SOX18_HUMAN
ID SOX18_HUMAN Reviewed; 384 AA.
AC P35713; Q0VGA9; Q9NPH8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Transcription factor SOX-18;
GN Name=SOX18;
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].
RX PubMed=10858556; DOI=10.1016/s0167-4781(00)00078-6;
RA Stanojcic S., Stevanovic M.;
RT "The human SOX18 gene: cDNA cloning and high resolution mapping.";
RL Biochim. Biophys. Acta 1492:237-241(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10807548; DOI=10.1007/s100380050210;
RA Azuma T., Seki N., Yoshikawa T., Saito T., Masuho Y., Muramatsu M.;
RT "cDNA cloning, tissue expression, and chromosome mapping of human homolog
RT of SOX18.";
RL J. Hum. Genet. 45:192-195(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11130989; DOI=10.1007/s003350010216;
RA Pennisi D.J., James K.M., Hosking B.M., Muscat G.E., Koopman P.;
RT "Structure, mapping, and expression of human SOX18.";
RL Mamm. Genome 11:1147-1149(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Ovary, and PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 96-149.
RX PubMed=1614875; DOI=10.1093/nar/20.11.2887;
RA Denny P., Swift S., Brand N., Dabhade N., Barton P., Ashworth A.;
RT "A conserved family of genes related to the testis determining gene, SRY.";
RL Nucleic Acids Res. 20:2887-2887(1992).
RN [7]
RP 9AATAD MOTIF, AND MUTAGENESIS OF 330-TYR-LEU-331.
RX PubMed=17603017; DOI=10.1016/j.bbrc.2007.06.095;
RA Sandholzer J., Hoeth M., Piskacek M., Mayer H., de Martin R.;
RT "A novel 9-amino-acid transactivation domain in the C-terminal part of
RT Sox18.";
RL Biochem. Biophys. Res. Commun. 360:370-374(2007).
RN [8]
RP INVOLVEMENT IN HLTS, VARIANTS HLTS ARG-95 AND PRO-104, AND INVOLVEMENT IN
RP HLTRS.
RX PubMed=12740761; DOI=10.1086/375614;
RA Irrthum A., Devriendt K., Chitayat D., Matthijs G., Glade C.,
RA Steijlen P.M., Fryns J.-P., Van Steensel M.A.M., Vikkula M.;
RT "Mutations in the transcription factor gene SOX18 underlie recessive and
RT dominant forms of hypotrichosis-lymphedema-telangiectasia.";
RL Am. J. Hum. Genet. 72:1470-1478(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INVOLVEMENT IN HLTRS.
RX PubMed=24697860; DOI=10.1111/cge.12388;
RA Moalem S., Brouillard P., Kuypers D., Legius E., Harvey E., Taylor G.,
RA Francois M., Vikkula M., Chitayat D.;
RT "Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a
RT truncating mutation in the SOX18 gene.";
RL Clin. Genet. 87:378-382(2015).
CC -!- FUNCTION: Transcriptional activator that binds to the consensus
CC sequence 5'-AACAAAG-3' in the promoter of target genes and plays an
CC essential role in embryonic cardiovascular development and
CC lymphangiogenesis. Activates transcription of PROX1 and other genes
CC coding for lymphatic endothelial markers. Plays an essential role in
CC triggering the differentiation of lymph vessels, but is not required
CC for the maintenance of differentiated lymphatic endothelial cells.
CC Plays an important role in postnatal angiogenesis, where it is
CC functionally redundant with SOX17. Interaction with MEF2C enhances
CC transcriptional activation. Besides, required for normal hair
CC development. {ECO:0000250|UniProtKB:P43680}.
CC -!- SUBUNIT: Interacts (via C-terminus) with MEF2C (via MADS box).
CC {ECO:0000250|UniProtKB:P43680}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267}.
CC -!- TISSUE SPECIFICITY: Detected in heart, lung, placenta, skeletal muscle,
CC liver, kidney, spleen, prostate, ovary, msosmall intestine and colon.
CC {ECO:0000269|PubMed:10807548, ECO:0000269|PubMed:11130989}.
CC -!- DOMAIN: Binds target DNA via the HMG box domain.
CC {ECO:0000250|UniProtKB:P43680}.
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:17603017}.
CC -!- DISEASE: Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS)
CC [MIM:607823]: A syndrome characterized by absent eyebrows and
CC eyelashes, lymphatic edemas of the inferior members or eyelids, and
CC peripheral vein anomalies. {ECO:0000269|PubMed:12740761}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
CC (HLTRS) [MIM:137940]: A syndrome characterized by sparse hair,
CC lymphatic edemas, peripheral vein anomalies, and renal disease.
CC {ECO:0000269|PubMed:12740761, ECO:0000269|PubMed:24697860}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- CAUTION: Was originally termed SOX-8. {ECO:0000305|PubMed:1614875}.
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DR EMBL; AJ243896; CAB95835.1; -; mRNA.
DR EMBL; AB033888; BAA94874.1; -; mRNA.
DR EMBL; AF270652; AAG48577.1; -; mRNA.
DR EMBL; AL355803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038590; AAH38590.1; -; mRNA.
DR EMBL; BC073971; AAH73971.1; -; mRNA.
DR EMBL; BC111390; AAI11391.1; -; mRNA.
DR EMBL; X65664; CAA46615.1; -; mRNA.
DR CCDS; CCDS13552.1; -.
DR PIR; S22941; S22941.
DR RefSeq; NP_060889.1; NM_018419.2.
DR AlphaFoldDB; P35713; -.
DR SMR; P35713; -.
DR BioGRID; 119936; 4.
DR IntAct; P35713; 2.
DR STRING; 9606.ENSP00000341815; -.
DR ChEMBL; CHEMBL4523220; -.
DR iPTMnet; P35713; -.
DR PhosphoSitePlus; P35713; -.
DR BioMuta; SOX18; -.
DR DMDM; 12644232; -.
DR jPOST; P35713; -.
DR MassIVE; P35713; -.
DR PaxDb; P35713; -.
DR PeptideAtlas; P35713; -.
DR PRIDE; P35713; -.
DR ProteomicsDB; 55145; -.
DR Antibodypedia; 15501; 178 antibodies from 28 providers.
DR DNASU; 54345; -.
DR Ensembl; ENST00000340356.9; ENSP00000341815.7; ENSG00000203883.7.
DR GeneID; 54345; -.
DR KEGG; hsa:54345; -.
DR MANE-Select; ENST00000340356.9; ENSP00000341815.7; NM_018419.3; NP_060889.1.
DR UCSC; uc002yhs.4; human.
DR CTD; 54345; -.
DR DisGeNET; 54345; -.
DR GeneCards; SOX18; -.
DR HGNC; HGNC:11194; SOX18.
DR HPA; ENSG00000203883; Low tissue specificity.
DR MalaCards; SOX18; -.
DR MIM; 137940; phenotype.
DR MIM; 601618; gene.
DR MIM; 607823; phenotype.
DR neXtProt; NX_P35713; -.
DR OpenTargets; ENSG00000203883; -.
DR Orphanet; 69735; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome.
DR PharmGKB; PA36031; -.
DR VEuPathDB; HostDB:ENSG00000203883; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000162709; -.
DR HOGENOM; CLU_044994_1_0_1; -.
DR InParanoid; P35713; -.
DR OMA; HNLSQPC; -.
DR OrthoDB; 1042753at2759; -.
DR PhylomeDB; P35713; -.
DR PathwayCommons; P35713; -.
DR SignaLink; P35713; -.
DR SIGNOR; P35713; -.
DR BioGRID-ORCS; 54345; 14 hits in 1102 CRISPR screens.
DR GeneWiki; SOX18; -.
DR GenomeRNAi; 54345; -.
DR Pharos; P35713; Tbio.
DR PRO; PR:P35713; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P35713; protein.
DR Bgee; ENSG00000203883; Expressed in apex of heart and 95 other tissues.
DR Genevisible; P35713; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0035050; P:embryonic heart tube development; 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:0061028; P:establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:0022405; P:hair cycle process; IMP:UniProtKB.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0001946; P:lymphangiogenesis; IMP:UniProtKB.
DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0048866; P:stem cell fate specification; IEA:Ensembl.
DR GO; GO:0001944; P:vasculature development; ISS:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL.
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 Activator; Disease variant; DNA-binding; Hypotrichosis; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..384
FT /note="Transcription factor SOX-18"
FT /id="PRO_0000048767"
FT DOMAIN 263..383
FT /note="Sox C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00849"
FT DNA_BIND 85..153
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..100
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P43680"
FT REGION 111..123
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P43680"
FT REGION 146..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 166..231
FT /note="Important for transcriptional activation"
FT /evidence="ECO:0000250|UniProtKB:P43680"
FT REGION 293..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 325..333
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:17603017"
FT COMPBIAS 45..65
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..165
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..189
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..308
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 95
FT /note="W -> R (in HLTS; dbSNP:rs28936693)"
FT /evidence="ECO:0000269|PubMed:12740761"
FT /id="VAR_016210"
FT VARIANT 104
FT /note="A -> P (in HLTS; dbSNP:rs28936692)"
FT /evidence="ECO:0000269|PubMed:12740761"
FT /id="VAR_016211"
FT MUTAGEN 330..331
FT /note="YL->QS: Greatly reduced transactivating activity."
FT /evidence="ECO:0000269|PubMed:17603017"
SQ SEQUENCE 384 AA; 40891 MW; 327462E519770062 CRC64;
MQRSPPGYGA QDDPPARRDC AWAPGHGAAA DTRGLAAGPA ALAAPAAPAS PPSPQRSPPR
SPEPGRYGLS PAGRGERQAA DESRIRRPMN AFMVWAKDER KRLAQQNPDL HNAVLSKMLG
KAWKELNAAE KRPFVEEAER LRVQHLRDHP NYKYRPRRKK QARKARRLEP GLLLPGLAPP
QPPPEPFPAA SGSARAFREL PPLGAEFDGL GLPTPERSPL DGLEPGEAAF FPPPAAPEDC
ALRPFRAPYA PTELSRDPGG CYGAPLAEAL RTAPPAAPLA GLYYGTLGTP GPYPGPLSPP
PEAPPLESAE PLGPAADLWA DVDLTEFDQY LNCSRTRPDA PGLPYHVALA KLGPRAMSCP
EESSLISALS DASSAVYYSA CISG
