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Transcription factor SOX-17

 SOX17_HUMAN             Reviewed;         414 AA.
Q9H6I2;
10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
01-MAR-2001, sequence version 1.
12-SEP-2018, entry version 145.
RecName: Full=Transcription factor SOX-17;
Name=SOX17;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=11786926;
Katoh M.;
"Molecular cloning and characterization of human SOX17.";
Int. J. Mol. Med. 9:153-157(2002).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
STRUCTURE BY NMR OF 62-139.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the HMG box of human transcription factor SOX-
17.";
Submitted (APR-2008) to the PDB data bank.
[4]
VARIANTS VUR3 17-GLN--GLN-19 INS; CYS-178 AND ASN-259.
PubMed=20960469; DOI=10.1002/humu.21378;
Gimelli S., Caridi G., Beri S., McCracken K., Bocciardi R., Zordan P.,
Dagnino M., Fiorio P., Murer L., Benetti E., Zuffardi O., Giorda R.,
Wells J.M., Gimelli G., Ghiggeri G.M.;
"Mutations in SOX17 are associated with congenital anomalies of the
kidney and the urinary tract.";
Hum. Mutat. 31:1352-1359(2010).
[5]
VARIANT ASP-33.
PubMed=27592148; DOI=10.1016/j.ejmg.2016.08.012;
Varma H., Faust P.L., Iglesias A.D., Lagana S.M., Wou K., Hirano M.,
DiMauro S., Mansukani M.M., Hoff K.E., Nagy P.L., Copeland W.C.,
Naini A.B.;
"Whole exome sequencing identifies a homozygous POLG2 missense variant
in an infant with fulminant hepatic failure and mitochondrial DNA
depletion.";
Eur. J. Med. Genet. 59:540-545(2016).
-!- FUNCTION: Acts as transcription regulator that binds target
promoter DNA and bends the DNA. Binds to the sequences 5'-
AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation
via WNT3A. Inhibits Wnt signaling. Promotes degradation of
activated CTNNB1. Plays a key role in the regulation of embryonic
development. Required for normal looping of the embryonic heart
tube. Required for normal development of the definitive gut
endoderm. Probable transcriptional activator in the premeiotic
germ cells (By similarity). {ECO:0000250}.
-!- SUBUNIT: Interacts with CTNNB1, LEF1 and TCF4. {ECO:0000250}.
-!- INTERACTION:
P35222:CTNNB1; NbExp=2; IntAct=EBI-9106753, EBI-491549;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00267}.
-!- TISSUE SPECIFICITY: Expressed in adult heart, lung, spleen,
testis, ovary, placenta, fetal lung, and kidney. In normal
gastrointestinal tract, it is preferentially expressed in
esophagus, stomach and small intestine than in colon and rectum.
{ECO:0000269|PubMed:11786926}.
-!- DISEASE: Vesicoureteral reflux 3 (VUR3) [MIM:613674]: A disease
belonging to the group of congenital anomalies of the kidney and
urinary tract. It is characterized by the reflux of urine from the
bladder into the ureters and sometimes into the kidneys, and is a
risk factor for urinary tract infections. Primary disease results
from a developmental defect of the ureterovesical junction. In
combination with intrarenal reflux, the resulting inflammatory
reaction may result in renal injury or scarring, also called
reflux nephropathy. Extensive renal scarring impairs renal
function and may predispose patients to hypertension, proteinuria,
renal insufficiency and end-stage renal disease.
{ECO:0000269|PubMed:20960469}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
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EMBL; AB073988; BAB83867.1; -; mRNA.
EMBL; AK025905; BAB15277.1; -; mRNA.
CCDS; CCDS6159.1; -.
RefSeq; NP_071899.1; NM_022454.3.
UniGene; Hs.98367; -.
PDB; 2YUL; NMR; -; A=68-136.
PDB; 4A3N; X-ray; 2.40 A; A=68-136.
PDBsum; 2YUL; -.
PDBsum; 4A3N; -.
ProteinModelPortal; Q9H6I2; -.
SMR; Q9H6I2; -.
BioGrid; 122134; 4.
IntAct; Q9H6I2; 7.
STRING; 9606.ENSP00000297316; -.
iPTMnet; Q9H6I2; -.
PhosphoSitePlus; Q9H6I2; -.
BioMuta; SOX17; -.
DMDM; 23822216; -.
PaxDb; Q9H6I2; -.
PeptideAtlas; Q9H6I2; -.
PRIDE; Q9H6I2; -.
ProteomicsDB; 80988; -.
DNASU; 64321; -.
Ensembl; ENST00000297316; ENSP00000297316; ENSG00000164736.
GeneID; 64321; -.
KEGG; hsa:64321; -.
UCSC; uc003xsb.5; human.
CTD; 64321; -.
DisGeNET; 64321; -.
EuPathDB; HostDB:ENSG00000164736.5; -.
GeneCards; SOX17; -.
H-InvDB; HIX0034521; -.
HGNC; HGNC:18122; SOX17.
HPA; CAB025594; -.
HPA; HPA068399; -.
MalaCards; SOX17; -.
MIM; 610928; gene.
MIM; 613674; phenotype.
neXtProt; NX_Q9H6I2; -.
OpenTargets; ENSG00000164736; -.
Orphanet; 289365; Familial vesicoureteral reflux.
PharmGKB; PA38296; -.
eggNOG; ENOG410KD20; Eukaryota.
eggNOG; ENOG41114B8; LUCA.
GeneTree; ENSGT00760000118988; -.
HOGENOM; HOG000069999; -.
HOVERGEN; HBG000517; -.
InParanoid; Q9H6I2; -.
KO; K04495; -.
OMA; HMGGHYR; -.
OrthoDB; EOG091G0CYU; -.
PhylomeDB; Q9H6I2; -.
Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
SIGNOR; Q9H6I2; -.
EvolutionaryTrace; Q9H6I2; -.
GenomeRNAi; 64321; -.
PRO; PR:Q9H6I2; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000164736; Expressed in 142 organ(s), highest expression level in endometrium.
CleanEx; HS_SOX17; -.
Genevisible; Q9H6I2; HS.
GO; GO:0044798; C:nuclear transcription factor complex; IEA:Ensembl.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; ISA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; ISS:BHF-UCL.
GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISS:BHF-UCL.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0001525; P:angiogenesis; ISS:BHF-UCL.
GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0060913; P:cardiac cell fate determination; IMP:BHF-UCL.
GO; GO:0003142; P:cardiogenic plate morphogenesis; ISS:BHF-UCL.
GO; GO:0042074; P:cell migration involved in gastrulation; IEA:Ensembl.
GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
GO; GO:0061009; P:common bile duct development; IEA:Ensembl.
GO; GO:0048617; P:embryonic foregut morphogenesis; ISS:BHF-UCL.
GO; GO:0035050; P:embryonic heart tube development; ISS:BHF-UCL.
GO; GO:0003143; P:embryonic heart tube morphogenesis; ISS:BHF-UCL.
GO; GO:0060956; P:endocardial cell differentiation; ISS:BHF-UCL.
GO; GO:0060214; P:endocardium formation; ISS:BHF-UCL.
GO; GO:0001706; P:endoderm formation; IDA:UniProtKB.
GO; GO:0007493; P:endodermal cell fate determination; IEA:Ensembl.
GO; GO:0061031; P:endodermal digestive tract morphogenesis; ISS:BHF-UCL.
GO; GO:0061010; P:gall bladder development; IEA:Ensembl.
GO; GO:0060914; P:heart formation; TAS:BHF-UCL.
GO; GO:0001947; P:heart looping; ISS:UniProtKB.
GO; GO:0001828; P:inner cell mass cellular morphogenesis; IEA:Ensembl.
GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:BHF-UCL.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
GO; GO:0042662; P:negative regulation of mesodermal cell fate specification; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
GO; GO:0003308; P:negative regulation of Wnt signaling pathway involved in heart development; IEA:Ensembl.
GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
GO; GO:0031648; P:protein destabilization; IMP:BHF-UCL.
GO; GO:0050821; P:protein stabilization; IMP:BHF-UCL.
GO; GO:2000043; P:regulation of cardiac cell fate specification; IEA:Ensembl.
GO; GO:0045995; P:regulation of embryonic development; ISS:UniProtKB.
GO; GO:2000035; P:regulation of stem cell division; IEA:Ensembl.
GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
GO; GO:0060807; P:regulation of transcription from RNA polymerase II promoter involved in definitive endodermal cell fate specification; ISS:BHF-UCL.
GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0072001; P:renal system development; IMP:BHF-UCL.
GO; GO:0021903; P:rostrocaudal neural tube patterning; IEA:Ensembl.
GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
GO; GO:0048866; P:stem cell fate specification; IEA:Ensembl.
GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL.
Gene3D; 1.10.30.10; -; 1.
InterPro; IPR009071; HMG_box_dom.
InterPro; IPR036910; HMG_box_dom_sf.
InterPro; IPR033392; Sox7/17/18_central.
InterPro; IPR021934; Sox_C.
Pfam; PF00505; HMG_box; 1.
Pfam; PF12067; Sox17_18_mid; 1.
SMART; SM00398; HMG; 1.
SUPFAM; SSF47095; SSF47095; 1.
PROSITE; PS50118; HMG_BOX_2; 1.
PROSITE; PS51516; SOX_C; 1.
1: Evidence at protein level;
3D-structure; Activator; Complete proteome; Disease mutation;
DNA-binding; Nucleus; Reference proteome; Transcription;
Transcription regulation; Wnt signaling pathway.
CHAIN 1 414 Transcription factor SOX-17.
/FTId=PRO_0000048765.
DOMAIN 280 413 Sox C-terminal. {ECO:0000255|PROSITE-
ProRule:PRU00849}.
DNA_BIND 68 136 HMG box. {ECO:0000255|PROSITE-
ProRule:PRU00267}.
COMPBIAS 312 351 Gln/Pro-rich.
VARIANT 17 17 Q -> QTQ (in VUR3).
/FTId=VAR_065168.
VARIANT 33 33 A -> D (in dbSNP:rs189384157).
{ECO:0000269|PubMed:27592148}.
/FTId=VAR_078774.
VARIANT 178 178 G -> C (in VUR3; dbSNP:rs267607082).
{ECO:0000269|PubMed:20960469}.
/FTId=VAR_065169.
VARIANT 259 259 Y -> N (in VUR3; increased levels of the
mutant protein that is associated with
increased suppression of CTNNB1 signaling
of the Wnt pathway compared to wild-type;
dbSNP:rs267607083).
{ECO:0000269|PubMed:20960469}.
/FTId=VAR_065170.
HELIX 74 87 {ECO:0000244|PDB:4A3N}.
HELIX 95 108 {ECO:0000244|PDB:4A3N}.
HELIX 111 129 {ECO:0000244|PDB:4A3N}.
SEQUENCE 414 AA; 44117 MW; C78D1F24BA00ECD1 CRC64;
MSSPDAGYAS DDQSQTQSAL PAVMAGLGPC PWAESLSPIG DMKVKGEAPA NSGAPAGAAG
RAKGESRIRR PMNAFMVWAK DERKRLAQQN PDLHNAELSK MLGKSWKALT LAEKRPFVEE
AERLRVQHMQ DHPNYKYRPR RRKQVKRLKR VEGGFLHGLA EPQAAALGPE GGRVAMDGLG
LQFPEQGFPA GPPLLPPHMG GHYRDCQSLG APPLDGYPLP TPDTSPLDGV DPDPAFFAAP
MPGDCPAAGT YSYAQVSDYA GPPEPPAGPM HPRLGPEPAG PSIPGLLAPP SALHVYYGAM
GSPGAGGGRG FQMQPQHQHQ HQHQHHPPGP GQPSPPPEAL PCRDGTDPSQ PAELLGEVDR
TEFEQYLHFV CKPEMGLPYQ GHDSGVNLPD SHGAISSVVS DASSAVYYCN YPDV


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