SOX10_HUMAN
ID SOX10_HUMAN Reviewed; 466 AA.
AC P56693; B4DV62; Q6FHW7;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Transcription factor SOX-10;
GN Name=SOX10;
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] (ISOFORM 1), AND VARIANT WS4C LEU-ARG-161 INS.
RX PubMed=9462749; DOI=10.1038/ng0298-171;
RA Pingault V., Bondurand N., Kuhlbrodt K., Goerich D.E., Prehu M.O.,
RA Puliti A., Herbarth B., Hermans-Borgmeyer I., Legius E., Matthijs G.,
RA Amiel J., Lyonnet S., Ceccherini I., Romeo G., Clayton-Smith J., Read A.P.,
RA Wegner M., Goossens M.;
RT "SOX10 mutations in patients with Waardenburg-Hirschsprung disease.";
RL Nat. Genet. 18:171-173(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9760192; DOI=10.1007/s004390050793;
RA Pusch C., Hustert E., Pfeifer D., Sudbeck P., Kist R., Roe B., Wang Z.,
RA Balling R., Blin N., Scherer G.;
RT "The SOX10/Sox10 gene from human and mouse: sequence, expression, and
RT transactivation by the encoded HMG domain transcription factor.";
RL Hum. Genet. 103:115-123(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Skin;
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 [9]
RP CHARACTERIZATION.
RX PubMed=9722528; DOI=10.1074/jbc.273.36.23033;
RA Kuhlbrodt K., Schmidt C., Sock E., Pingault V., Bondurand N., Goossens M.,
RA Wegner M.;
RT "Functional analysis of Sox10 mutations found in human Waardenburg-
RT Hirschsprung patients.";
RL J. Biol. Chem. 273:23033-23038(1998).
RN [10]
RP NUCLEOCYTOPLASMIC SHUTTLING, AND SUBCELLULAR LOCATION.
RX PubMed=12138193; DOI=10.1128/mcb.22.16.5826-5834.2002;
RA Rehberg S., Lischka P., Glaser G., Stamminger T., Wegner M., Rosorius O.;
RT "Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is
RT crucial for Sox10-mediated transactivation.";
RL Mol. Cell. Biol. 22:5826-5834(2002).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH PAX3.
RX PubMed=21965087; DOI=10.1007/s00439-011-1098-2;
RA Zhang H., Chen H., Luo H., An J., Sun L., Mei L., He C., Jiang L.,
RA Jiang W., Xia K., Li J.D., Feng Y.;
RT "Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10
RT mutations: report of a dominant-negative SOX10 mutation in Waardenburg
RT syndrome type II.";
RL Hum. Genet. 131:491-503(2012).
RN [13]
RP VARIANT WS2E THR-135.
RX PubMed=10441344; DOI=10.1093/hmg/8.9.1785;
RA Bondurand N., Kuhlbrodt K., Pingault V., Enderich J., Sajus M.,
RA Tommerup N., Warburg M., Hennekam R.C.M., Read A.P., Wegner M.,
RA Goossens M.;
RT "A molecular analysis of the Yemenite deaf-blind hypopigmentation syndrome:
RT SOX10 dysfunction causes different neurocristopathies.";
RL Hum. Mol. Genet. 8:1785-1789(1999).
RN [14]
RP INVOLVEMENT IN PCWH.
RX PubMed=10762540; DOI=10.1086/302895;
RA Touraine R.L., Attie-Bitach T., Manceau E., Korsch E., Sarda P.,
RA Pingault V., Encha-Razavi F., Pelet A., Auge J., Nivelon-Chevallier A.,
RA Holschneider A.M., Munnes M., Doerfler W., Goossens M., Munnich A.,
RA Vekemans M., Lyonnet S.;
RT "Neurological phenotype in Waardenburg syndrome type 4 correlates with
RT novel SOX10 truncating mutations and expression in developing brain.";
RL Am. J. Hum. Genet. 66:1496-1503(2000).
RN [15]
RP ERRATUM OF PUBMED:10762540.
RA Touraine R.L., Attie-Bitach T., Manceau E., Korsch E., Sarda P.,
RA Pingault V., Encha-Razavi F., Pelet A., Auge J., Nivelon-Chevallier A.,
RA Holschneider A.M., Munnes M., Doerfler W., Goossens M., Munnich A.,
RA Vekemans M., Lyonnet S.;
RL Am. J. Hum. Genet. 66:2020-2020(2000).
RN [16]
RP INVOLVEMENT IN PCWH.
RX PubMed=15004559; DOI=10.1038/ng1322;
RA Inoue K., Khajavi M., Ohyama T., Hirabayashi S., Wilson J., Reggin J.D.,
RA Mancias P., Butler I.J., Wilkinson M.F., Wegner M., Lupski J.R.;
RT "Molecular mechanism for distinct neurological phenotypes conveyed by
RT allelic truncating mutations.";
RL Nat. Genet. 36:361-369(2004).
RN [17]
RP INVOLVEMENT IN WS2E.
RX PubMed=17999358; DOI=10.1086/522090;
RA Bondurand N., Dastot-Le Moal F., Stanchina L., Collot N., Baral V.,
RA Marlin S., Attie-Bitach T., Giurgea I., Skopinski L., Reardon W.,
RA Toutain A., Sarda P., Echaieb A., Lackmy-Port-Lis M., Touraine R.,
RA Amiel J., Goossens M., Pingault V.;
RT "Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and
RT 4.";
RL Am. J. Hum. Genet. 81:1169-1185(2007).
RN [18]
RP TRANSACTIVATION REGIONS.
RX PubMed=31194875; DOI=10.1093/nar/gkz523;
RA Haseeb A., Lefebvre V.;
RT "The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite
RT transactivation mechanism.";
RL Nucleic Acids Res. 47:6917-6931(2019).
RN [19]
RP VARIANT WS4C VAL-157.
RX PubMed=18348274; DOI=10.1002/ajmg.a.32181;
RA Morin M., Vinuela A., Rivera T., Villamar M., Moreno-Pelayo M.A.,
RA Moreno F., del Castillo I.;
RT "A de novo missense mutation in the gene encoding the SOX10 transcription
RT factor in a Spanish sporadic case of Waardenburg syndrome type IV.";
RL Am. J. Med. Genet. A 146:1032-1037(2008).
RN [20]
RP VARIANT PCWH PRO-174.
RX PubMed=19208381; DOI=10.1002/ajmg.a.32657;
RA Barnett C.P., Mendoza-Londono R., Blaser S., Gillis J., Dupuis L.,
RA Levin A.V., Chiang P.W., Spector E., Reardon W.;
RT "Aplasia of cochlear nerves and olfactory bulbs in association with SOX10
RT mutation.";
RL Am. J. Med. Genet. A 149:431-436(2009).
RN [21]
RP VARIANTS WS4C TRP-106; PRO-145 AND VAL-157, VARIANTS WS2E ILE-112 AND
RP HIS-161, VARIANTS PCWH ILE-112; HIS-131; ASN-150; PRO-174; ALA-175;
RP LEU-175; ARG-175 AND ARG-321, CHARACTERIZATION OF VARIANTS WS4C TRP-106;
RP PRO-145 AND VAL-157, CHARACTERIZATION OF VARIANTS WS2E ILE-112 AND HIS-161,
RP AND CHARACTERIZATION OF VARIANTS PCWH HIS-131; ASN-150; PRO-174; ALA-175;
RP LEU-175 AND ARG-175.
RX PubMed=21898658; DOI=10.1002/humu.21583;
RA Chaoui A., Watanabe Y., Touraine R., Baral V., Goossens M., Pingault V.,
RA Bondurand N.;
RT "Identification and functional analysis of SOX10 missense mutations in
RT different subtypes of Waardenburg syndrome.";
RL Hum. Mutat. 32:1436-1449(2011).
RN [22]
RP VARIANTS THR-108; VAL-111; GLY-135; CYS-151 AND CYS-161.
RX PubMed=25077900; DOI=10.1210/jc.2014-2110;
RA Marcos S., Sarfati J., Leroy C., Fouveaut C., Parent P., Metz C.,
RA Wolczynski S., Gerard M., Bieth E., Kurtz F., Verier-Mine O., Perrin L.,
RA Archambeaud F., Cabrol S., Rodien P., Hove H., Prescott T., Lacombe D.,
RA Christin-Maitre S., Touraine P., Hieronimus S., Dewailly D., Young J.,
RA Pugeat M., Hardelin J.P., Dode C.;
RT "The prevalence of CHD7 missense versus truncating mutations is higher in
RT patients with Kallmann syndrome than in typical CHARGE patients.";
RL J. Clin. Endocrinol. Metab. 99:E2138-2143(2014).
CC -!- FUNCTION: Transcription factor that plays a central role in developing
CC and mature glia (By similarity). Specifically activates expression of
CC myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15
CC and MYRF, thereby playing a central role in oligodendrocyte maturation
CC and CNS myelination (By similarity). Once induced, MYRF cooperates with
CC SOX10 to implement the myelination program (By similarity).
CC Transcriptional activator of MITF, acting synergistically with PAX3
CC (PubMed:21965087). Transcriptional activator of MBP, via binding to the
CC gene promoter (By similarity). {ECO:0000250|UniProtKB:O55170,
CC ECO:0000250|UniProtKB:Q04888, ECO:0000269|PubMed:21965087}.
CC -!- SUBUNIT: Monomer. Interacts with ARMCX3 at the mitochondrial outer
CC membrane surface. Interacts with PAX3 (PubMed:21965087).
CC {ECO:0000250|UniProtKB:Q04888, ECO:0000269|PubMed:21965087}.
CC -!- INTERACTION:
CC P56693; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-1167533, EBI-12809220;
CC P56693; O43186: CRX; NbExp=3; IntAct=EBI-1167533, EBI-748171;
CC P56693; Q15038: DAZAP2; NbExp=3; IntAct=EBI-1167533, EBI-724310;
CC P56693; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-1167533, EBI-12056251;
CC P56693; Q92993: KAT5; NbExp=3; IntAct=EBI-1167533, EBI-399080;
CC P56693; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-1167533, EBI-11742507;
CC P56693; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-1167533, EBI-716006;
CC P56693; Q13287: NMI; NbExp=2; IntAct=EBI-1167533, EBI-372942;
CC P56693; P23760: PAX3; NbExp=2; IntAct=EBI-1167533, EBI-1167564;
CC P56693; P20265: POU3F2; NbExp=3; IntAct=EBI-1167533, EBI-1167176;
CC P56693; P78424: POU6F2; NbExp=3; IntAct=EBI-1167533, EBI-12029004;
CC P56693; P62937-2: PPIA; NbExp=3; IntAct=EBI-1167533, EBI-25884072;
CC P56693; P17252: PRKCA; NbExp=3; IntAct=EBI-1167533, EBI-1383528;
CC P56693; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-1167533, EBI-9090795;
CC P56693; P56693: SOX10; NbExp=2; IntAct=EBI-1167533, EBI-1167533;
CC P56693; P63165: SUMO1; NbExp=2; IntAct=EBI-1167533, EBI-80140;
CC P56693; P63279: UBE2I; NbExp=2; IntAct=EBI-1167533, EBI-80168;
CC P56693; P61981: YWHAG; NbExp=3; IntAct=EBI-1167533, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12138193}. Nucleus
CC {ECO:0000269|PubMed:12138193}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q04888}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q04888}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q04888}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56693-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56693-2; Sequence=VSP_053874;
CC -!- TISSUE SPECIFICITY: Expressed in fetal brain and in adult brain, heart,
CC small intestine and colon.
CC -!- DOMAIN: The transactivation domains TAM and TAC (for transactivation
CC domain in the middle and at the C-terminus, respectively) are required
CC to contact transcriptional coactivators and basal transcriptional
CC machinery components and thereby induce gene transactivation.
CC {ECO:0000250|UniProtKB:P48436}.
CC -!- DISEASE: Waardenburg syndrome 2E (WS2E) [MIM:611584]: An autosomal
CC dominant auditory-pigmentary disorder characterized by sensorineural
CC deafness, pigmentary disturbances of the hair, skin and eyes, and
CC absence of dystopia canthorum which is the lateral displacement of the
CC inner canthus of each eye. Individuals with WS2E may have neurologic
CC abnormalities, including mental impairment, myelination defects, and
CC ataxia. Some patients can manifest features of Kallmann syndrome.
CC {ECO:0000269|PubMed:10441344, ECO:0000269|PubMed:17999358,
CC ECO:0000269|PubMed:21898658}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Waardenburg syndrome 4C (WS4C) [MIM:613266]: A disorder
CC characterized by the association of Waardenburg features
CC (depigmentation and deafness) with the absence of enteric ganglia in
CC the distal part of the intestine (Hirschsprung disease).
CC {ECO:0000269|PubMed:18348274, ECO:0000269|PubMed:21898658,
CC ECO:0000269|PubMed:9462749}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Peripheral demyelinating neuropathy, central dysmyelinating
CC leukodystrophy, Waardenburg syndrome and Hirschsprung disease (PCWH)
CC [MIM:609136]: A complex neurocristopathy that includes features of 4
CC distinct syndromes: peripheral demyelinating neuropathy, central
CC dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung
CC disease. {ECO:0000269|PubMed:10762540, ECO:0000269|PubMed:15004559,
CC ECO:0000269|PubMed:19208381, ECO:0000269|PubMed:21898658}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SOX10ID43768ch22q13.html";
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DR EMBL; AJ001183; CAA04576.1; -; mRNA.
DR EMBL; CR456584; CAG30470.1; -; mRNA.
DR EMBL; BT020029; AAV38832.1; -; mRNA.
DR EMBL; AK300945; BAG62574.1; -; mRNA.
DR EMBL; CR536571; CAG38808.1; -; mRNA.
DR EMBL; AL031587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002824; AAH02824.1; -; mRNA.
DR EMBL; BC007595; AAH07595.1; -; mRNA.
DR CCDS; CCDS13964.1; -. [P56693-1]
DR RefSeq; NP_008872.1; NM_006941.3. [P56693-1]
DR AlphaFoldDB; P56693; -.
DR SMR; P56693; -.
DR BioGRID; 112546; 66.
DR IntAct; P56693; 60.
DR MINT; P56693; -.
DR STRING; 9606.ENSP00000380093; -.
DR iPTMnet; P56693; -.
DR PhosphoSitePlus; P56693; -.
DR BioMuta; SOX10; -.
DR DMDM; 6175075; -.
DR jPOST; P56693; -.
DR MassIVE; P56693; -.
DR MaxQB; P56693; -.
DR PaxDb; P56693; -.
DR PeptideAtlas; P56693; -.
DR PRIDE; P56693; -.
DR ProteomicsDB; 5245; -.
DR ProteomicsDB; 56933; -. [P56693-1]
DR Antibodypedia; 3774; 1004 antibodies from 48 providers.
DR DNASU; 6663; -.
DR Ensembl; ENST00000360880.6; ENSP00000354130.2; ENSG00000100146.19. [P56693-1]
DR Ensembl; ENST00000396884.8; ENSP00000380093.2; ENSG00000100146.19. [P56693-1]
DR GeneID; 6663; -.
DR KEGG; hsa:6663; -.
DR MANE-Select; ENST00000396884.8; ENSP00000380093.2; NM_006941.4; NP_008872.1.
DR UCSC; uc003aun.2; human. [P56693-1]
DR CTD; 6663; -.
DR DisGeNET; 6663; -.
DR GeneCards; SOX10; -.
DR GeneReviews; SOX10; -.
DR HGNC; HGNC:11190; SOX10.
DR HPA; ENSG00000100146; Group enriched (brain, salivary gland).
DR MalaCards; SOX10; -.
DR MIM; 602229; gene.
DR MIM; 609136; phenotype.
DR MIM; 611584; phenotype.
DR MIM; 613266; phenotype.
DR neXtProt; NX_P56693; -.
DR OpenTargets; ENSG00000100146; -.
DR Orphanet; 478; Kallmann syndrome.
DR Orphanet; 163746; Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease.
DR Orphanet; 895; Waardenburg syndrome type 2.
DR Orphanet; 897; Waardenburg-Shah syndrome.
DR PharmGKB; PA36027; -.
DR VEuPathDB; HostDB:ENSG00000100146; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000158046; -.
DR HOGENOM; CLU_031800_0_0_1; -.
DR InParanoid; P56693; -.
DR OMA; PPHYADQ; -.
DR PhylomeDB; P56693; -.
DR PathwayCommons; P56693; -.
DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR SignaLink; P56693; -.
DR SIGNOR; P56693; -.
DR BioGRID-ORCS; 6663; 99 hits in 1104 CRISPR screens.
DR GeneWiki; SOX10; -.
DR GenomeRNAi; 6663; -.
DR Pharos; P56693; Tbio.
DR PRO; PR:P56693; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P56693; protein.
DR Bgee; ENSG00000100146; Expressed in inferior olivary complex and 162 other tissues.
DR ExpressionAtlas; P56693; baseline and differential.
DR Genevisible; P56693; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0031315; C:extrinsic component of mitochondrial outer membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; TAS:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0022010; P:central nervous system myelination; ISS:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0048484; P:enteric nervous system development; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0032808; P:lacrimal gland development; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0061138; P:morphogenesis of a branching epithelium; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; ISS:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0014015; P:positive regulation of gliogenesis; IEA:Ensembl.
DR GO; GO:0031643; P:positive regulation of myelination; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IEA:Ensembl.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR022151; Sox_N.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12444; Sox_N; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; Deafness; Disease variant;
KW DNA-binding; Hirschsprung disease; Kallmann syndrome; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Waardenburg syndrome.
FT CHAIN 1..466
FT /note="Transcription factor SOX-10"
FT /id="PRO_0000048746"
FT DNA_BIND 104..172
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 62..102
FT /note="Dimerization (DIM)"
FT /evidence="ECO:0000303|PubMed:31194875"
FT REGION 160..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 212..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..310
FT /note="Transactivation domain (TAM)"
FT /evidence="ECO:0000303|PubMed:31194875"
FT REGION 353..466
FT /note="Transactivation domain (TAC)"
FT /evidence="ECO:0000303|PubMed:31194875"
FT REGION 354..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 134..145
FT /note="Nuclear export signal"
FT COMPBIAS 53..67
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..266
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 262..441
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053874"
FT VARIANT 106
FT /note="R -> W (in WS4C; loss of DNA binding and
FT transactivation capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066747"
FT VARIANT 108
FT /note="M -> T (found in a patient with Kallmann syndrome)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072981"
FT VARIANT 111
FT /note="F -> V (found in a patient with Kallmann syndrome)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072982"
FT VARIANT 112
FT /note="M -> I (in WS2E and PCWH; increased DNA binding
FT capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066748"
FT VARIANT 131
FT /note="N -> H (in PCWH; reduced DNA binding capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066749"
FT VARIANT 135
FT /note="S -> G (found in a patient with Kallmann syndrome)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072983"
FT VARIANT 135
FT /note="S -> T (in WS2E; without neurologic involvement;
FT dbSNP:rs74315515)"
FT /evidence="ECO:0000269|PubMed:10441344"
FT /id="VAR_021386"
FT VARIANT 145
FT /note="L -> P (in WS4C; loss of DNA binding and
FT transactivation capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066750"
FT VARIANT 150
FT /note="K -> N (in PCWH; loss of DNA binding and
FT transactivation capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066751"
FT VARIANT 151
FT /note="R -> C (found in a patient with Kallmann syndrome;
FT dbSNP:rs1463736052)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072984"
FT VARIANT 157
FT /note="A -> V (in WS4C; loss of DNA binding and
FT transactivation capacity; dbSNP:rs121909117)"
FT /evidence="ECO:0000269|PubMed:18348274,
FT ECO:0000269|PubMed:21898658"
FT /id="VAR_066752"
FT VARIANT 161
FT /note="R -> C (found in a patient with Kallmann syndrome)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072985"
FT VARIANT 161
FT /note="R -> H (in WS2E; reduced DNA binding capacity;
FT dbSNP:rs750566714)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066753"
FT VARIANT 161
FT /note="R -> RLR (in WS4C)"
FT /evidence="ECO:0000269|PubMed:9462749"
FT /id="VAR_003743"
FT VARIANT 174
FT /note="Q -> P (in PCWH; without Hirschsprung disease;
FT reduced DNA binding capacity; dbSNP:rs267607081)"
FT /evidence="ECO:0000269|PubMed:19208381,
FT ECO:0000269|PubMed:21898658"
FT /id="VAR_066754"
FT VARIANT 175
FT /note="P -> A (in PCWH; reduced DNA binding capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066755"
FT VARIANT 175
FT /note="P -> L (in PCWH; reduced DNA binding capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066756"
FT VARIANT 175
FT /note="P -> R (in PCWH; reduced DNA binding capacity)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066757"
FT VARIANT 321
FT /note="G -> R (in PCWH)"
FT /evidence="ECO:0000269|PubMed:21898658"
FT /id="VAR_066758"
FT CONFLICT 222
FT /note="P -> L (in Ref. 5; CAG38808)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="T -> M (in Ref. 5; CAG38808)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 466 AA; 49911 MW; FAA1EC108D4DE6A1 CRC64;
MAEEQDLSEV ELSPVGSEEP RCLSPGSAPS LGPDGGGGGS GLRASPGPGE LGKVKKEQQD
GEADDDKFPV CIREAVSQVL SGYDWTLVPM PVRVNGASKS KPHVKRPMNA FMVWAQAARR
KLADQYPHLH NAELSKTLGK LWRLLNESDK RPFIEEAERL RMQHKKDHPD YKYQPRRRKN
GKAAQGEAEC PGGEAEQGGT AAIQAHYKSA HLDHRHPGEG SPMSDGNPEH PSGQSHGPPT
PPTTPKTELQ SGKADPKRDG RSMGEGGKPH IDFGNVDIGE ISHEVMSNME TFDVAELDQY
LPPNGHPGHV SSYSAAGYGL GSALAVASGH SAWISKPPGV ALPTVSPPGV DAKAQVKTET
AGPQGPPHYT DQPSTSQIAY TSLSLPHYGS AFPSISRPQF DYSDHQPSGP YYGHSGQASG
LYSAFSYMGP SQRPLYTAIS DPSPSGPQSH SPTHWEQPVY TTLSRP
