HASP_HUMAN
ID HASP_HUMAN Reviewed; 798 AA.
AC Q8TF76; Q5U5K3; Q96MN1; Q9BXS7;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Serine/threonine-protein kinase haspin;
DE EC=2.7.11.1 {ECO:0000269|PubMed:19918049, ECO:0000269|PubMed:19918057};
DE AltName: Full=Germ cell-specific gene 2 protein;
DE AltName: Full=H-haspin;
DE AltName: Full=Haploid germ cell-specific nuclear protein kinase;
GN Name=HASPIN {ECO:0000312|HGNC:HGNC:19682};
GN Synonyms=GSG2 {ECO:0000312|HGNC:HGNC:19682};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND CHROMOSOMAL LOCATION.
RC TISSUE=Testis;
RX PubMed=11228240; DOI=10.1093/molehr/7.3.211;
RA Tanaka H., Iguchi N., Nakamura Y., Kohroki J., de Carvalho C.E.,
RA Nishimune Y.;
RT "Cloning and characterization of human haspin gene encoding haploid germ
RT cell-specific nuclear protein kinase.";
RL Mol. Hum. Reprod. 7:211-218(2001).
RN [2]
RP SEQUENCE REVISION TO 204; 328 AND 378.
RA Tanaka H.;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP CYS-82; ASP-204; THR-328 AND ALA-378.
RC TISSUE=Testis {ECO:0000312|EMBL:AAK30300.1};
RX PubMed=11311556; DOI=10.1016/s0378-1119(01)00387-0;
RA Higgins J.M.G.;
RT "The Haspin gene: location in an intron of the Integrin Alpha-E gene,
RT associated transcription of an Integrin alpha-E-derived RNA and expression
RT in diploid as well as haploid cells.";
RL Gene 267:55-69(2001).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT CYS-82.
RC TISSUE=Peripheral blood {ECO:0000269|PubMed:14702039};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS CYS-82;
RP ASP-204; THR-328 AND ALA-378.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION.
RX PubMed=15681610; DOI=10.1101/gad.1267105;
RA Dai J., Sultan S., Taylor S.S., Higgins J.M.G.;
RT "The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation
RT and normal metaphase chromosome alignment.";
RL Genes Dev. 19:472-488(2005).
RN [8]
RP FUNCTION IN CHROMOSOME COHESION.
RX PubMed=17084365; DOI=10.1016/j.devcel.2006.09.018;
RA Dai J., Sullivan B.A., Higgins J.M.;
RT "Regulation of mitotic chromosome cohesion by Haspin and Aurora B.";
RL Dev. Cell 11:741-750(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; THR-97 AND SER-147, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP FUNCTION.
RX PubMed=20705812; DOI=10.1126/science.1189435;
RA Wang F., Dai J., Daum J.R., Niedzialkowska E., Banerjee B.,
RA Stukenberg P.T., Gorbsky G.J., Higgins J.M.;
RT "Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at
RT centromeres in mitosis.";
RL Science 330:231-235(2010).
RN [12]
RP FUNCTION.
RX PubMed=20929775; DOI=10.1126/science.1194498;
RA Yamagishi Y., Honda T., Tanno Y., Watanabe Y.;
RT "Two histone marks establish the inner centromere and chromosome bi-
RT orientation.";
RL Science 330:239-243(2010).
RN [13]
RP PHOSPHORYLATION AT SER-93 AND SER-143 BY AURKB, ACTIVITY REGULATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21658950; DOI=10.1016/j.cub.2011.05.016;
RA Wang F., Ulyanova N.P., van der Waal M.S., Patnaik D., Lens S.M.,
RA Higgins J.M.;
RT "A positive feedback loop involving Haspin and Aurora B promotes CPC
RT accumulation at centromeres in mitosis.";
RL Curr. Biol. 21:1061-1069(2011).
RN [14]
RP ACTIVITY REGULATION.
RX PubMed=21804608; DOI=10.1038/onc.2011.335;
RA Huertas D., Soler M., Moreto J., Villanueva A., Martinez A., Vidal A.,
RA Charlton M., Moffat D., Patel S., McDermott J., Owen J., Brotherton D.,
RA Krige D., Cuthill S., Esteller M.;
RT "Antitumor activity of a small-molecule inhibitor of the histone kinase
RT Haspin.";
RL Oncogene 31:1408-1418(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 465-798 IN COMPLEX WITH AMP AND
RP INHIBITOR IODOTUBERCIDIN, COFACTOR, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF LYS-511 AND HIS-651.
RX PubMed=19918057; DOI=10.1073/pnas.0901989106;
RA Eswaran J., Patnaik D., Filippakopoulos P., Wang F., Stein R.L.,
RA Murray J.W., Higgins J.M., Knapp S.;
RT "Structure and functional characterization of the atypical human kinase
RT haspin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20198-20203(2009).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 452-798, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF GLU-492; HIS-651; ASP-707; ASP-709; GLY-713 AND ASP-716.
RX PubMed=19918049; DOI=10.1073/pnas.0908485106;
RA Villa F., Capasso P., Tortorici M., Forneris F., de Marco A., Mattevi A.,
RA Musacchio A.;
RT "Crystal structure of the catalytic domain of Haspin, an atypical kinase
RT implicated in chromatin organization.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20204-20209(2009).
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-76; CYS-82; HIS-145; ASP-204; SER-283;
RP LEU-301; THR-328; ALA-378 AND VAL-706.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase that phosphorylates histone
CC H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both
CC position and modulate activation of AURKB and other components of the
CC chromosomal passenger complex (CPC) at centromeres to ensure proper
CC chromatid cohesion, metaphase alignment and normal progression through
CC the cell cycle. {ECO:0000269|PubMed:11228240,
CC ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365,
CC ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:19918049, ECO:0000269|PubMed:19918057};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19918049,
CC ECO:0000269|PubMed:19918057};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:19918057};
CC -!- ACTIVITY REGULATION: Constitutive activity that does not require
CC phosphorylation. Specifically inhibited by 3-(1H-indazol-5-yl)-N-
CC propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494).
CC {ECO:0000269|PubMed:19918057, ECO:0000269|PubMed:21658950,
CC ECO:0000269|PubMed:21804608}.
CC -!- INTERACTION:
CC Q8TF76; O75031: HSF2BP; NbExp=3; IntAct=EBI-1237328, EBI-7116203;
CC Q8TF76; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1237328, EBI-352572;
CC Q8TF76; Q99750: MDFI; NbExp=3; IntAct=EBI-1237328, EBI-724076;
CC Q8TF76-1; P84228: H3c7; Xeno; NbExp=3; IntAct=EBI-15815652, EBI-2658213;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15681610}. Chromosome
CC {ECO:0000269|PubMed:15681610}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:15681610}. Note=Nuclear during interphase and
CC associates with the chromosomes and spindle apparatus during mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:11311556};
CC IsoId=Q8TF76-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:14702039};
CC IsoId=Q8TF76-2; Sequence=VSP_050671, VSP_050672;
CC -!- TISSUE SPECIFICITY: Strongly expressed in testis. Also present in
CC thymus and bone marrow and low levels observed in prostate, intestine,
CC lung, spleen and lymph node. Expressed in fetal skin, liver, kidney and
CC small intestine and also in proliferating but not non-proliferating
CC cell lines. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:11311556}.
CC -!- PTM: Autophosphorylated on both serine and threonine residues (By
CC similarity). Strongly phosphorylated during mitosis but this does not
CC appear to significantly affect its intrinsic kinase activity.
CC Phosphorylation by AURKB is required for full activity toward histone
CC H3 at 'Ser-3' in mitosis. {ECO:0000250, ECO:0000269|PubMed:15681610,
CC ECO:0000269|PubMed:21658950}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. Haspin subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AB039834; BAB21938.3; -; mRNA.
DR EMBL; AF289865; AAK30300.1; -; mRNA.
DR EMBL; AK056691; BAB71255.1; -; mRNA.
DR EMBL; AC116914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047457; AAH47457.1; -; mRNA.
DR CCDS; CCDS11036.1; -. [Q8TF76-1]
DR RefSeq; NP_114171.2; NM_031965.2. [Q8TF76-1]
DR PDB; 2VUW; X-ray; 1.80 A; A=465-798.
DR PDB; 2WB8; X-ray; 2.15 A; A=452-798.
DR PDB; 3DLZ; X-ray; 1.85 A; A=465-798.
DR PDB; 3E7V; X-ray; 2.00 A; A=471-798.
DR PDB; 3F2N; X-ray; 1.80 A; A=465-798.
DR PDB; 3FMD; X-ray; 2.00 A; A=470-798.
DR PDB; 3IQ7; X-ray; 2.00 A; A=465-798.
DR PDB; 4OUC; X-ray; 1.90 A; A=465-798.
DR PDB; 4QTC; X-ray; 1.40 A; A=465-798.
DR PDB; 5HTB; X-ray; 1.70 A; A=465-798.
DR PDB; 5HTC; X-ray; 1.50 A; A=465-798.
DR PDB; 6G34; X-ray; 1.76 A; A=465-798.
DR PDB; 6G35; X-ray; 1.55 A; A=465-798.
DR PDB; 6G36; X-ray; 1.46 A; A=465-798.
DR PDB; 6G37; X-ray; 1.48 A; A=465-798.
DR PDB; 6G38; X-ray; 1.47 A; A=465-798.
DR PDB; 6G39; X-ray; 1.45 A; A=465-798.
DR PDB; 6G3A; X-ray; 1.43 A; A=465-798.
DR PDB; 6Z56; X-ray; 1.90 A; A=465-798.
DR PDB; 6Z57; X-ray; 1.50 A; A=465-798.
DR PDB; 6Z58; X-ray; 1.80 A; A=465-798.
DR PDB; 6Z59; X-ray; 2.00 A; A=465-798.
DR PDB; 6Z5A; X-ray; 1.55 A; A=465-798.
DR PDB; 6Z5B; X-ray; 1.90 A; A=465-798.
DR PDB; 6Z5C; X-ray; 1.75 A; A=465-798.
DR PDB; 6Z5D; X-ray; 1.75 A; A=465-798.
DR PDB; 6Z5E; X-ray; 1.50 A; A=465-798.
DR PDB; 7AVQ; X-ray; 1.65 A; A=465-798.
DR PDB; 7OPS; X-ray; 2.38 A; A=465-798.
DR PDB; 7SQM; X-ray; 1.78 A; A=445-798.
DR PDBsum; 2VUW; -.
DR PDBsum; 2WB8; -.
DR PDBsum; 3DLZ; -.
DR PDBsum; 3E7V; -.
DR PDBsum; 3F2N; -.
DR PDBsum; 3FMD; -.
DR PDBsum; 3IQ7; -.
DR PDBsum; 4OUC; -.
DR PDBsum; 4QTC; -.
DR PDBsum; 5HTB; -.
DR PDBsum; 5HTC; -.
DR PDBsum; 6G34; -.
DR PDBsum; 6G35; -.
DR PDBsum; 6G36; -.
DR PDBsum; 6G37; -.
DR PDBsum; 6G38; -.
DR PDBsum; 6G39; -.
DR PDBsum; 6G3A; -.
DR PDBsum; 6Z56; -.
DR PDBsum; 6Z57; -.
DR PDBsum; 6Z58; -.
DR PDBsum; 6Z59; -.
DR PDBsum; 6Z5A; -.
DR PDBsum; 6Z5B; -.
DR PDBsum; 6Z5C; -.
DR PDBsum; 6Z5D; -.
DR PDBsum; 6Z5E; -.
DR PDBsum; 7AVQ; -.
DR PDBsum; 7OPS; -.
DR PDBsum; 7SQM; -.
DR AlphaFoldDB; Q8TF76; -.
DR SMR; Q8TF76; -.
DR BioGRID; 123814; 61.
DR DIP; DIP-38174N; -.
DR IntAct; Q8TF76; 97.
DR MINT; Q8TF76; -.
DR STRING; 9606.ENSP00000325290; -.
DR BindingDB; Q8TF76; -.
DR ChEMBL; CHEMBL1075163; -.
DR DrugBank; DB08004; (2S)-2-{[3-(3-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}-3-methylbutan-1-ol.
DR DrugBank; DB07698; 3-(3-aminophenyl)-N-(3-chlorophenyl)pyrazolo[1,5-a]pyrimidin-5-amine.
DR DrugBank; DB04604; 5-iodotubercidin.
DR DrugBank; DB07995; H-89.
DR GuidetoPHARMACOLOGY; 2028; -.
DR GlyGen; Q8TF76; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TF76; -.
DR PhosphoSitePlus; Q8TF76; -.
DR BioMuta; HASPIN; -.
DR DMDM; 296439330; -.
DR EPD; Q8TF76; -.
DR jPOST; Q8TF76; -.
DR MassIVE; Q8TF76; -.
DR MaxQB; Q8TF76; -.
DR PaxDb; Q8TF76; -.
DR PeptideAtlas; Q8TF76; -.
DR PRIDE; Q8TF76; -.
DR ProteomicsDB; 74576; -. [Q8TF76-1]
DR ProteomicsDB; 74577; -. [Q8TF76-2]
DR Antibodypedia; 23135; 155 antibodies from 24 providers.
DR DNASU; 83903; -.
DR Ensembl; ENST00000325418.5; ENSP00000325290.4; ENSG00000177602.5. [Q8TF76-1]
DR GeneID; 83903; -.
DR KEGG; hsa:83903; -.
DR MANE-Select; ENST00000325418.5; ENSP00000325290.4; NM_031965.2; NP_114171.2.
DR UCSC; uc002fwp.4; human. [Q8TF76-1]
DR CTD; 83903; -.
DR DisGeNET; 83903; -.
DR GeneCards; HASPIN; -.
DR HGNC; HGNC:19682; HASPIN.
DR HPA; ENSG00000177602; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MIM; 609240; gene.
DR neXtProt; NX_Q8TF76; -.
DR OpenTargets; ENSG00000177602; -.
DR PharmGKB; PA134909705; -.
DR VEuPathDB; HostDB:ENSG00000177602; -.
DR eggNOG; KOG2464; Eukaryota.
DR GeneTree; ENSGT00390000013015; -.
DR HOGENOM; CLU_355235_0_0_1; -.
DR InParanoid; Q8TF76; -.
DR OMA; LCQHSLF; -.
DR PhylomeDB; Q8TF76; -.
DR TreeFam; TF313895; -.
DR PathwayCommons; Q8TF76; -.
DR SignaLink; Q8TF76; -.
DR SIGNOR; Q8TF76; -.
DR BioGRID-ORCS; 83903; 74 hits in 1117 CRISPR screens.
DR EvolutionaryTrace; Q8TF76; -.
DR GeneWiki; GSG2; -.
DR GenomeRNAi; 83903; -.
DR Pharos; Q8TF76; Tchem.
DR PRO; PR:Q8TF76; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TF76; protein.
DR Bgee; ENSG00000177602; Expressed in pancreatic ductal cell and 102 other tissues.
DR Genevisible; Q8TF76; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0072354; F:histone kinase activity (H3-T3 specific); IMP:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IMP:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0071459; P:protein localization to chromosome, centromeric region; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR IDEAL; IID00574; -.
DR InterPro; IPR024604; GSG2_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR SMART; SM01331; DUF3635; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle;
KW Chromatin regulator; Chromosome; Cytoplasm; Cytoskeleton; Kinase;
KW Magnesium; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..798
FT /note="Serine/threonine-protein kinase haspin"
FT /id="PRO_0000085989"
FT DOMAIN 484..798
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT REGION 1..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..350
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 649
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 490..498
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 511
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 606..611
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19918057,
FT ECO:0007744|PDB:3DLZ"
FT BINDING 649..654
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19918057,
FT ECO:0007744|PDB:3DLZ"
FT BINDING 687..689
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19918057"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 93
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000269|PubMed:21658950,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 97
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 143
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000269|PubMed:21658950"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 314
FT /note="Q -> H (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_050671"
FT VAR_SEQ 315..798
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_050672"
FT VARIANT 76
FT /note="V -> E (in dbSNP:rs11653889)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040540"
FT VARIANT 82
FT /note="R -> C (in dbSNP:rs9907144)"
FT /evidence="ECO:0000269|PubMed:11311556,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_040541"
FT VARIANT 145
FT /note="R -> H (in dbSNP:rs55991903)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040542"
FT VARIANT 204
FT /note="G -> D (in dbSNP:rs220462)"
FT /evidence="ECO:0000269|PubMed:11311556,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846"
FT /id="VAR_027405"
FT VARIANT 283
FT /note="G -> S (in dbSNP:rs56224301)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040543"
FT VARIANT 301
FT /note="Q -> L (in dbSNP:rs55649477)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040544"
FT VARIANT 328
FT /note="I -> T (in dbSNP:rs220461)"
FT /evidence="ECO:0000269|PubMed:11311556,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846"
FT /id="VAR_027406"
FT VARIANT 378
FT /note="V -> A (in dbSNP:rs3809806)"
FT /evidence="ECO:0000269|PubMed:11311556,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846"
FT /id="VAR_027407"
FT VARIANT 422
FT /note="N -> D (in dbSNP:rs7223226)"
FT /id="VAR_027408"
FT VARIANT 706
FT /note="M -> V (in dbSNP:rs56134695)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040545"
FT MUTAGEN 492
FT /note="E->A: Markedly reduced affinity for histone H3 and
FT reduced histone H3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19918049"
FT MUTAGEN 511
FT /note="K->A: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:19918057"
FT MUTAGEN 651
FT /note="H->A: Strongly reduced enzyme activity, markedly
FT reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:19918049,
FT ECO:0000269|PubMed:19918057"
FT MUTAGEN 707
FT /note="D->L: Markedly reduced affinity for histone H3 and
FT reduced histone H3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19918049"
FT MUTAGEN 709
FT /note="D->N: Markedly reduced affinity for histone H3 and
FT reduced histone H3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19918049"
FT MUTAGEN 713
FT /note="G->F: Markedly reduced affinity for histone H3 and
FT reduced histone H3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19918049"
FT MUTAGEN 716
FT /note="D->L: Markedly reduced histone H3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19918049"
FT CONFLICT 273
FT /note="R -> S (in Ref. 4; BAB71255)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="K -> E (in Ref. 6; AAH47457)"
FT /evidence="ECO:0000305"
FT HELIX 454..466
FT /evidence="ECO:0007829|PDB:7SQM"
FT HELIX 475..478
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 481..485
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 488..493
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 496..503
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 506..516
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 529..544
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 545..547
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 549..552
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 554..556
FT /evidence="ECO:0007829|PDB:3F2N"
FT STRAND 559..568
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 571..583
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 599..606
FT /evidence="ECO:0007829|PDB:4QTC"
FT TURN 612..618
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 622..643
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 655..659
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 663..669
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 672..677
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 681..685
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 692..695
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 709..711
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 717..729
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 739..754
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 758..760
FT /evidence="ECO:0007829|PDB:7SQM"
FT HELIX 765..780
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:4QTC"
FT STRAND 784..786
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 787..793
FT /evidence="ECO:0007829|PDB:4QTC"
FT HELIX 795..797
FT /evidence="ECO:0007829|PDB:4QTC"
SQ SEQUENCE 798 AA; 88495 MW; E0EDF8F0C58ADA31 CRC64;
MAASLPGPGS RLFRTYGAAD GRRQRRPGRE AAQWFPPQDR RRFFNSSGSS DASIGDPSQS
DDPDDPDDPD FPGSPVRRRR RRPGGRVPKD RPSLTVTPKR WKLRARPSLT VTPRRLGLRA
RPPQKCSTPC GPLRLPPFPS RDSGRLSPDL SVCGQPRDGD ELGISASLFS SLASPCPGSP
TPRDSVISIG TSACLVAASA VPSGLHLPEV SLDRASLPCS QEEATGGAKD TRMVHQTRAS
LRSVLFGLMN SGTPEDSEFR ADGKNMRESC CKRKLVVGNG PEGPGLSSTG KRRATGQDSC
QERGLQEAVR REHQEASVPK GRIVPRGIDR LERTRSSRKS KHQEATETSL LHSHRFKKGQ
KLGKDSFPTQ DLTPLQNVCF WTKTRASFSF HKKKIVTDVS EVCSIYTTAT SLSGSLLSEC
SNRPVMNRTS GAPSSWHSSS MYLLSPLNTL SISNKKASDA EKVYGECSQK GPVPFSHCLP
TEKLQRCEKI GEGVFGEVFQ TIADHTPVAI KIIAIEGPDL VNGSHQKTFE EILPEIIISK
ELSLLSGEVC NRTEGFIGLN SVHCVQGSYP PLLLKAWDHY NSTKGSANDR PDFFKDDQLF
IVLEFEFGGI DLEQMRTKLS SLATAKSILH QLTASLAVAE ASLRFEHRDL HWGNVLLKKT
SLKKLHYTLN GKSSTIPSCG LQVSIIDYTL SRLERDGIVV FCDVSMDEDL FTGDGDYQFD
IYRLMKKENN NRWGEYHPYS NVLWLHYLTD KMLKQMTFKT KCNTPAMKQI KRKIQEFHRT
MLNFSSATDL LCQHSLFK
