ID   CDKA2_HUMAN             Reviewed;         126 AA.
AC   O75956;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Cyclin-dependent kinase 2-associated protein 2;
DE            Short=CDK2-associated protein 2;
DE   AltName: Full=DOC-1-related protein;
DE            Short=DOC-1R;
GN   Name=CDK2AP2; Synonyms=DOC1R;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=10082655; DOI=10.1006/bbrc.1999.0148;
RA   Zhang X., Tsao H., Tsuji T., Minoshima S., McBride J., Majewski P.,
RA   Todd R., Shimizu N., Wong D.T., Housman D.E., Haluska F.G.;
RT   "Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-
RT   related gene.";
RL   Biochem. Biophys. Res. Commun. 255:59-63(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Ovary;
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   [4]
RP   INTERACTION WITH CDK2AP1.
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   [5]
RP   FUNCTION, AND INTERACTION WITH CDK2.
RX   PubMed=23781148; DOI=10.7150/ijbs.5763;
RA   Liu Q., Liu X., Gao J., Shi X., Hu X., Wang S., Luo Y.;
RT   "Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing
RT   CDK2 expression and activation.";
RL   Int. J. Biol. Sci. 9:541-549(2013).
RN   [6]
RP   FUNCTION, IDENTIFICATION IN THE NURD COMPLEX, IDENTIFICATION BY MASS
RP   SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX   PubMed=33283408; DOI=10.1111/febs.15650;
RA   Spruijt C.G., Graewe C., Kleinendorst S.C., Baltissen M.P.A., Vermeulen M.;
RT   "Cross-linking mass spectrometry reveals the structural topology of
RT   peripheral NuRD subunits relative to the core complex.";
RL   FEBS J. 288:3231-3245(2021).
CC   -!- FUNCTION: Acts as a component of the histone deacetylase NuRD complex
CC       which participates in the remodeling of chromatin (PubMed:33283408).
CC       Inhibits cell cycle G1/S phase transition by repressing CDK2 expression
CC       and activation; represses CDK2 activation by inhibiting its interaction
CC       with cyclin E and A (PubMed:23781148). Plays a role in regulating the
CC       self-renewal of embryonic stem cells (ESCs) and in maintaining cell
CC       survival during terminal differentiation of ESCs (By similarity).
CC       Regulates microtubule organization of metaphase II oocytes (By
CC       similarity). {ECO:0000250|UniProtKB:Q9CPY4,
CC       ECO:0000269|PubMed:23781148, ECO:0000269|PubMed:33283408}.
CC   -!- SUBUNIT: Component of the nucleosome remodeling and deacetylase (NuRD)
CC       repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4,
CC       RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins
CC       CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5
CC       (PubMed:33283408). The exact stoichiometry of the NuRD complex is
CC       unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B,
CC       and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes
CC       (PubMed:33283408). Interacts with CDK2AP1 (PubMed:14985111). Interacts
CC       with CDK2 (PubMed:23781148). Interacts with MAPK1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9CPY4, ECO:0000269|PubMed:14985111,
CC       ECO:0000269|PubMed:23781148, ECO:0000269|PubMed:33283408}.
CC   -!- INTERACTION:
CC       O75956; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-2808135, EBI-748896;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10082655}. Nucleus
CC       {ECO:0000269|PubMed:10082655, ECO:0000269|PubMed:33283408}.
CC       Note=Accumulates in immature oocytes in the nucleus. During the first
CC       meiotic division, accumulates in the cytoplasm and localizes in dots in
CC       the vicinity of the chromosomes in a region enriched in microtubules.
CC       {ECO:0000250|UniProtKB:Q9CPY4}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10082655}.
CC   -!- PTM: Phosphorylated by MAPK1 and CDK2. {ECO:0000250|UniProtKB:Q9CPY4}.
CC   -!- SIMILARITY: Belongs to the CDK2AP family. {ECO:0000305}.
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DR   EMBL; AF089814; AAC61745.1; -; mRNA.
DR   EMBL; BT006909; AAP35555.1; -; mRNA.
DR   EMBL; BC002850; AAH02850.1; -; mRNA.
DR   EMBL; BC016704; AAH16704.1; -; mRNA.
DR   CCDS; CCDS8169.1; -.
DR   RefSeq; NP_005842.1; NM_005851.4.
DR   PDB; 2M1L; NMR; -; A/B=61-126.
DR   PDBsum; 2M1L; -.
DR   AlphaFoldDB; O75956; -.
DR   BMRB; O75956; -.
DR   SMR; O75956; -.
DR   BioGRID; 115555; 47.
DR   IntAct; O75956; 18.
DR   MINT; O75956; -.
DR   STRING; 9606.ENSP00000301488; -.
DR   BindingDB; O75956; -.
DR   ChEMBL; CHEMBL6010; -.
DR   iPTMnet; O75956; -.
DR   PhosphoSitePlus; O75956; -.
DR   BioMuta; CDK2AP2; -.
DR   EPD; O75956; -.
DR   jPOST; O75956; -.
DR   MassIVE; O75956; -.
DR   PaxDb; 9606-ENSP00000301488; -.
DR   PeptideAtlas; O75956; -.
DR   ProteomicsDB; 50322; -.
DR   Pumba; O75956; -.
DR   Antibodypedia; 30451; 186 antibodies from 23 providers.
DR   DNASU; 10263; -.
DR   Ensembl; ENST00000301488.8; ENSP00000301488.4; ENSG00000167797.8.
DR   GeneID; 10263; -.
DR   KEGG; hsa:10263; -.
DR   MANE-Select; ENST00000301488.8; ENSP00000301488.4; NM_005851.5; NP_005842.1.
DR   AGR; HGNC:30833; -.
DR   CTD; 10263; -.
DR   DisGeNET; 10263; -.
DR   GeneCards; CDK2AP2; -.
DR   HGNC; HGNC:30833; CDK2AP2.
DR   HPA; ENSG00000167797; Low tissue specificity.
DR   MIM; 620061; gene.
DR   neXtProt; NX_O75956; -.
DR   OpenTargets; ENSG00000167797; -.
DR   PharmGKB; PA128394572; -.
DR   VEuPathDB; HostDB:ENSG00000167797; -.
DR   eggNOG; KOG4713; Eukaryota.
DR   GeneTree; ENSGT00940000160334; -.
DR   HOGENOM; CLU_130479_0_0_1; -.
DR   InParanoid; O75956; -.
DR   OMA; KHRVDRP; -.
DR   OrthoDB; 5396585at2759; -.
DR   PhylomeDB; O75956; -.
DR   TreeFam; TF101037; -.
DR   PathwayCommons; O75956; -.
DR   SignaLink; O75956; -.
DR   BioGRID-ORCS; 10263; 34 hits in 1159 CRISPR screens.
DR   ChiTaRS; CDK2AP2; human.
DR   GenomeRNAi; 10263; -.
DR   Pharos; O75956; Tbio.
DR   PRO; PR:O75956; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; O75956; Protein.
DR   Bgee; ENSG00000167797; Expressed in mucosa of transverse colon and 191 other cell types or tissues.
DR   ExpressionAtlas; O75956; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0016581; C:NuRD complex; IDA:UniProtKB.
DR   GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:2000035; P:regulation of stem cell division; ISS:UniProtKB.
DR   Gene3D; 6.10.140.1300; -; 1.
DR   InterPro; IPR017266; DOC_1/2.
DR   PANTHER; PTHR22607:SF4; CYCLIN-DEPENDENT KINASE 2-ASSOCIATED PROTEIN 2; 1.
DR   PANTHER; PTHR22607; DELETED IN ORAL CANCER 1/CDK2-ASSOCIATED PROTEIN 1; 1.
DR   Pfam; PF09806; CDK2AP; 1.
DR   PIRSF; PIRSF037709; CDK2-associated_p2; 1.
DR   Genevisible; O75956; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..126
FT                   /note="Cyclin-dependent kinase 2-associated protein 2"
FT                   /id="PRO_0000079963"
FT   REGION          1..48
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          64..106
FT                   /note="Interaction with CDK2"
FT                   /evidence="ECO:0000269|PubMed:23781148"
FT   COMPBIAS        12..28
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   STRAND          67..70
FT                   /evidence="ECO:0007829|PDB:2M1L"
FT   HELIX           72..85
FT                   /evidence="ECO:0007829|PDB:2M1L"
FT   HELIX           88..92
FT                   /evidence="ECO:0007829|PDB:2M1L"
FT   HELIX           96..120
FT                   /evidence="ECO:0007829|PDB:2M1L"
SQ   SEQUENCE   126 AA;  13101 MW;  D668D3FA8CE70CA5 CRC64;
     MSYKPIAPAP SSTPGSSTPG PGTPVPTGSV PSPSGSVPGA GAPFRPLFND FGPPSMGYVQ
     AMKPPGAQGS QSTYTDLLSV IEEMGKEIRP TYAGSKSAME RLKRGIIHAR ALVRECLAET
     ERNART
//