CDK4_CAEEL
ID CDK4_CAEEL Reviewed; 406 AA.
AC Q9XTR1; G5EFI3;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Cyclin-dependent kinase 4 homolog {ECO:0000305};
DE Short=CDK4/6 {ECO:0000303|PubMed:10518501};
DE EC=2.7.11.22 {ECO:0000269|PubMed:25562820};
DE AltName: Full=Cell division protein kinase 4 {ECO:0000305};
GN Name=cdk-4 {ECO:0000312|WormBase:F18H3.5b};
GN ORFNames=F18H3.5 {ECO:0000312|WormBase:F18H3.5b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAD48898.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH CYD-1,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=10518501; DOI=10.1242/dev.126.21.4849;
RA Park M., Krause M.W.;
RT "Regulation of postembryonic G(1) cell cycle progression in Caenorhabditis
RT elegans by a cyclin D/CDK-like complex.";
RL Development 126:4849-4860(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [3] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-149.
RX PubMed=11684669; DOI=10.1242/dev.128.21.4349;
RA Boxem M., van den Heuvel S.;
RT "lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1
RT progression in C. elegans.";
RL Development 128:4349-4359(2001).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=16198291; DOI=10.1016/j.devcel.2005.09.004;
RA Tilmann C., Kimble J.;
RT "Cyclin D regulation of a sexually dimorphic asymmetric cell division.";
RL Dev. Cell 9:489-499(2005).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-191.
RX PubMed=25562820; DOI=10.1038/ncomms6906;
RA The I., Ruijtenberg S., Bouchet B.P., Cristobal A., Prinsen M.B.,
RA van Mourik T., Koreth J., Xu H., Heck A.J., Akhmanova A., Cuppen E.,
RA Boxem M., Munoz J., van den Heuvel S.;
RT "Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and
RT human cancer cells.";
RL Nat. Commun. 6:5906-5906(2015).
CC -!- FUNCTION: Serine/threonine-protein kinase which, in association with
CC cyclin D-like protein cyd-1, is required for the progression through
CC the G1 phase of the cell cycle during postembryonic development by
CC phosphorylating and inhibiting lin-35 and fzr-1 (PubMed:10518501,
CC PubMed:11684669, PubMed:25562820). In complex with cyd-1, involved in
CC sex determination during gonadogenesis by regulating the asymmetric
CC division of the somatic gonadal precursor cell (SGP) (PubMed:16198291).
CC {ECO:0000269|PubMed:10518501, ECO:0000269|PubMed:11684669,
CC ECO:0000269|PubMed:16198291, ECO:0000269|PubMed:25562820}.
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=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:25562820};
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=2.7.11.22; Evidence={ECO:0000269|PubMed:25562820};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P24941};
CC -!- SUBUNIT: Interacts with cyd-1; the interaction is likely involved in
CC regulating cdk-4 activity. {ECO:0000269|PubMed:10518501}.
CC -!- INTERACTION:
CC Q9XTR1; Q9U2M5: cyd-1; NbExp=2; IntAct=EBI-14063019, EBI-2420074;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:F18H3.5b};
CC IsoId=Q9XTR1-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F18H3.5a};
CC IsoId=Q9XTR1-2; Sequence=VSP_057762;
CC -!- DEVELOPMENTAL STAGE: Expression initiates during mid-embryogenesis
CC primarily in post-proliferative hypodermal cells and neurons in the
CC head, ventral cord and tail, then declines until hatching where it is
CC mainly seen in seam cells. Expressed throughout larval development in
CC several blast cell linages. In the P lineage, expression is restricted
CC to proliferating cells, whereas it persists in somatic gonads and seam
CC cells. Expressed in uterus and intestine and to a lesser extent in
CC spermatheca. {ECO:0000269|PubMed:10518501}.
CC -!- DISRUPTION PHENOTYPE: Arrested cell division in the G1 phase during
CC larval development (PubMed:25562820). RNAi-mediated knockdown results
CC in L4 stage arrest which is associated with uncoordinated movements and
CC a protruding vulva (PubMed:10518501). Impaired cell division of P blast
CC cells, somatic gonad precursors Z1 and Z4 and intestinal cells
CC (PubMed:10518501). Severe defect in the proliferation of P blast cells,
CC intestinal cells, vulva cell precursors and somatic gonad precursors
CC (PubMed:10518501). Mesoblast M cell division is normal
CC (PubMed:10518501). Double knockout with lin-35 rescues the cell cycle
CC progression defect in the single cdk-4 mutants (PubMed:11684669,
CC PubMed:25562820). {ECO:0000269|PubMed:10518501,
CC ECO:0000269|PubMed:11684669, ECO:0000269|PubMed:25562820}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AF083878; AAD48898.1; -; mRNA.
DR EMBL; BX284606; CAA90447.1; -; Genomic_DNA.
DR EMBL; Z99773; CAA90447.1; JOINED; Genomic_DNA.
DR EMBL; BX284606; CAB16923.2; -; Genomic_DNA.
DR PIR; T21098; T21098.
DR PIR; T23050; T23050.
DR RefSeq; NP_001024591.1; NM_001029420.1.
DR RefSeq; NP_510256.1; NM_077855.4. [Q9XTR1-2]
DR AlphaFoldDB; Q9XTR1; -.
DR SMR; Q9XTR1; -.
DR ComplexPortal; CPX-1126; Cyclin cyd-1-cdk4 complex.
DR IntAct; Q9XTR1; 1.
DR STRING; 6239.F18H3.5b; -.
DR EPD; Q9XTR1; -.
DR PaxDb; Q9XTR1; -.
DR PeptideAtlas; Q9XTR1; -.
DR EnsemblMetazoa; F18H3.5.1; F18H3.5.1; WBGene00000406. [Q9XTR1-2]
DR GeneID; 181472; -.
DR KEGG; cel:CELE_F18H3.5; -.
DR CTD; 181472; -.
DR WormBase; F18H3.5a; CE18608; WBGene00000406; cdk-4. [Q9XTR1-2]
DR WormBase; F18H3.5b; CE28918; WBGene00000406; cdk-4. [Q9XTR1-1]
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000167918; -.
DR InParanoid; Q9XTR1; -.
DR OMA; MLSYDLH; -.
DR OrthoDB; 988547at2759; -.
DR PhylomeDB; Q9XTR1; -.
DR PRO; PR:Q9XTR1; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000406; Expressed in embryo and 4 other tissues.
DR GO; GO:0097128; C:cyclin D1-CDK4 complex; IPI:ComplexPortal.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion 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; IDA:WormBase.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IBA:GO_Central.
DR GO; GO:0044843; P:cell cycle G1/S phase transition; TAS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:ComplexPortal.
DR GO; GO:0040035; P:hermaphrodite genitalia development; IGI:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IGI:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:0032877; P:positive regulation of DNA endoreduplication; IMP:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:WormBase.
DR GO; GO:0009791; P:post-embryonic development; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; ISS:WormBase.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0007530; P:sex determination; IGI:UniProtKB.
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 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell cycle; Cell division; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..406
FT /note="Cyclin-dependent kinase 4 homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433388"
FT DOMAIN 102..388
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 233
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 108..116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 238
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT BINDING 251
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT VAR_SEQ 1..105
FT /note="MTIRHILAIRKKSLELPSDLKTFLRVLANCQHLKKNKKCRRTIFSVDFQNNQ
FT RQKPSNFHFWTVIKKFSKKILKSFIIKFGNNGTIAVVFSIFPTGATPSLTFLF -> MC
FT ENLYGEEYKMEILRLQKMMNNMTCGQMAKPLTMKDFQIH (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_057762"
FT MUTAGEN 149
FT /note="E->K: In he110; lack of postembryonic blast cell
FT division."
FT /evidence="ECO:0000269|PubMed:11684669"
FT MUTAGEN 191
FT /note="D->N: Loss of activity. Arrest at an early larval
FT stage associated with a lack of cell division in several
FT postembryonic blast cells."
FT /evidence="ECO:0000269|PubMed:25562820"
SQ SEQUENCE 406 AA; 46694 MW; 108B72F0B96B2DD4 CRC64;
MTIRHILAIR KKSLELPSDL KTFLRVLANC QHLKKNKKCR RTIFSVDFQN NQRQKPSNFH
FWTVIKKFSK KILKSFIIKF GNNGTIAVVF SIFPTGATPS LTFLFQALGK GAYGNVYRVR
SLHDGKDYAL KQIMISSKNE GIPQSVLREI TVMKHLARKA HPNIISLKSV FHQLDPVRAI
LKINMIMERC DWDLHTFLRN IPRGVPEQQA KHVTAQIVRA LDFLHTHSII HRDLKPQNIL
LNRDQTVKLA DFGLSKEYSN TTAFTTLVVT LWYRSPEVLL QSYYNSTVDM WALGCIVSEI
YCRQPLFVGQ NEAEQLTDIF KKMGTPVGKD WPSESVIARD SFPQYRPTNL KDLSPQMSKQ
AIEFVQQCLR YDHSKRLSAR GALSHPFLKP AVATKSRVLK QINFNK
