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P41225 (SOX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor SOX-3
Gene names
Name:SOX3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length446 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. Required also within the pharyngeal epithelia for craniofacial morphogenesis. Controls a genetic switch in male development. Is necessary for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells By similarity. Ref.6

Subunit structure

Interacts with SOX2 and FGFR1 By similarity.

Subcellular location

Nucleus.

Involvement in disease

Panhypopituitarism X-linked (PHPX) [MIM:312000]: Affected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Mental retardation, X-linked, with isolated growth hormone deficiency (MRXGH) [MIM:300123]: A disorder characterized by the association of variable degrees of mental retardation with panhypopituitarism, variable combinations of hypothyroidism, delayed pubertal development, and short stature due to growth hormone deficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

46,XX sex reversal 3 (SRXX3) [MIM:300833]: A condition in which male gonads develop in a genetic female (female to male sex reversal).
Note: The disease is caused by mutations affecting the gene represented in this entry. Copy number variations (CNV) encompassing or in close proximity to SOX3 are responsible for XX male reversal. These variations include two duplications of approximately 123 kb and 85 kb, the former of which spans the entire SOX3 gene; a 343 kb deletion immediately upstream of SOX3 that is probably responsible of altered regulation (and not increased dosage) of SOX3; a large (approximately 6 Mb) duplication that encompasses SOX3 and at least 18 additional distally located genes. Its proximal breakpoint falls within the SOX3 regulatory region. This large rearrangement has been found in a patient with XX male reversal and a complex phenotype that also includes a scrotal hypoplasia, microcephaly, developmental delay, and growth retardation. Ref.6

Sequence similarities

Contains 1 HMG box DNA-binding domain.

Caution

Was originally (Ref.5) termed SOX-9.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Mental retardation
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Traceable author statement PubMed 8625802. Source: ProtInc

face development

Inferred from sequence or structural similarity. Source: UniProtKB

hypothalamus development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

pituitary gland development

Inferred from sequence or structural similarity. Source: UniProtKB

sensory organ development

Inferred from sequence or structural similarity. Source: UniProtKB

sex determination

Inferred from mutant phenotype Ref.6. Source: UniProtKB

spermatid differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Traceable author statement PubMed 8625802. Source: ProtInc

RNA polymerase II core promoter sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 446446Transcription factor SOX-3
PRO_0000048720

Regions

DNA binding139 – 20769HMG box
Compositional bias129 – 1335Poly-Gly
Compositional bias234 – 24815Poly-Ala
Compositional bias290 – 2945Poly-Pro
Compositional bias324 – 3307Poly-Ala
Compositional bias340 – 3478Poly-Ala
Compositional bias353 – 36412Poly-Ala

Natural variations

Natural variant431A → T. Ref.9
Corresponds to variant rs73637709 [ dbSNP | Ensembl ].
VAR_026451
Natural variant2481A → AAAAAAAA in PHPX; reduced transcriptional activity and impaired nuclear localization. Ref.8 Ref.9
VAR_026452
Natural variant2481A → AAAAAAAAAAAA in MRXGH. Ref.8 Ref.9
VAR_033258

Experimental info

Sequence conflict1591L → Q in CAA46616. Ref.5
Sequence conflict1761D → E in CAA46616. Ref.5
Sequence conflict2021E → D in CAA46616. Ref.5
Sequence conflict297 – 2993Missing in CAA50465. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P41225 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: F79E79C2D16BB929

FASTA44645,210
        10         20         30         40         50         60 
MRPVRENSSG ARSPRVPADL ARSILISLPF PPDSLAHRPP SSAPTESQGL FTVAAPAPGA 

        70         80         90        100        110        120 
PSPPATLAHL LPAPAMYSLL ETELKNPVGT PTQAAGTGGP AAPGGAGKSS ANAAGGANSG 

       130        140        150        160        170        180 
GGSSGGASGG GGGTDQDRVK RPMNAFMVWS RGQRRKMALE NPKMHNSEIS KRLGADWKLL 

       190        200        210        220        230        240 
TDAEKRPFID EAKRLRAVHM KEYPDYKYRP RRKTKTLLKK DKYSLPSGLL PPGAAAAAAA 

       250        260        270        280        290        300 
AAAAAAAASS PVGVGQRLDT YTHVNGWANG AYSLVQEQLG YAQPPSMSSP PPPPALPPMH 

       310        320        330        340        350        360 
RYDMAGLQYS PMMPPGAQSY MNVAAAAAAA SGYGGMAPSA TAAAAAAYGQ QPATAAAAAA 

       370        380        390        400        410        420 
AAAAMSLGPM GSVVKSEPSS PPPAIASHSQ RACLGDLRDM ISMYLPPGGD AADAASPLPG 

       430        440 
GRLHGVHQHY QGAGTAVNGT VPLTHI 

« Hide

References

« Hide 'large scale' references
[1]"SOX3 is an X-linked gene related to SRY."
Stevanovic M., Lovell-Badge R., Collignon J., Goodfellow P.N.
Hum. Mol. Genet. 2:2013-2018(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Clarification of the genomic sequence for human SOX3."
Gorry M.C., Hart P.S., Sashi V., Hart T.C.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"A conserved family of genes related to the testis determining gene, SRY."
Denny P., Swift S., Brand N., Dabhade N., Barton P., Ashworth A.
Nucleic Acids Res. 20:2887-2887(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-203.
[6]"Identification of SOX3 as an XX male sex reversal gene in mice and humans."
Sutton E., Hughes J., White S., Sekido R., Tan J., Arboleda V., Rogers N., Knower K., Rowley L., Eyre H., Rizzoti K., McAninch D., Goncalves J., Slee J., Turbitt E., Bruno D., Bengtsson H., Harley V. expand/collapse author list , Vilain E., Sinclair A., Lovell-Badge R., Thomas P.
J. Clin. Invest. 121:328-341(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INVOLVEMENT IN SRXX3.
[7]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency."
Laumonnier F., Ronce N., Hamel B.C.J., Thomas P., Lespinasse J., Raynaud M., Paringaux C., Van Bokhoven H., Kalscheuer V., Fryns J.-P., Chelly J., Moraine C., Briault S.
Am. J. Hum. Genet. 71:1450-1455(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRXGH ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS.
[9]"Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism."
Woods K.S., Cundall M., Turton J., Rizotti K., Mehta A., Palmer R., Wong J., Chong W.K., Al-Zyoud M., El-Ali M., Otonkoski T., Martinez-Barbera J.-P., Thomas P.Q., Robinson I.C., Lovell-Badge R., Woodward K.J., Dattani M.T.
Am. J. Hum. Genet. 76:833-849(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHPX ALA-ALA-ALA-ALA-ALA-ALA-ALA-248 INS, VARIANT THR-43.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X71135 Genomic DNA. Translation: CAA50465.1.
AF264713 Genomic DNA. Translation: AAF73059.1.
AL121875 Genomic DNA. Translation: CAB87584.1.
BC093863 mRNA. Translation: AAH93863.1.
BC093865 mRNA. Translation: AAH93865.1.
X65665 mRNA. Translation: CAA46616.1.
PIRI38239.
S22942.
RefSeqNP_005625.2. NM_005634.2.
UniGeneHs.157429.

3D structure databases

ProteinModelPortalP41225.
SMRP41225. Positions 137-215.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112541. 1 interaction.
IntActP41225. 1 interaction.
STRING9606.ENSP00000359567.

PTM databases

PhosphoSiteP41225.

Polymorphism databases

DMDM48429228.

Proteomic databases

PaxDbP41225.
PRIDEP41225.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370536; ENSP00000359567; ENSG00000134595.
GeneID6658.
KEGGhsa:6658.
UCSCuc004fbd.1. human.

Organism-specific databases

CTD6658.
GeneCardsGC0XM139585.
HGNCHGNC:11199. SOX3.
MIM300123. phenotype.
300833. phenotype.
312000. phenotype.
313430. gene.
neXtProtNX_P41225.
Orphanet393. 46,XX testicular disorder of sex development.
90695. Panhypopituitarism.
3157. Septo-optic dysplasia.
79495. X-linked congenital generalized hypertrichosis.
67045. X-linked intellectual deficit with isolated growth hormone deficiency.
PharmGKBPA36036.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG321816.
HOGENOMHOG000231647.
HOVERGENHBG105663.
InParanoidP41225.
KOK09267.
OMASGYGGMA.
OrthoDBEOG7TMZVP.
PhylomeDBP41225.
TreeFamTF351735.

Gene expression databases

BgeeP41225.
CleanExHS_SOX3.
GenevestigatorP41225.

Family and domain databases

Gene3D1.10.30.10. 1 hit.
InterProIPR009071. HMG_box_dom.
IPR022097. TF_SOX.
[Graphical view]
PfamPF00505. HMG_box. 1 hit.
PF12336. SOXp. 1 hit.
[Graphical view]
SMARTSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMSSF47095. SSF47095. 1 hit.
PROSITEPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSOX3.
GenomeRNAi6658.
NextBio25955.
PROP41225.
SOURCESearch...

Entry information

Entry nameSOX3_HUMAN
AccessionPrimary (citable) accession number: P41225
Secondary accession number(s): P35714, Q5JWI3, Q9NP49
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: June 7, 2004
Last modified: April 16, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM