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 24-JAN-2024, entry version 176. 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 THR-GLN-17 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 a 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9606-ENSP00000297316; -. DR PeptideAtlas; Q9H6I2; -. DR ProteomicsDB; 80988; -. DR Pumba; Q9H6I2; -. DR Antibodypedia; 11698; 525 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 AGR; HGNC:18122; -. DR CTD; 64321; -. DR DisGeNET; 64321; -. DR GeneCards; SOX17; -. DR HGNC; HGNC:18122; SOX17. DR HPA; ENSG00000164736; Tissue enhanced (adipose). 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; 2902801at2759; -. DR PhylomeDB; Q9H6I2; -. DR PathwayCommons; Q9H6I2; -. DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-9823730; Formation of definitive endoderm. DR Reactome; R-HSA-9827857; Specification of primordial germ cells. DR SignaLink; Q9H6I2; -. DR SIGNOR; Q9H6I2; -. DR BioGRID-ORCS; 64321; 23 hits in 1179 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 123 other cell types or tissues. 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; ISS:ARUK-UCL. 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: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:gallbladder development; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0007507; P:heart development; ISS:ARUK-UCL. 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:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; 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: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; ISS:ARUK-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. 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: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 CDD; cd22047; HMG-box_SoxF_SOX17; 1. DR Gene3D; 1.10.30.10; High mobility group box domain; 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 PANTHER; PTHR10270; SOX TRANSCRIPTION FACTOR; 1. DR PANTHER; PTHR10270:SF216; TRANSCRIPTION FACTOR SOX-17; 1. DR Pfam; PF00505; HMG_box; 1. DR Pfam; PF12067; Sox17_18_mid; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; HMG-box; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. DR PROSITE; PS51516; SOX_C; 1. DR Genevisible; Q9H6I2; HS. 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 /evidence="ECO:0000269|PubMed:20960469" 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 //