HASP_DROME
ID HASP_DROME Reviewed; 566 AA.
AC P83103; Q7PLN2;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Serine/threonine-protein kinase haspin homolog {ECO:0000303|PubMed:32750047};
DE EC=2.7.11.1 {ECO:0000305|PubMed:32750047};
GN Name=Haspin {ECO:0000303|PubMed:32750047, ECO:0000312|FlyBase:FBgn0046706};
GN ORFNames=CG40080 {ECO:0000312|FlyBase:FBgn0046706};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, INTERACTION WITH PDS5 AND VTD, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF LYS-282.
RX PubMed=32750047; DOI=10.1371/journal.pgen.1008962;
RA Fresan U., Rodriguez-Sanchez M.A., Reina O., Corces V.G., Espinas M.L.;
RT "Haspin kinase modulates nuclear architecture and Polycomb-dependent gene
RT silencing.";
RL PLoS Genet. 16:e1008962-e1008962(2020).
CC -!- FUNCTION: Serine/threonine-protein kinase that phosphorylates histone
CC H3 at 'Thr-4' (H3T3ph) during mitosis and interphase (PubMed:32750047).
CC Function is essential for chromosome organization during mitosis and
CC genome organization in interphase cells, thus playing a functional role
CC in gene regulation (PubMed:32750047). During mitosis, may act through
CC H3T3ph to both position and modulate activation of AURKB and other
CC components of the chromosomal passenger complex (CPC) at centromeres to
CC ensure proper chromatid cohesion, metaphase alignment and normal
CC progression through the cell cycle (By similarity). During interphase,
CC associates with the cohesion complex and mediates pds5 binding to
CC chromatin to ensure correct sister chromatid cohesion, chromatin
CC organization, and also functions with Pds5-cohesin to modify Polycomb-
CC dependent homeotic transformations (PubMed:32750047). Function during
CC interphase is required for insulator activity, nuclear compaction,
CC heterochromatin-induced position-effect variegation and PcG-mediated
CC pairing-sensitive silencing (PubMed:32750047).
CC {ECO:0000250|UniProtKB:Q8TF76, ECO:0000269|PubMed:32750047}.
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:0000305|PubMed:32750047};
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:0000305|PubMed:32750047};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8TF76};
CC -!- SUBUNIT: Interacts with pds5 and vtd. {ECO:0000269|PubMed:32750047}.
CC -!- SUBCELLULAR LOCATION: Nucleus lamina {ECO:0000269|PubMed:32750047}.
CC Chromosome {ECO:0000269|PubMed:32750047}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000250|UniProtKB:Q8TF76}.
CC -!- DISRUPTION PHENOTYPE: Viable, however adults display a decrease in
CC survival which is stronger in females than males, and both sexes
CC display a decrease in fertility (PubMed:32750047). Loss of
CC phosphorylation of histone H3 leading to reduced centromeric cohesion
CC (PubMed:32750047). RNAi-mediated knockdown reduces the size of salivary
CC gland nuclei (PubMed:32750047). Also results in a strong decrease in
CC chromosome-bound pds5 in larval salivary glands and a significant
CC decrease in chromatin-bound vtd in mitotic and interphase embryo cells
CC (PubMed:32750047). {ECO:0000269|PubMed:32750047}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. Haspin subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE013599; EAA46104.2; -; Genomic_DNA.
DR EMBL; AY118897; AAM50757.1; -; mRNA.
DR RefSeq; NP_001015349.2; NM_001015349.4.
DR AlphaFoldDB; P83103; -.
DR SMR; P83103; -.
DR BioGRID; 78189; 2.
DR STRING; 7227.FBpp0112507; -.
DR PaxDb; P83103; -.
DR DNASU; 3355064; -.
DR EnsemblMetazoa; FBtr0113784; FBpp0112507; FBgn0046706.
DR GeneID; 3355064; -.
DR KEGG; dme:Dmel_CG40080; -.
DR UCSC; CG40080-RA; d. melanogaster.
DR CTD; 83903; -.
DR FlyBase; FBgn0046706; Haspin.
DR VEuPathDB; VectorBase:FBgn0046706; -.
DR eggNOG; KOG2464; Eukaryota.
DR GeneTree; ENSGT00940000167518; -.
DR HOGENOM; CLU_019002_2_0_1; -.
DR InParanoid; P83103; -.
DR OMA; CHYNDLS; -.
DR OrthoDB; 1374355at2759; -.
DR PhylomeDB; P83103; -.
DR BioGRID-ORCS; 3355064; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 3355064; -.
DR PRO; PR:P83103; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0046706; Expressed in cleaving embryo and 23 other tissues.
DR Genevisible; P83103; DM.
DR GO; GO:0000785; C:chromatin; IMP:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005652; C:nuclear lamina; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0072354; F:histone kinase activity (H3-T3 specific); IMP:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:2000720; P:positive regulation of maintenance of mitotic sister chromatid cohesion, centromeric; IMP:UniProtKB.
DR GO; GO:0034093; P:positive regulation of maintenance of sister chromatid cohesion; IMP:UniProtKB.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
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 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 ATP-binding; Chromosome; Cytoplasm; Cytoskeleton; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..566
FT /note="Serine/threonine-protein kinase haspin homolog"
FT /id="PRO_0000085991"
FT DOMAIN 248..566
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 418
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 254..262
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 377..382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8TF76"
FT BINDING 418..423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8TF76"
FT BINDING 456..458
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8TF76"
FT MUTAGEN 282
FT /note="K->M: Loss of catalytic activity. Reduced nuclear
FT size in larval salivary glands."
FT /evidence="ECO:0000269|PubMed:32750047"
SQ SEQUENCE 566 AA; 65323 MW; 46363EAAFAF66967 CRC64;
MLSISKTKMD FLEEGRWKDP FDELLDSRTK LSKMNIVKQN VRVTYNIDSS VENSSYIEIK
EPNHKNEPLT LEDCSIKVYC PSDSISTPCD KRLGGTTGLF ETDLSPITRL KLEGVEDSRD
KCADTNEADL YVNVEILFQN INSSPKKCSN FGKKRLSNLN KMVTAVHPSI SLNPGKWRKS
LNNFIRSKIT ETNFTKKVER RSSICQDRKS LVLKGEHKFE NKYEEDVLKY CHQCTPLPFN
TAYEQHKLLN TKKIGEGAYG EVFRCSRNQE VLKDHISDIV LKIIPLEGST VINGEKQKTF
SQILPEIIIT KKMCSLRTSK TNSTNGFVSI QKVSLVKGRY PPHFIKLWEK YDNEKGSEND
HPELFGDNQL FAVLELKFAG SDMANFKFLN SEQSYYALQQ IILALAVGEE EYQFEHRDLH
LGNILIEYTN KKHIVCTFKS SNLTLLSKGV NVTIIDYTLS RVTINDCCYF NDLSRDEELF
QATGDYQYDV YRMMRNELKN NWSSFSPKTN IIWLSYVIVK VLDSVKYKSI NTKVHRMYID
KIKELKNIIM TFESASHCAN YLFNLN
