Q05066 (SRY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	204 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 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. Promotes 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'. Ref.12 Ref.16 Ref.20 Ref.25
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. Ref.9 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.21
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. Ref.12 Ref.17 Ref.19
Domain	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.
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	46,XY sex reversal 1 (SRXY1) [MIM:400044]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25 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.44 Ref.46 Ref.47 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 A 45,X chromosomal aberration involving SRY is 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. 46,XX sex reversal 1 (SRXX1) [MIM:400045]: A condition in which male gonads develop in a genetic female (female to male sex reversal). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.45 Ref.48
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	Calmodulin-binding DNA-binding
Molecular function	Activator Repressor
PTM	ADP-ribosylation Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW male sex determination Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of male gonad development Inferred from direct assay PubMed 21412441. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 21412441. Source: UniProtKB sex differentiation 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 nucleus Inferred from direct assay PubMed 21412441. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay Ref.6Ref.7. Source: UniProtKB RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 21412441. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD3	P84022	3	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 SRXY1. Ref.54

VAR_030019

Natural variant

18

1

S → N in SRXY1; partial; also in two patients with a Turner syndrome phenotype. Ref.43 Ref.50

VAR_003717

Natural variant

60

1

V → A in SRXY1. Ref.40

VAR_003718

Natural variant

60

1

V → L in SRXY1. Ref.29 Ref.31

VAR_003719

Natural variant

62

1

R → G in SRXY1. Ref.30

VAR_003720

Natural variant

64

1

M → I in SRXY1; alters interaction with DNA and DNA bending. Ref.25 Ref.29

VAR_003721

Natural variant

64

1

M → R in SRXY1. Ref.42

VAR_017298

Natural variant

67

1

F → V in SRXY1. Ref.42

VAR_017299

Natural variant

68

1

I → T in SRXY1. Ref.38

VAR_003722

Natural variant

76

1

R → S in SRXY1. Ref.46

VAR_017300

Natural variant

78

1

M → T in SRXY1. Ref.30

VAR_003723

Natural variant

87

1

N → Y in SRXY1. Ref.51

VAR_017301

Natural variant

90

1

I → M in SRXY1. Ref.32 Ref.44 Ref.53

VAR_003724

Natural variant

91

1

S → G in SRXY1. Ref.39

VAR_003725

Natural variant

95

1

G → E in SRXY1. Ref.49

VAR_017302

Natural variant

95

1

G → R in SRXY1. Ref.33

VAR_003726

Natural variant

101

1

L → H in SRXY1. Ref.34

VAR_003727

Natural variant

106

1

K → I in SRXY1. Ref.32

VAR_003728

Natural variant

108

1

P → R in SRXY1. Ref.47

VAR_003729

Natural variant

109

1

F → S in SRXY1. Ref.35

VAR_003730

Natural variant

113

1

A → T in SRXY1. Ref.36

VAR_003731

Natural variant

125

1

P → L in SRXY1. Ref.39

VAR_003732

Natural variant

127

1

Y → C in SRXY1. Ref.37

VAR_003733

Natural variant

127

1

Y → F in SRXY1. Ref.52

VAR_017303

Natural variant

131

1

P → R in SRXY1. Ref.41

VAR_017304

Natural variant

133

1

R → W in SRXY1. Ref.30

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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 56-131 IN COMPLEX WITH DNA.
[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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 57-218 IN COMPLEX WITH DNA, CHARACTERIZATION OF VARIANT SRXY1 ILE-64, FUNCTION.
[26]	"Structure of a complex of tandem HMG boxes and DNA." Stott K., Tang G.S., Lee K.B., Thomas J.O. J. Mol. Biol. 360:90-104(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 56-130 IN COMPLEX WITH DNA.
[27]	"Mutational analysis of SRY in XY females." Hawkins J.R. Hum. Mutat. 2:347-350(1993) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[28]	"Mutations in SRY and SOX9: testis-determining genes." Cameron F.J., Sinclair A.H. Hum. Mutat. 9:388-395(1997) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SRXY1 LEU-60 AND ILE-64.
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SRXY1 GLY-62; THR-78 AND TRP-133.
[31]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 LEU-60.
[32]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SRXY1 MET-90 AND ILE-106.
[33]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 ARG-95.
[34]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 HIS-101.
[35]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 SER-109.
[36]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 THR-113.
[37]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 CYS-127.
[38]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 THR-68.
[39]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SRXY1 GLY-91 AND LEU-125.
[40]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 ALA-60.
[41]	"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 SRXY1 ARG-131.
[42]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SRXY1 ARG-64 AND VAL-67.
[43]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 ASN-18.
[44]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 MET-90.
[45]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SRXX1.
[46]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 SER-76.
[47]	"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 SRXY1 ARG-108.
[48]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SRXX1.
[49]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 GLU-95.
[50]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 ASN-18.
[51]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 TYR-87.
[52]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 PHE-127.
[53]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 MET-90.
[54]	"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] [Europe PMC] [Abstract] Cited for: VARIANT SRXY1 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

EMBL
GenBank
DDBJ

X53772 Genomic DNA. Translation: CAA37790.1.
L10101 mRNA. Translation: AAA60590.1.
L10102 Genomic DNA. Translation: AAA60591.1.
L08063 Genomic 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. NM_003140.1.

UniGene

Hs.1992.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2GZK	NMR	-	A	56-130	[»]

ProteinModelPortal

Q05066.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q05066. 1 interaction.

MINT

MINT-1367278.

STRING

9606.ENSP00000372547.

PTM databases

PhosphoSite

Q05066.

Polymorphism databases

DMDM

548983.

Proteomic databases

PaxDb

Q05066.

PRIDE

Q05066.

Protocols and materials databases

DNASU

6736.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000383070; ENSP00000372547; ENSG00000184895.

GeneID

6736.

KEGG

hsa:6736.

UCSC

uc004fqg.1. human.

Organism-specific databases

CTD

6736.

GeneCards

GC0YM002698.

HGNC

HGNC:11311. SRY.

HPA

HPA003959.

MIM

400044. phenotype.
400045. phenotype.
480000. gene.

neXtProt

NX_Q05066.

Orphanet

1772. 45,X/46,XY mixed gonadal dysgenesis.
393. 46,XX testicular disorder of sex development.
242. 46,XY complete gonadal dysgenesis.
251510. 46,XY partial gonadal dysgenesis.
983. Bilateral anorchia.

PharmGKB

PA36135.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG130659.

HOGENOM

HOG000008601.

HOVERGEN

HBG008712.

InParanoid

Q05066.

KO

K09266.

OMA

QSYASAM.

OrthoDB

EOG49079Z.

PhylomeDB

Q05066.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_tf_pathway. Regulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q05066.

Bgee

Q05066.

CleanEx

HS_SRY.

Genevestigator

Q05066.

GermOnline

ENSG00000184895. Homo sapiens.

Family and domain databases

Gene3D

1.10.30.10. 1 hit.

InterPro

IPR009071. HMG_box_dom.
IPR017253. TF_Sry.
[Graphical view]

PANTHER

PTHR10270:SF48. PTHR10270:SF48. 1 hit.

Pfam

PF00505. HMG_box. 1 hit.
[Graphical view]

PIRSF

PIRSF037653. SRY. 1 hit.

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

EvolutionaryTrace

Q05066.

GenomeRNAi

6736.

NextBio

26276.

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:	May 1, 2013
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.