Reviewed, UniProtKB/Swiss-Prot Q05066 (SRY_HUMAN)

Names and origin

Protein names

Recommended name:
    Sex-determining region Y protein
Alternative name(s):
    Testis-determining factor

Gene names

Name:	SRY
Synonyms:	TDF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	204 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 By similarity. 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 By similarity. Facilitates DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' By similarity.
Subunit structure	Interacts with CALM, EP300, HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1, SLC9A3R2 and WT1. The interaction with EP300 modulates its DNA-binding activity. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form By similarity. Interaction with PARP1 impaired its DNA-binding activity By similarity.
Subcellular location	Nucleus speckle. Cytoplasm. Note: Colocalizes with SOX6 in speckles. Colocalizes with CAML in the nucleus. Colocalizes in the nucleus with ZNF208 isoform KRAB-O and tyrosine hydroxylase (TH) By similarity.
Post-translational modification	Phosphorylated on serine residues by PKA. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression. Acetylation of Lys-136 contributes to its nuclear localization and enhances its interaction with KPNB1. Deacetylated by HDAC3. Poly-ADP-ribosylated by PARP1. ADP-ribosylation reduces its DNA-binding activity. Ref.10
Involvement in disease	Defects in SRY are a cause of gonadal dysgenesis XY female type (GDXY) [MIM:306100]; also known as 'XY females' or Swyer syndrome. Patients are found to have a 46,XY karyotype. They suffer rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal. In contrast, subjects with 46,XY partial gonadal dysgenesis have ambiguous genitalia, a mix of Muellerian and Wolffian structures, and dysgenic gonads. Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.45 Ref.46 Ref.48 Ref.49 Ref.50 Ref.51 Ref.53 Defects in SRY are found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, "streak gonads", variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female. Turner syndrome has its basis in a 45,X chromosomal aberration. Defects in SRY are a cause of true hermaphroditism [MIM:235600]. A true hermaphrodite must have both mature ovarian and mature testicular tissue with histologic evidence of follicles and tubules, respectively. It is a genetically heterogeneous condition. The genotype of most affected individuals is 46,XX, but many have 46,XY or a mosaic of 46,XX/46,XY. True hermaphroditism can be caused also by chromosomal translocation. Ref.44 Ref.47 Ref.52
Miscellaneous	DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse 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
Coding sequence diversity	Chromosomal rearrangement
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	ADP-ribosylation Acetylation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW male sex determination Ref.1 Non-traceable author statement. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct transcription activator activity Non-traceable author statement. Source: UniProtKB transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD3	P84022	1	EBI-464987,EBI-347161

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 204

204

Sex-determining region Y protein

PRO_0000048671

Regions

DNA binding

60 – 128

69

HMG box Ref.6 Ref.7 Ref.8 Ref.14 Ref.16

Region

59 – 136

78

Sufficient for interaction with KPNB1

Region

61 – 77

17

Required for nuclear localization

Region

107 – 139

33

Sufficient for interaction with EP300

Region

130 – 136

7

Required for nuclear localization

Region

138 – 155

18

Necessary for interaction with ZNF208 isoform KRAB-O

Region

198 – 204

7

Necessary for interaction with SLC9A3R2

Amino acid modifications

Modified residue

136

1

N6-acetyllysine Ref.17

Natural variations

Natural variant

3

1

S → L in GDXY. Ref.53

VAR_030019

Natural variant

18

1

S → N in GDXY; partial; also in two patients with a Turner syndrome phenotype. Ref.42 Ref.49

VAR_003717

Natural variant

60

1

V → A in GDXY. Ref.28 Ref.30 Ref.39

VAR_003718

Natural variant

60

1

V → L in GDXY. Ref.28 Ref.30 Ref.39

VAR_003719

Natural variant

62

1

R → G in GDXY. Ref.29

VAR_003720

Natural variant

64

1

M → I in GDXY. Ref.28 Ref.41

VAR_003721

Natural variant

64

1

M → R in GDXY. Ref.28 Ref.41

VAR_017298

Natural variant

67

1

F → V in GDXY. Ref.41

VAR_017299

Natural variant

68

1

I → T in GDXY. Ref.37

VAR_003722

Natural variant

76

1

R → S in GDXY; XY sex reversal. Ref.45

VAR_017300

Natural variant

78

1

M → T in GDXY. Ref.29

VAR_003723

Natural variant

87

1

N → Y in GDXY; XY sex reversal. Ref.50

VAR_017301

Natural variant

90

1

I → M in GDXY and true hermaphroditism.

VAR_003724

Natural variant

91

1

S → G in GDXY; XY sex reversal. Ref.38

VAR_003725

Natural variant

95

1

G → E in GDXY. Ref.32 Ref.48

VAR_017302

Natural variant

95

1

G → R in GDXY. Ref.32 Ref.48

VAR_003726

Natural variant

101

1

L → H in GDXY. Ref.33

VAR_003727

Natural variant

106

1

K → I in GDXY. Ref.31

VAR_003728

Natural variant

108

1

P → R in GDXY. Ref.46

VAR_003729

Natural variant

109

1

F → S in GDXY. Ref.34

VAR_003730

Natural variant

113

1

A → T in GDXY. Ref.35

VAR_003731

Natural variant

125

1

P → L in GDXY; XY sex reversal. Ref.38

VAR_003732

Natural variant

127

1

Y → C in GDXY; XY sex reversal. Ref.36 Ref.51

VAR_003733

Natural variant

127

1

Y → F in GDXY. Ref.36 Ref.51

VAR_017303

Natural variant

131

1

P → R in GDXY; XY sex reversal. Ref.40

VAR_017304

Natural variant

133

1

R → W in GDXY. Ref.29

VAR_003734

Experimental info

Mutagenesis

31 – 33

3

SSS → AAA: Abolishes its phosphorylation by PKA. Does not enhance its DNA-binding activity. Abolishes stimulation of transcription repression. Ref.10

Mutagenesis

62

1

R → G: Strongly reduces nuclear localization. Strongly reduces nuclear localization; when associated with W-133. Reduces interaction with KPNB1. Abolishes DNA-binding. Ref.14

Mutagenesis

64

1

M → I: Abolishes nuclear localization. Ref.20

Mutagenesis

75

1

R → N: Strongly reduces nuclear localization. Abolishes DNA-binding. Does not reduce interaction with KPNB1 and CAML. Ref.14 Ref.19

Mutagenesis

76

1

R → P: Reduces nuclear localization. Reduces DNA-binding. Does not reduce interaction with KPNB1 and CAML. Ref.14 Ref.19

Mutagenesis

115

1

K → R: Does not abolish acetylation activity. Ref.17

Mutagenesis

123

1

K → R: Does not abolish acetylation. Ref.17

Mutagenesis

128

1

K → R: Does not abolish acetylation. Ref.17

Mutagenesis

133

1

R → W: Reduces nuclear localization. Strongly reduces nuclear localization; when associated with G-62. Reduces interaction with KPNB1. Does not reduce interaction with CAML. Does not abolish DNA-binding. Ref.14 Ref.19

Mutagenesis

134

1

K → R: Does not abolish acetylation. Ref.17

Mutagenesis

136

1

K → R: Abolishes acetylation. Does not abolish interaction with EP300. Does not abolish DNA-binding. Enhances cytoplasmic localization. Abolishes interaction with KPNB1. Ref.17

Secondary structure

1

.

.

.

.

.

.

.

.

.

204

Helix Strand Turn

Details...

Helix

66 – 81

16

Beta strand

86 – 88

3

Helix

89 – 99

11

Helix

103 – 123

21

Beta strand

124 – 126

3

Sequences

	Sequence		Length	Mass (Da)
	Q05066-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 84323C30A9C2173E	FASTA	204	23,884
	10 20 30 40 50 60 MQSYASAMLS VFNSDDYSPA VQENIPALRR SSSFLCTESC NSKYQCETGE NSKGNVQDRV 70 80 90 100 110 120 KRPMNAFIVW SRDQRRKMAL ENPRMRNSEI SKQLGYQWKM LTEAEKWPFF QEAQKLQAMH 130 140 150 160 170 180 REKYPNYKYR PRRKAKMLPK NCSLLPADPA SVLCSEVQLD NRLYRDDCTK ATHSRMEHQL 190 200 GHLPPINAAS SPQQRDRYSH WTKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif." Sinclair A.H., Berta P., Palmer M.S., Hawkins J.R., Griffiths B.L., Smith M.J., Foster J.W., Frischauf A.-M., Lovell-Badge R., Goodfellow P.N. Nature 346:240-244(1990) [PubMed: 1695712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Identification of the transcriptional unit, structural organization, and promoter sequence of the human sex-determining region Y (SRY) gene, using a reverse genetic approach." Su H., Lau Y.-F.C. Am. J. Hum. Genet. 52:24-38(1993) [PubMed: 8434602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Evidence that the SRY protein is encoded by a single exon on the human Y chromosome." Behlke M.A., Bogan J.S., Beer-Romero P., Page D.C. Genomics 17:736-739(1993) [PubMed: 8244390] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome." Whitfield L.S., Hawkins J.R., Goodfellow P.N., Sulston J. Genomics 27:306-311(1995) [PubMed: 7557997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"SRY, like HMG1, recognizes sharp angles in DNA." Ferrari S., Harley V.R., Pontiggia A., Goodfellow P.N., Lovell-Badge R., Bianchi M.E. EMBO J. 11:4497-4506(1992) [PubMed: 1425584] [Abstract] Cited for: CHARACTERIZATION OF DNA-BINDING.
[7]	"The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove: a topological mechanism of sequence specificity." King C.Y., Weiss M.A. Proc. Natl. Acad. Sci. U.S.A. 90:11990-11994(1993) [PubMed: 8265659] [Abstract] Cited for: CHARACTERIZATION OF DNA-BINDING.
[8]	"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.
[9]	"The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains." Poulat F., de Santa Barbara P., Desclozeaux M., Soullier S., Moniot B., Bonneaud N., Boizet B., Berta P. J. Biol. Chem. 272:7167-7172(1997) [PubMed: 9054412] [Abstract] Cited for: INTERACTION WITH SLC9A3R2.
[10]	"Phosphorylation of an N-terminal motif enhances DNA-binding activity of the human SRY protein." Desclozeaux M., Poulat F., de Santa Barbara P., Capony J.-P., Turowski P., Jay P., Mejean C., Moniot B., Boizet B., Berta P. J. Biol. Chem. 273:7988-7995(1998) [PubMed: 9525897] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF 31-SER--SER-33.
[11]	"The Y-chromosomal genes SRY and ZFY are transcribed in adult human brain." Mayer A., Lahr G., Swaab D.F., Pilgrim C., Reisert I. Neurogenetics 1:281-288(1998) [PubMed: 10732804] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"A direct role of SRY and SOX proteins in pre-mRNA splicing." Ohe K., Lalli E., Sassone-Corsi P. Proc. Natl. Acad. Sci. U.S.A. 99:1146-1151(2002) [PubMed: 11818535] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]	"Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1." Matsuzawa-Watanabe Y., Inoue J., Semba K. Oncogene 22:7900-7904(2003) [PubMed: 12970737] [Abstract] Cited for: INTERACTION WITH WT1.
[14]	"Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations." Harley V.R., Layfield S., Mitchell C.L., Forwood J.K., John A.P., Briggs L.J., McDowall S.G., Jans D.A. Proc. Natl. Acad. Sci. U.S.A. 100:7045-7050(2003) [PubMed: 12764225] [Abstract] Cited for: INTERACTION WITH KPNB1, DNA-BINDING, MUTAGENESIS OF ARG-62; ARG-75; ARG-76 AND ARG-133.
[15]	"Recombinant expression, purification and characterisation of the HMG domain of human SRY." Kelly S., Yotis J., Macris M., Harley V. Protein Pept. Lett. 10:281-286(2003) [PubMed: 12871148] [Abstract] Cited for: INTERACTION WITH CALM.
[16]	"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, DNA-BINDING.
[17]	"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: INTERACTION WITH EP300; HDAC3 AND KPNB1, ACETYLATION AT LYS-136, MUTAGENESIS OF LYS-115; LYS-123; LYS-128; LYS-134 AND LYS-136, SUBCELLULAR LOCATION.
[18]	"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.
[19]	"Defective calmodulin-mediated nuclear transport of the sex-determining region of the Y chromosome (SRY) in XY sex reversal." Sim H., Rimmer K., Kelly S., Ludbrook L.M., Clayton A.H., Harley V.R. Mol. Endocrinol. 19:1884-1892(2005) [PubMed: 15746192] [Abstract] Cited for: INTERACTION WITH CALM, MUTAGENESIS OF ARG-75; ARG-76 AND ARG-133, SUBCELLULAR LOCATION.
[20]	"SRY-directed DNA bending and human sex reversal: reassessment of a clinical mutation uncovers a global coupling between the HMG box and its tail." Li B., Phillips N.B., Jancso-Radek A., Ittah V., Singh R., Jones D.N., Haas E., Weiss M.A. J. Mol. Biol. 360:310-328(2006) [PubMed: 16762365] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF MET-64.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex." Werner M.H., Huth J.R., Gronenborn A.M., Clore G.M. Cell 81:705-714(1995) [PubMed: 7774012] [Abstract] Cited for: STRUCTURE BY NMR OF 56-131.
[25]	"Structural basis for SRY-dependent 46-X,Y sex reversal: modulation of DNA bending by a naturally occurring point mutation." Murphy E.C., Zhurkin V.B., Louis J.M., Cornilescu G., Clore G.M. J. Mol. Biol. 312:481-499(2001) [PubMed: 11563911] [Abstract] Cited for: STRUCTURE BY NMR OF 57-218.
[26]	"Mutational analysis of SRY in XY females." Hawkins J.R. Hum. Mutat. 2:347-350(1993) [PubMed: 8257986] [Abstract] Cited for: REVIEW ON VARIANTS.
[27]	"Mutations in SRY and SOX9: testis-determining genes." Cameron F.J., Sinclair A.H. Hum. Mutat. 9:388-395(1997) [PubMed: 9143916] [Abstract] Cited for: REVIEW ON VARIANTS.
[28]	"Genetic evidence equating SRY and the testis-determining factor." Berta P., Hawkins J.R., Sinclair A.H., Taylor A., Griffiths B.L., Goodfellow P.N., Fellous M. Nature 348:448-450(1990) [PubMed: 2247149] [Abstract] Cited for: VARIANTS GDXY LEU-60 AND ILE-64.
[29]	"Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain." Affara N.A., Chalmers I.J., Ferguson-Smith M.A. Hum. Mol. Genet. 2:785-789(1993) [PubMed: 8353496] [Abstract] Cited for: VARIANTS GDXY GLY-62; THR-78 AND TRP-133.
[30]	"Familial case with sequence variant in the testis-determining region associated with two sex phenotypes." Vilain E., McElreavey K., Jaubert F., Raymond J.-P., Richaud F., Fellous M. Am. J. Hum. Genet. 50:1008-1011(1992) [PubMed: 1570829] [Abstract] Cited for: VARIANT GDXY LEU-60.
[31]	"Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis." Hawkins J.R., Taylor A., Goodfellow P.N., Migeon C.J., Smith K.D., Berkovitz G.D. Am. J. Hum. Genet. 51:979-984(1992) [PubMed: 1415266] [Abstract] Cited for: VARIANTS GDXY MET-90 AND ILE-106.
[32]	"Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal." Hawkins J.R., Taylor A., Berta P., Levilliers J., van der Auwera B., Goodfellow P.N. Hum. Genet. 88:471-474(1992) [PubMed: 1339396] [Abstract] Cited for: VARIANT GDXY ARG-95.
[33]	"True hermaphroditism in a 46,XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): molecular genetics and histological findings in a sporadic case." Braun A., Kammerer S., Cleve H., Loehrs U., Schwarz H.-P., Kuhnle U. Am. J. Hum. Genet. 52:578-585(1993) [PubMed: 8447323] [Abstract] Cited for: VARIANT GDXY HIS-101.
[34]	"A familial mutation in the testis-determining gene SRY shared by both sexes." Jaeger R.J., Harley V.R., Pfeiffer R.A., Goodfellow P.N., Scherer G. Hum. Genet. 90:350-355(1992) [PubMed: 1483689] [Abstract] Cited for: VARIANT GDXY SER-109.
[35]	"A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis." Zeng Y., Ren Z., Zhang M., Huang Y., Zeng F., Huang S. J. Med. Genet. 30:655-657(1993) [PubMed: 8105086] [Abstract] Cited for: VARIANT GDXY THR-113.
[36]	"Description and functional implications of a novel mutation in the sex-determining gene SRY." Poulat F., Soulier S., Goze C., Heitz F., Calas B., Berta P. Hum. Mutat. 3:200-204(1994) [PubMed: 8019555] [Abstract] Cited for: VARIANT GDXY CYS-127.
[37]	"Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY." Haqq C.M., King C.Y., Ukiyama E., Falsafi S., Haqq T.N., Donahoe P.K., Weiss M.A. Science 266:1494-1500(1994) [PubMed: 7985018] [Abstract] Cited for: VARIANT GDXY THR-68.
[38]	"Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers." Schmitt-Ney M., Thiele H., Kaltwasser P., Bardoni B., Cisternino M., Scherer G. Am. J. Hum. Genet. 56:862-869(1995) [PubMed: 7717397] [Abstract] Cited for: VARIANTS GDXY GLY-91 AND LEU-125.
[39]	"True hermaphroditism with 46,XY karyotype and a point mutation in the SRY gene." Hiort O., Klaubert G.T. J. Pediatr. 126:1022-1022(1995) [PubMed: 7776083] [Abstract] Cited for: VARIANT GDXY ALA-60.
[40]	"Novel missense mutation (P131R) in the HMG box of SRY in XY sex reversal." Lundberg Y., Ritzen M., Harlin J., Wedell A. Hum. Mutat. Suppl. 1:S328-S328(1998) Cited for: VARIANT GDXY ARG-131.
[41]	"Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations." Scherer G., Held M., Erdel M., Meschede D., Horst J., Lesniewicz R., Midro A.T. Cytogenet. Cell Genet. 80:188-192(1998) [PubMed: 9678356] [Abstract] Cited for: VARIANTS GDXY ARG-64 AND VAL-67.
[42]	"A novel missense mutation (S18N) in the 5' non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives." Domenice S., Nishi M.Y., Billerbeck A.E.C., Latronico A.C., Medeiros M.A., Russell A.J., Vass K., Carvalho F.M., Costa-Frade E.M., Arnhold I.J.P., Mendonca B.B. Hum. Genet. 102:213-215(1998) [PubMed: 9521592] [Abstract] Cited for: VARIANT GDXY ASN-18.
[43]	"Independent observation of SRY mutation I90M in a patient with complete gonadal dysgenesis." Doerk T., Stuhrmann M., Miller K., Schmidtke J. Hum. Mutat. 11:90-91(1998) [PubMed: 9450909] [Abstract] Cited for: VARIANT GDXY MET-90.
[44]	"A rare case of 46,XX true hermaphroditism with hidden mosaicism with sex-determining region Y chromosome-bearing cells in the gonads." Inoue H., Nomura M., Yanase T., Ichino I., Goto K., Ikuyama S., Takayanagi R., Nawata H. Intern. Med. 37:467-471(1998) [PubMed: 9652903] [Abstract] Cited for: INVOLVEMENT IN TRUE HERMAPHRODITISM.
[45]	"A novel sex-determining region on Y (SRY) missense mutation identified in a 46,XY female and also in the father." Imai A., Takagi A., Tamaya T. Endocr. J. 46:735-739(1999) [PubMed: 10670762] [Abstract] Cited for: VARIANT GDXY SER-76.
[46]	"Another mutation within the HMG-box of the SRY gene associated with Swyer syndrome." Jakubiczka S., Bettecken T., Stumm M., Neulen J., Wieacker P. Hum. Mutat. 13:85-85(1999) Cited for: VARIANT GDXY ARG-108.
[47]	"SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite." Margarit E., Coll M.D., Oliva R., Gomez D., Soler A., Ballesta F. Am. J. Med. Genet. 90:25-28(2000) [PubMed: 10602113] [Abstract] Cited for: INVOLVEMENT IN TRUE HERMAPHRODITISM.
[48]	"Identification of a new missense mutation (Gly95Glu) in a highly conserved codon within the high-mobility group box of the sex-determining region Y gene: report on a 46,XY female with gonadal dysgenesis and yolk-sac tumor." Schaeffler A., Barth N., Winkler K., Zietz B., Ruemmele P., Knuechel R., Schoelmerich J., Palitzsch K.-D. J. Clin. Endocrinol. Metab. 85:2287-2292(2000) [PubMed: 10852465] [Abstract] Cited for: VARIANT GDXY GLU-95.
[49]	"A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism." Canto P., de la Chesnaye E., Lopez M., Cervantes A., Chavez B., Vilchis F., Reyes E., Ulloa-Aguirre A., Kofman-Alfaro S., Mendez J.P. J. Clin. Endocrinol. Metab. 85:1908-1911(2000) [PubMed: 10843173] [Abstract] Cited for: VARIANT GDXY/TURNER SYNDROME ASN-18.
[50]	"A novel missense mutation in the HMG box region of the SRY gene in a Japanese patient with an XY sex reversal." Okuhara K., Tajima T., Nakae J., Fujieda K. J. Hum. Genet. 45:112-114(2000) [PubMed: 10721678] [Abstract] Cited for: VARIANT GDXY TYR-87.
[51]	"Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father." Jordan B.K., Jain M., Natarajan S., Frasier S.D., Vilain E. J. Clin. Endocrinol. Metab. 87:3428-3432(2002) [PubMed: 12107262] [Abstract] Cited for: VARIANT GDXY PHE-127.
[52]	"True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene." Maier E.M., Leitner C., Lohrs U., Kuhnle U. J. Pediatr. Endocrinol. Metab. 16:575-580(2003) [PubMed: 12793612] [Abstract] Cited for: VARIANT TRUE HERMAPHRODITISM MET-90.
[53]	"Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis." Gimelli G., Gimelli S., Dimasi N., Bocciardi R., Battista E.D., Pramparo T., Zuffardi O. Eur. J. Hum. Genet. 15:76-80(2007) [PubMed: 17063144] [Abstract] Cited for: VARIANT GDXY LEU-3.
+	Additional computationally mapped references.

Web resources

GeneReviews

Protein Spotlight

The tenuous nature of sex - Issue 80 of March 2007

Wikipedia

SRY entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X53772 Genomic DNA. Translation: CAA37790.1.
L10101 mRNA. Translation: AAA60590.1.
L10102 Genomic DNA. Translation: AAA60591.1.
L08063 Unassigned DNA. Translation: AAA16878.1.
X96421 Genomic DNA. Translation: CAA65281.1.
S53156 mRNA. Translation: AAB25008.1.
S56543 mRNA. Translation: AAB25716.1.
BC074923 mRNA. Translation: AAH74923.1.
BC074924 mRNA. Translation: AAH74924.1.

IPI

IPI00011568.

PIR

A47533.

RefSeq

NP_003131.1.
XP_001713743.1.

UniGene

Hs.1992

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HRY	NMR	-	A	56-131	[»]
1HRZ	NMR	-	A	56-131	[»]
1J46	NMR	-	A	57-140	[»]
1J47	NMR	-	A	57-140	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q05066. 1 interaction.

Proteomic databases

PRIDE

Q05066.

Genome annotation databases

Ensembl

ENSG00000184895. Homo sapiens. [Contig view]

GeneID

100130809.
6736.

KEGG

hsa:100130809.
hsa:6736.

Organism-specific databases

GeneCards

GC0YM002698.
GC0YM002714.

H-InvDB

HIX0056699.

HGNC

HGNC:11311. SRY.

HPA

HPA003959.

MIM

235600. phenotype.
306100. gene+phenotype.
480000. gene.

Orphanet

983. Anorchidia, bilateral.
1772. Gonadal dysgenesis, mixed.
242. Gonadal dysgenesis, XY female type.
393. XX, male syndrome.

PharmGKB

PA36135.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q05066.

HOVERGEN

Q05066.

OMA

Q05066. ALENPRM.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_tf_pathway. Regulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q05066.

CleanEx

HS_SRY.

GermOnline

ENSG00000184895. Homo sapiens.

Family and domain databases

InterPro

IPR000910. HMG_HMG1/HMG2.
IPR017253. Sex-determining_region_Y.
[Graphical view]

Gene3D

G3DSA:1.10.30.10. HMG-box. 1 hit.

Pfam

PF00505. HMG_box. 1 hit.
[Graphical view]

PIRSF

PIRSF037653. SRY. 1 hit.

SMART

SM00398. HMG. 1 hit.
[Graphical view]

PROSITE

PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

SRY_HUMAN

Accession

Primary (citable) accession number: Q05066

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	June 16, 2009
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)