CDKA1_HUMAN
ID CDKA1_HUMAN Reviewed; 115 AA.
AC O14519; F5GYA4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Cyclin-dependent kinase 2-associated protein 1;
DE Short=CDK2-associated protein 1;
DE AltName: Full=Deleted in oral cancer 1;
DE Short=DOC-1;
DE AltName: Full=Putative oral cancer suppressor;
GN Name=CDK2AP1; Synonyms=CDKAP1, DOC1;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9331572;
RX DOI=10.1002/(sici)1098-2264(199710)20:2<204::aid-gcc12>3.0.co;2-q;
RA Daigo Y., Suzuki K., Maruyama O., Miyoshi Y., Yasuda T., Kabuto T.,
RA Imaoka S., Fujiwara T., Takahashi E., Fujino M.A., Nakamura Y.;
RT "Isolation, mapping and mutation analysis of a human cDNA homologous to the
RT doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral
RT cancer.";
RL Genes Chromosomes Cancer 20:204-207(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=9506968; DOI=10.1074/jbc.273.12.6704;
RA Tsuji T., Duh F.-M., Latif F., Popescu N.C., Zimonjic D.B., McBride J.,
RA Matsuo K., Ohyama H., Todd R., Nagata E., Terakado N., Sasaki A.,
RA Matsumura T., Lerman M.I., Wong D.T.;
RT "Cloning, mapping, expression, function, and mutation analyses of the human
RT ortholog of the hamster putative tumor suppressor gene Doc-1.";
RL J. Biol. Chem. 273:6704-6709(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Arakawa T., Carninci P., Fukuda S., Hasegawa A., Hayashida K., Hori F.,
RA Kai C., Kawai J., Kojima M., Murata M., Nakamura M., Nishiyori H.,
RA Nomura K., Ohno M., Sasaki D., Shibazaki E., Tagami M., Tagami Y.,
RA Hayashizaki Y.;
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [6]
RP INTERACTION WITH CDK2AP2.
RX PubMed=14985111; DOI=10.1016/j.bbrc.2004.02.003;
RA Buajeeb W., Zhang X., Ohyama H., Han D., Surarit R., Kim Y., Wong D.T.;
RT "Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its
RT homolog, p14(DOC-1R).";
RL Biochem. Biophys. Res. Commun. 315:998-1003(2004).
RN [7]
RP STRUCTURE BY NMR OF 61-115, SUBUNIT, PHOSPHORYLATION AT SER-46, DISULFIDE
RP BOND, AND MUTAGENESIS OF CYS-105.
RX PubMed=22427660; DOI=10.1074/jbc.m112.343863;
RA Ertekin A., Aramini J.M., Rossi P., Leonard P.G., Janjua H., Xiao R.,
RA Maglaqui M., Lee H.W., Prestegard J.H., Montelione G.T.;
RT "Human cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is dimeric
RT in its disulfide-reduced state, with natively disordered N-terminal
RT region.";
RL J. Biol. Chem. 287:16541-16549(2012).
CC -!- FUNCTION: specific inhibitor of the cell-cycle kinase CDK2.
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (PubMed:22427660). Interacts with monomeric
CC unphosphorylated CDK2 (By similarity). Interacts with CDK2AP2
CC (PubMed:14985111). {ECO:0000250|UniProtKB:O35207,
CC ECO:0000269|PubMed:14985111, ECO:0000269|PubMed:22427660}.
CC -!- INTERACTION:
CC O14519; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-1052532, EBI-1166928;
CC O14519; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-1052532, EBI-11530605;
CC O14519; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-1052532, EBI-10171416;
CC O14519; P22607: FGFR3; NbExp=3; IntAct=EBI-1052532, EBI-348399;
CC O14519; Q96HT8: MRFAP1L1; NbExp=7; IntAct=EBI-1052532, EBI-748896;
CC O14519; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-1052532, EBI-741158;
CC O14519; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-1052532, EBI-79165;
CC O14519; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-1052532, EBI-742688;
CC O14519; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-1052532, EBI-14096082;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14519-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14519-2; Sequence=VSP_046436;
CC -!- PTM: Phosphorylated in vitro by IKBKE at Ser-46.
CC {ECO:0000269|PubMed:22427660}.
CC -!- SIMILARITY: Belongs to the CDK2AP family. {ECO:0000305}.
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DR EMBL; AB006077; BAA22937.1; -; mRNA.
DR EMBL; AF006484; AAC77831.1; -; mRNA.
DR EMBL; DB465022; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC068768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034717; AAH34717.1; -; mRNA.
DR CCDS; CCDS58289.1; -. [O14519-2]
DR CCDS; CCDS9245.1; -. [O14519-1]
DR RefSeq; NP_001257362.1; NM_001270433.1. [O14519-2]
DR RefSeq; NP_001257363.1; NM_001270434.1. [O14519-2]
DR RefSeq; NP_004633.1; NM_004642.3. [O14519-1]
DR PDB; 2KW6; NMR; -; A/B=61-115.
DR PDBsum; 2KW6; -.
DR AlphaFoldDB; O14519; -.
DR SMR; O14519; -.
DR BioGRID; 113770; 118.
DR IntAct; O14519; 55.
DR MINT; O14519; -.
DR STRING; 9606.ENSP00000261692; -.
DR BindingDB; O14519; -.
DR ChEMBL; CHEMBL5578; -.
DR iPTMnet; O14519; -.
DR PhosphoSitePlus; O14519; -.
DR BioMuta; CDK2AP1; -.
DR EPD; O14519; -.
DR jPOST; O14519; -.
DR MassIVE; O14519; -.
DR MaxQB; O14519; -.
DR PaxDb; O14519; -.
DR PeptideAtlas; O14519; -.
DR PRIDE; O14519; -.
DR ProteomicsDB; 24675; -.
DR ProteomicsDB; 48062; -. [O14519-1]
DR Antibodypedia; 31773; 202 antibodies from 27 providers.
DR DNASU; 8099; -.
DR Ensembl; ENST00000261692.7; ENSP00000261692.2; ENSG00000111328.7. [O14519-1]
DR Ensembl; ENST00000535979.5; ENSP00000442565.1; ENSG00000111328.7. [O14519-2]
DR Ensembl; ENST00000538446.5; ENSP00000442502.1; ENSG00000111328.7. [O14519-2]
DR Ensembl; ENST00000542174.5; ENSP00000440729.1; ENSG00000111328.7. [O14519-2]
DR Ensembl; ENST00000544658.5; ENSP00000438561.1; ENSG00000111328.7. [O14519-2]
DR Ensembl; ENST00000618072.4; ENSP00000479982.1; ENSG00000111328.7. [O14519-2]
DR Ensembl; ENST00000652466.1; ENSP00000498286.1; ENSG00000111328.7. [O14519-2]
DR GeneID; 8099; -.
DR KEGG; hsa:8099; -.
DR MANE-Select; ENST00000261692.7; ENSP00000261692.2; NM_004642.4; NP_004633.1.
DR UCSC; uc001ueq.5; human. [O14519-1]
DR CTD; 8099; -.
DR DisGeNET; 8099; -.
DR GeneCards; CDK2AP1; -.
DR HGNC; HGNC:14002; CDK2AP1.
DR HPA; ENSG00000111328; Low tissue specificity.
DR MIM; 602198; gene.
DR neXtProt; NX_O14519; -.
DR OpenTargets; ENSG00000111328; -.
DR PharmGKB; PA26308; -.
DR VEuPathDB; HostDB:ENSG00000111328; -.
DR eggNOG; KOG4713; Eukaryota.
DR GeneTree; ENSGT00940000155149; -.
DR HOGENOM; CLU_130479_1_0_1; -.
DR InParanoid; O14519; -.
DR OMA; ISDGHIC; -.
DR OrthoDB; 1630301at2759; -.
DR PhylomeDB; O14519; -.
DR TreeFam; TF101037; -.
DR PathwayCommons; O14519; -.
DR SignaLink; O14519; -.
DR SIGNOR; O14519; -.
DR BioGRID-ORCS; 8099; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; CDK2AP1; human.
DR EvolutionaryTrace; O14519; -.
DR GeneWiki; CDK2AP1; -.
DR GenomeRNAi; 8099; -.
DR Pharos; O14519; Tbio.
DR PRO; PR:O14519; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O14519; protein.
DR Bgee; ENSG00000111328; Expressed in parotid gland and 215 other tissues.
DR ExpressionAtlas; O14519; baseline and differential.
DR Genevisible; O14519; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006261; P:DNA-templated DNA replication; NAS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR DisProt; DP01303; -.
DR InterPro; IPR017266; DOC_1/2.
DR PANTHER; PTHR22607; PTHR22607; 1.
DR Pfam; PF09806; CDK2AP; 1.
DR PIRSF; PIRSF037709; CDK2-associated_p2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Disulfide bond;
KW Phosphoprotein; Reference proteome; Tumor suppressor.
FT CHAIN 1..115
FT /note="Cyclin-dependent kinase 2-associated protein 1"
FT /id="PRO_0000089452"
FT REGION 20..25
FT /note="Interaction with CDK2AP2"
FT /evidence="ECO:0000269|PubMed:14985111"
FT MOD_RES 46
FT /note="Phosphoserine; by IKKE"
FT /evidence="ECO:0000269|PubMed:22427660"
FT DISULFID 105
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046436"
FT MUTAGEN 105
FT /note="C->A: Does not alter homodimerization."
FT /evidence="ECO:0000269|PubMed:22427660"
FT HELIX 62..73
FT /evidence="ECO:0007829|PDB:2KW6"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:2KW6"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:2KW6"
FT HELIX 85..109
FT /evidence="ECO:0007829|PDB:2KW6"
FT TURN 110..114
FT /evidence="ECO:0007829|PDB:2KW6"
SQ SEQUENCE 115 AA; 12365 MW; F3149F72467598C2 CRC64;
MSYKPNLAAH MPAAALNAAG SVHSPSTSMA TSSQYRQLLS DYGPPSLGYT QGTGNSQVPQ
SKYAELLAII EELGKEIRPT YAGSKSAMER LKRGIIHARG LVRECLAETE RNARS
