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Q05738

- SRY_MOUSE

UniProt

Q05738 - SRY_MOUSE

Protein

Sex-determining region Y protein

Gene

Sry

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 2 (01 Feb 1996)
      Previous versions | rss
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    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. 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'.By similarity1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi5 – 7369HMG boxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. DNA binding, bending Source: UniProtKB
    3. protein binding Source: MGI
    4. protein heterodimerization activity Source: MGI
    5. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. male gonad development Source: MGI
    3. male sex determination Source: MGI
    4. negative regulation of gene expression Source: MGI
    5. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    6. sex determination Source: MGI
    7. transcription from RNA polymerase II promoter Source: GOC

    Keywords - Molecular functioni

    Activator, Repressor

    Keywords - Biological processi

    Differentiation, Sexual differentiation, Transcription, Transcription regulation

    Keywords - Ligandi

    Calmodulin-binding, DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sex-determining region Y protein
    Alternative name(s):
    Testis-determining factor
    Gene namesi
    Name:Sry
    Synonyms:Tdf, Tdy
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome Y

    Organism-specific databases

    MGIiMGI:98660. Sry.

    Subcellular locationi

    Nucleus speckle PROSITE-ProRule annotation. Cytoplasm 3 Publications
    Note: Colocalizes in the nucleus with ZNF208 isoform KRAB-O and tyrosine hydroxylase (TH). Colocalizes with SOX6 in speckles By similarity. Colocalizes with CAML in the nucleus By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nuclear speck Source: UniProtKB-SubCell
    3. nuclear transcription factor complex Source: MGI
    4. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi81 – 811K → R: Abolishes acetylation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 395395Sex-determining region Y proteinPRO_0000048687Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei81 – 811N6-acetyllysine1 Publication

    Post-translational modificationi

    Phosphorylated on serine residues by PKA. 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 KPNB1.1 Publication
    Poly-ADP-ribosylated by PARP1 By similarity. ADP-ribosylation reduces its DNA-binding activity.By similarity

    Keywords - PTMi

    Acetylation, ADP-ribosylation

    Proteomic databases

    PRIDEiQ05738.

    PTM databases

    PhosphoSiteiQ05738.

    Expressioni

    Tissue specificityi

    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.3 Publications

    Developmental stagei

    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).4 Publications

    Gene expression databases

    ArrayExpressiQ05738.
    BgeeiQ05738.
    CleanExiMM_SRY.
    GenevestigatoriQ05738.

    Interactioni

    Subunit structurei

    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.By similarity

    Protein-protein interaction databases

    MINTiMINT-1367342.
    STRINGi10090.ENSMUSP00000088717.

    Structurei

    3D structure databases

    ProteinModelPortaliQ05738.
    SMRiQ05738. Positions 5-75.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni4 – 8178Sufficient for interaction with KPNB1By similarityAdd
    BLAST
    Regioni6 – 2217Required for nuclear localizationBy similarityAdd
    BLAST
    Regioni52 – 8433Sufficient for interaction with EP300By similarityAdd
    BLAST
    Regioni75 – 817Required for nuclear localizationBy similarity
    Regioni92 – 14453Necessary for interaction with ZNF208 isoform KRAB-OAdd
    BLAST
    Regioni94 – 13845Necessary for interaction with SLC9A3R2 and nuclear accumulation of SLC9A3R2Add
    BLAST

    Domaini

    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.

    Sequence similaritiesi

    Belongs to the SRY family.Curated
    Contains 1 HMG box DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG321816.
    HOVERGENiHBG008712.
    InParanoidiQ05738.
    KOiK09266.
    OMAiQQFHDHH.
    OrthoDBiEOG7RNK18.

    Family and domain databases

    Gene3Di1.10.30.10. 1 hit.
    InterProiIPR009071. HMG_box_dom.
    [Graphical view]
    PfamiPF00505. HMG_box. 1 hit.
    [Graphical view]
    SMARTiSM00398. HMG. 1 hit.
    [Graphical view]
    SUPFAMiSSF47095. SSF47095. 1 hit.
    PROSITEiPS50118. HMG_BOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q05738-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEGHVKRPMN AFMVWSRGER HKLAQQNPSM QNTEISKQLG CRWKSLTEAE    50
    KRPFFQEAQR LKILHREKYP NYKYQPHRRA KVSQRSGILQ PAVASTKLYN 100
    LLQWDRNPHA ITYRQDWSRA AHLYSKNQQS FYWQPVDIPT GHLQQQQQQQ 150
    QQQQFHNHHQ QQQQFYDHHQ QQQQQQQQQQ QFHDHHQQKQ QFHDHHQQQQ 200
    QFHDHHHHHQ EQQFHDHHQQ QQQFHDHQQQ QQQQQQQQFH DHHQQKQQFH 250
    DHHHHQQQQQ FHDHQQQQQQ FHDHQQQQHQ FHDHPQQKQQ FHDHPQQQQQ 300
    FHDHHHQQQQ KQQFHDHHQQ KQQFHDHHQQ KQQFHDHHQQ QQQFHDHHQQ 350
    QQQQQQQQQQ QFHDQQLTYL LTADITGEHT PYQEHLSTAL WLAVS 395
    Length:395
    Mass (Da):49,494
    Last modified:February 1, 1996 - v2
    Checksum:iFFBE9C35161CD80C
    GO

    Polymorphismi

    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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti63 – 631I → T in strain: Torino.
    Natural varianti133 – 1331W → L in strain: Torino.
    Natural varianti143 – 1453LQQ → P in strain: Torino.
    Natural varianti169 – 1702Missing in strain: Torino.
    Natural varianti209 – 2091H → Q in strain: Torino.
    Natural varianti211 – 2111E → Q in strain: Torino.
    Natural varianti235 – 395161Missing in strain: Torino.
    Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X67204 Genomic DNA. Translation: CAB56798.1.
    U03645 Genomic DNA. Translation: AAB60446.1.
    X55491 Genomic DNA. Translation: CAA39111.1.
    CCDSiCCDS30545.1.
    PIRiS35565.
    S43344.
    RefSeqiNP_035694.1. NM_011564.1.
    UniGeneiMm.377114.

    Genome annotation databases

    EnsembliENSMUST00000091178; ENSMUSP00000088717; ENSMUSG00000069036.
    GeneIDi21674.
    KEGGimmu:21674.
    UCSCiuc012hrv.1. mouse.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    The tenuous nature of sex - Issue 80 of March 2007

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X67204 Genomic DNA. Translation: CAB56798.1 .
    U03645 Genomic DNA. Translation: AAB60446.1 .
    X55491 Genomic DNA. Translation: CAA39111.1 .
    CCDSi CCDS30545.1.
    PIRi S35565.
    S43344.
    RefSeqi NP_035694.1. NM_011564.1.
    UniGenei Mm.377114.

    3D structure databases

    ProteinModelPortali Q05738.
    SMRi Q05738. Positions 5-75.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-1367342.
    STRINGi 10090.ENSMUSP00000088717.

    PTM databases

    PhosphoSitei Q05738.

    Proteomic databases

    PRIDEi Q05738.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000091178 ; ENSMUSP00000088717 ; ENSMUSG00000069036 .
    GeneIDi 21674.
    KEGGi mmu:21674.
    UCSCi uc012hrv.1. mouse.

    Organism-specific databases

    CTDi 6736.
    MGIi MGI:98660. Sry.

    Phylogenomic databases

    eggNOGi NOG321816.
    HOVERGENi HBG008712.
    InParanoidi Q05738.
    KOi K09266.
    OMAi QQFHDHH.
    OrthoDBi EOG7RNK18.

    Miscellaneous databases

    NextBioi 300962.
    PROi Q05738.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q05738.
    Bgeei Q05738.
    CleanExi MM_SRY.
    Genevestigatori Q05738.

    Family and domain databases

    Gene3Di 1.10.30.10. 1 hit.
    InterProi IPR009071. HMG_box_dom.
    [Graphical view ]
    Pfami PF00505. HMG_box. 1 hit.
    [Graphical view ]
    SMARTi SM00398. HMG. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47095. SSF47095. 1 hit.
    PROSITEi PS50118. HMG_BOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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. 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. 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.

    Entry informationi

    Entry nameiSRY_MOUSE
    AccessioniPrimary (citable) accession number: Q05738
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 130 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3