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Showing Protein Sex-determining region Y protein (HMDBP08587)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP08587
Secondary Accession Numbers
  • 14302
Name Sex-determining region Y protein
Synonyms
  1. Testis-determining factor
Gene Name SRY
Protein Type Unknown
Biological Properties
General Function Involved in DNA binding
Specific 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. Involved in different aspects of gene regulation including promoter activation or repression. 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'
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
binding
protein binding
nucleic acid binding
dna binding
sequence-specific dna binding transcription factor activity
Process
developmental process involved in reproduction
sex determination
male sex determination
reproductive process
Cellular Location
  1. Cytoplasm
  2. Nucleus speckle
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs SRY
Gene Sequence 
>615 bp
ATGCAATCATATGCTTCTGCTATGTTAAGCGTATTCAACAGCGATGATTACAGTCCAGCT
GTGCAAGAGAATATTCCCGCTCTCCGGAGAAGCTCTTCCTTCCTTTGCACTGAAAGCTGT
AACTCTAAGTATCAGTGTGAAACGGGAGAAAACAGTAAAGGCAACGTCCAGGATAGAGTG
AAGCGACCCATGAACGCATTCATCGTGTGGTCTCGCGATCAGAGGCGCAAGATGGCTCTA
GAGAATCCCAGAATGCGAAACTCAGAGATCAGCAAGCAGCTGGGATACCAGTGGAAAATG
CTTACTGAAGCCGAAAAATGGCCATTCTTCCAGGAGGCACAGAAATTACAGGCCATGCAC
AGAGAGAAATACCCGAATTATAAGTATCGACCTCGTCGGAAGGCGAAGATGCTGCCGAAG
AATTGCAGTTTGCTTCCCGCAGATCCCGCTTCGGTACTCTGCAGCGAAGTGCAACTGGAC
AACAGGTTGTACAGGGATGACTGTACGAAAGCCACACACTCAAGAATGGAGCACCAGCTA
GGCCACTTACCGCCCATCAACGCAGCCAGCTCACCGCAGCAACGGGACCGCTACAGCCAC
TGGACAAAGCTGTAG
Protein Properties
Number of Residues 204
Molecular Weight 23884.0
Theoretical pI 9.91
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Sex-determining region Y protein
MQSYASAMLSVFNSDDYSPAVQENIPALRRSSSFLCTESCNSKYQCETGENSKGNVQDRV
KRPMNAFIVWSRDQRRKMALENPRMRNSEISKQLGYQWKMLTEAEKWPFFQEAQKLQAMH
REKYPNYKYRPRRKAKMLPKNCSLLPADPASVLCSEVQLDNRLYRDDCTKATHSRMEHQL
GHLPPINAASSPQQRDRYSHWTKL
GenBank ID Protein 49902356
UniProtKB/Swiss-Prot ID Q05066
UniProtKB/Swiss-Prot Entry Name SRY_HUMAN
PDB IDs
GenBank Gene ID BC074923
GeneCard ID SRY
GenAtlas ID SRY
HGNC ID HGNC:11311
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Thevenet L, Mejean C, Moniot B, Bonneaud N, Galeotti N, Aldrian-Herrada G, Poulat F, Berta P, Benkirane M, Boizet-Bonhoure B: Regulation of human SRY subcellular distribution by its acetylation/deacetylation. EMBO J. 2004 Aug 18;23(16):3336-45. Epub 2004 Aug 5. [PubMed:15297880 ]
  3. Li Y, Oh HJ, Lau YF: The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its biological functions. Mol Cell Endocrinol. 2006 Sep 26;257-258:35-46. Epub 2006 Aug 9. [PubMed:16904257 ]
  4. Kelly S, Yotis J, Macris M, Harley V: Recombinant expression, purification and characterisation of the HMG domain of human SRY. Protein Pept Lett. 2003 Jun;10(3):281-6. [PubMed:12871148 ]
  5. Sim H, Rimmer K, Kelly S, Ludbrook LM, Clayton AH, Harley VR: Defective calmodulin-mediated nuclear transport of the sex-determining region of the Y chromosome (SRY) in XY sex reversal. Mol Endocrinol. 2005 Jul;19(7):1884-92. Epub 2005 Mar 3. [PubMed:15746192 ]
  6. Poulat F, de Santa Barbara P, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B, Berta P: The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains. J Biol Chem. 1997 Mar 14;272(11):7167-72. [PubMed:9054412 ]
  7. Harley VR, Layfield S, Mitchell CL, Forwood JK, John AP, Briggs LJ, McDowall SG, Jans DA: Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7045-50. Epub 2003 May 22. [PubMed:12764225 ]
  8. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990 Jul 19;346(6281):240-4. [PubMed:1695712 ]
  9. Su H, Lau YF: Identification of the transcriptional unit, structural organization, and promoter sequence of the human sex-determining region Y (SRY) gene, using a reverse genetic approach. Am J Hum Genet. 1993 Jan;52(1):24-38. [PubMed:8434602 ]
  10. Behlke MA, Bogan JS, Beer-Romero P, Page DC: Evidence that the SRY protein is encoded by a single exon on the human Y chromosome. Genomics. 1993 Sep;17(3):736-9. [PubMed:8244390 ]
  11. Whitfield LS, Hawkins TL, Goodfellow PN, Sulston J: 41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome. Genomics. 1995 May 20;27(2):306-11. [PubMed:7557997 ]
  12. Ferrari S, Harley VR, Pontiggia A, Goodfellow PN, Lovell-Badge R, Bianchi ME: SRY, like HMG1, recognizes sharp angles in DNA. EMBO J. 1992 Dec;11(12):4497-506. [PubMed:1425584 ]
  13. King CY, Weiss MA: The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove: a topological mechanism of sequence specificity. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11990-4. [PubMed:8265659 ]
  14. Giese K, Pagel J, Grosschedl R: Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3368-72. [PubMed:8159753 ]
  15. Desclozeaux M, Poulat F, de Santa Barbara P, Capony JP, Turowski P, Jay P, Mejean C, Moniot B, Boizet B, Berta P: Phosphorylation of an N-terminal motif enhances DNA-binding activity of the human SRY protein. J Biol Chem. 1998 Apr 3;273(14):7988-95. [PubMed:9525897 ]
  16. Mayer A, Lahr G, Swaab DF, Pilgrim C, Reisert I: The Y-chromosomal genes SRY and ZFY are transcribed in adult human brain. Neurogenetics. 1998 Aug;1(4):281-8. [PubMed:10732804 ]
  17. Ohe K, Lalli E, Sassone-Corsi P: A direct role of SRY and SOX proteins in pre-mRNA splicing. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1146-51. Epub 2002 Jan 29. [PubMed:11818535 ]
  18. Matsuzawa-Watanabe Y, Inoue J, Semba K: Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1. Oncogene. 2003 Sep 11;22(39):7900-4. [PubMed:12970737 ]
  19. Phillips NB, Nikolskaya T, Jancso-Radek A, Ittah V, Jiang F, Singh R, Haas E, Weiss MA: Sry-directed sex reversal in transgenic mice is robust with respect to enhanced DNA bending: comparison of human and murine HMG boxes. Biochemistry. 2004 Jun 8;43(22):7066-81. [PubMed:15170344 ]
  20. Oh HJ, Li Y, Lau YF: Sry associates with the heterochromatin protein 1 complex by interacting with a KRAB domain protein. Biol Reprod. 2005 Feb;72(2):407-15. Epub 2004 Oct 6. [PubMed:15469996 ]
  21. Li B, Phillips NB, Jancso-Radek A, Ittah V, Singh R, Jones DN, Haas E, Weiss MA: SRY-directed DNA bending and human sex reversal: reassessment of a clinical mutation uncovers a global coupling between the HMG box and its tail. J Mol Biol. 2006 Jul 7;360(2):310-28. Epub 2006 May 9. [PubMed:16762365 ]
  22. Polanco JC, Koopman P: Sry and the hesitant beginnings of male development. Dev Biol. 2007 Feb 1;302(1):13-24. Epub 2006 Aug 24. [PubMed:16996051 ]
  23. Oh HJ, Lau YF: KRAB: a partner for SRY action on chromatin. Mol Cell Endocrinol. 2006 Mar 9;247(1-2):47-52. Epub 2006 Jan 18. [PubMed:16414182 ]
  24. Werner MH, Huth JR, Gronenborn AM, Clore GM: Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. Cell. 1995 Jun 2;81(5):705-14. [PubMed:7774012 ]
  25. Murphy EC, Zhurkin VB, Louis JM, Cornilescu G, Clore GM: Structural basis for SRY-dependent 46-X,Y sex reversal: modulation of DNA bending by a naturally occurring point mutation. J Mol Biol. 2001 Sep 21;312(3):481-99. [PubMed:11563911 ]
  26. Stott K, Tang GS, Lee KB, Thomas JO: Structure of a complex of tandem HMG boxes and DNA. J Mol Biol. 2006 Jun 30;360(1):90-104. Epub 2006 May 12. [PubMed:16813837 ]
  27. Hawkins JR: Mutational analysis of SRY in XY females. Hum Mutat. 1993;2(5):347-50. [PubMed:8257986 ]
  28. Cameron FJ, Sinclair AH: Mutations in SRY and SOX9: testis-determining genes. Hum Mutat. 1997;9(5):388-95. [PubMed:9143916 ]
  29. Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M: Genetic evidence equating SRY and the testis-determining factor. Nature. 1990 Nov 29;348(6300):448-50. [PubMed:2247149 ]
  30. Affara NA, Chalmers IJ, Ferguson-Smith MA: Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. Hum Mol Genet. 1993 Jun;2(6):785-9. [PubMed:8353496 ]
  31. Vilain E, McElreavey K, Jaubert F, Raymond JP, Richaud F, Fellous M: Familial case with sequence variant in the testis-determining region associated with two sex phenotypes. Am J Hum Genet. 1992 May;50(5):1008-11. [PubMed:1570829 ]
  32. Hawkins JR, Taylor A, Goodfellow PN, Migeon CJ, Smith KD, Berkovitz GD: Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. Am J Hum Genet. 1992 Nov;51(5):979-84. [PubMed:1415266 ]
  33. Hawkins JR, Taylor A, Berta P, Levilliers J, Van der Auwera B, Goodfellow PN: Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal. Hum Genet. 1992 Feb;88(4):471-4. [PubMed:1339396 ]
  34. Braun A, Kammerer S, Cleve H, Lohrs U, Schwarz HP, Kuhnle U: 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. Am J Hum Genet. 1993 Mar;52(3):578-85. [PubMed:8447323 ]
  35. Jager RJ, Harley VR, Pfeiffer RA, Goodfellow PN, Scherer G: A familial mutation in the testis-determining gene SRY shared by both sexes. Hum Genet. 1992 Dec;90(4):350-5. [PubMed:1483689 ]
  36. Zeng YT, Ren ZR, Zhang ML, Huang Y, Zeng FY, Huang SZ: A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis. J Med Genet. 1993 Aug;30(8):655-7. [PubMed:8105086 ]
  37. Poulat F, Soullier S, Goze C, Heitz F, Calas B, Berta P: Description and functional implications of a novel mutation in the sex-determining gene SRY. Hum Mutat. 1994;3(3):200-4. [PubMed:8019555 ]
  38. Haqq CM, King CY, Ukiyama E, Falsafi S, Haqq TN, Donahoe PK, Weiss MA: Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY. Science. 1994 Dec 2;266(5190):1494-500. [PubMed:7985018 ]
  39. Schmitt-Ney M, Thiele H, Kaltwasser P, Bardoni B, Cisternino M, Scherer G: Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers. Am J Hum Genet. 1995 Apr;56(4):862-9. [PubMed:7717397 ]
  40. Hiort O, Gramss B, Klauber GT: True hermaphroditism with 46,XY karyotype and a point mutation in the SRY gene. J Pediatr. 1995 Jun;126(6):1022. [PubMed:7776083 ]
  41. Scherer G, Held M, Erdel M, Meschede D, Horst J, Lesniewicz R, Midro AT: Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations. Cytogenet Cell Genet. 1998;80(1-4):188-92. [PubMed:9678356 ]
  42. Domenice S, Yumie Nishi M, Correia Billerbeck AE, Latronico AC, Aparecida Medeiros M, Russell AJ, Vass K, Marino Carvalho F, Costa Frade EM, Prado Arnhold IJ, Bilharinho Mendonca B: 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. Hum Genet. 1998 Feb;102(2):213-5. [PubMed:9521592 ]
  43. Dork T, Stuhrmann M, Miller K, Schmidtke J: Independent observation of SRY mutation I90M in a patient with complete gonadal dysgenesis. Hum Mutat. 1998;11(1):90-1. [PubMed:9450909 ]
  44. Inoue H, Nomura M, Yanase T, Ichino I, Goto K, Ikuyama S, Takayanagi R, Nawata H: A rare case of 46,XX true hermaphroditism with hidden mosaicism with sex-determining region Y chromosome-bearing cells in the gonads. Intern Med. 1998 May;37(5):467-71. [PubMed:9652903 ]
  45. Imai A, Takagi A, Tamaya T: A novel sex-determining region on Y (SRY) missense mutation identified in a 46,XY female and also in the father. Endocr J. 1999 Oct;46(5):735-9. [PubMed:10670762 ]
  46. Margarit E, Coll MD, Oliva R, Gomez D, Soler A, Ballesta F: SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite. Am J Med Genet. 2000 Jan 3;90(1):25-8. [PubMed:10602113 ]
  47. Schaffler A, Barth N, Winkler K, Zietz B, Rummele P, Knuchel R, Scholmerich J, Palitzsch KD: 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. J Clin Endocrinol Metab. 2000 Jun;85(6):2287-92. [PubMed:10852465 ]
  48. Canto P, de la Chesnaye E, Lopez M, Cervantes A, Chavez B, Vilchis F, Reyes E, Ulloa-Aguirre A, Kofman-Alfaro S, Mendez JP: A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism. J Clin Endocrinol Metab. 2000 May;85(5):1908-11. [PubMed:10843173 ]
  49. Okuhara K, Tajima T, Nakae J, Fujieda K: A novel missense mutation in the HMG box region of the SRY gene in a Japanese patient with an XY sex reversal. J Hum Genet. 2000;45(2):112-4. [PubMed:10721678 ]
  50. Jordan BK, Jain M, Natarajan S, Frasier SD, Vilain E: Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father. J Clin Endocrinol Metab. 2002 Jul;87(7):3428-32. [PubMed:12107262 ]
  51. Maier EM, Leitner C, Lohrs U, Kuhnle U: True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene. J Pediatr Endocrinol Metab. 2003 Apr-May;16(4):575-80. [PubMed:12793612 ]
  52. Gimelli G, Gimelli S, Dimasi N, Bocciardi R, Di Battista E, Pramparo T, Zuffardi O: Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis. Eur J Hum Genet. 2007 Jan;15(1):76-80. Epub 2006 Oct 25. [PubMed:17063144 ]