{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P43680","secondaryAccessions":["Q3UND6","Q9EQ73"],"uniProtkbId":"SOX18_MOUSE","entryAudit":{"firstPublicDate":"1995-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-10-10","entryVersion":183,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Transcription factor SOX-18"}}},"genes":[{"geneName":{"value":"Sox18"},"synonyms":[{"value":"Sox-18"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10742113"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11094083"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11554755"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12748961"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16895970"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18931657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19429912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26939885"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7651823"}],"value":"Transcriptional activator that binds to the consensus sequence 5'-AACAAAG-3' in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis (PubMed:10742113, PubMed:12748961, PubMed:18931657, PubMed:19429912, PubMed:26939885, PubMed:7651823). Activates transcription of PROX1 and other genes coding for lymphatic endothelial markers (PubMed:18931657, PubMed:26939885). Plays an essential role in triggering the differentiation of lymph vessels, but is not required for the maintenance of differentiated lymphatic endothelial cells (PubMed:18931657). Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX17 (PubMed:16895970). Interaction with MEF2C enhances transcriptional activation (PubMed:11554755). Besides, required for normal hair development (PubMed:11094083, PubMed:12748961)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11554755"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12748961"}],"value":"Interacts (via C-terminus) with MEF2C (via MADS box)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11554755"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7665083"}],"value":"Detected in adult lung, heart and skeletal muscles"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10742113"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18931657"}],"value":"Detected at 7.5 and 8.0 dpc in the allantois and blood islands of the yolk sac, and in cells fated to become the endocardium. At 8.5 dpc, detected in the allantois and the nascent vasculature of the yolk sac, the paired dorsal aortae and heart (PubMed:10742113). At 9.5 to 11.0 dpc, detected in endothelial cells of the paired dorsal aortae, in intersomitic vessels and in a network of smaller vessels in head and trunc mesenchyme, and in endothelial cells lining the dorsolateral sector of the cardinal vein (PubMed:10742113, PubMed:18931657). At 10.5 dpc, detected inprecursors of the lymphatic vasculature (PubMed:18931657). At 12.5 dpc, detected in branching vessels and in nascent vibrissae follicles. Detected in vibrissae follicles and pelage follicles at 14.0 dpc (PubMed:10742113). Detected in primary lymph sacs at 13.5 dpc, but is not detected in embryonic or adult lymph vessels (PubMed:18931657)"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26939885"}],"value":"Binds target DNA via the HMG box domain"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P35713"}],"value":"The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors"}],"commentType":"DOMAIN"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10742113"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12748961"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18931657"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19429912"}],"value":"Defects in this protein are the cause of the ragged, ragged-like and opossum phenotypes (PubMed:10742113, PubMed:12748961, PubMed:18931657, PubMed:19429912). In all these, missense mutations give rise to a truncated protein that retains DNA-binding ability, but lacks regions required for transcription activation (PubMed:10742113, PubMed:12748961). Homozygous ragged and ragged-like mice are almost completely naked, display prenatal edema and frequently die in utero or shortly after birth. Heterozygous ragged and ragged-like mice are mostly viable, but have a thin, ragged coat (PubMed:12748961). Homozygous opossum mice display no visible phenotype up to 11.5 dpc (PubMed:19429912). From 12.5 dpc onwards, mutant embryos display enlarged surface microvasculature and severe subcutaneaous edema, followed by vascular rupture and hemorrhage beginning at 13.5 dpc (PubMed:18931657, PubMed:19429912). All die shortly after 14.5 dpc (PubMed:12748961, PubMed:18931657, PubMed:19429912). Heterozygous opossum mice are almost completely naked, display prenatal edema and frequently die in utero or shortly after birth (PubMed:12748961). Heterozygous opossum mice display defects in development and patterning of the lymph vessels (PubMed:18931657)"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11094083"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16895970"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18931657"}],"value":"Deletion of the DNA-binding and the C-terminal transcription activation domains causes no visible phenotype, excepting slightly darker coat pigmentation and a decreased proportion of auchene and zigzag hairs (PubMed:11094083). The mild phenotype is due to functional redundancy with other Sox genes (PubMed:11094083, PubMed:16895970). The phenotype apparently depends on the genetic context: backcrossing the mutant into a pure C57BL/6 background leads to defective lymphangiogenesis and the same embryonic lethality as observed for opossum mutants (PubMed:18931657)"}],"commentType":"MISCELLANEOUS"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":377,"modifier":"EXACT"}},"description":"Transcription factor SOX-18","featureId":"PRO_0000048768"},{"type":"Domain","location":{"start":{"value":256,"modifier":"EXACT"},"end":{"value":376,"modifier":"EXACT"}},"description":"Sox C-terminal","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00849"}]},{"type":"DNA binding","location":{"start":{"value":79,"modifier":"EXACT"},"end":{"value":147,"modifier":"EXACT"}},"description":"HMG box","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26939885"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":81,"modifier":"EXACT"},"end":{"value":94,"modifier":"EXACT"}},"description":"Interaction with DNA","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26939885"}]},{"type":"Region","location":{"start":{"value":105,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"Interaction with DNA","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26939885"}]},{"type":"Region","location":{"start":{"value":160,"modifier":"EXACT"},"end":{"value":225,"modifier":"EXACT"}},"description":"Important for transcriptional activation","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10742113"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7651823"}]},{"type":"Motif","location":{"start":{"value":318,"modifier":"EXACT"},"end":{"value":326,"modifier":"EXACT"}},"description":"9aaTAD","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P35713"}]},{"type":"Compositional bias","location":{"start":{"value":21,"modifier":"EXACT"},"end":{"value":34,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":41,"modifier":"EXACT"},"end":{"value":52,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Sequence conflict","location":{"start":{"value":14,"modifier":"EXACT"},"end":{"value":14,"modifier":"EXACT"}},"description":"in Ref. 4; 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