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Transcription factor SOX-3

 SOX3_HUMAN              Reviewed;         446 AA.
P41225; P35714; Q5JWI3; Q9NP49;
01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
07-JUN-2004, sequence version 2.
25-OCT-2017, entry version 149.
RecName: Full=Transcription factor SOX-3;
Name=SOX3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=8111369; DOI=10.1093/hmg/2.12.2013;
Stevanovic M., Lovell-Badge R., Collignon J., Goodfellow P.N.;
"SOX3 is an X-linked gene related to SRY.";
Hum. Mol. Genet. 2:2013-2018(1993).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Gorry M.C., Hart P.S., Sashi V., Hart T.C.;
"Clarification of the genomic sequence for human SOX3.";
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15772651; DOI=10.1038/nature03440;
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence of the human X chromosome.";
Nature 434:325-337(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 150-203.
PubMed=1614875; DOI=10.1093/nar/20.11.2887;
Denny P., Swift S., Brand N., Dabhade N., Barton P., Ashworth A.;
"A conserved family of genes related to the testis determining gene,
SRY.";
Nucleic Acids Res. 20:2887-2887(1992).
[6]
FUNCTION, AND INVOLVEMENT IN SRXX3.
PubMed=21183788; DOI=10.1172/JCI42580;
Sutton E., Hughes J., White S., Sekido R., Tan J., Arboleda V.,
Rogers N., Knower K., Rowley L., Eyre H., Rizzoti K., McAninch D.,
Goncalves J., Slee J., Turbitt E., Bruno D., Bengtsson H., Harley V.,
Vilain E., Sinclair A., Lovell-Badge R., Thomas P.;
"Identification of SOX3 as an XX male sex reversal gene in mice and
humans.";
J. Clin. Invest. 121:328-341(2011).
[7]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21406692; DOI=10.1126/scisignal.2001570;
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
Blagoev B.;
"System-wide temporal characterization of the proteome and
phosphoproteome of human embryonic stem cell differentiation.";
Sci. Signal. 4:RS3-RS3(2011).
[8]
VARIANT MRXGH ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS.
PubMed=12428212; DOI=10.1086/344661;
Laumonnier F., Ronce N., Hamel B.C.J., Thomas P., Lespinasse J.,
Raynaud M., Paringaux C., Van Bokhoven H., Kalscheuer V., Fryns J.-P.,
Chelly J., Moraine C., Briault S.;
"Transcription factor SOX3 is involved in X-linked mental retardation
with growth hormone deficiency.";
Am. J. Hum. Genet. 71:1450-1455(2002).
[9]
VARIANT PHPX ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS, AND VARIANT THR-43.
PubMed=15800844; DOI=10.1086/430134;
Woods K.S., Cundall M., Turton J., Rizotti K., Mehta A., Palmer R.,
Wong J., Chong W.K., Al-Zyoud M., El-Ali M., Otonkoski T.,
Martinez-Barbera J.-P., Thomas P.Q., Robinson I.C., Lovell-Badge R.,
Woodward K.J., Dattani M.T.;
"Over- and underdosage of SOX3 is associated with infundibular
hypoplasia and hypopituitarism.";
Am. J. Hum. Genet. 76:833-849(2005).
-!- FUNCTION: Transcription factor required during the formation of
the hypothalamo-pituitary axis. May function as a switch in
neuronal development. Keeps neural cells undifferentiated by
counteracting the activity of proneural proteins and suppresses
neuronal differentiation. Required also within the pharyngeal
epithelia for craniofacial morphogenesis. Controls a genetic
switch in male development. Is necessary for initiating male sex
determination by directing the development of supporting cell
precursors (pre-Sertoli cells) as Sertoli rather than granulosa
cells (By similarity). {ECO:0000250, ECO:0000269|PubMed:21183788}.
-!- SUBUNIT: Interacts with SOX2 and FGFR1. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus.
-!- DISEASE: Panhypopituitarism X-linked (PHPX) [MIM:312000]: Affected
individuals have absent infundibulum, anterior pituitary
hypoplasia, and ectopic posterior pituitary.
{ECO:0000269|PubMed:15800844}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Mental retardation, X-linked, with isolated growth
hormone deficiency (MRXGH) [MIM:300123]: A disorder characterized
by the association of variable degrees of mental retardation with
panhypopituitarism, variable combinations of hypothyroidism,
delayed pubertal development, and short stature due to growth
hormone deficiency. {ECO:0000269|PubMed:12428212}. Note=The
disease is caused by mutations affecting the gene represented in
this entry.
-!- DISEASE: 46,XX sex reversal 3 (SRXX3) [MIM:300833]: A condition in
which male gonads develop in a genetic female (female to male sex
reversal). {ECO:0000269|PubMed:21183788}. Note=The disease is
caused by mutations affecting the gene represented in this entry.
Copy number variations (CNV) encompassing or in close proximity to
SOX3 are responsible for XX male reversal. These variations
include two duplications of approximately 123 kb and 85 kb, the
former of which spans the entire SOX3 gene; a 343 kb deletion
immediately upstream of SOX3 that is probably responsible of
altered regulation (and not increased dosage) of SOX3; a large
(approximately 6 Mb) duplication that encompasses SOX3 and at
least 18 additional distally located genes. Its proximal
breakpoint falls within the SOX3 regulatory region. This large
rearrangement has been found in a patient with XX male reversal
and a complex phenotype that also includes a scrotal hypoplasia,
microcephaly, developmental delay, and growth retardation.
-!- CAUTION: Was originally termed SOX-9.
{ECO:0000305|PubMed:1614875}.
-----------------------------------------------------------------------
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EMBL; X71135; CAA50465.1; -; Genomic_DNA.
EMBL; AF264713; AAF73059.1; -; Genomic_DNA.
EMBL; AL121875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC093863; AAH93863.1; -; mRNA.
EMBL; BC093865; AAH93865.1; -; mRNA.
EMBL; X65665; CAA46616.1; -; mRNA.
CCDS; CCDS14669.1; -.
PIR; I38239; I38239.
PIR; S22942; S22942.
RefSeq; NP_005625.2; NM_005634.2.
UniGene; Hs.157429; -.
ProteinModelPortal; P41225; -.
SMR; P41225; -.
BioGrid; 112541; 1.
IntAct; P41225; 3.
STRING; 9606.ENSP00000359567; -.
iPTMnet; P41225; -.
PhosphoSitePlus; P41225; -.
BioMuta; SOX3; -.
DMDM; 48429228; -.
EPD; P41225; -.
PaxDb; P41225; -.
PeptideAtlas; P41225; -.
PRIDE; P41225; -.
Ensembl; ENST00000370536; ENSP00000359567; ENSG00000134595.
GeneID; 6658; -.
KEGG; hsa:6658; -.
UCSC; uc004fbd.2; human.
CTD; 6658; -.
DisGeNET; 6658; -.
EuPathDB; HostDB:ENSG00000134595.7; -.
GeneCards; SOX3; -.
HGNC; HGNC:11199; SOX3.
HPA; HPA054720; -.
HPA; HPA075003; -.
MalaCards; SOX3; -.
MIM; 300123; phenotype.
MIM; 300833; phenotype.
MIM; 312000; phenotype.
MIM; 313430; gene.
neXtProt; NX_P41225; -.
OpenTargets; ENSG00000134595; -.
Orphanet; 393; 46,XX testicular disorder of sex development.
Orphanet; 90695; Panhypopituitarism.
Orphanet; 3157; Septo-optic dysplasia.
Orphanet; 79495; X-linked congenital generalized hypertrichosis.
Orphanet; 67045; X-linked intellectual disability with isolated growth hormone deficiency.
PharmGKB; PA36036; -.
eggNOG; KOG0527; Eukaryota.
eggNOG; ENOG410XT0K; LUCA.
GeneTree; ENSGT00760000118988; -.
HOGENOM; HOG000231647; -.
HOVERGEN; HBG105663; -.
InParanoid; P41225; -.
KO; K09267; -.
OMA; HQHYQSA; -.
OrthoDB; EOG091G0F15; -.
PhylomeDB; P41225; -.
TreeFam; TF351735; -.
Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
SIGNOR; P41225; -.
GeneWiki; SOX3; -.
GenomeRNAi; 6658; -.
PRO; PR:P41225; -.
Proteomes; UP000005640; Chromosome X.
Bgee; ENSG00000134595; -.
CleanEx; HS_SOX3; -.
Genevisible; P41225; HS.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0003677; F:DNA binding; TAS:ProtInc.
GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; ISS:UniProtKB.
GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
GO; GO:0060324; P:face development; ISS:UniProtKB.
GO; GO:0021854; P:hypothalamus development; ISS:UniProtKB.
GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
GO; GO:0021983; P:pituitary gland development; ISS:UniProtKB.
GO; GO:0007423; P:sensory organ development; ISS:UniProtKB.
GO; GO:0007530; P:sex determination; IMP:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
Gene3D; 1.10.30.10; -; 1.
InterPro; IPR009071; HMG_box_dom.
InterPro; IPR036910; HMG_box_dom_sf.
InterPro; IPR022097; SOX_fam.
Pfam; PF00505; HMG_box; 1.
Pfam; PF12336; SOXp; 1.
SMART; SM00398; HMG; 1.
SUPFAM; SSF47095; SSF47095; 1.
PROSITE; PS50118; HMG_BOX_2; 1.
1: Evidence at protein level;
Complete proteome; Developmental protein; Disease mutation;
DNA-binding; Mental retardation; Nucleus; Polymorphism;
Reference proteome; Transcription; Transcription regulation.
CHAIN 1 446 Transcription factor SOX-3.
/FTId=PRO_0000048720.
DNA_BIND 139 207 HMG box. {ECO:0000255|PROSITE-
ProRule:PRU00267}.
COMPBIAS 129 133 Poly-Gly.
COMPBIAS 234 248 Poly-Ala.
COMPBIAS 290 294 Poly-Pro.
COMPBIAS 324 330 Poly-Ala.
COMPBIAS 340 347 Poly-Ala.
COMPBIAS 353 364 Poly-Ala.
VARIANT 43 43 A -> T (in dbSNP:rs73637709).
{ECO:0000269|PubMed:15800844}.
/FTId=VAR_026451.
VARIANT 248 248 A -> AAAAAAAA (in PHPX; reduced
transcriptional activity and impaired
nuclear localization).
{ECO:0000269|PubMed:15800844}.
/FTId=VAR_026452.
VARIANT 248 248 A -> AAAAAAAAAAAA (in MRXGH).
{ECO:0000269|PubMed:12428212}.
/FTId=VAR_033258.
CONFLICT 159 159 L -> Q (in Ref. 5; CAA46616).
{ECO:0000305}.
CONFLICT 176 176 D -> E (in Ref. 5; CAA46616).
{ECO:0000305}.
CONFLICT 202 202 E -> D (in Ref. 5; CAA46616).
{ECO:0000305}.
CONFLICT 297 299 Missing (in Ref. 2; CAA50465).
{ECO:0000305}.
SEQUENCE 446 AA; 45210 MW; F79E79C2D16BB929 CRC64;
MRPVRENSSG ARSPRVPADL ARSILISLPF PPDSLAHRPP SSAPTESQGL FTVAAPAPGA
PSPPATLAHL LPAPAMYSLL ETELKNPVGT PTQAAGTGGP AAPGGAGKSS ANAAGGANSG
GGSSGGASGG GGGTDQDRVK RPMNAFMVWS RGQRRKMALE NPKMHNSEIS KRLGADWKLL
TDAEKRPFID EAKRLRAVHM KEYPDYKYRP RRKTKTLLKK DKYSLPSGLL PPGAAAAAAA
AAAAAAAASS PVGVGQRLDT YTHVNGWANG AYSLVQEQLG YAQPPSMSSP PPPPALPPMH
RYDMAGLQYS PMMPPGAQSY MNVAAAAAAA SGYGGMAPSA TAAAAAAYGQ QPATAAAAAA
AAAAMSLGPM GSVVKSEPSS PPPAIASHSQ RACLGDLRDM ISMYLPPGGD AADAASPLPG
GRLHGVHQHY QGAGTAVNGT VPLTHI


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