UniProtKB - P41225 (SOX3_HUMAN)
Protein
Transcription factor SOX-3
Gene
SOX3
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity1 Publication
Caution
Was originally termed SOX-9.1 Publication
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 139 – 207 | HMG boxPROSITE-ProRule annotationAdd BLAST | 69 |
GO - Molecular functioni
- DNA binding Source: ProtInc
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- anatomical structure morphogenesis Source: GO_Central
- cell differentiation Source: GO_Central
- central nervous system development Source: ProtInc
- face development Source: UniProtKB
- hypothalamus development Source: UniProtKB
- negative regulation of neuron differentiation Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: GO_Central
- pituitary gland development Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- regulation of transcription, DNA-templated Source: GO_Central
- sensory organ development Source: UniProtKB
- sex determination Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P41225 |
Reactomei | R-HSA-3769402, Deactivation of the beta-catenin transactivating complex |
SIGNORi | P41225 |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription factor SOX-3 |
Gene namesi | Name:SOX3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000134595.7 |
HGNCi | HGNC:11199, SOX3 |
MIMi | 313430, gene |
neXtProti | NX_P41225 |
Subcellular locationi
Nucleus
Nucleus
- nuclear chromatin Source: NTNU_SB
- nucleoplasm Source: HPA
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Panhypopituitarism X-linked (PHPX)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAffected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026452 | 248 | A → AAAAAAAA in PHPX; reduced transcriptional activity and impaired nuclear localization. 1 Publication | 1 |
Mental retardation, X-linked, with isolated growth hormone deficiency (MRXGH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_033258 | 248 | A → AAAAAAAAAAAA in MRXGH. 1 Publication | 1 |
46,XX sex reversal 3 (SRXX3)1 Publication
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.
Disease descriptionA condition in which male gonads develop in a genetic female (female to male sex reversal).
Related information in OMIMHypoparathyroidism, X-linked (HYPX)1 Publication
The gene represented in this entry may be involved in disease pathogenesis. A disease causing, complex chromosomal rearrangement [del(X)(q27.1)inv ins(X;2)(q27.1;p25.3)] has been found in a family with X-linked hypoparathyroidism. This chromosomal abnormality is located 67 kb downstream of SOX3 and likely results in altered SOX3 expression with pathological consequences.1 Publication
Disease descriptionAn X-linked form of true hypoparathyroidism characterized by neonatal or infantile onset and absence of parathyroid glands. Clinical features are hypocalcemia, hyperphosphatemia, seizures, tetany and cramps.
Related information in OMIMKeywords - Diseasei
Disease mutation, Mental retardationOrganism-specific databases
DisGeNETi | 6658 |
MalaCardsi | SOX3 |
MIMi | 300123, phenotype 300833, phenotype 307700, phenotype 312000, phenotype |
OpenTargetsi | ENSG00000134595 |
Orphaneti | 393, 46,XX testicular disorder of sex development 90695, Non-acquired panhypopituitarism 3157, Septo-optic dysplasia spectrum 79495, X-linked congenital generalized hypertrichosis 67045, X-linked intellectual disability with isolated growth hormone deficiency |
PharmGKBi | PA36036 |
Miscellaneous databases
Pharosi | P41225, Tbio |
Polymorphism and mutation databases
BioMutai | SOX3 |
DMDMi | 48429228 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000048720 | 1 – 446 | Transcription factor SOX-3Add BLAST | 446 |
Proteomic databases
EPDi | P41225 |
jPOSTi | P41225 |
MassIVEi | P41225 |
PaxDbi | P41225 |
PeptideAtlasi | P41225 |
PRIDEi | P41225 |
ProteomicsDBi | 55433 |
PTM databases
iPTMneti | P41225 |
PhosphoSitePlusi | P41225 |
Expressioni
Gene expression databases
Bgeei | ENSG00000134595, Expressed in ventricular zone and 49 other tissues |
Genevisiblei | P41225, HS |
Organism-specific databases
HPAi | ENSG00000134595, Tissue enhanced (fallopian tube, testis) |
Interactioni
Subunit structurei
Interacts with SOX2 and FGFR1.
By similarityBinary interactionsi
Hide detailsP41225
With | #Exp. | IntAct |
---|---|---|
ATXN1 [P54253] | 3 | EBI-9078386,EBI-930964 |
CRX [O43186] | 3 | EBI-9078386,EBI-748171 |
TRAF2 [Q12933] | 3 | EBI-9078386,EBI-355744 |
Protein-protein interaction databases
BioGRIDi | 112541, 16 interactors |
IntActi | P41225, 4 interactors |
STRINGi | 9606.ENSP00000359567 |
Miscellaneous databases
RNActi | P41225, protein |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 129 – 133 | Poly-Gly | 5 | |
Compositional biasi | 234 – 248 | Poly-AlaAdd BLAST | 15 | |
Compositional biasi | 290 – 294 | Poly-Pro | 5 | |
Compositional biasi | 324 – 330 | Poly-Ala | 7 | |
Compositional biasi | 340 – 347 | Poly-Ala | 8 | |
Compositional biasi | 353 – 364 | Poly-AlaAdd BLAST | 12 |
Phylogenomic databases
eggNOGi | KOG0527, Eukaryota |
GeneTreei | ENSGT00940000162359 |
HOGENOMi | CLU_021123_0_0_1 |
InParanoidi | P41225 |
OMAi | EQLGYGQ |
OrthoDBi | 1161594at2759 |
PhylomeDBi | P41225 |
TreeFami | TF351735 |
Family and domain databases
Gene3Di | 1.10.30.10, 1 hit |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf IPR022097, SOX_fam |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit PF12336, SOXp, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 1 hit |
SUPFAMi | SSF47095, SSF47095, 1 hit |
PROSITEi | View protein in PROSITE PS50118, HMG_BOX_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P41225-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRPVRENSSG ARSPRVPADL ARSILISLPF PPDSLAHRPP SSAPTESQGL
60 70 80 90 100
FTVAAPAPGA PSPPATLAHL LPAPAMYSLL ETELKNPVGT PTQAAGTGGP
110 120 130 140 150
AAPGGAGKSS ANAAGGANSG GGSSGGASGG GGGTDQDRVK RPMNAFMVWS
160 170 180 190 200
RGQRRKMALE NPKMHNSEIS KRLGADWKLL TDAEKRPFID EAKRLRAVHM
210 220 230 240 250
KEYPDYKYRP RRKTKTLLKK DKYSLPSGLL PPGAAAAAAA AAAAAAAASS
260 270 280 290 300
PVGVGQRLDT YTHVNGWANG AYSLVQEQLG YAQPPSMSSP PPPPALPPMH
310 320 330 340 350
RYDMAGLQYS PMMPPGAQSY MNVAAAAAAA SGYGGMAPSA TAAAAAAYGQ
360 370 380 390 400
QPATAAAAAA AAAAMSLGPM GSVVKSEPSS PPPAIASHSQ RACLGDLRDM
410 420 430 440
ISMYLPPGGD AADAASPLPG GRLHGVHQHY QGAGTAVNGT VPLTHI
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 159 | L → Q in CAA46616 (PubMed:1614875).Curated | 1 | |
Sequence conflicti | 176 | D → E in CAA46616 (PubMed:1614875).Curated | 1 | |
Sequence conflicti | 202 | E → D in CAA46616 (PubMed:1614875).Curated | 1 | |
Sequence conflicti | 297 – 299 | Missing in CAA50465 (Ref. 2) Curated | 3 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026451 | 43 | A → T1 PublicationCorresponds to variant dbSNP:rs73637709EnsemblClinVar. | 1 | |
Natural variantiVAR_026452 | 248 | A → AAAAAAAA in PHPX; reduced transcriptional activity and impaired nuclear localization. 1 Publication | 1 | |
Natural variantiVAR_033258 | 248 | A → AAAAAAAAAAAA in MRXGH. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X71135 Genomic DNA Translation: CAA50465.1 AF264713 Genomic DNA Translation: AAF73059.1 AL121875 Genomic DNA No translation available. BC093863 mRNA Translation: AAH93863.1 BC093865 mRNA Translation: AAH93865.1 X65665 mRNA Translation: CAA46616.1 |
CCDSi | CCDS14669.1 |
PIRi | I38239 S22942 |
RefSeqi | NP_005625.2, NM_005634.2 |
Genome annotation databases
Ensembli | ENST00000370536; ENSP00000359567; ENSG00000134595 |
GeneIDi | 6658 |
KEGGi | hsa:6658 |
UCSCi | uc004fbd.2, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X71135 Genomic DNA Translation: CAA50465.1 AF264713 Genomic DNA Translation: AAF73059.1 AL121875 Genomic DNA No translation available. BC093863 mRNA Translation: AAH93863.1 BC093865 mRNA Translation: AAH93865.1 X65665 mRNA Translation: CAA46616.1 |
CCDSi | CCDS14669.1 |
PIRi | I38239 S22942 |
RefSeqi | NP_005625.2, NM_005634.2 |
3D structure databases
SMRi | P41225 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112541, 16 interactors |
IntActi | P41225, 4 interactors |
STRINGi | 9606.ENSP00000359567 |
PTM databases
iPTMneti | P41225 |
PhosphoSitePlusi | P41225 |
Polymorphism and mutation databases
BioMutai | SOX3 |
DMDMi | 48429228 |
Proteomic databases
EPDi | P41225 |
jPOSTi | P41225 |
MassIVEi | P41225 |
PaxDbi | P41225 |
PeptideAtlasi | P41225 |
PRIDEi | P41225 |
ProteomicsDBi | 55433 |
Protocols and materials databases
Antibodypediai | 16808, 282 antibodies |
Genome annotation databases
Ensembli | ENST00000370536; ENSP00000359567; ENSG00000134595 |
GeneIDi | 6658 |
KEGGi | hsa:6658 |
UCSCi | uc004fbd.2, human |
Organism-specific databases
CTDi | 6658 |
DisGeNETi | 6658 |
EuPathDBi | HostDB:ENSG00000134595.7 |
GeneCardsi | SOX3 |
HGNCi | HGNC:11199, SOX3 |
HPAi | ENSG00000134595, Tissue enhanced (fallopian tube, testis) |
MalaCardsi | SOX3 |
MIMi | 300123, phenotype 300833, phenotype 307700, phenotype 312000, phenotype 313430, gene |
neXtProti | NX_P41225 |
OpenTargetsi | ENSG00000134595 |
Orphaneti | 393, 46,XX testicular disorder of sex development 90695, Non-acquired panhypopituitarism 3157, Septo-optic dysplasia spectrum 79495, X-linked congenital generalized hypertrichosis 67045, X-linked intellectual disability with isolated growth hormone deficiency |
PharmGKBi | PA36036 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0527, Eukaryota |
GeneTreei | ENSGT00940000162359 |
HOGENOMi | CLU_021123_0_0_1 |
InParanoidi | P41225 |
OMAi | EQLGYGQ |
OrthoDBi | 1161594at2759 |
PhylomeDBi | P41225 |
TreeFami | TF351735 |
Enzyme and pathway databases
PathwayCommonsi | P41225 |
Reactomei | R-HSA-3769402, Deactivation of the beta-catenin transactivating complex |
SIGNORi | P41225 |
Miscellaneous databases
BioGRID-ORCSi | 6658, 8 hits in 492 CRISPR screens |
GeneWikii | SOX3 |
GenomeRNAii | 6658 |
Pharosi | P41225, Tbio |
PROi | PR:P41225 |
RNActi | P41225, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134595, Expressed in ventricular zone and 49 other tissues |
Genevisiblei | P41225, HS |
Family and domain databases
Gene3Di | 1.10.30.10, 1 hit |
InterProi | View protein in InterPro IPR009071, HMG_box_dom IPR036910, HMG_box_dom_sf IPR022097, SOX_fam |
Pfami | View protein in Pfam PF00505, HMG_box, 1 hit PF12336, SOXp, 1 hit |
SMARTi | View protein in SMART SM00398, HMG, 1 hit |
SUPFAMi | SSF47095, SSF47095, 1 hit |
PROSITEi | View protein in PROSITE PS50118, HMG_BOX_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SOX3_HUMAN | |
Accessioni | P41225Primary (citable) accession number: P41225 Secondary accession number(s): P35714, Q5JWI3, Q9NP49 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | June 7, 2004 | |
Last modified: | December 2, 2020 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations