HIPK_CAEEL
ID HIPK_CAEEL Reviewed; 846 AA.
AC Q8MQ70; Q19632; Q8MQ69;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Homeodomain-interacting protein kinase 1 {ECO:0000305|PubMed:23904186};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q86Z02};
GN Name=hpk-1 {ECO:0000312|WormBase:F20B6.8b};
GN ORFNames=F20B6.8 {ECO:0000312|WormBase:F20B6.8b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12618396; DOI=10.1093/genetics/163.2.571;
RA Raich W.B., Moorman C., Lacefield C.O., Lehrer J., Bartsch D.,
RA Plasterk R.H., Kandel E.R., Hobert O.;
RT "Characterization of Caenorhabditis elegans homologs of the Down syndrome
RT candidate gene DYRK1A.";
RL Genetics 163:571-580(2003).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=23904186; DOI=10.1002/dvdy.24023;
RA Berber S., Llamosas E., Thaivalappil P., Boag P.R., Crossley M.,
RA Nicholas H.R.;
RT "Homeodomain interacting protein kinase (HPK-1) is required in the soma for
RT robust germline proliferation in C. elegans.";
RL Dev. Dyn. 242:1250-1261(2013).
RN [4]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26791749; DOI=10.1038/srep19582;
RA Berber S., Wood M., Llamosas E., Thaivalappil P., Lee K., Liao B.M.,
RA Chew Y.L., Rhodes A., Yucel D., Crossley M., Nicholas H.R.;
RT "Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses
RT and ageing in C. elegans.";
RL Sci. Rep. 6:19582-19582(2016).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=29036198; DOI=10.1371/journal.pgen.1007038;
RA Das R., Melo J.A., Thondamal M., Morton E.A., Cornwell A.B., Crick B.,
RA Kim J.H., Swartz E.W., Lamitina T., Douglas P.M., Samuelson A.V.;
RT "The homeodomain-interacting protein kinase HPK-1 preserves protein
RT homeostasis and longevity through master regulatory control of the HSF-1
RT chaperone network and TORC1-restricted autophagy in Caenorhabditis
RT elegans.";
RL PLoS Genet. 13:E1007038-E1007038(2017).
CC -!- FUNCTION: Serine/threonine-protein kinase required in the somatic
CC gonadal cells to regulate germline proliferation during larval
CC development and in adulthood (PubMed:23904186). Plays a role in the
CC development/differentiation of gonadal distal tip cells
CC (PubMed:23904186). Required for normal lifespan in a pha-4 and mxl-2-
CC dependent manner (PubMed:26791749, PubMed:29036198). Also contributes
CC to survival following heat or oxidative stress (PubMed:26791749).
CC Prevents sumoylation and inactivation of heat shock transcription
CC factor hsf-1 which enhances hsf-1-dependent transcriptional induction
CC of chaperones in response to heat shock (PubMed:29036198). Also
CC required for hormetic extension of longevity in response to heat stress
CC (PubMed:29036198). Provides protection against polyglutamine aggregate
CC formation and associated locomotory toxicity (PubMed:29036198). Also
CC contributes to longevity by promoting autophagy under nutrient stress
CC conditions through induction of autophagosome formation and autophagy
CC gene expression (PubMed:29036198). {ECO:0000269|PubMed:23904186,
CC ECO:0000269|PubMed:26791749, ECO:0000269|PubMed:29036198}.
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:0000250|UniProtKB:Q86Z02};
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:0000250|UniProtKB:Q86Z02};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12618396,
CC ECO:0000269|PubMed:23904186, ECO:0000269|PubMed:29036198}.
CC Note=Localizes to nuclear moving puncta. Puncta number and intensity
CC decrease in the adult (PubMed:12618396). In some large cells, a nuclear
CC speckle pattern can be detected (PubMed:23904186).
CC {ECO:0000269|PubMed:12618396, ECO:0000269|PubMed:23904186}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:F20B6.8b};
CC IsoId=Q8MQ70-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F20B6.8a};
CC IsoId=Q8MQ70-2; Sequence=VSP_057642;
CC Name=c {ECO:0000312|WormBase:F20B6.8c};
CC IsoId=Q8MQ70-3; Sequence=VSP_057641;
CC -!- TISSUE SPECIFICITY: Broadly expressed during embryogenesis
CC (PubMed:12618396, PubMed:29036198). Expression becomes more restricted
CC during larval development (PubMed:29036198). L3 larvae display robust
CC expression in many head and motor neurons, and lower levels of
CC expression in the intestine and the seam cells of the hypodermis
CC (PubMed:29036198). By late L4 stage, expression is largely restricted
CC to neurons and is maintained in nerve cells of the head and nerve cord
CC during adulthood (PubMed:29036198). Expressed in adult pharyngeal
CC cells, hypodermal cells, gonadal sheath cells and distal tip cells but
CC not in germline cells (PubMed:23904186). {ECO:0000269|PubMed:12618396,
CC ECO:0000269|PubMed:23904186, ECO:0000269|PubMed:29036198}.
CC -!- INDUCTION: Induced by heat stress (PubMed:23904186, PubMed:26791749,
CC PubMed:29036198). Transcription from the hpk-1 promoter is not altered
CC by heat shock treatment, suggesting that heat shock affects hpk-1
CC levels through a post-transcriptional mechanism (PubMed:26791749).
CC Induction is greatest in hypodermal seam cells and neurons with much
CC lower levels of induction in intestinal cells (PubMed:29036198).
CC {ECO:0000269|PubMed:23904186, ECO:0000269|PubMed:26791749,
CC ECO:0000269|PubMed:29036198}.
CC -!- DISRUPTION PHENOTYPE: Enhanced sensitivity to heat and oxidative stress
CC with reduced survival under both conditions (PubMed:26791749,
CC PubMed:29036198). Following exposure to gamma irradiation, no effect on
CC DNA damage response in the germline but significantly reduced embryonic
CC survival (PubMed:26791749). Significantly reduced lifespan with a more
CC rapid decline in body movement and pharyngeal pumping, indicative of
CC accelerated aging (PubMed:26791749, PubMed:29036198). Premature
CC accumulation of polyglutamine aggregates and increased polyglutamine-
CC associated paralysis at day 8 of adulthood (PubMed:29036198). RNAi-
CC mediated knockdown results in small and underdeveloped germlines with a
CC reduction in the number of cells in G2/M stages (PubMed:23904186).
CC RNAi-mediated knockdown from the L1 larval stage onwards results in
CC shortened lifespan while RNAi-mediated knockdown initiated at the L4
CC larval stage decreases lifespan to a smaller but significant extent
CC (PubMed:29036198). RNAi-mediated knockdown in the intestine, hypodermis
CC or neurons reduces lifespan while RNAi-mediated knockdown in muscle
CC cells does not (PubMed:29036198). {ECO:0000269|PubMed:23904186,
CC ECO:0000269|PubMed:26791749, ECO:0000269|PubMed:29036198}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. HIPK subfamily. {ECO:0000305}.
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DR EMBL; FO081186; CCD69762.1; -; Genomic_DNA.
DR EMBL; FO081186; CCD69761.1; -; Genomic_DNA.
DR EMBL; FO081186; CCD69763.1; -; Genomic_DNA.
DR PIR; T34232; T34232.
DR RefSeq; NP_741761.1; NM_171662.5. [Q8MQ70-1]
DR RefSeq; NP_741762.1; NM_171663.1. [Q8MQ70-2]
DR RefSeq; NP_741763.1; NM_171664.5. [Q8MQ70-3]
DR AlphaFoldDB; Q8MQ70; -.
DR SMR; Q8MQ70; -.
DR IntAct; Q8MQ70; 1.
DR STRING; 6239.F20B6.8b; -.
DR EPD; Q8MQ70; -.
DR PaxDb; Q8MQ70; -.
DR PeptideAtlas; Q8MQ70; -.
DR PRIDE; Q8MQ70; -.
DR EnsemblMetazoa; F20B6.8a.1; F20B6.8a.1; WBGene00001994. [Q8MQ70-2]
DR EnsemblMetazoa; F20B6.8b.1; F20B6.8b.1; WBGene00001994. [Q8MQ70-1]
DR EnsemblMetazoa; F20B6.8c.1; F20B6.8c.1; WBGene00001994. [Q8MQ70-3]
DR EnsemblMetazoa; F20B6.8c.2; F20B6.8c.2; WBGene00001994. [Q8MQ70-3]
DR EnsemblMetazoa; F20B6.8c.3; F20B6.8c.3; WBGene00001994. [Q8MQ70-3]
DR GeneID; 180695; -.
DR KEGG; cel:CELE_F20B6.8; -.
DR UCSC; F20B6.8c.5; c. elegans.
DR CTD; 180695; -.
DR WormBase; F20B6.8a; CE04430; WBGene00001994; hpk-1. [Q8MQ70-2]
DR WormBase; F20B6.8b; CE30961; WBGene00001994; hpk-1. [Q8MQ70-1]
DR WormBase; F20B6.8c; CE30962; WBGene00001994; hpk-1. [Q8MQ70-3]
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000164472; -.
DR InParanoid; Q8MQ70; -.
DR OMA; CDRIDRQ; -.
DR OrthoDB; 369079at2759; -.
DR PhylomeDB; Q8MQ70; -.
DR Reactome; R-CEL-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-CEL-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR PRO; PR:Q8MQ70; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00001994; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0009408; P:response to heat; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:WormBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Autophagy; Developmental protein;
KW Kinase; Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..846
FT /note="Homeodomain-interacting protein kinase 1"
FT /id="PRO_0000432999"
FT DOMAIN 147..483
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 47..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 749..790
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 272
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 153..161
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..106
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057641"
FT VAR_SEQ 1..52
FT /note="MPKRKNSGQSTDLNSRSPKTIDEALRILAPPQALLVQSQLNLTAPANPFSIQ
FT -> MNFHFTLDNDRKRRRSLSIDIDINFND (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_057642"
SQ SEQUENCE 846 AA; 93228 MW; 946D937A5F568951 CRC64;
MPKRKNSGQS TDLNSRSPKT IDEALRILAP PQALLVQSQL NLTAPANPFS IQKAPGTSSD
NEQRAPKRRA DEEAVNAVPK NLLTTSSTFA RAVIPAAPAI SSANNKMAPQ SVTATAKTTT
NRGKVSGEGE YQLIKNEVLC SPYGNQYEVL EFLGKGTFGQ VVKAWKKGTS EIVAIKILKK
HPSYARQGQI EVSILSRLSN ENSEEFNFVR AFECFNHKSH TCLVFEMLEQ NLYDFLKQNK
FMPLPLNAIR PILFQVLTAL LKLKSLGLIH ADLKPENIML VDPQQQPYRV KVIDFGSASH
RSKAVTNTYL QSRYYRAPEI ILGLPFNESI DMWSLGCVIA ELFLGWPLYP GSSEYDQIRF
IIQTQGLPPT SMLESASKLH RFFKEVKSES PNHTNVGGSY YRLKTVEEYE ASSSTAKSKE
TRKYIFNVID DISRVCYGFE SDPVEHLCDR IDRQEFVDVL KKMLVLNPDF RITPAEGLES
KFVTMTHING YNFANYVHEA HKRMEICRKP GPAMATPYRA ANVATPITPV EKPPAPKLQQ
PMIAVLPQLN QIAATNIPPV PTQPDLTNLM HHYSQMAAAT GSAATAAQFF YQPLPPAPLF
QYAQLHHPFA ARPPHFLSLA TPSHMVPQFV PVPIMDPSML QGQWPPGAAQ QFAVLANDIM
RVPAPQGINQ MFASTPQTFS LPQFLSSSIP SATTAFNGNA PNIPFPEENS SWALGTAAQQ
QQQQAQRAQS MINGNVKVKP LAAQPKKNSP APSVITLSSD EDSNGAGSSN SGSTTRTGAV
NPVRNDTLPM GNTIKTEDIL VPPTTFDGQL PNLQYFPGSH LFDPKTVAGL LPNPFLDTSH
IPRAFN
