Reviewed, UniProtKB/Swiss-Prot Q05738 (SRY_MOUSE)

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcriptional regulator which control 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. Facilitates DNA bending. Also involved in pre-mRNA splicing By similarity. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'.
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.
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.
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
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.
Miscellaneous	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 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	DNA-binding
Molecular function	Activator Repressor
PTM	ADP-ribosylation Acetylation
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW male sex determination Inferred from genetic interaction. Source: MGI regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW sex differentiation Inferred from electronic annotation. Source: UniProtKB-KW transcription 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
Molecular function	DNA bending activity Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: MGI
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	69	HMG box Ref.17 Ref.5 Ref.6 Ref.12
	Region	4 – 81	78	Sufficient for interaction with KPNB1 By similarity
	Region	6 – 22	17	Required for nuclear localization By similarity
	Region	52 – 84	33	Sufficient for interaction with EP300 By similarity
	Region	75 – 81	7	Required for nuclear localization By similarity
	Region	92 – 144	53	Necessary for interaction with ZNF208 isoform KRAB-O
	Region	94 – 138	45	Necessary for interaction with SLC9A3R2 and nuclear accumulation of SLC9A3R2
Amino acid modifications
	Modified residue	81	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	63	1	I → T in strain: Torino.
	Natural variant	133	1	W → L in strain: Torino.
	Natural variant	143 – 145	3	LQQ → P in strain: Torino.
	Natural variant	169 – 170	2	Missing in strain: Torino.
	Natural variant	209	1	H → Q in strain: Torino.
	Natural variant	211	1	E → Q in strain: Torino.
	Natural variant	235 – 395	161	Missing in strain: Torino.
Experimental info
	Mutagenesis	81	1	K → R: Abolishes acetylation. Ref.13

Sequences

	Sequence		Length	Mass (Da)
	Q05738-1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: FFBE9C35161CD80C	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

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: 1518820] [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: 8355784] [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: 8012385] [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: 2374589] [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: 8190643] [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: 8159753] [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: 7600978] [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: 7670499] [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: 11085593] [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: 11784049] [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: 11535586] [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: 15170344] [Abstract] Cited for: FUNCTION AND 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: 15297880] [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: 15469996] [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: 16166090] [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: 16488877] [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: 16904257] [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: 16996051] [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: 16414182] [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
EMBLGenBankDDBJ	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.
UniGene	Mm.377114
3D structure databases
HSSP	HSSP built from PDB template 1HRY based on UniProtKB Q05066.
ModBase	Search...
Protein-protein interaction databases
STRING	Q05738.
Proteomic databases
PRIDE	Q05738.
Genome annotation databases
Ensembl	ENSMUST00000091178; ENSMUSP00000088717; ENSMUSG00000069036; Mus musculus. [Genome view]
GeneID	21674.
KEGG	mmu:21674.
Organism-specific databases
CTD	21674.
MGI	MGI:98660. Sry.
Phylogenomic databases
HOVERGEN	Q05738.
OMA	QQFHDHH.
Gene expression databases
ArrayExpress	Q05738.
Bgee	Q05738.
CleanEx	MM_SRY.
Genevestigator	Q05738.
GermOnline	ENSMUSG00000069036. Mus musculus.
Family and domain databases
InterPro	IPR000910. HMG_HMG1/HMG2. [Graphical view]
Gene3D	G3DSA:1.10.30.10. HMG-box. 1 hit.
Pfam	PF00505. HMG_box. 1 hit. [Graphical view]
SMART	SM00398. HMG. 1 hit. [Graphical view]
PROSITE	PS50118. HMG_BOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 3, 2009
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)