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Q05738 (SRY_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Sex-determining region Y protein
Alternative name(s):
Testis-determining factor
Gene names
Name:Sry
Synonyms:Tdf, Tdy
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Promotes DNA bending. Also involved in pre-mRNA splicing By similarity. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. Ref.12

Subunit structure

Interacts with KPNB1, ZNF208 isoform KRAB-O PARP1 and SLC9A3R2. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form. Interaction with PARP1 impaired its DNA-binding activity. Interacts with CALM, EP300, HDAC3 and WT1 By similarity. The interaction with EP300 modulates its DNA-binding activity By similarity. Ref.11 Ref.14 Ref.15 Ref.17

Subcellular location

Nucleus speckle By similarity. Cytoplasm. Note: Colocalizes in the nucleus with ZNF208 isoform KRAB-Oand tyrosine hydroxylase (TH). Colocalizes with SOX6 in speckles By similarity. Colocalizes with CAML in the nucleus By similarity. Ref.11 Ref.14 Ref.16

Tissue specificity

Expressed in the substantia nigra of the brain (at protein level). Expressed in diencephalon, cortex, the substantia nigra of the midbrain and the medial mammillary bodies of the hypothalamus of male, but not female. Ref.9 Ref.14 Ref.16

Developmental stage

Expressed in gonadal somatic pre-Sertoli cells from 10.5 to 11.5 dpc. Expressed in pre-Sertoli cells located centrally in the genital ridge and then later in cells located at the cranial and caudal poles (at protein level). Ref.7 Ref.8 Ref.10 Ref.17

Domain

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

Post-translational modification

Phosphorylated on serine residues by PKA By similarity. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression By similarity.

Acetylation of Lys-81 contributes to its nuclear localization and enhances its interaction with KPNB1. Ref.13

Poly-ADP-ribosylated by PARP1 By similarity. ADP-ribosylation reduces its DNA-binding activity.

Polymorphism

Different alleles occur in strains of Mus musculus (molossinus or domesticus). In particular the poly-Gln region in 167-177 is polymorphic with either 11, 12 or 13 Gln. The nature of this poly-Gln tract could affect the protein's function by disturbing its secondary structure, perhaps by preventing efficient contact with another protein.

Sequence similarities

Belongs to the SRY family.

Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Sexual differentiation
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandCalmodulin-binding
DNA-binding
   Molecular functionActivator
Repressor
   PTMAcetylation
ADP-ribosylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

male gonad development

Inferred from direct assay PubMed 19457926. Source: MGI

male sex determination

Inferred from genetic interaction PubMed 15879091PubMed 16700629. Source: MGI

negative regulation of gene expression

Inferred from direct assay PubMed 11869290. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 19850934. Source: MGI

sex determination

Inferred from genetic interaction PubMed 9486644. Source: MGI

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 22344693. Source: GOC

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear speck

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear transcription factor complex

Inferred from direct assay PubMed 22344693. Source: MGI

nucleus

Inferred from direct assay Ref.14PubMed 16185683PubMed 22514746. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 8625802. Source: MGI

DNA binding, bending

Inferred from direct assay PubMed 7774816. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10410901Ref.14PubMed 19850934. Source: MGI

protein heterodimerization activity

Inferred from direct assay PubMed 22344693. Source: MGI

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 22344693. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395Sex-determining region Y protein
PRO_0000048687

Regions

DNA binding5 – 7369HMG box Ref.5 Ref.6 Ref.12 Ref.17
Region4 – 8178Sufficient for interaction with KPNB1 By similarity
Region6 – 2217Required for nuclear localization By similarity
Region52 – 8433Sufficient for interaction with EP300 By similarity
Region75 – 817Required for nuclear localization By similarity
Region92 – 14453Necessary for interaction with ZNF208 isoform KRAB-O
Region94 – 13845Necessary for interaction with SLC9A3R2 and nuclear accumulation of SLC9A3R2

Amino acid modifications

Modified residue811N6-acetyllysine Ref.13

Natural variations

Natural variant631I → T in strain: Torino.
Natural variant1331W → L in strain: Torino.
Natural variant143 – 1453LQQ → P in strain: Torino.
Natural variant169 – 1702Missing in strain: Torino.
Natural variant2091H → Q in strain: Torino.
Natural variant2111E → Q in strain: Torino.
Natural variant235 – 395161Missing in strain: Torino.

Experimental info

Mutagenesis811K → R: Abolishes acetylation. Ref.13

Sequences

Sequence LengthMass (Da)Tools
Q05738 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: FFBE9C35161CD80C

FASTA39549,494
        10         20         30         40         50         60 
MEGHVKRPMN AFMVWSRGER HKLAQQNPSM QNTEISKQLG CRWKSLTEAE KRPFFQEAQR 

        70         80         90        100        110        120 
LKILHREKYP NYKYQPHRRA KVSQRSGILQ PAVASTKLYN LLQWDRNPHA ITYRQDWSRA 

       130        140        150        160        170        180 
AHLYSKNQQS FYWQPVDIPT GHLQQQQQQQ QQQQFHNHHQ QQQQFYDHHQ QQQQQQQQQQ 

       190        200        210        220        230        240 
QFHDHHQQKQ QFHDHHQQQQ QFHDHHHHHQ EQQFHDHHQQ QQQFHDHQQQ QQQQQQQQFH 

       250        260        270        280        290        300 
DHHQQKQQFH DHHHHQQQQQ FHDHQQQQQQ FHDHQQQQHQ FHDHPQQKQQ FHDHPQQQQQ 

       310        320        330        340        350        360 
FHDHHHQQQQ KQQFHDHHQQ KQQFHDHHQQ KQQFHDHHQQ QQQFHDHHQQ QQQQQQQQQQ 

       370        380        390 
QFHDQQLTYL LTADITGEHT PYQEHLSTAL WLAVS 

« Hide

References

[1]"Inverted repeat structure of the Sry locus in mice."
Gubbay J., Vivian N., Economou A., Jackson D., Goodfellow P.
Proc. Natl. Acad. Sci. U.S.A. 89:7953-7957(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129.
Tissue: Spleen.
[2]"Rapid evolution of the sex determining locus in Old World mice and rats."
Tucker P.K., Lundrigan B.L.
Nature 364:715-717(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Polymorphism of a CAG trinucleotide repeat within Sry correlates with B6.YDom sex reversal."
Coward P., Nagai K., Chen D., Thomas H.D., Nagamine C.M., Lau Y.-F.C.
Nat. Genet. 6:245-250(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Torino.
Tissue: Liver.
[4]"A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes."
Gubbay J., Collignon J., Koopman P., Capel B., Economou A., Munsterberg A., Vivian N., Goodfellow P., Lovell-Badge R.
Nature 346:245-250(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-124.
Strain: 129.
[5]"Definition of a consensus DNA binding site for SRY."
Harley V.R., Lovell-Badge R., Goodfellow P.N.
Nucleic Acids Res. 22:1500-1501(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF DNA-BINDING.
[6]"Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors."
Giese K., Pagel J., Grosschedl R.
Proc. Natl. Acad. Sci. U.S.A. 91:3368-3372(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF DNA-BINDING.
[7]"Expression of Sry, the mouse sex determining gene."
Hacker A., Capel B., Goodfellow P., Lovell-Badge R.
Development 121:1603-1614(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[8]"Expression of a linear Sry transcript in the mouse genital ridge."
Jeske Y.W., Bowles J., Greenfield A., Koopman P.
Nat. Genet. 10:480-482(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[9]"Developmental profile of Sry transcripts in mouse brain."
Mayer A., Mosler G., Just W., Pilgrim C., Reisert I.
Neurogenetics 3:25-30(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor."
Albrecht K.H., Eicher E.M.
Dev. Biol. 240:92-107(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[11]"The C-terminal nuclear localization signal of the sex-determining region Y (SRY) high mobility group domain mediates nuclear import through importin beta 1."
Forwood J.K., Harley V., Jans D.A.
J. Biol. Chem. 276:46575-46582(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KPNB1, SUBCELLULAR LOCATION.
[12]"Sry-directed sex reversal in transgenic mice is robust with respect to enhanced DNA bending: comparison of human and murine HMG boxes."
Phillips N.B., Nikolskaya T., Jancso-Radek A., Ittah V., Jiang F., Singh R., Haas E., Weiss M.A.
Biochemistry 43:7066-7081(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[13]"Regulation of human SRY subcellular distribution by its acetylation/deacetylation."
Thevenet L., Mejean C., Moniot B., Bonneaud N., Galeotti N., Aldrian-Herrada G., Poulat F., Berta P., Benkirane M., Boizet-Bonhoure B.
EMBO J. 23:3336-3345(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-81, MUTAGENESIS OF LYS-81.
[14]"Sry associates with the heterochromatin protein 1 complex by interacting with a KRAB domain protein."
Oh H.J., Li Y., Lau Y.-F.C.
Biol. Reprod. 72:407-415(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF208 ISOFORM KRAB-O, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[15]"NHERF2/SIP-1 interacts with mouse SRY via a different mechanism than human SRY."
Thevenet L., Albrecht K.H., Malki S., Berta P., Boizet-Bonhoure B., Poulat F.
J. Biol. Chem. 280:38625-38630(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC9A3R2.
[16]"Direct regulation of adult brain function by the male-specific factor SRY."
Dewing P., Chiang C.W., Sinchak K., Sim H., Fernagut P.-O., Kelly S., Chesselet M.-F., Micevych P.E., Albrecht K.H., Harley V.R., Vilain E.
Curr. Biol. 16:415-420(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[17]"The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its biological functions."
Li Y., Oh H.J., Lau Y.-F.C.
Mol. Cell. Endocrinol. 257:35-46(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARP1, ADP-RIBOSYLATION, DNA-BINDING, DEVELOPMENTAL STAGE.
[18]"Sry and the hesitant beginnings of male development."
Polanco J.C., Koopman P.
Dev. Biol. 302:13-24(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[19]"KRAB: a partner for SRY action on chromatin."
Oh H.J., Lau Y.F.
Mol. Cell. Endocrinol. 247:47-52(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The tenuous nature of sex - Issue 80 of March 2007

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67204 Genomic DNA. Translation: CAB56798.1.
U03645 Genomic DNA. Translation: AAB60446.1.
X55491 Genomic DNA. Translation: CAA39111.1.
CCDSCCDS30545.1.
PIRS35565.
S43344.
RefSeqNP_035694.1. NM_011564.1.
UniGeneMm.377114.

3D structure databases

ProteinModelPortalQ05738.
SMRQ05738. Positions 5-75.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-1367342.
STRING10090.ENSMUSP00000088717.

PTM databases

PhosphoSiteQ05738.

Proteomic databases

PRIDEQ05738.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000091178; ENSMUSP00000088717; ENSMUSG00000069036.
GeneID21674.
KEGGmmu:21674.
UCSCuc012hrv.1. mouse.

Organism-specific databases

CTD6736.
MGIMGI:98660. Sry.

Phylogenomic databases

eggNOGNOG321816.
HOVERGENHBG008712.
InParanoidQ05738.
KOK09266.
OMAQQFHDHH.
OrthoDBEOG7RNK18.

Gene expression databases

ArrayExpressQ05738.
BgeeQ05738.
CleanExMM_SRY.
GenevestigatorQ05738.

Family and domain databases

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

Other

NextBio300962.
PROQ05738.
SOURCESearch...

Entry information

Entry nameSRY_MOUSE
AccessionPrimary (citable) accession number: Q05738
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot