P41225 (SOX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor SOX-3

Gene names

Name:

SOX3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	446 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mental retardation
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell development Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 446	446	Transcription factor SOX-3		PRO_0000048720
Regions
	DNA binding	139 – 207	69	HMG box
	Compositional bias	129 – 133	5	Poly-Gly
	Compositional bias	234 – 248	15	Poly-Ala
	Compositional bias	290 – 294	5	Poly-Pro
	Compositional bias	324 – 330	7	Poly-Ala
	Compositional bias	340 – 347	8	Poly-Ala
	Compositional bias	353 – 364	12	Poly-Ala
Natural variations
	Natural variant	43	1	A → T. Ref.9		VAR_026451
	Natural variant	248	1	A → AAAAAAAA in PHPX; reduced transcriptional activity and impaired nuclear localization. Ref.8 Ref.9		VAR_026452
	Natural variant	248	1	A → AAAAAAAAAAAA in MRXGH. Ref.8 Ref.9		VAR_033258
Experimental info
	Sequence conflict	159	1	L → Q in CAA46616. Ref.5
	Sequence conflict	176	1	D → E in CAA46616. Ref.5
	Sequence conflict	202	1	E → D in CAA46616. Ref.5
	Sequence conflict	297 – 299	3	Missing in CAA50465. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P41225 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: F79E79C2D16BB929	FASTA	446	45,210
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

GeneReviews

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.
IPI	IPI00240510.
PIR	I38239. S22942.
RefSeq	NP_005625.2. NM_005634.2.
UniGene	Hs.157429.
3D structure databases
ProteinModelPortal	P41225.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000359567.
PTM databases
PhosphoSite	P41225.
Polymorphism databases
DMDM	48429228.
Proteomic databases
PaxDb	P41225.
PRIDE	P41225.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370536; ENSP00000359567; ENSG00000134595.
GeneID	6658.
KEGG	hsa:6658.
UCSC	uc004fbd.1. human.
Organism-specific databases
CTD	6658.
GeneCards	GC0XM139585.
HGNC	HGNC:11199. SOX3.
MIM	300123. phenotype. 300833. phenotype. 312000. phenotype. 313430. gene.
neXtProt	NX_P41225.
Orphanet	90695. Panhypopituitarism. 3157. Septo-optic dysplasia. 79495. X-linked congenital generalized hypertrichosis. 67045. X-linked intellectual deficit with isolated growth hormone deficiency.
PharmGKB	PA36036.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG321816.
HOGENOM	HOG000231647.
HOVERGEN	HBG105663.
InParanoid	P41225.
KO	K09267.
OMA	AQSYMNV.
PhylomeDB	P41225.
Gene expression databases
Bgee	P41225.
CleanEx	HS_SOX3.
Genevestigator	P41225.
GermOnline	ENSG00000134595. Homo sapiens.
Family and domain databases
Gene3D	1.10.30.10. 1 hit.
InterPro	IPR009071. HMG_box_dom. IPR022097. TF_SOX. [Graphical view]
Pfam	PF00505. HMG_box. 1 hit. PF12336. SOXp. 1 hit. [Graphical view]
SMART	SM00398. HMG. 1 hit. [Graphical view]
SUPFAM	SSF47095. HMG-box. 1 hit.
PROSITE	PS50118. HMG_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6658.
NextBio	25955.
SOURCE	Search...

Entry information

Entry name

SOX3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.