ID SOX18_MOUSE Reviewed; 377 AA. AC P43680; Q3UND6; Q9EQ73; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2002, sequence version 3. DT 27-MAR-2024, entry version 173. DE RecName: Full=Transcription factor SOX-18; GN Name=Sox18; Synonyms=Sox-18; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Heart muscle; RX PubMed=7665083; DOI=10.1016/0378-1119(95)00280-j; RA Dunn T.L., Mynett-Johnson L., Wright E.M., Hosking B.M., Koopman P.A., RA Muscat G.E.O.; RT "Sequence and expression of Sox-18 encoding a new HMG-box transcription RT factor."; RL Gene 161:223-225(1995). RN [2] RP SEQUENCE REVISION. RA Dunn T.L.; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. 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 MRNA]. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE25811.1}; RC TISSUE=Lung {ECO:0000312|EMBL:BAE25811.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 OF 83-142. RC STRAIN=BALB/cJ; TISSUE=Heart muscle; RA Layfield R., Mynett-Johnson L., Yarwood P.J., Muscat G.E.O., Koopman P.A., RA Hume D.A.; RL Submitted (FEB-1994) to the EMBL/GenBank/DDBJ databases. RN [7] RP FUNCTION. RX PubMed=7651823; DOI=10.1093/nar/23.14.2626; RA Hosking B.M., Muscat G.E.O., Koopman P.A., Dowhan D.H., Dunn T.L.; RT "Trans-activation and DNA-binding properties of the transcription factor, RT Sox-18."; RL Nucleic Acids Res. 23:2626-2628(1995). RN [8] RP FUNCTION, AND MISCELLANEOUS. RX PubMed=11094083; DOI=10.1128/mcb.20.24.9331-9336.2000; RA Pennisi D., Bowles J., Nagy A., Muscat G., Koopman P.; RT "Mice null for sox18 are viable and display a mild coat defect."; RL Mol. Cell. Biol. 20:9331-9336(2000). RN [9] RP FUNCTION, DISEASE, AND DEVELOPMENTAL STAGE. RX PubMed=10742113; DOI=10.1038/74301; RA Pennisi D., Gardner J., Chambers D., Hosking B., Peters J., Muscat G., RA Abbott C., Koopman P.; RT "Mutations in Sox18 underlie cardiovascular and hair follicle defects in RT ragged mice."; RL Nat. Genet. 24:434-437(2000). RN [10] RP FUNCTION, INTERACTION WITH MEF2C, AND SUBCELLULAR LOCATION. RX PubMed=11554755; DOI=10.1006/bbrc.2001.5589; RA Hosking B.M., Wang S.C., Chen S.L., Penning S., Koopman P., Muscat G.E.; RT "SOX18 directly interacts with MEF2C in endothelial cells."; RL Biochem. Biophys. Res. Commun. 287:493-500(2001). RN [11] RP FUNCTION, DISEASE, AND INTERACTION WITH MEF2C. RX PubMed=12748961; DOI=10.1002/gene.10190; RA James K., Hosking B., Gardner J., Muscat G.E., Koopman P.; RT "Sox18 mutations in the ragged mouse alleles ragged-like and opossum."; RL Genesis 36:1-6(2003). RN [12] RP FUNCTION. RX PubMed=16895970; DOI=10.1242/jcs.03081; RA Matsui T., Kanai-Azuma M., Hara K., Matoba S., Hiramatsu R., Kawakami H., RA Kurohmaru M., Koopman P., Kanai Y.; RT "Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice."; RL J. Cell Sci. 119:3513-3526(2006). RN [13] RP FUNCTION, DISEASE, DEVELOPMENTAL STAGE, AND MISCELLANEOUS. RX PubMed=18931657; DOI=10.1038/nature07391; RA Francois M., Caprini A., Hosking B., Orsenigo F., Wilhelm D., Browne C., RA Paavonen K., Karnezis T., Shayan R., Downes M., Davidson T., Tutt D., RA Cheah K.S., Stacker S.A., Muscat G.E., Achen M.G., Dejana E., Koopman P.; RT "Sox18 induces development of the lymphatic vasculature in mice."; RL Nature 456:643-647(2008). RN [14] RP FUNCTION, AND DISEASE. RX PubMed=19429912; DOI=10.1093/hmg/ddp219; RA Downes M., Francois M., Ferguson C., Parton R.G., Koopman P.; RT "Vascular defects in a mouse model of hypotrichosis-lymphedema- RT telangiectasia syndrome indicate a role for SOX18 in blood vessel RT maturation."; RL Hum. Mol. Genet. 18:2839-2850(2009). RN [15] {ECO:0007744|PDB:4Y60} RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 77-155 IN COMPLEX WITH DNA, RP FUNCTION, AND DOMAIN. RX PubMed=26939885; DOI=10.1093/nar/gkw130; RA Klaus M., Prokoph N., Girbig M., Wang X., Huang Y.H., Srivastava Y., RA Hou L., Narasimhan K., Kolatkar P.R., Francois M., Jauch R.; RT "Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA RT interaction."; RL Nucleic Acids Res. 44:3922-3935(2016). 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 (PubMed:7651823, PubMed:10742113, PubMed:12748961, CC PubMed:18931657, PubMed:19429912, PubMed:26939885). Activates CC transcription of PROX1 and other genes coding for lymphatic endothelial CC markers (PubMed:18931657, PubMed:26939885). 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 (PubMed:18931657). Plays an important role in postnatal angiogenesis, CC where it is functionally redundant with SOX17 (PubMed:16895970). CC Interaction with MEF2C enhances transcriptional activation CC (PubMed:11554755). Besides, required for normal hair development CC (PubMed:11094083, PubMed:12748961). {ECO:0000269|PubMed:10742113, CC ECO:0000269|PubMed:11094083, ECO:0000269|PubMed:11554755, CC ECO:0000269|PubMed:12748961, ECO:0000269|PubMed:16895970, CC ECO:0000269|PubMed:18931657, ECO:0000269|PubMed:19429912, CC ECO:0000269|PubMed:26939885, ECO:0000269|PubMed:7651823}. CC -!- SUBUNIT: Interacts (via C-terminus) with MEF2C (via MADS box). CC {ECO:0000269|PubMed:11554755, ECO:0000269|PubMed:12748961}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, CC ECO:0000269|PubMed:11554755}. CC -!- TISSUE SPECIFICITY: Detected in adult lung, heart and skeletal muscles. CC {ECO:0000269|PubMed:7665083}. CC -!- DEVELOPMENTAL STAGE: Detected at 7.5 and 8.0 dpc in the allantois and CC blood islands of the yolk sac, and in cells fated to become the CC endocardium. At 8.5 dpc, detected in the allantois and the nascent CC vasculature of the yolk sac, the paired dorsal aortae and heart CC (PubMed:10742113). At 9.5 to 11.0 dpc, detected in endothelial cells of CC the paired dorsal aortae, in intersomitic vessels and in a network of CC smaller vessels in head and trunc mesenchyme, and in endothelial cells CC lining the dorsolateral sector of the cardinal vein (PubMed:10742113, CC PubMed:18931657). At 10.5 dpc, detected inprecursors of the lymphatic CC vasculature (PubMed:18931657). At 12.5 dpc, detected in branching CC vessels and in nascent vibrissae follicles. Detected in vibrissae CC follicles and pelage follicles at 14.0 dpc (PubMed:10742113). Detected CC in primary lymph sacs at 13.5 dpc, but is not detected in embryonic or CC adult lymph vessels (PubMed:18931657). {ECO:0000269|PubMed:10742113, CC ECO:0000269|PubMed:18931657}. CC -!- DOMAIN: Binds target DNA via the HMG box domain. CC {ECO:0000269|PubMed:26939885}. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000250|UniProtKB:P35713}. CC -!- DISEASE: Note=Defects in this protein are the cause of the ragged, CC ragged-like and opossum phenotypes (PubMed:10742113, PubMed:12748961, CC PubMed:18931657, PubMed:19429912). In all these, missense mutations CC give rise to a truncated protein that retains DNA-binding ability, but CC lacks regions required for transcription activation (PubMed:10742113, CC PubMed:12748961). Homozygous ragged and ragged-like mice are almost CC completely naked, display prenatal edema and frequently die in utero or CC shortly after birth. Heterozygous ragged and ragged-like mice are CC mostly viable, but have a thin, ragged coat (PubMed:12748961). CC Homozygous opossum mice display no visible phenotype up to 11.5 dpc CC (PubMed:19429912). From 12.5 dpc onwards, mutant embryos display CC enlarged surface microvasculature and severe subcutaneaous edema, CC followed by vascular rupture and hemorrhage beginning at 13.5 dpc CC (PubMed:18931657, PubMed:19429912). All die shortly after 14.5 dpc CC (PubMed:12748961, PubMed:18931657, PubMed:19429912). Heterozygous CC opossum mice are almost completely naked, display prenatal edema and CC frequently die in utero or shortly after birth (PubMed:12748961). CC Heterozygous opossum mice display defects in development and patterning CC of the lymph vessels (PubMed:18931657). {ECO:0000269|PubMed:10742113, CC ECO:0000269|PubMed:12748961, ECO:0000269|PubMed:18931657, CC ECO:0000269|PubMed:19429912}. CC -!- MISCELLANEOUS: Deletion of the DNA-binding and the C-terminal CC transcription activation domains causes no visible phenotype, excepting CC slightly darker coat pigmentation and a decreased proportion of auchene CC and zigzag hairs (PubMed:11094083). The mild phenotype is due to CC functional redundancy with other Sox genes (PubMed:11094083, CC PubMed:16895970). The phenotype apparently depends on the genetic CC context: backcrossing the mutant into a pure C57BL/6 background leads CC to defective lymphangiogenesis and the same embryonic lethality as CC observed for opossum mutants (PubMed:18931657). CC {ECO:0000269|PubMed:11094083, ECO:0000269|PubMed:16895970, CC ECO:0000269|PubMed:18931657}. 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; L35032; AAB18615.1; -; mRNA. DR EMBL; AF288518; AAG48578.1; -; Genomic_DNA. DR EMBL; AK144281; BAE25811.1; -; mRNA. DR EMBL; BC006612; AAH06612.1; -; mRNA. DR EMBL; L29086; AAA56844.1; -; mRNA. DR CCDS; CCDS17218.1; -. DR RefSeq; NP_033262.2; NM_009236.2. DR PDB; 4Y60; X-ray; 1.75 A; C=77-155. DR PDBsum; 4Y60; -. DR AlphaFoldDB; P43680; -. DR SMR; P43680; -. DR BioGRID; 203404; 1. DR STRING; 10090.ENSMUSP00000062759; -. DR BindingDB; P43680; -. DR ChEMBL; CHEMBL4523228; -. DR iPTMnet; P43680; -. DR PhosphoSitePlus; P43680; -. DR MaxQB; P43680; -. DR PaxDb; 10090-ENSMUSP00000062759; -. DR ProteomicsDB; 261555; -. DR Antibodypedia; 15501; 207 antibodies from 29 providers. DR DNASU; 20672; -. DR Ensembl; ENSMUST00000054491.6; ENSMUSP00000062759.6; ENSMUSG00000046470.6. DR GeneID; 20672; -. DR KEGG; mmu:20672; -. DR UCSC; uc008ona.1; mouse. DR AGR; MGI:103559; -. DR CTD; 54345; -. DR MGI; MGI:103559; Sox18. DR VEuPathDB; HostDB:ENSMUSG00000046470; -. DR eggNOG; KOG0527; Eukaryota. DR GeneTree; ENSGT00940000162709; -. DR HOGENOM; CLU_044994_1_0_1; -. DR InParanoid; P43680; -. DR OMA; FSMSHHG; -. DR OrthoDB; 2902801at2759; -. DR PhylomeDB; P43680; -. DR BioGRID-ORCS; 20672; 3 hits in 80 CRISPR screens. DR PRO; PR:P43680; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P43680; Protein. DR Bgee; ENSMUSG00000046470; Expressed in kidney vasculature and 224 other cell types or tissues. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI. DR GO; GO:0001525; P:angiogenesis; IGI:MGI. DR GO; GO:0001568; P:blood vessel development; IMP:MGI. DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:0048469; P:cell maturation; IDA:MGI. DR GO; GO:0035050; P:embryonic heart tube development; IGI:MGI. DR GO; GO:0060956; P:endocardial cell differentiation; IGI:MGI. DR GO; GO:0060214; P:endocardium formation; IGI:MGI. DR GO; GO:0061028; P:establishment of endothelial barrier; ISO:MGI. DR GO; GO:0022405; P:hair cycle process; ISO:MGI. DR GO; GO:0001942; P:hair follicle development; IMP:MGI. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0001945; P:lymph vessel development; IMP:MGI. DR GO; GO:0001946; P:lymphangiogenesis; IMP:MGI. DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; IMP:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0072091; P:regulation of stem cell proliferation; IDA:MGI. DR GO; GO:0048866; P:stem cell fate specification; IDA:MGI. DR GO; GO:0001944; P:vasculature development; IMP:MGI. DR GO; GO:0001570; P:vasculogenesis; IGI:MGI. DR CDD; cd22048; HMG-box_SoxF_SOX18; 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:SF204; TRANSCRIPTION FACTOR SOX-18; 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; P43680; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; DNA-binding; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..377 FT /note="Transcription factor SOX-18" FT /id="PRO_0000048768" FT DOMAIN 256..376 FT /note="Sox C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00849" FT DNA_BIND 79..147 FT /note="HMG box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267, FT ECO:0000269|PubMed:26939885" FT REGION 1..76 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 81..94 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:26939885" FT REGION 105..117 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:26939885" FT REGION 160..225 FT /note="Important for transcriptional activation" FT /evidence="ECO:0000269|PubMed:10742113, FT ECO:0000269|PubMed:7651823" FT MOTIF 318..326 FT /note="9aaTAD" FT /evidence="ECO:0000250|UniProtKB:P35713" FT CONFLICT 14 FT /note="P -> Q (in Ref. 4; BAE25811)" FT /evidence="ECO:0000305" FT CONFLICT 156 FT /note="A -> E (in Ref. 1; AAB18615)" FT /evidence="ECO:0000305" FT CONFLICT 260 FT /note="A -> G (in Ref. 1; AAB18615)" FT /evidence="ECO:0000305" FT HELIX 85..100 FT /evidence="ECO:0007829|PDB:4Y60" FT HELIX 106..119 FT /evidence="ECO:0007829|PDB:4Y60" FT HELIX 122..142 FT /evidence="ECO:0007829|PDB:4Y60" SQ SEQUENCE 377 AA; 40898 MW; 29F4C9B9D50F94D0 CRC64; MQRSPPGYGA QDDPPSRRDC AWAPGIGAAA EARGLPVTNV SPTSPASPSS LPRSPPRSPE SGRYGFGRGE RQTADELRIR RPMNAFMVWA KDERKRLAQQ NPDLHNAVLS KMLGKAWKEL NTAEKRPFVE EAERLRVQHL RDHPNYKYRP RRKKQARKVR RLEPGLLLPG LVQPSAPPEA FAAASGSARS FRELPTLGAE FDGLGLPTPE RSPLDGLEPG EASFFPPPLA PEDCALRAFR APYAPELARD PSFCYGAPLA EALRTAPPAA PLAGLYYGTL GTPGPFPNPL SPPPESPSLE GTEQLEPTAD LWADVDLTEF DQYLNCSRTR PDATTLPYHV ALAKLGPRAM SCPEESSLIS ALSDASSAVY YSACISG //