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Q05738

- SRY_MOUSE

UniProt

Q05738 - SRY_MOUSE

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Protein

Sex-determining region Y protein

Gene
Sry, Tdf, Tdy
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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. 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'.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi5 – 7369HMG box4 PublicationsAdd
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
Complete GO annotation...

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 By similarity. Cytoplasm
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.3 Publications

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
Complete GO annotation...

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 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 KPNB1.1 Publication
Poly-ADP-ribosylated by PARP1 By similarity. ADP-ribosylation reduces its DNA-binding activity.

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.4 Publications

Protein-protein interaction databases

MINTiMINT-1367342.
STRINGi10090.ENSMUSP00000088717.

Structurei

3D structure databases

ProteinModelPortaliQ05738.
SMRiQ05738. Positions 5-75.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni4 – 8178Sufficient for interaction with KPNB1 By similarityAdd
BLAST
Regioni6 – 2217Required for nuclear localization By similarityAdd
BLAST
Regioni52 – 8433Sufficient for interaction with EP300 By similarityAdd
BLAST
Regioni75 – 817Required for nuclear localization By 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.

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

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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: July 9, 2014
This is version 129 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

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