Sex-determining region Y protein - Mus musculus (Mouse)

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Q05738 (SRY_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 118. History...

Clusters with 100%, 90%, 50% identity |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Sex-determining region Y protein

Alternative name(s):
Testis-determining factor

Gene names

Name:	Sry
Synonyms:	Tdf, Tdy

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence 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-O and 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. Deacetylated by HDAC3 By similarity. Poly-ADP-ribosylated by PARP1 By similarity. ADP-ribosylation reduces its DNA-binding activity By similarity.
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 process	Differentiation Sexual differentiation Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	Calmodulin-binding DNA-binding
Molecular function	Activator Repressor
PTM	ADP-ribosylation Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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 15879091 PubMed 16700629. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction PubMed 19850934. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.14 PubMed 16185683 PubMed 22514746. Source: MGI
Molecular_function	DNA binding, bending Inferred from direct assay PubMed 7774816. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 395

395

Sex-determining region Y protein

PRO_0000048687

Regions

DNA binding

5 – 73

HMG box Ref.5 Ref.6 Ref.12 Ref.17

Region

4 – 81

Sufficient for interaction with KPNB1 By similarity

Region

6 – 22

Required for nuclear localization By similarity

Region

52 – 84

Sufficient for interaction with EP300 By similarity

Region

75 – 81

Required for nuclear localization By similarity

Region

92 – 144

Necessary for interaction with ZNF208 isoform KRAB-O

Region

94 – 138

Necessary for interaction with SLC9A3R2 and nuclear accumulation of SLC9A3R2

Natural variations

Natural variant

I → T in strain: Torino.

Natural variant

133

W → L in strain: Torino.

Natural variant

143 – 145

LQQ → P in strain: Torino.

Natural variant

169 – 170

Missing in strain: Torino.

Natural variant

209

H → Q in strain: Torino.

Natural variant

211

E → Q in strain: Torino.

Natural variant

235 – 395

161

Missing in strain: Torino.

Experimental info

Mutagenesis

K → R: Abolishes acetylation. Ref.13

Sequences

Sequence

Length

Mass (Da)

Tools

Q05738 [UniParc].

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

FASTA

395

49,494

        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

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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, 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.
IPI	IPI00113716.
PIR	S35565. S43344.
RefSeq	NP_035694.1. NM_011564.1.
UniGene	Mm.377114.
3D structure databases
ProteinModelPortal	Q05738.
SMR	Q05738. Positions 5-75.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1367342.
STRING	10090.ENSMUSP00000088717.
PTM databases
PhosphoSite	Q05738.
Proteomic databases
PRIDE	Q05738.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000091178; ENSMUSP00000088717; ENSMUSG00000069036.
GeneID	21674.
KEGG	mmu:21674.
Organism-specific databases
CTD	6736.
MGI	MGI:98660. Sry.
Phylogenomic databases
eggNOG	NOG321816.
HOVERGEN	HBG008712.
InParanoid	Q05738.
KO	K09266.
OrthoDB	EOG49079Z.
Gene expression databases
ArrayExpress	Q05738.
Bgee	Q05738.
CleanEx	MM_SRY.
Genevestigator	Q05738.
GermOnline	ENSMUSG00000069036. Mus musculus.
Family and domain databases
Gene3D	1.10.30.10. 1 hit.
InterPro	IPR009071. HMG_box_dom. IPR027151. TF_Sry_rodentia. [Graphical view]
PANTHER	PTHR10270:SF84. PTHR10270:SF84. 1 hit.
Pfam	PF00505. HMG_box. 1 hit. [Graphical view]
SMART	SM00398. HMG. 1 hit. [Graphical view]
SUPFAM	SSF47095. HMG-box. 1 hit.
PROSITE	PS50118. HMG_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	300962.
SOURCE	Search...

Entry information

Entry name

SRY_MOUSE

Accession

Primary (citable) accession number: Q05738

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents