SOX17_HUMAN
ID SOX17_HUMAN Reviewed; 414 AA.
AC Q9H6I2;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Transcription factor SOX-17;
GN Name=SOX17;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11786926;
RA Katoh M.;
RT "Molecular cloning and characterization of human SOX17.";
RL Int. J. Mol. Med. 9:153-157(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP 9AATAD MOTIF.
RX PubMed=34342803; DOI=10.1007/s12015-021-10225-8;
RA Piskacek M., Otasevic T., Repko M., Knight A.;
RT "The 9aaTAD Activation Domains in the Yamanaka Transcription Factors Oct4,
RT Sox2, Myc, and Klf4.";
RL Stem. Cell. Rev. Rep. 17:1934-1936(2021).
RN [4]
RP STRUCTURE BY NMR OF 62-139.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the HMG box of human transcription factor SOX-17.";
RL Submitted (APR-2008) to the PDB data bank.
RN [5]
RP VARIANTS VUR3 17-GLN--GLN-19 INS; CYS-178 AND ASN-259.
RX PubMed=20960469; DOI=10.1002/humu.21378;
RA Gimelli S., Caridi G., Beri S., McCracken K., Bocciardi R., Zordan P.,
RA Dagnino M., Fiorio P., Murer L., Benetti E., Zuffardi O., Giorda R.,
RA Wells J.M., Gimelli G., Ghiggeri G.M.;
RT "Mutations in SOX17 are associated with congenital anomalies of the kidney
RT and the urinary tract.";
RL Hum. Mutat. 31:1352-1359(2010).
RN [6]
RP VARIANT ASP-33.
RX PubMed=27592148; DOI=10.1016/j.ejmg.2016.08.012;
RA Varma H., Faust P.L., Iglesias A.D., Lagana S.M., Wou K., Hirano M.,
RA DiMauro S., Mansukani M.M., Hoff K.E., Nagy P.L., Copeland W.C.,
RA Naini A.B.;
RT "Whole exome sequencing identifies a homozygous POLG2 missense variant in
RT an infant with fulminant hepatic failure and mitochondrial DNA depletion.";
RL Eur. J. Med. Genet. 59:540-545(2016).
CC -!- FUNCTION: Acts as transcription regulator that binds target promoter
CC DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-
CC AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits
CC Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key
CC role in the regulation of embryonic development. Required for normal
CC development of the definitive gut endoderm. Required for normal looping
CC of the embryonic heart tube. Plays an important role in embryonic and
CC postnatal vascular development, including development of arteries.
CC Plays an important role in postnatal angiogenesis, where it is
CC functionally redundant with SOX18. Required for the generation and
CC maintenance of fetal hematopoietic stem cells, and for fetal
CC hematopoiesis. Probable transcriptional activator in the premeiotic
CC germ cells. {ECO:0000250|UniProtKB:Q61473}.
CC -!- SUBUNIT: Interacts with CTNNB1, LEF1 and TCF4.
CC {ECO:0000250|UniProtKB:Q61473}.
CC -!- INTERACTION:
CC Q9H6I2; P35222: CTNNB1; NbExp=2; IntAct=EBI-9106753, EBI-491549;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267}.
CC -!- TISSUE SPECIFICITY: Expressed in adult heart, lung, spleen, testis,
CC ovary, placenta, fetal lung, and kidney. In normal gastrointestinal
CC tract, it is preferentially expressed in esophagus, stomach and small
CC intestine than in colon and rectum. {ECO:0000269|PubMed:11786926}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:34342803}.
CC -!- DISEASE: Vesicoureteral reflux 3 (VUR3) [MIM:613674]: A disease
CC belonging to the group of congenital anomalies of the kidney and
CC urinary tract. It is characterized by the reflux of urine from the
CC bladder into the ureters and sometimes into the kidneys, and is a risk
CC factor for urinary tract infections. Primary disease results from a
CC developmental defect of the ureterovesical junction. In combination
CC with intrarenal reflux, the resulting inflammatory reaction may result
CC in renal injury or scarring, also called reflux nephropathy. Extensive
CC renal scarring impairs renal function and may predispose patients to
CC hypertension, proteinuria, renal insufficiency and end-stage renal
CC disease. {ECO:0000269|PubMed:20960469}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
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DR EMBL; AB073988; BAB83867.1; -; mRNA.
DR EMBL; AK025905; BAB15277.1; -; mRNA.
DR CCDS; CCDS6159.1; -.
DR RefSeq; NP_071899.1; NM_022454.3.
DR PDB; 2YUL; NMR; -; A=68-136.
DR PDB; 4A3N; X-ray; 2.40 A; A=68-136.
DR PDBsum; 2YUL; -.
DR PDBsum; 4A3N; -.
DR AlphaFoldDB; Q9H6I2; -.
DR SMR; Q9H6I2; -.
DR BioGRID; 122134; 80.
DR IntAct; Q9H6I2; 81.
DR STRING; 9606.ENSP00000297316; -.
DR ChEMBL; CHEMBL4523455; -.
DR iPTMnet; Q9H6I2; -.
DR PhosphoSitePlus; Q9H6I2; -.
DR BioMuta; SOX17; -.
DR DMDM; 23822216; -.
DR jPOST; Q9H6I2; -.
DR MassIVE; Q9H6I2; -.
DR PaxDb; Q9H6I2; -.
DR PeptideAtlas; Q9H6I2; -.
DR PRIDE; Q9H6I2; -.
DR ProteomicsDB; 80988; -.
DR Antibodypedia; 11698; 468 antibodies from 42 providers.
DR DNASU; 64321; -.
DR Ensembl; ENST00000297316.5; ENSP00000297316.4; ENSG00000164736.6.
DR GeneID; 64321; -.
DR KEGG; hsa:64321; -.
DR MANE-Select; ENST00000297316.5; ENSP00000297316.4; NM_022454.4; NP_071899.1.
DR UCSC; uc003xsb.5; human.
DR CTD; 64321; -.
DR DisGeNET; 64321; -.
DR GeneCards; SOX17; -.
DR HGNC; HGNC:18122; SOX17.
DR HPA; ENSG00000164736; Tissue enhanced (adipose tissue, breast).
DR MalaCards; SOX17; -.
DR MIM; 610928; gene.
DR MIM; 613674; phenotype.
DR neXtProt; NX_Q9H6I2; -.
DR OpenTargets; ENSG00000164736; -.
DR Orphanet; 289365; Familial vesicoureteral reflux.
DR PharmGKB; PA38296; -.
DR VEuPathDB; HostDB:ENSG00000164736; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000156694; -.
DR HOGENOM; CLU_044994_0_1_1; -.
DR InParanoid; Q9H6I2; -.
DR OMA; HYRDCQS; -.
DR OrthoDB; 1042753at2759; -.
DR PhylomeDB; Q9H6I2; -.
DR PathwayCommons; Q9H6I2; -.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR SignaLink; Q9H6I2; -.
DR SIGNOR; Q9H6I2; -.
DR BioGRID-ORCS; 64321; 22 hits in 1095 CRISPR screens.
DR EvolutionaryTrace; Q9H6I2; -.
DR GenomeRNAi; 64321; -.
DR Pharos; Q9H6I2; Tbio.
DR PRO; PR:Q9H6I2; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H6I2; protein.
DR Bgee; ENSG00000164736; Expressed in endothelial cell and 121 other tissues.
DR Genevisible; Q9H6I2; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISS:BHF-UCL.
DR GO; GO:0060913; P:cardiac cell fate determination; IMP:BHF-UCL.
DR GO; GO:0003142; P:cardiogenic plate morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IEA:Ensembl.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0061009; P:common bile duct development; IEA:Ensembl.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; ISS:BHF-UCL.
DR GO; GO:0035050; P:embryonic heart tube development; ISS:BHF-UCL.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060956; P:endocardial cell differentiation; ISS:BHF-UCL.
DR GO; GO:0060214; P:endocardium formation; ISS:BHF-UCL.
DR GO; GO:0001706; P:endoderm formation; IDA:UniProtKB.
DR GO; GO:0007493; P:endodermal cell fate determination; IEA:Ensembl.
DR GO; GO:0001714; P:endodermal cell fate specification; ISS:BHF-UCL.
DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0061010; P:gall bladder development; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0060914; P:heart formation; TAS:BHF-UCL.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0001828; P:inner cell mass cellular morphogenesis; IEA:Ensembl.
DR GO; GO:0001656; P:metanephros development; IMP:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0003308; P:negative regulation of Wnt signaling pathway involved in heart development; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:1903226; P:positive regulation of endodermal cell differentiation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0031648; P:protein destabilization; IMP:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:BHF-UCL.
DR GO; GO:2000043; P:regulation of cardiac cell fate specification; IEA:Ensembl.
DR GO; GO:0045995; P:regulation of embryonic development; ISS:UniProtKB.
DR GO; GO:2000035; P:regulation of stem cell division; IEA:Ensembl.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0021903; P:rostrocaudal neural tube patterning; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0048866; P:stem cell fate specification; IEA:Ensembl.
DR GO; GO:0072189; P:ureter development; IMP:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR033392; Sox7/17/18_central.
DR InterPro; IPR021934; Sox_C.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12067; Sox17_18_mid; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
DR PROSITE; PS51516; SOX_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Disease variant; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Wnt signaling pathway.
FT CHAIN 1..414
FT /note="Transcription factor SOX-17"
FT /id="PRO_0000048765"
FT DOMAIN 280..413
FT /note="Sox C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00849"
FT DNA_BIND 68..136
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 36..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 256..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 361..369
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:34342803"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..285
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..342
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 17
FT /note="Q -> QTQ (in VUR3)"
FT /id="VAR_065168"
FT VARIANT 33
FT /note="A -> D (in dbSNP:rs189384157)"
FT /evidence="ECO:0000269|PubMed:27592148"
FT /id="VAR_078774"
FT VARIANT 178
FT /note="G -> C (in VUR3; dbSNP:rs267607082)"
FT /evidence="ECO:0000269|PubMed:20960469"
FT /id="VAR_065169"
FT VARIANT 259
FT /note="Y -> N (in VUR3; increased levels of the mutant
FT protein that is associated with increased suppression of
FT CTNNB1 signaling of the Wnt pathway compared to wild-type;
FT dbSNP:rs267607083)"
FT /evidence="ECO:0000269|PubMed:20960469"
FT /id="VAR_065170"
FT HELIX 74..87
FT /evidence="ECO:0007829|PDB:4A3N"
FT HELIX 95..108
FT /evidence="ECO:0007829|PDB:4A3N"
FT HELIX 111..129
FT /evidence="ECO:0007829|PDB:4A3N"
SQ 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
