SOX3_HUMAN
ID SOX3_HUMAN Reviewed; 446 AA.
AC P41225; P35714; Q5JWI3; Q9NP49;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Transcription factor SOX-3;
GN Name=SOX3;
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 [GENOMIC DNA].
RX PubMed=8111369; DOI=10.1093/hmg/2.12.2013;
RA Stevanovic M., Lovell-Badge R., Collignon J., Goodfellow P.N.;
RT "SOX3 is an X-linked gene related to SRY.";
RL Hum. Mol. Genet. 2:2013-2018(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gorry M.C., Hart P.S., Sashi V., Hart T.C.;
RT "Clarification of the genomic sequence for human SOX3.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 150-203.
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 [6]
RP FUNCTION, AND INVOLVEMENT IN SRXX3.
RX PubMed=21183788; DOI=10.1172/jci42580;
RA Sutton E., Hughes J., White S., Sekido R., Tan J., Arboleda V., Rogers N.,
RA Knower K., Rowley L., Eyre H., Rizzoti K., McAninch D., Goncalves J.,
RA Slee J., Turbitt E., Bruno D., Bengtsson H., Harley V., Vilain E.,
RA Sinclair A., Lovell-Badge R., Thomas P.;
RT "Identification of SOX3 as an XX male sex reversal gene in mice and
RT humans.";
RL J. Clin. Invest. 121:328-341(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
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 [9]
RP VARIANT MRXGH ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS.
RX PubMed=12428212; DOI=10.1086/344661;
RA Laumonnier F., Ronce N., Hamel B.C.J., Thomas P., Lespinasse J.,
RA Raynaud M., Paringaux C., Van Bokhoven H., Kalscheuer V., Fryns J.-P.,
RA Chelly J., Moraine C., Briault S.;
RT "Transcription factor SOX3 is involved in X-linked mental retardation with
RT growth hormone deficiency.";
RL Am. J. Hum. Genet. 71:1450-1455(2002).
RN [10]
RP VARIANT PHPX ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS, AND VARIANT THR-43.
RX PubMed=15800844; DOI=10.1086/430134;
RA Woods K.S., Cundall M., Turton J., Rizotti K., Mehta A., Palmer R.,
RA Wong J., Chong W.K., Al-Zyoud M., El-Ali M., Otonkoski T.,
RA Martinez-Barbera J.-P., Thomas P.Q., Robinson I.C., Lovell-Badge R.,
RA Woodward K.J., Dattani M.T.;
RT "Over- and underdosage of SOX3 is associated with infundibular hypoplasia
RT and hypopituitarism.";
RL Am. J. Hum. Genet. 76:833-849(2005).
RN [11]
RP INVOLVEMENT IN HYPX, AND CHROMOSOMAL REARRANGEMENT.
RX PubMed=16167084; DOI=10.1172/jci24156;
RA Bowl M.R., Nesbit M.A., Harding B., Levy E., Jefferson A., Volpi E.,
RA Rizzoti K., Lovell-Badge R., Schlessinger D., Whyte M.P., Thakker R.V.;
RT "An interstitial deletion-insertion involving chromosomes 2p25.3 and
RT Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.";
RL J. Clin. Invest. 115:2822-2831(2005).
CC -!- FUNCTION: Transcription factor required during the formation of the
CC hypothalamo-pituitary axis. May function as a switch in neuronal
CC development. Keeps neural cells undifferentiated by counteracting the
CC activity of proneural proteins and suppresses neuronal differentiation.
CC Required also within the pharyngeal epithelia for craniofacial
CC morphogenesis. Controls a genetic switch in male development. Is
CC necessary for initiating male sex determination by directing the
CC development of supporting cell precursors (pre-Sertoli cells) as
CC Sertoli rather than granulosa cells (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:21183788}.
CC -!- SUBUNIT: Interacts with SOX2 and FGFR1. {ECO:0000250}.
CC -!- INTERACTION:
CC P41225; P54253: ATXN1; NbExp=3; IntAct=EBI-9078386, EBI-930964;
CC P41225; O43186: CRX; NbExp=3; IntAct=EBI-9078386, EBI-748171;
CC P41225; Q12933: TRAF2; NbExp=3; IntAct=EBI-9078386, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Nucleus.
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: Panhypopituitarism X-linked (PHPX) [MIM:312000]: Affected
CC individuals have absent infundibulum, anterior pituitary hypoplasia,
CC and ectopic posterior pituitary. {ECO:0000269|PubMed:15800844}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, with isolated
CC growth hormone deficiency (MRXGH) [MIM:300123]: A disorder
CC characterized by the association of variable degrees of intellectual
CC disability with panhypopituitarism, variable combinations of
CC hypothyroidism, delayed pubertal development, and short stature due to
CC growth hormone deficiency. {ECO:0000269|PubMed:12428212}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: 46,XX sex reversal 3 (SRXX3) [MIM:300833]: A condition in
CC which male gonads develop in a genetic female (female to male sex
CC reversal). {ECO:0000269|PubMed:21183788}. Note=The disease is caused by
CC variants affecting the gene represented in this entry. Copy number
CC variations (CNV) encompassing or in close proximity to SOX3 are
CC responsible for XX male reversal. These variations include two
CC duplications of approximately 123 kb and 85 kb, the former of which
CC spans the entire SOX3 gene; a 343 kb deletion immediately upstream of
CC SOX3 that is probably responsible of altered regulation (and not
CC increased dosage) of SOX3; a large (approximately 6 Mb) duplication
CC that encompasses SOX3 and at least 18 additional distally located
CC genes. Its proximal breakpoint falls within the SOX3 regulatory region.
CC This large rearrangement has been found in a patient with XX male
CC reversal and a complex phenotype that also includes a scrotal
CC hypoplasia, microcephaly, developmental delay, and growth retardation.
CC -!- DISEASE: Hypoparathyroidism, X-linked (HYPX) [MIM:307700]: An X-linked
CC form of true hypoparathyroidism characterized by neonatal or infantile
CC onset and absence of parathyroid glands. Clinical features are
CC hypocalcemia, hyperphosphatemia, seizures, tetany and cramps.
CC {ECO:0000269|PubMed:16167084}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis. A disease causing, complex
CC chromosomal rearrangement [del(X)(q27.1)inv ins(X;2)(q27.1;p25.3)] has
CC been found in a family with X-linked hypoparathyroidism. This
CC chromosomal abnormality is located 67 kb downstream of SOX3 and likely
CC results in altered SOX3 expression with pathological consequences.
CC {ECO:0000269|PubMed:16167084}.
CC -!- CAUTION: Was originally termed SOX-9. {ECO:0000305|PubMed:1614875}.
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DR EMBL; X71135; CAA50465.1; -; Genomic_DNA.
DR EMBL; AF264713; AAF73059.1; -; Genomic_DNA.
DR EMBL; AL121875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093863; AAH93863.1; -; mRNA.
DR EMBL; BC093865; AAH93865.1; -; mRNA.
DR EMBL; X65665; CAA46616.1; -; mRNA.
DR CCDS; CCDS14669.1; -.
DR PIR; I38239; I38239.
DR PIR; S22942; S22942.
DR RefSeq; NP_005625.2; NM_005634.2.
DR AlphaFoldDB; P41225; -.
DR SMR; P41225; -.
DR BioGRID; 112541; 16.
DR IntAct; P41225; 4.
DR STRING; 9606.ENSP00000359567; -.
DR GlyGen; P41225; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P41225; -.
DR PhosphoSitePlus; P41225; -.
DR BioMuta; SOX3; -.
DR DMDM; 48429228; -.
DR EPD; P41225; -.
DR jPOST; P41225; -.
DR MassIVE; P41225; -.
DR PaxDb; P41225; -.
DR PeptideAtlas; P41225; -.
DR PRIDE; P41225; -.
DR ProteomicsDB; 55433; -.
DR Antibodypedia; 16808; 296 antibodies from 34 providers.
DR DNASU; 6658; -.
DR Ensembl; ENST00000370536.5; ENSP00000359567.2; ENSG00000134595.9.
DR GeneID; 6658; -.
DR KEGG; hsa:6658; -.
DR MANE-Select; ENST00000370536.5; ENSP00000359567.2; NM_005634.3; NP_005625.2.
DR UCSC; uc004fbd.2; human.
DR CTD; 6658; -.
DR DisGeNET; 6658; -.
DR GeneCards; SOX3; -.
DR HGNC; HGNC:11199; SOX3.
DR HPA; ENSG00000134595; Tissue enhanced (brain, fallopian tube, testis).
DR MalaCards; SOX3; -.
DR MIM; 300123; phenotype.
DR MIM; 300833; phenotype.
DR MIM; 307700; phenotype.
DR MIM; 312000; phenotype.
DR MIM; 313430; gene.
DR neXtProt; NX_P41225; -.
DR OpenTargets; ENSG00000134595; -.
DR Orphanet; 393; 46,XX testicular disorder of sex development.
DR Orphanet; 90695; Non-acquired panhypopituitarism.
DR Orphanet; 3157; Septo-optic dysplasia spectrum.
DR Orphanet; 79495; X-linked congenital generalized hypertrichosis.
DR Orphanet; 67045; X-linked intellectual disability with isolated growth hormone deficiency.
DR PharmGKB; PA36036; -.
DR VEuPathDB; HostDB:ENSG00000134595; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000162359; -.
DR HOGENOM; CLU_021123_0_0_1; -.
DR InParanoid; P41225; -.
DR OMA; AYPQHHG; -.
DR OrthoDB; 1161594at2759; -.
DR PhylomeDB; P41225; -.
DR TreeFam; TF351735; -.
DR PathwayCommons; P41225; -.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR SignaLink; P41225; -.
DR SIGNOR; P41225; -.
DR BioGRID-ORCS; 6658; 15 hits in 717 CRISPR screens.
DR GeneWiki; SOX3; -.
DR GenomeRNAi; 6658; -.
DR Pharos; P41225; Tbio.
DR PRO; PR:P41225; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P41225; protein.
DR Bgee; ENSG00000134595; Expressed in ventricular zone and 43 other tissues.
DR Genevisible; P41225; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
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; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0060324; P:face development; ISS:UniProtKB.
DR GO; GO:0021854; P:hypothalamus development; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021983; P:pituitary gland development; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0007423; P:sensory organ development; ISS:UniProtKB.
DR GO; GO:0007530; P:sex determination; IMP:UniProtKB.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR029550; SOX-3.
DR InterPro; IPR022097; SOX_fam.
DR PANTHER; PTHR10270:SF111; PTHR10270:SF111; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12336; SOXp; 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 Developmental protein; Disease variant; DNA-binding;
KW Intellectual disability; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..446
FT /note="Transcription factor SOX-3"
FT /id="PRO_0000048720"
FT DNA_BIND 139..207
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 29..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 399..407
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:34342803"
FT VARIANT 43
FT /note="A -> T (in dbSNP:rs73637709)"
FT /evidence="ECO:0000269|PubMed:15800844"
FT /id="VAR_026451"
FT VARIANT 248
FT /note="A -> AAAAAAAA (in PHPX; reduced transcriptional
FT activity and impaired nuclear localization)"
FT /evidence="ECO:0000269|PubMed:15800844"
FT /id="VAR_026452"
FT VARIANT 248
FT /note="A -> AAAAAAAAAAAA (in MRXGH)"
FT /evidence="ECO:0000269|PubMed:12428212"
FT /id="VAR_033258"
FT CONFLICT 159
FT /note="L -> Q (in Ref. 5; CAA46616)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="D -> E (in Ref. 5; CAA46616)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="E -> D (in Ref. 5; CAA46616)"
FT /evidence="ECO:0000305"
FT CONFLICT 297..299
FT /note="Missing (in Ref. 2; CAA50465)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 446 AA; 45210 MW; F79E79C2D16BB929 CRC64;
MRPVRENSSG ARSPRVPADL ARSILISLPF PPDSLAHRPP SSAPTESQGL FTVAAPAPGA
PSPPATLAHL LPAPAMYSLL ETELKNPVGT PTQAAGTGGP AAPGGAGKSS ANAAGGANSG
GGSSGGASGG GGGTDQDRVK RPMNAFMVWS RGQRRKMALE NPKMHNSEIS KRLGADWKLL
TDAEKRPFID EAKRLRAVHM KEYPDYKYRP RRKTKTLLKK DKYSLPSGLL PPGAAAAAAA
AAAAAAAASS PVGVGQRLDT YTHVNGWANG AYSLVQEQLG YAQPPSMSSP PPPPALPPMH
RYDMAGLQYS PMMPPGAQSY MNVAAAAAAA SGYGGMAPSA TAAAAAAYGQ QPATAAAAAA
AAAAMSLGPM GSVVKSEPSS PPPAIASHSQ RACLGDLRDM ISMYLPPGGD AADAASPLPG
GRLHGVHQHY QGAGTAVNGT VPLTHI
