Serine/threonine-protein kinase haspin

Details

Name

Serine/threonine-protein kinase haspin

Synonyms

• 2.7.11.1
• Germ cell-specific gene 2 protein
• H-haspin
• Haploid germ cell-specific nuclear protein kinase

Gene Name

GSG2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0037262|Serine/threonine-protein kinase haspin
MAASLPGPGSRLFRTYGAADGRRQRRPGREAAQWFPPQDRRRFFNSSGSSDASIGDPSQS
DDPDDPDDPDFPGSPVRRRRRRPGGRVPKDRPSLTVTPKRWKLRARPSLTVTPRRLGLRA
RPPQKCSTPCGPLRLPPFPSRDSGRLSPDLSVCGQPRDGDELGISASLFSSLASPCPGSP
TPRDSVISIGTSACLVAASAVPSGLHLPEVSLDRASLPCSQEEATGGAKDTRMVHQTRAS
LRSVLFGLMNSGTPEDSEFRADGKNMRESCCKRKLVVGNGPEGPGLSSTGKRRATGQDSC
QERGLQEAVRREHQEASVPKGRIVPRGIDRLERTRSSRKSKHQEATETSLLHSHRFKKGQ
KLGKDSFPTQDLTPLQNVCFWTKTRASFSFHKKKIVTDVSEVCSIYTTATSLSGSLLSEC
SNRPVMNRTSGAPSSWHSSSMYLLSPLNTLSISNKKASDAEKVYGECSQKGPVPFSHCLP
TEKLQRCEKIGEGVFGEVFQTIADHTPVAIKIIAIEGPDLVNGSHQKTFEEILPEIIISK
ELSLLSGEVCNRTEGFIGLNSVHCVQGSYPPLLLKAWDHYNSTKGSANDRPDFFKDDQLF
IVLEFEFGGIDLEQMRTKLSSLATAKSILHQLTASLAVAEASLRFEHRDLHWGNVLLKKT
SLKKLHYTLNGKSSTIPSCGLQVSIIDYTLSRLERDGIVVFCDVSMDEDLFTGDGDYQFD
IYRLMKKENNNRWGEYHPYSNVLWLHYLTDKMLKQMTFKTKCNTPAMKQIKRKIQEFHRT
MLNFSSATDLLCQHSLFK

Number of residues

798

Molecular Weight

88494.565

Theoretical pI

9.37

GO Classification

Functions

ATP binding / histone kinase activity (H3-T3 specific) / protein kinase activity

Processes

histone H3-T3 phosphorylation involved in chromosome passenger complex localization to kinetochore / intracellular signal transduction / mitotic sister chromatid cohesion / protein localization to chromosome, centromeric region / protein phosphorylation / regulation of spindle checkpoint

Components

centrosome / chromosome / cytoplasm / nucleus / spindle

General Function

Protein kinase activity

Specific Function

Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.

Pfam Domain Function

• Pkinase (PF00069)
• DUF3635 (PF12330)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0017229|Serine/threonine-protein kinase haspin (GSG2)
ATGGCGGCTTCGCTCCCGGGACCTGGGAGCCGGCTTTTCCGCACATATGGGGCTGCGGAC
GGCAGGAGACAGCGGCGGCCGGGCCGGGAAGCCGCGCAGTGGTTCCCGCCGCAGGACCGG
AGGCGTTTCTTCAACAGCAGCGGCAGCAGCGACGCCAGCATCGGCGACCCCTCGCAGTCC
GACGATCCTGACGATCCCGACGACCCCGACTTCCCCGGCAGCCCGGTGAGGCGGCGGCGG
AGGCGTCCCGGCGGCCGAGTGCCCAAGGACCGGCCCAGCCTGACCGTGACCCCAAAGCGC
TGGAAGCTGCGAGCTCGCCCAAGCCTAACCGTGACCCCAAGACGCCTGGGGCTGCGAGCT
CGGCCCCCGCAGAAGTGCAGCACACCCTGCGGCCCGCTCCGACTTCCGCCCTTCCCCAGC
CGCGACTCCGGCCGCCTCAGCCCGGACCTCAGCGTGTGCGGCCAGCCCAGGGACGGCGAC
GAGCTGGGCATCAGTGCCTCCCTGTTCAGCTCTCTGGCCTCGCCCTGCCCCGGGTCCCCA
ACGCCAAGGGACAGTGTCATCTCGATCGGCACCTCCGCCTGTCTGGTTGCAGCCTCAGCC
GTCCCGAGCGGCCTCCACCTCCCAGAAGTCTCCCTGGACCGAGCATCTCTCCCCTGCTCC
CAGGAGGAAGCGACAGGAGGAGCCAAGGACACCAGGATGGTCCACCAAACCCGCGCCAGC
CTCAGGTCAGTTCTCTTTGGCCTTATGAACTCAGGAACCCCTGAGGATTCTGAGTTTCGG
GCAGATGGGAAGAATATGAGAGAGTCCTGCTGTAAAAGGAAACTGGTGGTGGGAAATGGA
CCAGAGGGTCCAGGTCTGTCAAGCACAGGCAAGAGGAGGGCCACAGGCCAGGACTCTTGT
CAAGAGAGAGGGCTTCAAGAGGCCGTCCGGAGAGAGCATCAGGAGGCCAGTGTTCCCAAG
GGCCGCATTGTGCCAAGGGGAATAGACAGGCTGGAGAGAACTAGATCAAGCCGGAAGAGC
AAACATCAGGAGGCAACGGAAACCTCTCTCCTCCATTCCCACCGCTTTAAAAAGGGCCAA
AAGCTGGGAAAAGATTCGTTCCCCACCCAGGACCTGACTCCTTTACAGAATGTCTGCTTT
TGGACCAAAACCAGGGCTTCCTTCAGTTTCCACAAGAAGAAAATTGTGACTGATGTGTCA
GAGGTCTGCAGCATCTATACCACTGCCACTTCTCTCTCTGGATCCCTCCTATCAGAATGT
TCAAACCGGCCTGTCATGAACAGAACAAGTGGTGCTCCGTCCTCTTGGCACTCCTCCTCT
ATGTATTTGCTAAGCCCCTTAAACACTCTAAGTATTTCAAACAAAAAGGCATCTGATGCT
GAAAAGGTTTATGGGGAATGCAGTCAGAAGGGTCCTGTCCCCTTTAGCCATTGCCTTCCC
ACAGAAAAACTGCAACGCTGTGAGAAGATTGGGGAAGGGGTGTTTGGCGAAGTGTTTCAA
ACAATTGCTGATCACACACCCGTAGCCATAAAAATCATTGCTATTGAAGGACCAGATTTA
GTCAATGGATCCCATCAGAAAACCTTTGAGGAAATCCTGCCAGAGATCATCATCTCCAAA
GAGTTGAGCCTCTTATCCGGTGAAGTGTGCAACCGCACAGAAGGCTTTATCGGGCTGAAC
TCAGTGCACTGTGTCCAGGGATCTTACCCTCCCTTGCTCCTCAAAGCCTGGGATCACTAT
AATTCAACCAAAGGCTCTGCAAATGACCGGCCTGATTTTTTTAAAGACGACCAGCTCTTC
ATTGTGCTGGAATTTGAGTTTGGAGGGATTGACTTAGAGCAAATGCGAACCAAGTTGTCT
TCCTTGGCTACTGCAAAGAGCATTCTACACCAGCTCACAGCCTCCCTCGCAGTGGCAGAG
GCATCACTGCGCTTTGAGCACCGAGACTTACACTGGGGGAACGTGCTCTTAAAGAAAACC
AGCCTCAAAAAACTCCACTACACCCTCAATGGGAAGAGCAGCACTATCCCCAGCTGTGGG
TTGCAAGTGAGCATCATTGACTACACCCTGTCGCGCTTGGAACGGGATGGGATTGTGGTT
TTCTGTGACGTTTCCATGGATGAGGACCTGTTTACCGGTGACGGTGACTACCAGTTTGAC
ATCTACAGGCTCATGAAGAAGGAGAATAACAACCGCTGGGGTGAATATCACCCTTATAGT
AATGTGCTCTGGTTACATTACCTGACAGACAAGATGCTGAAACAAATGACCTTCAAGACT
AAATGTAACACTCCTGCCATGAAGCAAATTAAGAGAAAAATCCAGGAGTTCCACAGGACA
ATGCTGAACTTCAGCTCTGCCACTGACTTGCTCTGCCAGCACAGTCTGTTTAAGTAA

Chromosome Location

17

Locus

17p13

External Identifiers

Resource	Link
UniProtKB ID	Q8TF76
UniProtKB Entry Name	HASP_HUMAN
GenBank Protein ID	118421077
GenBank Gene ID	AB039834
HGNC ID	HGNC:19682

General References

1. Tanaka H, Iguchi N, Nakamura Y, Kohroki J, de Carvalho CE, Nishimune Y: Cloning and characterization of human haspin gene encoding haploid germ cell-specific nuclear protein kinase. Mol Hum Reprod. 2001 Mar;7(3):211-8. [Article]
2. Higgins JM: The Haspin gene: location in an intron of the integrin alphaE gene, associated transcription of an integrin alphaE-derived RNA and expression in diploid as well as haploid cells. Gene. 2001 Apr 4;267(1):55-69. [Article]
3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
4. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
5. 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. [Article]
6. Dai J, Sultan S, Taylor SS, Higgins JM: The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev. 2005 Feb 15;19(4):472-88. Epub 2005 Jan 28. [Article]
7. Dai J, Sullivan BA, Higgins JM: Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Dev Cell. 2006 Nov;11(5):741-50. [Article]
8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
9. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
10. Wang F, Dai J, Daum JR, Niedzialkowska E, Banerjee B, Stukenberg PT, Gorbsky GJ, Higgins JM: Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science. 2010 Oct 8;330(6001):231-5. doi: 10.1126/science.1189435. Epub 2010 Aug 12. [Article]
11. Yamagishi Y, Honda T, Tanno Y, Watanabe Y: Two histone marks establish the inner centromere and chromosome bi-orientation. Science. 2010 Oct 8;330(6001):239-43. doi: 10.1126/science.1194498. [Article]
12. Wang F, Ulyanova NP, van der Waal MS, Patnaik D, Lens SM, Higgins JM: A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr Biol. 2011 Jun 21;21(12):1061-9. doi: 10.1016/j.cub.2011.05.016. Epub 2011 Jun 9. [Article]
13. Huertas D, Soler M, Moreto J, Villanueva A, Martinez A, Vidal A, Charlton M, Moffat D, Patel S, McDermott J, Owen J, Brotherton D, Krige D, Cuthill S, Esteller M: Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin. Oncogene. 2012 Mar 15;31(11):1408-18. doi: 10.1038/onc.2011.335. Epub 2011 Aug 1. [Article]
14. Eswaran J, Patnaik D, Filippakopoulos P, Wang F, Stein RL, Murray JW, Higgins JM, Knapp S: Structure and functional characterization of the atypical human kinase haspin. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20198-203. doi: 10.1073/pnas.0901989106. Epub 2009 Nov 16. [Article]
15. Villa F, Capasso P, Tortorici M, Forneris F, de Marco A, Mattevi A, Musacchio A: Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20204-9. doi: 10.1073/pnas.0908485106. Epub 2009 Nov 16. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB04604	5-iodotubercidin	experimental	unknown		Details
DB07698	3-(3-aminophenyl)-N-(3-chlorophenyl)pyrazolo[1,5-a]pyrimidin-5-amine	experimental	unknown		Details
DB07995	H-89	experimental	unknown		Details
DB08004	(2S)-2-{[3-(3-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}-3-methylbutan-1-ol	experimental	unknown		Details