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Protein

Sex-determining region Y protein

Gene

SRY

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional regulator that controls a genetic switch in male development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity). Involved in different aspects of gene regulation including promoter activation or repression (By similarity). Promotes DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'.By similarity4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi60 – 128HMG boxPROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • male sex determination Source: UniProtKB
  • positive regulation of male gonad development Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • sex differentiation Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, Calmodulin-binding, DNA-binding, Repressor
Biological processDifferentiation, Sexual differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-3769402 Deactivation of the beta-catenin transactivating complex
SignaLinkiQ05066
SIGNORiQ05066

Names & Taxonomyi

Protein namesi
Recommended name:
Sex-determining region Y protein
Alternative name(s):
Testis-determining factor
Gene namesi
Name:SRY
Synonyms:TDF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome Y

Organism-specific databases

EuPathDBiHostDB:ENSG00000184895.7
HGNCiHGNC:11311 SRY
MIMi480000 gene
neXtProtiNX_Q05066

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

46,XY sex reversal 1 (SRXY1)26 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal.
See also OMIM:400044
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0300193S → L in SRXY1. 1 Publication1
Natural variantiVAR_00371718S → N in SRXY1; partial; also in two patients with a Turner syndrome phenotype. 2 PublicationsCorresponds to variant dbSNP:rs104894971EnsemblClinVar.1
Natural variantiVAR_00371860V → A in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs764249635Ensembl.1
Natural variantiVAR_00371960V → L in SRXY1. 2 PublicationsCorresponds to variant dbSNP:rs104894957EnsemblClinVar.1
Natural variantiVAR_00372062R → G in SRXY1. 1 Publication1
Natural variantiVAR_00372164M → I in SRXY1; alters interaction with DNA and DNA bending. 2 PublicationsCorresponds to variant dbSNP:rs104894969EnsemblClinVar.1
Natural variantiVAR_01729864M → R in SRXY1. 1 Publication1
Natural variantiVAR_01729967F → V in SRXY1. 1 Publication1
Natural variantiVAR_00372268I → T in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894968EnsemblClinVar.1
Natural variantiVAR_07843375R → M in SRXY1; localizes mainly in the cytoplasm. 1 Publication1
Natural variantiVAR_01730076R → S in SRXY1. 1 Publication1
Natural variantiVAR_00372378M → T in SRXY1. 1 Publication1
Natural variantiVAR_01730187N → Y in SRXY1. 1 Publication1
Natural variantiVAR_00372490I → M in SRXY1. 3 PublicationsCorresponds to variant dbSNP:rs104894959EnsemblClinVar.1
Natural variantiVAR_00372591S → G in SRXY1. 1 Publication1
Natural variantiVAR_01730295G → E in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894972EnsemblClinVar.1
Natural variantiVAR_00372695G → R in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894974EnsemblClinVar.1
Natural variantiVAR_003727101L → H in SRXY1. 1 Publication1
Natural variantiVAR_003728106K → I in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894964EnsemblClinVar.1
Natural variantiVAR_003729108P → R in SRXY1. 1 Publication1
Natural variantiVAR_003730109F → S in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894956EnsemblClinVar.1
Natural variantiVAR_003731113A → T in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894966EnsemblClinVar.1
Natural variantiVAR_003732125P → L in SRXY1. 1 Publication1
Natural variantiVAR_003733127Y → C in SRXY1. 1 Publication1
Natural variantiVAR_017303127Y → F in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894973EnsemblClinVar.1
Natural variantiVAR_017304131P → R in SRXY1. 1 Publication1
Natural variantiVAR_003734133R → W in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894976EnsemblClinVar.1
A 45,X chromosomal aberration involving SRY is found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, "streak gonads", variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female.
46,XX sex reversal 1 (SRXX1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition in which male gonads develop in a genetic female (female to male sex reversal).
See also OMIM:400045

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31 – 33SSS → AAA: Abolishes its phosphorylation by PKA. Does not enhance its DNA-binding activity. Abolishes stimulation of transcription repression. 1 Publication3
Mutagenesisi62R → G: Strongly reduces nuclear localization. Strongly reduces nuclear localization; when associated with W-133. Reduces interaction with KPNB1. Abolishes DNA-binding. 1 Publication1
Mutagenesisi64M → I: Abolishes nuclear localization. 1 Publication1
Mutagenesisi75R → N: Strongly reduces nuclear localization. Abolishes DNA-binding. Does not reduce interaction with KPNB1 and CAML. 2 Publications1
Mutagenesisi76R → P: Reduces nuclear localization. Reduces DNA-binding. Does not reduce interaction with KPNB1 and CAML. 2 Publications1
Mutagenesisi115K → R: Does not abolish acetylation activity. 1 Publication1
Mutagenesisi123K → R: Does not abolish acetylation. 1 Publication1
Mutagenesisi128K → R: Does not abolish acetylation. 1 Publication1
Mutagenesisi133R → W: Reduces nuclear localization. Strongly reduces nuclear localization; when associated with G-62. Reduces interaction with KPNB1. Does not reduce interaction with CAML. Does not abolish DNA-binding. 2 Publications1
Mutagenesisi134K → R: Does not abolish acetylation. 1 Publication1
Mutagenesisi136K → R: Abolishes acetylation. Does not abolish interaction with EP300. Does not abolish DNA-binding. Enhances cytoplasmic localization. Abolishes interaction with KPNB1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6736
GeneReviewsiSRY
MalaCardsiSRY
MIMi400044 phenotype
400045 phenotype
OpenTargetsiENSG00000184895
Orphaneti1772 45,X/46,XY mixed gonadal dysgenesis
2138 46,XX ovotesticular disorder of sex development
393 46,XX testicular disorder of sex development
242 46,XY complete gonadal dysgenesis
251510 46,XY partial gonadal dysgenesis
PharmGKBiPA36135

Polymorphism and mutation databases

DMDMi548983

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000486711 – 204Sex-determining region Y proteinAdd BLAST204

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei136N6-acetyllysine1 Publication1

Post-translational modificationi

Phosphorylated on serine residues by PKA. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression.1 Publication
Acetylation of Lys-136 contributes to its nuclear localization and enhances its interaction with KPNB1. Deacetylated by HDAC3.1 Publication
Poly-ADP-ribosylated by PARP1. ADP-ribosylation reduces its DNA-binding activity.

Keywords - PTMi

Acetylation, ADP-ribosylation

Proteomic databases

PaxDbiQ05066
PRIDEiQ05066
ProteomicsDBi58304

PTM databases

iPTMnetiQ05066
PhosphoSitePlusiQ05066

Expressioni

Gene expression databases

BgeeiENSG00000184895
CleanExiHS_SRY
ExpressionAtlasiQ05066 baseline and differential
GenevisibleiQ05066 HS

Interactioni

Subunit structurei

Interacts with CALM, EP300, HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1, SLC9A3R2 and WT1. The interaction with EP300 modulates its DNA-binding activity. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form (By similarity). Interaction with PARP1 impaired its DNA-binding activity (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB-KW
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112614, 19 interactors
IntActiQ05066, 2 interactors
MINTiQ05066
STRINGi9606.ENSP00000372547

Structurei

Secondary structure

1204
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi66 – 81Combined sources16
Beta strandi86 – 88Combined sources3
Helixi89 – 99Combined sources11
Helixi103 – 123Combined sources21
Beta strandi124 – 126Combined sources3

3D structure databases

ProteinModelPortaliQ05066
SMRiQ05066
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ05066

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni59 – 136Sufficient for interaction with KPNB1Add BLAST78
Regioni61 – 77Required for nuclear localizationAdd BLAST17
Regioni107 – 139Sufficient for interaction with EP3001 PublicationAdd BLAST33
Regioni130 – 136Required for nuclear localization7
Regioni138 – 155Necessary for interaction with ZNF208 isoform KRAB-OAdd BLAST18
Regioni198 – 204Necessary for interaction with SLC9A3R21 Publication7

Domaini

DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse SRY.

Sequence similaritiesi

Belongs to the SRY family.Curated

Phylogenomic databases

eggNOGiKOG0527 Eukaryota
ENOG410XT0K LUCA
GeneTreeiENSGT00760000118988
HOGENOMiHOG000008601
HOVERGENiHBG008712
InParanoidiQ05066
KOiK09266
OMAiDCTKATH
OrthoDBiEOG091G0JDD
PhylomeDBiQ05066

Family and domain databases

Gene3Di1.10.30.10, 1 hit
InterProiView protein in InterPro
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR017253 SRY
PANTHERiPTHR10270:SF199 PTHR10270:SF199, 1 hit
PfamiView protein in Pfam
PF00505 HMG_box, 1 hit
PIRSFiPIRSF037653 SRY, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 1 hit
SUPFAMiSSF47095 SSF47095, 1 hit
PROSITEiView protein in PROSITE
PS50118 HMG_BOX_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q05066-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSYASAMLS VFNSDDYSPA VQENIPALRR SSSFLCTESC NSKYQCETGE
60 70 80 90 100
NSKGNVQDRV KRPMNAFIVW SRDQRRKMAL ENPRMRNSEI SKQLGYQWKM
110 120 130 140 150
LTEAEKWPFF QEAQKLQAMH REKYPNYKYR PRRKAKMLPK NCSLLPADPA
160 170 180 190 200
SVLCSEVQLD NRLYRDDCTK ATHSRMEHQL GHLPPINAAS SPQQRDRYSH

WTKL
Length:204
Mass (Da):23,884
Last modified:June 1, 1994 - v1
Checksum:i84323C30A9C2173E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0300193S → L in SRXY1. 1 Publication1
Natural variantiVAR_00371718S → N in SRXY1; partial; also in two patients with a Turner syndrome phenotype. 2 PublicationsCorresponds to variant dbSNP:rs104894971EnsemblClinVar.1
Natural variantiVAR_00371860V → A in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs764249635Ensembl.1
Natural variantiVAR_00371960V → L in SRXY1. 2 PublicationsCorresponds to variant dbSNP:rs104894957EnsemblClinVar.1
Natural variantiVAR_00372062R → G in SRXY1. 1 Publication1
Natural variantiVAR_00372164M → I in SRXY1; alters interaction with DNA and DNA bending. 2 PublicationsCorresponds to variant dbSNP:rs104894969EnsemblClinVar.1
Natural variantiVAR_01729864M → R in SRXY1. 1 Publication1
Natural variantiVAR_01729967F → V in SRXY1. 1 Publication1
Natural variantiVAR_00372268I → T in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894968EnsemblClinVar.1
Natural variantiVAR_07843375R → M in SRXY1; localizes mainly in the cytoplasm. 1 Publication1
Natural variantiVAR_01730076R → S in SRXY1. 1 Publication1
Natural variantiVAR_00372378M → T in SRXY1. 1 Publication1
Natural variantiVAR_01730187N → Y in SRXY1. 1 Publication1
Natural variantiVAR_00372490I → M in SRXY1. 3 PublicationsCorresponds to variant dbSNP:rs104894959EnsemblClinVar.1
Natural variantiVAR_00372591S → G in SRXY1. 1 Publication1
Natural variantiVAR_01730295G → E in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894972EnsemblClinVar.1
Natural variantiVAR_00372695G → R in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894974EnsemblClinVar.1
Natural variantiVAR_003727101L → H in SRXY1. 1 Publication1
Natural variantiVAR_003728106K → I in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894964EnsemblClinVar.1
Natural variantiVAR_003729108P → R in SRXY1. 1 Publication1
Natural variantiVAR_003730109F → S in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894956EnsemblClinVar.1
Natural variantiVAR_003731113A → T in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894966EnsemblClinVar.1
Natural variantiVAR_003732125P → L in SRXY1. 1 Publication1
Natural variantiVAR_003733127Y → C in SRXY1. 1 Publication1
Natural variantiVAR_017303127Y → F in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894973EnsemblClinVar.1
Natural variantiVAR_017304131P → R in SRXY1. 1 Publication1
Natural variantiVAR_003734133R → W in SRXY1. 1 PublicationCorresponds to variant dbSNP:rs104894976EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53772 Genomic DNA Translation: CAA37790.1
L10101 mRNA Translation: AAA60590.1
L10102 Genomic DNA Translation: AAA60591.1
L08063 Genomic DNA Translation: AAA16878.1
X96421 Genomic DNA Translation: CAA65281.1
S53156 mRNA Translation: AAB25008.1
S56543 mRNA Translation: AAB25716.1
BC074923 mRNA Translation: AAH74923.1
BC074924 mRNA Translation: AAH74924.1
CCDSiCCDS14772.1
PIRiA47533
RefSeqiNP_003131.1, NM_003140.2
UniGeneiHs.1992

Genome annotation databases

EnsembliENST00000383070; ENSP00000372547; ENSG00000184895
GeneIDi6736
KEGGihsa:6736
UCSCiuc004fqg.3 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiSRY_HUMAN
AccessioniPrimary (citable) accession number: Q05066
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 18, 2018
This is version 191 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome Y
    Human chromosome Y: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

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