HSK1_SCHPO
ID HSK1_SCHPO Reviewed; 507 AA.
AC P50582; O94678;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Cell cycle serine/threonine-protein kinase hsk1;
DE EC=2.7.11.1;
DE AltName: Full=Cdc7-related kinase;
DE AltName: Full=Minichromosome maintenance protein kinase;
GN Name=hsk1; ORFNames=SPBC776.12c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=JY2;
RX PubMed=7621824; DOI=10.1002/j.1460-2075.1995.tb07312.x;
RA Masai H., Miyake T., Arai K.;
RT "hsk1+, a Schizosaccharomyces pombe gene related to Saccharomyces
RT cerevisiae CDC7, is required for chromosomal replication.";
RL EMBO J. 14:3094-3104(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION, KINASE ACTIVITY, SUBUNIT, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP LYS-129; ASP-216 AND THR-291.
RX PubMed=9705352; DOI=10.1074/jbc.273.34.22083;
RA Brown G.W., Kelly T.J.;
RT "Purification of Hsk1, a minichromosome maintenance protein kinase from
RT fission yeast.";
RL J. Biol. Chem. 273:22083-22090(1998).
RN [4]
RP ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=10411894; DOI=10.1073/pnas.96.15.8443;
RA Brown G.W., Kelly T.J.;
RT "Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:8443-8448(1999).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION BY
RP CDS1, AND MUTAGENESIS OF SER-314.
RX PubMed=11027263; DOI=10.1128/mcb.20.21.7922-7932.2000;
RA Snaith H.A., Brown G.W., Forsburg S.L.;
RT "Schizosaccharomyces pombe Hsk1p is a potential cds1p target required for
RT genome integrity.";
RL Mol. Cell. Biol. 20:7922-7932(2000).
RN [6]
RP FUNCTION, KINASE ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF ASP-337;
RP GLU-403 AND LEU-416.
RX PubMed=11359920; DOI=10.1091/mbc.12.5.1257;
RA Takeda T., Ogino K., Tatebayashi K., Ikeda H., Arai K., Masai H.;
RT "Regulation of initiation of S phase, replication checkpoint signaling, and
RT maintenance of mitotic chromosome structures during S phase by Hsk1 kinase
RT in the fission yeast.";
RL Mol. Biol. Cell 12:1257-1274(2001).
RN [7]
RP INTERACTION WITH MCM10.
RX PubMed=12604790; DOI=10.1073/pnas.0237384100;
RA Lee J.-K., Seo Y.-S., Hurwitz J.;
RT "The Cdc23 (Mcm10) protein is required for the phosphorylation of
RT minichromosome maintenance complex by the Dfp1-Hsk1 kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2334-2339(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-493, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
CC -!- FUNCTION: Required for G1/S transition. Plays a role in DNA replication
CC checkpoint signaling through regulating rad3 and cds1. Involved in the
CC maintenance of mitotic chromosome structures during S phase through
CC regulating the function of rad21. Required for initiation of mitotic
CC DNA replication through phosphorylating mcm2/cdc19. Required for genome
CC integrity. {ECO:0000269|PubMed:11027263, ECO:0000269|PubMed:11359920,
CC ECO:0000269|PubMed:9705352}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Phosphorylation of exogenous substrates activated
CC by Dfp1. {ECO:0000269|PubMed:10411894}.
CC -!- SUBUNIT: Heterodimer with the regulatory subunit him1/dfp1. May form
CC homooligomeric complexes. Interacts with mcm10.
CC {ECO:0000269|PubMed:10411894, ECO:0000269|PubMed:12604790,
CC ECO:0000269|PubMed:9705352}.
CC -!- INTERACTION:
CC P50582; O42709: mcm10; NbExp=3; IntAct=EBI-908476, EBI-1387246;
CC P50582; P40377: mcm2; NbExp=2; IntAct=EBI-908476, EBI-783248;
CC P50582; P40381: swi6; NbExp=2; IntAct=EBI-908476, EBI-926939;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11027263}.
CC Note=Nuclear throughout the cell cycle.
CC -!- PTM: Autophosphorylated. Phosphorylated by cds1 in vitro.
CC {ECO:0000269|PubMed:11027263, ECO:0000269|PubMed:18257517}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDC7 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; D50493; BAA09087.1; -; Genomic_DNA.
DR EMBL; CU329671; CAA22885.1; -; Genomic_DNA.
DR PIR; S56143; S56143.
DR PIR; T40683; T40683.
DR RefSeq; NP_596328.1; NM_001022249.2.
DR AlphaFoldDB; P50582; -.
DR SMR; P50582; -.
DR BioGRID; 277680; 42.
DR IntAct; P50582; 6.
DR STRING; 4896.SPBC776.12c.1; -.
DR iPTMnet; P50582; -.
DR MaxQB; P50582; -.
DR PaxDb; P50582; -.
DR PRIDE; P50582; -.
DR EnsemblFungi; SPBC776.12c.1; SPBC776.12c.1:pep; SPBC776.12c.
DR GeneID; 2541165; -.
DR KEGG; spo:SPBC776.12c; -.
DR PomBase; SPBC776.12c; hsk1.
DR VEuPathDB; FungiDB:SPBC776.12c; -.
DR eggNOG; KOG1167; Eukaryota.
DR HOGENOM; CLU_000288_118_2_1; -.
DR InParanoid; P50582; -.
DR OMA; IQYRTFM; -.
DR PhylomeDB; P50582; -.
DR BRENDA; 2.7.11.1; 5613.
DR Reactome; R-SPO-176187; Activation of ATR in response to replication stress.
DR Reactome; R-SPO-68962; Activation of the pre-replicative complex.
DR PRO; PR:P50582; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031431; C:Dbf4-dependent protein kinase complex; IDA:PomBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:PomBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IMP:PomBase.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IMP:PomBase.
DR GO; GO:0043392; P:negative regulation of DNA binding; IMP:PomBase.
DR GO; GO:0010620; P:negative regulation of transcription by transcription factor catabolism; IMP:PomBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1903468; P:positive regulation of DNA replication initiation; IMP:PomBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0048478; P:replication fork protection; IGI:PomBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell division; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..507
FT /note="Cell cycle serine/threonine-protein kinase hsk1"
FT /id="PRO_0000086003"
FT DOMAIN 68..433
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 475..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 475..498
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 216
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 74..82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 129
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 291
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MUTAGEN 129
FT /note="K->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:9705352"
FT MUTAGEN 216
FT /note="D->N: Reduced activity."
FT /evidence="ECO:0000269|PubMed:9705352"
FT MUTAGEN 291
FT /note="T->A,E: Inactive."
FT /evidence="ECO:0000269|PubMed:9705352"
FT MUTAGEN 314
FT /note="S->I: Temperature-sensitive phenotype. Defects in
FT DNA replication and checkpoint responses."
FT /evidence="ECO:0000269|PubMed:11027263"
FT MUTAGEN 337
FT /note="D->P: Reduced activity; when associated with K-403
FT and P-416."
FT /evidence="ECO:0000269|PubMed:11359920"
FT MUTAGEN 403
FT /note="E->K: Reduced activity; when associated With P-337
FT and P-416."
FT /evidence="ECO:0000269|PubMed:11359920"
FT MUTAGEN 416
FT /note="L->P: Reduced activity; when associated With P-337
FT and K-403."
FT /evidence="ECO:0000269|PubMed:11359920"
SQ SEQUENCE 507 AA; 58408 MW; 04970E58218441EE CRC64;
MAEAHITLSP KVTHEQQTDI DSECEITEVD DENVNENKSQ EMIQDIPARD REEIENITRT
FVELQENYRL IEKIGEGTFS SVYKAEDLHY GRYINDWDIQ SEVLKESSFG KEKIPVNEDS
RKPKYVAIKK IYATSSPARI YNELEILYLL RGSSVIAPLI TALRNEDQVL VVLPYYEHTD
FRQYYSTFSY RDMSIYFRCL FQAMQQTQTL GIIHRDIKPS NFLFDVRTKH GVLVDFGLAE
RYDGRQQSHS CRCTNSNAAE LAHDFSIAQE TSLGYIKNDT RPSKRANRAG TRGFRAPEVL
FKCSSQSPKV DIWSAGVILL SFLTKRFPMF NSKDDVDALM EIACIFGKSE MRQCAALHGC
TFETNVSTLT EKRVNFRKLI LWASCGSASI YKEKLRHKPS QEERLCLDFL EKCLELDCNK
RISAEEALDH DFLYLDNLAY EKKDDDTAFD NSFGETSFEK DEDLTAKHLS HILDFKEQEE
TDEPTSLSKR KRSIDEILPN DALQDGA
