J. Med. Genet. A 136:345-345(2005).
[35]
VARIANT HPE3 GLN-140.
PubMed=15942953; DOI=10.1002/ajmg.a.30625;
Ribeiro L.A., Richieri-Costa A.;
"Single median maxillary central incisor, hypophyseal tumor, and SHH
mutation.";
Am. J. Med. Genet. A 136:346-347(2005).
[36]
CHARACTERIZATION OF VARIANTS HPE3 ARG-31; VAL-88; HIS-100; LYS-115;
ARG-117; GLY-117 AND GLN-188.
PubMed=16282375; DOI=10.1073/pnas.0507848102;
Maity T., Fuse N., Beachy P.A.;
"Molecular mechanisms of Sonic hedgehog mutant effects in
holoprosencephaly.";
Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005).
[37]
VARIANTS HPE3 GLN-140; PRO-218 AND TYR-363.
PubMed=17001669; DOI=10.1002/ajmg.a.31378;
Richieri-Costa A., Ribeiro L.A.;
"Holoprosencephaly-like phenotype: clinical and genetic
perspectives.";
Am. J. Med. Genet. A 140:2587-2593(2006).
[38]
VARIANTS HPE3 THR-6; PRO-17; LEU-26; ALA-27; ARG-31; PRO-39; LYS-53;
VAL-83; PHE-84; VAL-88; HIS-100; ARG-102; TYR-102; 106-LEU-ASN-107
DEL; PHE-109; THR-110; ASP-110; PHE-111; ASN-111; LYS-115; GLY-117;
ARG-117; MET-124; LYS-136; PRO-140; GLN-140; ASP-143; PRO-144;
ASN-147; ARG-150; LYS-150; ARG-156; CYS-170; HIS-171; 176-GLU--LYS-178
DEL; ARG-183; PHE-183; TYR-183; LEU-184; GLN-188; GLU-196;
196-GLY--PRO-200 DEL; VAL-197; SER-198; PHE-198; PRO-218; ASN-222;
GLU-224; THR-226; VAL-231; GLY-232; PRO-234; ARG-236; ASN-236;
VAL-241; LEU-241; ASN-255; 263-ARG--ALA-269 DEL; ILE-267; PRO-271;
GLU-275; TRP-280; ASP-290; ALA-296; CYS-310; SER-321; ALA-332;
VAL-346; ARG-347; GLN-347; LEU-347; THR-354; LEU-362; TYR-363;
CYS-364; THR-373; ARG-374; ASP-376; SER-377; 378-ALA--PHE-380 DEL;
PRO-381; PRO-382; THR-383; THR-391; 402-GLY--GLY-409 DEL;
405-ASP--GLY-409 DEL; GLY-411 INS; ALA-416; ALA-424; ASN-435; LEU-436
AND ARG-456.
PubMed=19603532; DOI=10.1002/humu.21090;
Roessler E., El-Jaick K.B., Dubourg C., Velez J.I., Solomon B.D.,
Pineda-Alvarez D.E., Lacbawan F., Zhou N., Ouspenskaia M.,
Paulussen A., Smeets H.J., Hehr U., Bendavid C., Bale S., Odent S.,
David V., Muenke M.;
"The mutational spectrum of holoprosencephaly-associated changes
within the SHH gene in humans predicts loss-of-function through either
key structural alterations of the ligand or its altered synthesis.";
Hum. Mutat. 30:E921-E935(2009).
-!- FUNCTION: Sonic hedgehog protein: The C-terminal part of the sonic
hedgehog protein precursor displays an autoproteolysis and a
cholesterol transferase activity (By similarity). Both activities
result in the cleavage of the full-length protein into two parts
(ShhN and ShhC) followed by the covalent attachment of a
cholesterol moiety to the C-terminal of the newly generated ShhN
(By similarity). Both activities occur in the reticulum
endoplasmic (By similarity). Once cleaved, ShhC is degraded in the
endoplasmic reticulum (By similarity).
{ECO:0000250|UniProtKB:Q62226}.
-!- FUNCTION: Sonic hedgehog protein N-product: The dually lipidated
sonic hedgehog protein N-product (ShhNp) is a morphogen which is
essential for a variety of patterning events during development.
Induces ventral cell fate in the neural tube and somites
(PubMed:24863049). Involved in the patterning of the anterior-
posterior axis of the developing limb bud (By similarity).
Essential for axon guidance (By similarity). Binds to the patched
(PTCH1) receptor, which functions in association with smoothened
(SMO), to activate the transcription of target genes
(PubMed:10753901). In the absence of SHH, PTCH1 represses the
constitutive signaling activity of SMO (PubMed:10753901).
{ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:10753901,
ECO:0000269|PubMed:24863049, ECO:0000303|PubMed:24522195}.
-!- SUBUNIT: Interacts with HHATL/GUP1 which negatively regulates
HHAT-mediated palmitoylation of the SHH N-terminus (By
similarity). ShhNp is active as a multimer (PubMed:24522195).
Interacts with BOC and CDON (By similarity). Interacts with HHIP
(PubMed:19561609). Interacts with DISP1 via its cholesterol anchor
(PubMed:22902404, PubMed:22677548). Interacts with SCUBE2
(PubMed:24522195, PubMed:22677548). {ECO:0000250|UniProtKB:Q15465,
ECO:0000269|PubMed:19561609, ECO:0000269|PubMed:22677548,
ECO:0000269|PubMed:22902404, ECO:0000269|PubMed:24522195}.
-!- INTERACTION:
Q96QV1:HHIP; NbExp=10; IntAct=EBI-11666886, EBI-6598521;
Q13635:PTCH1; NbExp=2; IntAct=EBI-11666886, EBI-8775406;
-!- SUBCELLULAR LOCATION: Sonic hedgehog protein N-product: Cell
membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor
{ECO:0000250|UniProtKB:Q62226}. Note=The dual-lipidated sonic
hedgehog protein N-product (ShhNp) is firmly tethered to the cell
membrane where it forms multimers (PubMed:24522195). Further
solubilization and release from the cell surface seem to be
achieved through different mechanisms, including the interaction
with DISP1 and SCUBE2, movement by lipoprotein particles,
transport by cellular extensions called cytonemes or by the
proteolytic removal of both terminal lipidated peptides
(PubMed:26875496, PubMed:24522195). {ECO:0000305|PubMed:24522195,
ECO:0000305|PubMed:26875496}.
-!- DOMAIN: Sonic hedgehog protein N-product: Binds calcium and zinc
ions; this stabilizes the protein fold and is essential for
protein-protein interactions mediated by this domain.
{ECO:0000269|PubMed:10753901, ECO:0000269|PubMed:19561609,
ECO:0000269|PubMed:20504762}.
-!- DOMAIN: Sonic hedgehog protein N-product: The Cardin-Weintraub
(CW) motif is required for heparan sulfate binding of the
solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated
peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub
(CW) motif site (PubMed:24522195). The cleavage reduced the
interactions with heparan sulfate. The cleavage is enhanced by
SCUBE2 (PubMed:24522195). {ECO:0000269|PubMed:23118222,
ECO:0000269|PubMed:24522195}.
-!- PTM: Sonic hedgehog protein: The C-terminal domain displays an
autoproteolysis activity and a cholesterol transferase activity
(By similarity). Both activities result in the cleavage of the
full-length protein and covalent attachment of a cholesterol
moiety to the C-terminal of the newly generated N-terminal
fragment (ShhN) (By similarity). Cholesterylation is required for
the sonic hedgehog protein N-product targeting to lipid rafts and
multimerization (PubMed:24522195, PubMed:26875496). ShhN is the
active species in both local and long-range signaling, whereas the
C-product (ShhC) is degraded in the reticulum endoplasmic (By
similarity). {ECO:0000250|UniProtKB:Q62226,
ECO:0000303|PubMed:26875496, ECO:0000305|PubMed:24522195}.
-!- PTM: Sonic hedgehog protein N-product: N-palmitoylation by HHAT of
ShhN is required for sonic hedgehog protein N-product
multimerization and full activity (By similarity). It is a
prerequisite for the membrane-proximal positioning and the
subsequent shedding of this N-terminal peptide (PubMed:24522195).
{ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:24522195}.
-!- PTM: Sonic hedgehog protein N-product: The lipidated N- and C-
terminal peptides of ShhNp can be cleaved
(shedding)(PubMed:24522195). The N-terminal palmitoylated peptide
is cleaved at the Cardin-Weintraub (CW) motif site
(PubMed:24522195). The cleavage reduced the interactions with
heparan sulfate. The cleavage is enhanced by SCUBE2
(PubMed:24522195, PubMed:23118222). {ECO:0000269|PubMed:23118222,
ECO:0000269|PubMed:24522195}.
-!- MASS SPECTROMETRY: Mass=19.560; Method=Electrospray; Range=24-197;
Note=Sonic hedgehog protein N-product: soluble product, purified
from insect cells.; Evidence={ECO:0000269|PubMed:9593755};
-!- MASS SPECTROMETRY: Mass=20.167; Method=Electrospray; Range=24-197;
Note=Sonic hedgehog protein N-product: Membrane-bound product,
purified from insect cells.;
Evidence={ECO:0000269|PubMed:9593755};
-!- DISEASE: Microphthalmia, isolated, with coloboma, 5 (MCOPCB5)
[MIM:611638]: A disorder of eye formation, ranging from small size
of a single eye to complete bilateral absence of ocular tissues.
Ocular abnormalities like opacities of the cornea and lens,
scaring of the retina and choroid, and other abnormalities may
also be present. Ocular colobomas are a set of malformations
resulting from abnormal morphogenesis of the optic cup and stalk,
and the fusion of the fetal fissure (optic fissure).
{ECO:0000269|PubMed:12503095}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Holoprosencephaly 3 (HPE3) [MIM:142945]: A structural
anomaly of the brain, in which the developing forebrain fails to
correctly separate into right and left hemispheres.
Holoprosencephaly is genetically heterogeneous and associated with
several distinct facies and phenotypic variability. The majority
of holoprosencephaly type 3 cases are apparently sporadic,
although clear examples of autosomal dominant inheritance have
been described. {ECO:0000269|PubMed:10441331,
ECO:0000269|PubMed:10556296, ECO:0000269|PubMed:11479728,
ECO:0000269|PubMed:15107988, ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:15942952, ECO:0000269|PubMed:15942953,
ECO:0000269|PubMed:16282375, ECO:0000269|PubMed:17001669,
ECO:0000269|PubMed:19603532, ECO:0000269|PubMed:8896572,
ECO:0000269|PubMed:9302262}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Solitary median maxillary central incisor (SMMCI)
[MIM:147250]: Rare dental anomaly characterized by the congenital
absence of one maxillary central incisor.
{ECO:0000269|PubMed:11471164, ECO:0000269|PubMed:15103725}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Triphalangeal thumb-polysyndactyly syndrome (TPTPS)
[MIM:174500]: Autosomal dominant syndrome. It is characterized by
a wide spectrum of pre- and post-axial abnormalities due to
altered SHH expression pattern during limb development.
{ECO:0000269|PubMed:12837695, ECO:0000269|PubMed:18417549}.
Note=The gene represented in this entry is involved in disease
pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a
long-range, cis-regulatory element of SHH expression.
-!- DISEASE: Preaxial polydactyly 2 (PPD2) [MIM:174500]: Polydactyly
consists of duplication of the distal phalanx. The thumb in PPD2
is usually opposable and possesses a normal metacarpal.
{ECO:0000269|PubMed:12837695}. Note=The gene represented in this
entry is involved in disease pathogenesis. Mutations located in
intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of
SHH and result in abnormal, ectopic SHH expression with
pathological consequences (PubMed:12837695).
{ECO:0000269|PubMed:12837695}.
-!- DISEASE: Hypoplasia or aplasia of tibia with polydactyly (THYP)
[MIM:188740]: An autosomal dominant disease characterized by
hypoplastic or absent tibia, and polydactyly.
{ECO:0000269|PubMed:19847792, ECO:0000269|PubMed:24965254}.
Note=The gene represented in this entry is involved in disease
pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a
long-range, cis-regulatory element of SHH and result in abnormal,
ectopic SHH expression with pathological consequences.
{ECO:0000303|PubMed:19847792, ECO:0000303|PubMed:24965254}.
-!- DISEASE: Laurin-Sandrow syndrome (LSS) [MIM:135750]: A rare
autosomal dominant disorder characterized by polysyndactyly of
hands and/or feet, mirror image duplication of the feet, nasal
defects, and loss of identity between fibula and tibia. Some
patients do not have nasal abnormalities (segmental Laurin-Sandrow
syndrome). {ECO:0000269|PubMed:24456159}. Note=The gene
represented in this entry is involved in disease pathogenesis.
Abnormal SHH limb expression with pathological consequences is
caused by duplications (16-75 kb) involving the ZPA regulatory
sequence (ZRS), a SHH long-range cis-regulatory element, located
in LMBR1 intron 5 (PubMed:24456159).
-!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
-!- CAUTION: The several steps and mechanisms that permit controlled
Shh dispersion and gradient formation remain controversial. The
ShhNC C-terminal domain displays an autoproteolysis activity and a
cholesterol transferase activity resulting in the cleavage and
covalent attachment of a cholesterol moiety to the C-terminal of
the newly generated N-terminal fragment (ShhN). The protein is
further modified by covalent addition of palmitate at the N-
terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp).
ShhNp is firmly tethered to the cell membrane where it forms
multimers. Further solubilization and release from the cell
surface seem to be achieved through different mechanisms,
including the interaction with DISP1 and SCUBE2, movement by
lipoprotein particles, transport by cellular extensions called
cytonemes or by proteolytic removal of both terminal lipidated
peptides (PubMed:26875496). Once released, the fully processed Shh
can signal within embryonic tissues both at short and long-range.
{ECO:0000269|PubMed:24522195, ECO:0000303|PubMed:26875496,
ECO:0000305|PubMed:22677548, ECO:0000305|PubMed:22902404}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/SHHID378.html";
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/shh/";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; L38518; AAA62179.1; -; mRNA.
EMBL; AY422195; AAQ87879.1; -; Genomic_DNA.
EMBL; AC002484; AAB67604.1; -; Genomic_DNA.
EMBL; AC078834; AAS01990.1; -; Genomic_DNA.
EMBL; CH236954; EAL23913.1; -; Genomic_DNA.
CCDS; CCDS5942.1; -.
RefSeq; NP_000184.1; NM_000193.3.
UniGene; Hs.164537; -.
UniGene; Hs.606487; -.
UniGene; Hs.738995; -.
PDB; 3HO5; X-ray; 3.01 A; H=29-197.
PDB; 3M1N; X-ray; 1.85 A; A/B=23-197.
PDB; 3MXW; X-ray; 1.83 A; A=29-197.
PDBsum; 3HO5; -.
PDBsum; 3M1N; -.
PDBsum; 3MXW; -.
ProteinModelPortal; Q15465; -.
SMR; Q15465; -.
BioGrid; 112365; 8.
DIP; DIP-61763N; -.
IntAct; Q15465; 3.
STRING; 9606.ENSP00000297261; -.
BindingDB; Q15465; -.
ChEMBL; CHEMBL5602; -.
MEROPS; C46.002; -.
iPTMnet; Q15465; -.
PhosphoSitePlus; Q15465; -.
BioMuta; SHH; -.
DMDM; 6094283; -.
PaxDb; Q15465; -.
PeptideAtlas; Q15465; -.
PRIDE; Q15465; -.
DNASU; 6469; -.
Ensembl; ENST00000297261; ENSP00000297261; ENSG00000164690.
GeneID; 6469; -.
KEGG; hsa:6469; -.
UCSC; uc003wmk.2; human.
CTD; 6469; -.
DisGeNET; 6469; -.
EuPathDB; HostDB:ENSG00000164690.7; -.
GeneCards; SHH; -.
GeneReviews; SHH; -.
HGNC; HGNC:10848; SHH.
MalaCards; SHH; -.
MIM; 135750; phenotype.
MIM; 142945; phenotype.
MIM; 147250; phenotype.
MIM; 174500; phenotype.
MIM; 188740; phenotype.
MIM; 600725; gene.
MIM; 611638; phenotype.
neXtProt; NX_Q15465; -.
OpenTargets; ENSG00000164690; -.
Orphanet; 93925; Alobar holoprosencephaly.
Orphanet; 98938; Colobomatous microphthalmia.
Orphanet; 3332; Hypoplastic tibiae - postaxial polydactyly.
Orphanet; 93924; Lobar holoprosencephaly.
Orphanet; 280200; Microform holoprosencephaly.
Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly.
Orphanet; 194; Ocular coloboma.
Orphanet; 295150; Polydactyly of a triphalangeal thumb, bilateral.
Orphanet; 295148; Polydactyly of a triphalangeal thumb, unilateral.
Orphanet; 295071; Radial hemimelia, bilateral.
Orphanet; 295069; Radial hemimelia, unilateral.
Orphanet; 799; Schizencephaly.
Orphanet; 220386; Semilobar holoprosencephaly.
Orphanet; 280195; Septopreoptic holoprosencephaly.
Orphanet; 2286; Solitary median maxillary central incisor syndrome.
Orphanet; 93405; Syndactyly type 4.
Orphanet; 2950; Triphalangeal thumb - polysyndactyly syndrome.
PharmGKB; PA35752; -.
eggNOG; KOG3638; Eukaryota.
eggNOG; ENOG410XQA3; LUCA.
GeneTree; ENSGT00390000001117; -.
HOGENOM; HOG000233428; -.
HOVERGEN; HBG005480; -.
InParanoid; Q15465; -.
KO; K11988; -.
OMA; EHSWAHR; -.
OrthoDB; EOG091G0N90; -.
PhylomeDB; Q15465; -.
TreeFam; TF106458; -.
Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
Reactome; R-HSA-5362768; Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
Reactome; R-HSA-5362798; Release of Hh-Np from the secreting cell.
Reactome; R-HSA-5632681; Ligand-receptor interactions.
Reactome; R-HSA-5632684; Hedgehog 'on' state.
Reactome; R-HSA-5635838; Activation of SMO.
Reactome; R-HSA-5658034; HHAT G278V abrogates palmitoylation of Hh-Np.
SignaLink; Q15465; -.
SIGNOR; Q15465; -.
ChiTaRS; SHH; human.
EvolutionaryTrace; Q15465; -.
GeneWiki; Sonic_hedgehog; -.
GenomeRNAi; 6469; -.
PRO; PR:Q15465; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000164690; -.
CleanEx; HS_SHH; -.
ExpressionAtlas; Q15465; baseline and differential.
Genevisible; Q15465; HS.
GO; GO:0009986; C:cell surface; ISS:UniProtKB.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0005578; C:proteinaceous extracellular matrix; IEA:Ensembl.
GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
GO; GO:0043237; F:laminin-1 binding; ISS:UniProtKB.
GO; GO:0016015; F:morphogen activity; TAS:ParkinsonsUK-UCL.
GO; GO:0005113; F:patched binding; IDA:BHF-UCL.
GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0008209; P:androgen metabolic process; ISS:UniProtKB.
GO; GO:0048645; P:animal organ formation; IEA:Ensembl.
GO; GO:0097190; P:apoptotic signaling pathway; ISS:UniProtKB.
GO; GO:0060840; P:artery development; IEA:Ensembl.
GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISS:UniProtKB.
GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl.
GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
GO; GO:0060447; P:bud outgrowth involved in lung branching; IEA:Ensembl.
GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0043369; P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; IDA:BHF-UCL.
GO; GO:0048468; P:cell development; ISS:UniProtKB.
GO; GO:0001708; P:cell fate specification; ISS:UniProtKB.
GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
GO; GO:0021930; P:cerebellar granule cell precursor proliferation; ISS:UniProtKB.
GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; ISS:BHF-UCL.
GO; GO:0071542; P:dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
GO; GO:0009953; P:dorsal/ventral pattern formation; ISS:UniProtKB.
GO; GO:0007398; P:ectoderm development; IEA:Ensembl.
GO; GO:0009790; P:embryo development; ISS:UniProtKB.
GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
GO; GO:0042733; P:embryonic digit morphogenesis; ISS:UniProtKB.
GO; GO:0048617; P:embryonic foregut morphogenesis; IEA:Ensembl.
GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
GO; GO:0030326; P:embryonic limb morphogenesis; ISS:UniProtKB.
GO; GO:0009880; P:embryonic pattern specification; TAS:BHF-UCL.
GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
GO; GO:0006897; P:endocytosis; IEA:Ensembl.
GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IEA:Ensembl.
GO; GO:0060738; P:epithelial-mesenchymal signaling involved in prostate gland development; IDA:MGI.
GO; GO:0030010; P:establishment of cell polarity; IEA:Ensembl.
GO; GO:0030900; P:forebrain development; ISS:UniProtKB.
GO; GO:0048859; P:formation of anatomical boundary; IEA:Ensembl.
GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
GO; GO:0007507; P:heart development; ISS:UniProtKB.
GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
GO; GO:0030902; P:hindbrain development; ISS:UniProtKB.
GO; GO:0007442; P:hindgut morphogenesis; IEA:Ensembl.
GO; GO:0048839; P:inner ear development; IEA:Ensembl.
GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
GO; GO:0045109; P:intermediate filament organization; IEA:Ensembl.
GO; GO:0060459; P:left lung development; IEA:Ensembl.
GO; GO:0060174; P:limb bud formation; IEA:Ensembl.
GO; GO:0030324; P:lung development; ISS:UniProtKB.
GO; GO:0060428; P:lung epithelium development; IEA:Ensembl.
GO; GO:0060463; P:lung lobe morphogenesis; IEA:Ensembl.
GO; GO:0060484; P:lung-associated mesenchyme development; IEA:Ensembl.
GO; GO:0002320; P:lymphoid progenitor cell differentiation; IMP:BHF-UCL.
GO; GO:0030539; P:male genitalia development; ISS:UniProtKB.
GO; GO:0060916; P:mesenchymal cell proliferation involved in lung development; IEA:Ensembl.
GO; GO:0060783; P:mesenchymal smoothened signaling pathway involved in prostate gland development; IEA:Ensembl.
GO; GO:0072136; P:metanephric mesenchymal cell proliferation involved in metanephros development; ISS:UniProtKB.
GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl.
GO; GO:0014902; P:myotube differentiation; IEA:Ensembl.
GO; GO:0046639; P:negative regulation of alpha-beta T cell differentiation; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0045596; P:negative regulation of cell differentiation; ISS:UniProtKB.
GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
GO; GO:0090370; P:negative regulation of cholesterol efflux; ISS:BHF-UCL.
GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; IEA:Ensembl.
GO; GO:2000357; P:negative regulation of kidney smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IEA:Ensembl.
GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
GO; GO:2000062; P:negative regulation of ureter smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0045060; P:negative thymic T cell selection; ISS:UniProtKB.
GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
GO; GO:0007405; P:neuroblast proliferation; ISS:UniProtKB.
GO; GO:0048663; P:neuron fate commitment; ISS:UniProtKB.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
GO; GO:0060021; P:palate development; IEA:Ensembl.
GO; GO:0031016; P:pancreas development; IEA:Ensembl.
GO; GO:0007389; P:pattern specification process; ISS:UniProtKB.
GO; GO:0009949; P:polarity specification of anterior/posterior axis; ISS:UniProtKB.
GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISS:UniProtKB.
GO; GO:0051781; P:positive regulation of cell division; IDA:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:BHF-UCL.
GO; GO:0060769; P:positive regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
GO; GO:0007228; P:positive regulation of hh target transcription factor activity; ISS:BHF-UCL.
GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; ISS:BHF-UCL.
GO; GO:2000358; P:positive regulation of kidney smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:2000729; P:positive regulation of mesenchymal cell proliferation involved in ureter development; ISS:UniProtKB.
GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
GO; GO:0061189; P:positive regulation of sclerotome development; IDA:BHF-UCL.
GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; IEA:Ensembl.
GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl.
GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:UniProtKB.
GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; IEA:Ensembl.
GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
GO; GO:2000063; P:positive regulation of ureter smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IEA:Ensembl.
GO; GO:0045059; P:positive thymic T cell selection; ISS:UniProtKB.
GO; GO:0060516; P:primary prostatic bud elongation; IEA:Ensembl.
GO; GO:0060523; P:prostate epithelial cord elongation; IEA:Ensembl.
GO; GO:0030850; P:prostate gland development; ISS:UniProtKB.
GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
GO; GO:0042127; P:regulation of cell proliferation; ISS:UniProtKB.
GO; GO:0060782; P:regulation of mesenchymal cell proliferation involved in prostate gland development; IEA:Ensembl.
GO; GO:1900175; P:regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; NAS:BHF-UCL.
GO; GO:0042481; P:regulation of odontogenesis; ISS:BHF-UCL.
GO; GO:0060685; P:regulation of prostatic bud formation; IEA:Ensembl.
GO; GO:1900180; P:regulation of protein localization to nucleus; IDA:BHF-UCL.
GO; GO:0030162; P:regulation of proteolysis; ISS:UniProtKB.
GO; GO:0072001; P:renal system development; IEP:UniProtKB.
GO; GO:0060458; P:right lung development; IEA:Ensembl.
GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl.
GO; GO:0007224; P:smoothened signaling pathway; IEP:UniProtKB.
GO; GO:0021938; P:smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; IEA:Ensembl.
GO; GO:0061053; P:somite development; ISS:BHF-UCL.
GO; GO:0021513; P:spinal cord dorsal/ventral patterning; IEA:Ensembl.
GO; GO:0021522; P:spinal cord motor neuron differentiation; IEA:Ensembl.
GO; GO:0048864; P:stem cell development; ISS:UniProtKB.
GO; GO:0014706; P:striated muscle tissue development; IEA:Ensembl.
GO; GO:0033077; P:T cell differentiation in thymus; ISS:BHF-UCL.
GO; GO:0021978; P:telencephalon regionalization; IEA:Ensembl.
GO; GO:0021794; P:thalamus development; IEA:Ensembl.
GO; GO:0048538; P:thymus development; ISS:UniProtKB.
GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
GO; GO:0060439; P:trachea morphogenesis; IEA:Ensembl.
GO; GO:1905327; P:tracheoesophageal septum formation; IEA:Ensembl.
GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
GO; GO:0007418; P:ventral midline development; TAS:BHF-UCL.
Gene3D; 3.30.1380.10; -; 1.
InterPro; IPR001657; Hedgehog.
InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
InterPro; IPR000320; Hedgehog_signalling_dom.
InterPro; IPR001767; Hint_dom.
InterPro; IPR003586; Hint_dom_C.
InterPro; IPR003587; Hint_dom_N.
InterPro; IPR036844; Hint_dom_sf.
InterPro; IPR006141; Intein_N.
Pfam; PF01085; HH_signal; 1.
Pfam; PF01079; Hint; 1.
PIRSF; PIRSF009400; Peptidase_C46; 1.
PRINTS; PR00632; SONICHHOG.
SMART; SM00305; HintC; 1.
SMART; SM00306; HintN; 1.
SUPFAM; SSF51294; SSF51294; 1.
SUPFAM; SSF55166; SSF55166; 1.
PROSITE; PS50817; INTEIN_N_TER; 1.
1: Evidence at protein level;
3D-structure; Autocatalytic cleavage; Calcium; Cell membrane;
Complete proteome; Developmental protein; Direct protein sequencing;
Disease mutation; Glycoprotein; Holoprosencephaly; Hydrolase;
Lipoprotein; Membrane; Metal-binding; Microphthalmia; Palmitate;
Protease; Reference proteome; Signal; Zinc.
SIGNAL 1 23 {ECO:0000269|PubMed:9593755}.
CHAIN 24 462 Sonic hedgehog protein.
/FTId=PRO_0000013208.
CHAIN 24 197 Sonic hedgehog protein N-product.
/FTId=PRO_0000013209.
MOTIF 32 38 Cardin-Weintraub.
{ECO:0000269|PubMed:23118222}.
COMPBIAS 407 411 Poly-Gly.
METAL 89 89 Calcium 1. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 90 90 Calcium 1. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 90 90 Calcium 2. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 95 95 Calcium 1. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 125 125 Calcium 1; via carbonyl oxygen.
{ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 126 126 Calcium 1. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 126 126 Calcium 2. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 129 129 Calcium 2. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 131 131 Calcium 2. {ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:20504762}.
METAL 140 140 Zinc. {ECO:0000244|PDB:3M1N,
ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:10753901,
ECO:0000269|PubMed:20504762}.
METAL 147 147 Zinc. {ECO:0000244|PDB:3M1N,
ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:10753901,
ECO:0000269|PubMed:20504762}.
METAL 182 182 Zinc. {ECO:0000244|PDB:3M1N,
ECO:0000244|PDB:3MXW,
ECO:0000269|PubMed:10753901,
ECO:0000269|PubMed:20504762}.
SITE 197 198 Cleavage; by autolysis. {ECO:0000250}.
SITE 243 243 Involved in cholesterol transfer.
{ECO:0000250}.
SITE 267 267 Involved in auto-cleavage. {ECO:0000250}.
SITE 270 270 Essential for auto-cleavage.
{ECO:0000250}.
LIPID 24 24 N-palmitoyl cysteine.
{ECO:0000269|PubMed:9593755}.
LIPID 197 197 Cholesterol glycine ester. {ECO:0000250}.
CARBOHYD 278 278 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16335952}.
VARIANT 6 6 R -> T (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023804.
VARIANT 17 17 L -> P (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062592.
VARIANT 26 26 P -> L (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062593.
VARIANT 27 27 G -> A (in HPE3).
{ECO:0000269|PubMed:15107988,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039888.
VARIANT 31 31 G -> R (in HPE3; the same mutation in the
mouse sequence introduces a cleavage site
for a furin-like protease resulting in
abnormal protein processing; cleavage at
this site removes 11 amino acids from the
N-terminal domain and reduces affinity of
Shh for Ptch1 and signaling potency in
assays using chicken embryo neural plate
explants and mouse C3H10T1/2 stem cells;
dbSNP:rs28936675).
{ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:8896572,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_003619.
VARIANT 39 39 L -> P (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062594.
VARIANT 53 53 E -> K (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062595.
VARIANT 83 83 D -> V (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062596.
VARIANT 84 84 I -> F (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062597.
VARIANT 88 88 D -> V (in HPE3; familial; the same
mutation in the mouse sequence moderately
reduces Ptch1 binding in vitro and
signaling potency in chicken embryo
neural plate explant assays compared with
wild-type sequence; dbSNP:rs104894050).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009163.
VARIANT 100 100 Q -> H (in HPE3; sporadic; in the mouse
sequence does not affect signaling
activity in any of Shh signaling assays
and causes no apparent defects in
cholesterol-mediated autoprocessing
reactions; dbSNP:rs587778792).
{ECO:0000269|PubMed:10441331,
ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009164.
VARIANT 102 102 C -> R (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062598.
VARIANT 102 102 C -> Y (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062599.
VARIANT 106 107 Missing (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023805.
VARIANT 109 109 L -> F (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062600.
VARIANT 110 110 A -> D (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023806.
VARIANT 110 110 A -> T (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062601.
VARIANT 111 111 I -> F (in SMMCI; dbSNP:rs104894049).
{ECO:0000269|PubMed:11471164,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_017883.
VARIANT 111 111 I -> N (in HPE3).
{ECO:0000269|PubMed:15942952,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039889.
VARIANT 115 115 N -> K (in HPE3; familial; in the mouse
sequence shows no change in activities at
different temperatures;
dbSNP:rs267607047).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009165.
VARIANT 117 117 W -> G (in HPE3; the same mutation in the
mouse sequence causes a failure of Shh
processing leading to retention of the
immature glycosylated protein within the
endoplasmic reticulum of transfected
cells; causes a temperature-dependent
conformational change that allows Shh to
bind Ptch1 at 4 or 32 degrees Celsius but
not at 37 degrees Celsius; the mutation
drastically reduces signaling potency in
chicken embryo neural plate explant
assays; dbSNP:rs104894040).
{ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:8896572,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_003620.
VARIANT 117 117 W -> R (in HPE3; the same mutation in the
mouse sequence causes a failure of Shh
processing leading to retention of the
immature glycosylated protein within the
endoplasmic reticulum of transfected
cells; causes a temperature-dependent
conformational change that allows Shh to
bind Ptch1 at 4 or 32 degrees Celsius but
not at 37 degrees Celsius; drastically
reduces signaling potency in chicken
embryo neural plate explant assays;
dbSNP:rs104894040).
{ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:8896572,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_003621.
VARIANT 124 124 V -> M (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062602.
VARIANT 136 136 E -> K (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062603.
VARIANT 140 140 H -> P (in HPE3).
{ECO:0000269|PubMed:11479728,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039890.
VARIANT 140 140 H -> Q (in HPE3).
{ECO:0000269|PubMed:15942953,
ECO:0000269|PubMed:17001669,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039891.
VARIANT 143 143 G -> D (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062604.
VARIANT 144 144 R -> P (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062605.
VARIANT 147 147 D -> N (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062606.
VARIANT 150 150 T -> K (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062607.
VARIANT 150 150 T -> R (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023807.
VARIANT 156 156 S -> R (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062608.
VARIANT 170 170 F -> C (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062609.
VARIANT 171 171 D -> H (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062610.
VARIANT 176 178 Missing (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023808.
VARIANT 183 183 C -> F (in HPE3).
{ECO:0000269|PubMed:11479728,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039892.
VARIANT 183 183 C -> R (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062611.
VARIANT 183 183 C -> Y (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062612.
VARIANT 184 184 S -> L (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062613.
VARIANT 188 188 E -> Q (in HPE3; familial;
dbSNP:rs587778799).
{ECO:0000269|PubMed:10441331,
ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:16282375,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009166.
VARIANT 196 200 Missing (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062614.
VARIANT 196 196 G -> E (in HPE3; dbSNP:rs752650571).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062615.
VARIANT 197 197 G -> V (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062616.
VARIANT 198 198 C -> F (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062617.
VARIANT 198 198 C -> S (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062618.
VARIANT 218 218 L -> P (in HPE3).
{ECO:0000269|PubMed:17001669,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_062619.
VARIANT 222 222 D -> N (in HPE3; familial;
dbSNP:rs587778805).
{ECO:0000269|PubMed:10441331,
ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009167.
VARIANT 224 224 V -> E (in HPE3; dbSNP:rs104894042).
{ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_009168.
VARIANT 226 226 A -> T (in HPE3; familial;
dbSNP:rs104894043).
{ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_009169.
VARIANT 231 231 G -> V (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062620.
VARIANT 232 232 R -> G (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062621.
VARIANT 234 234 L -> P (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062622.
VARIANT 236 236 S -> N (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062623.
VARIANT 236 236 S -> R (in HPE3; familial;
dbSNP:rs587778806).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009170.
VARIANT 241 241 F -> L (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062624.
VARIANT 241 241 F -> V (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062625.
VARIANT 255 255 I -> N (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062626.
VARIANT 263 269 Missing (in HPE3; sporadic).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009171.
VARIANT 267 267 T -> I (in HPE3).
{ECO:0000269|PubMed:15107988,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039893.
VARIANT 271 271 L -> P (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023809.
VARIANT 275 275 A -> E (in HPE3; dbSNP:rs556192490).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062627.
VARIANT 280 280 S -> W (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062628.
VARIANT 290 290 G -> D (in HPE3; sporadic;
dbSNP:rs104894047).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009172.
VARIANT 296 296 G -> A (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062629.
VARIANT 310 310 R -> C (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062630.
VARIANT 321 321 R -> S (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062631.
VARIANT 332 332 V -> A (in HPE3 and SMMCI;
dbSNP:rs104894052).
{ECO:0000269|PubMed:15103725,
ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023810.
VARIANT 346 346 A -> V (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062632.
VARIANT 347 347 P -> L (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062633.
VARIANT 347 347 P -> Q (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023811.
VARIANT 347 347 P -> R (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062634.
VARIANT 354 354 I -> T (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023812.
VARIANT 362 362 S -> L (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062635.
VARIANT 363 363 C -> Y (in HPE3).
{ECO:0000269|PubMed:17001669,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_062636.
VARIANT 364 364 Y -> C (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062637.
VARIANT 373 373 A -> T (in HPE3).
{ECO:0000269|PubMed:15107988,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_039894.
VARIANT 374 374 H -> R (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062638.
VARIANT 376 376 A -> D (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062639.
VARIANT 377 377 F -> S (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062640.
VARIANT 378 380 Missing (in HPE3; familial).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_009173.
VARIANT 381 381 R -> P (in HPE3).
{ECO:0000269|PubMed:15221788,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_023813.
VARIANT 382 382 L -> P (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062641.
VARIANT 383 383 A -> T (in HPE3; sporadic;
dbSNP:rs137853341).
{ECO:0000269|PubMed:19603532,
ECO:0000269|PubMed:9302262}.
/FTId=VAR_009174.
VARIANT 391 391 A -> T (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062642.
VARIANT 401 408 Missing (in ocular coloboma).
{ECO:0000269|PubMed:12503095}.
/FTId=VAR_017884.
VARIANT 402 409 Missing (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062643.
VARIANT 404 408 Missing (in HPE3; familial).
/FTId=VAR_009175.
VARIANT 405 409 Missing (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062644.
VARIANT 411 411 G -> GG (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062645.
VARIANT 416 416 T -> A (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062646.
VARIANT 424 424 P -> A (in HPE3; familial;
dbSNP:rs104894048).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009176.
VARIANT 435 435 Y -> N (in HPE3).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062647.
VARIANT 436 436 S -> L (in HPE3; sporadic).
{ECO:0000269|PubMed:10556296,
ECO:0000269|PubMed:19603532}.
/FTId=VAR_009177.
VARIANT 456 456 G -> R (in HPE3; unknown pathological
significance).
{ECO:0000269|PubMed:19603532}.
/FTId=VAR_062648.
MUTAGEN 24 24 C->S: Abolishes palmitoylation.
{ECO:0000269|PubMed:9593755}.
STRAND 30 32 {ECO:0000244|PDB:3M1N}.
STRAND 47 51 {ECO:0000244|PDB:3MXW}.
TURN 56 59 {ECO:0000244|PDB:3MXW}.
HELIX 72 75 {ECO:0000244|PDB:3MXW}.
STRAND 84 86 {ECO:0000244|PDB:3MXW}.
STRAND 91 93 {ECO:0000244|PDB:3MXW}.
HELIX 94 96 {ECO:0000244|PDB:3MXW}.
HELIX 100 116 {ECO:0000244|PDB:3MXW}.
STRAND 122 128 {ECO:0000244|PDB:3MXW}.
HELIX 139 142 {ECO:0000244|PDB:3MXW}.
STRAND 145 150 {ECO:0000244|PDB:3MXW}.
HELIX 155 157 {ECO:0000244|PDB:3MXW}.
HELIX 158 167 {ECO:0000244|PDB:3MXW}.
STRAND 171 177 {ECO:0000244|PDB:3MXW}.
STRAND 180 184 {ECO:0000244|PDB:3MXW}.
HELIX 188 190 {ECO:0000244|PDB:3MXW}.
SEQUENCE 462 AA; 49607 MW; DD687AFA582A4749 CRC64;
MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN VAEKTLGASG
RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ RCKDKLNALA ISVMNQWPGV
KLRVTEGWDE DGHHSEESLH YEGRAVDITT SDRDRSKYGM LARLAVEAGF DWVYYESKAH
IHCSVKAENS VAAKSGGCFP GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT
FLDRDDGAKK VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG
PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA QGTILINRVL
ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD SGGGDRGGGG GRVALTAPGA
ADAPGAGATA GIHWYSQLLY QIGTWLLDSE ALHPLGMAVK SS


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orb80100 Human Sonic HedgeHog protein Sonic HedgeHog Recombinant Human produced in E.coli is a single, non-glycosylated polypeptide chain containing 175 amino acids and having a molecular mass of 19,683 Dalton 5
103-M269 Sonic Hedgehog (Shh) C-terminal Anti-Mouse Host: Rat Shh; Hx; Dsh; Hhg1; Hxl3; M100081; 9530036O11Rik 100
103-M269 Sonic Hedgehog (Shh) C-terminal, Host: Rat, Species: Anti-Mouse, Synonyms: Shh; Hx; Dsh; Hhg1; Hxl3; M100081; 9530036O11Rik 100 ug
100-153 Sonic Hedgehog Human Host: E. coli Sonic Hedgehog 25
31-337 SDCBP was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains tandemly repeated PDZ domains that bind the cytoplasmic, C-terminal 0.1 mg
28-521 ANXA11 is a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain the calciu 0.1 mg
27-363 Members of the CELF_BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM 0.05 mg
29-261 Members of the CELF_BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM 0.05 mg
29-260 Members of the CELF_BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM 0.1 mg
25-600 Members of the CELF_BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM 0.05 mg
hAP-0240 Mouse anti human Sonic Hedgehog (N-terminal) Anti-Human antibodies 100.00 ug
mAP-0128 Rat monoclonal anti mouse Sonic Hedgehog (Shh) C-Terminal Anti-Mouse antibodies 100.00 ug
18-272-196208 Sonic Hedgehog - Goat polyclonal to Sonic Hedgehog Polyclonal 0.05 mg
28-565 The KCTD11 gene encodes a protein that has been identified as a suppressor of Hedgehog signaling. Its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblasto 0.1 mg
28-319 The KCTD11 gene encodes a protein that has been identified as a suppressor of Hedgehog signaling. Its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblasto 0.1 mg
CSB-EL021266RA Rat Sonic hedgehog protein(SHH) ELISA kit 96T
ER601 Sonic hedgehog protein Elisa Kit 96T
H2301 Sonic hedgehog protein (SHH), Rat, ELISA Kit 96T
EH605 Sonic hedgehog protein Elisa Kit 96T
orb90959 Human Sonic Hedgehog gene Human Sonic Hedgehog gene is a cDNA gene. For research use only. 10
27-092 SH3BP2 has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 a 0.05 mg
AJ1731a Sonic-Hedgehog (SHH) Antibody (C-Product)
CSB-EL021266CH Chicken Sonic hedgehog protein(SHH) ELISA kit 96T


 

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