CDN2D_HUMAN
ID CDN2D_HUMAN Reviewed; 166 AA.
AC P55273; Q13102; Q6FGE9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Cyclin-dependent kinase 4 inhibitor D;
DE AltName: Full=p19-INK4d;
GN Name=CDKN2D;
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].
RC TISSUE=Bone marrow;
RX PubMed=8575754; DOI=10.1006/geno.1995.9957;
RA Okuda T., Hirai H., Valentine V.A., Shurtleff S.A., Kidd V.J., Lahti J.M.,
RA Sherr C.J., Downing J.R.;
RT "Molecular cloning, expression pattern, and chromosomal localization of
RT human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases.";
RL Genomics 29:623-630(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Thymus;
RX PubMed=7739548; DOI=10.1128/mcb.15.5.2682;
RA Chan F.K.M., Zhang J., Cheng L., Shapiro D.N., Winoto A.;
RT "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor
RT with homology to p16ink4.";
RL Mol. Cell. Biol. 15:2682-2688(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8741839; DOI=10.1091/mbc.7.1.57;
RA Guan K.L., Jenkins C.W., Li Y., O'Keefe C.L., Noh S., Wu X., Zariwala M.,
RA Matera A.G., Xiong Y.;
RT "Isolation and characterization of p19INK4d, a p16-related inhibitor
RT specific to CDK6 and CDK4.";
RL Mol. Biol. Cell 7:57-70(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10390011; DOI=10.1038/sj.bjc.6690354;
RA Newton Bishop J.A., Harland M., Bennett D.C., Bataille V., Goldstein A.M.,
RA Tucker M.A., Ponder B.A.J., Cuzick J., Selby P., Bishop D.T.;
RT "Mutation testing in melanoma families: INK4A, CDK4 and INK4D.";
RL Br. J. Cancer 80:295-300(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
RA Murthy S.K., Demetrick D.J.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PROTEIN SEQUENCE OF 1-7, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CDK6.
RX PubMed=9482106; DOI=10.1038/sj.onc.1201570;
RA Mahony D., Parry D.A., Lees E.;
RT "Active cdk6 complexes are predominantly nuclear and represent only a
RT minority of the cdk6 in T cells.";
RL Oncogene 16:603-611(1998).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CDK6.
RX PubMed=9751050; DOI=10.1038/26155;
RA Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P.;
RT "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the
RT tumour suppressor p16INK4a.";
RL Nature 395:237-243(1998).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9782052; DOI=10.1016/s0969-2126(98)00128-2;
RA Baumgartner R., Fernandez-Catalan C., Winoto A., Huber R., Engh R.A.,
RA Holak T.A.;
RT "Structure of human cyclin-dependent kinase inhibitor p19(INK4d):
RT comparison to known ankyrin-repeat-containing structures and implications
RT for the dysfunction of tumor suppressor p16(INK4a).";
RL Structure 6:1279-1290(1998).
CC -!- FUNCTION: Interacts strongly with CDK4 and CDK6 and inhibits them.
CC {ECO:0000269|PubMed:7739548, ECO:0000269|PubMed:8741839}.
CC -!- SUBUNIT: Interacts with CDK6. {ECO:0000269|PubMed:9482106}.
CC -!- INTERACTION:
CC P55273; Q6P1W5: C1orf94; NbExp=5; IntAct=EBI-745859, EBI-946029;
CC P55273; A4QMS7: C5orf49; NbExp=3; IntAct=EBI-745859, EBI-12039847;
CC P55273; P30281: CCND3; NbExp=3; IntAct=EBI-745859, EBI-375013;
CC P55273; P11802: CDK4; NbExp=25; IntAct=EBI-745859, EBI-295644;
CC P55273; Q00534: CDK6; NbExp=22; IntAct=EBI-745859, EBI-295663;
CC P55273; Q9UFW8: CGGBP1; NbExp=3; IntAct=EBI-745859, EBI-723153;
CC P55273; Q13363-2: CTBP1; NbExp=3; IntAct=EBI-745859, EBI-10171858;
CC P55273; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-745859, EBI-742054;
CC P55273; Q8WW35: DYNLT2B; NbExp=3; IntAct=EBI-745859, EBI-2692044;
CC P55273; Q04637-9: EIF4G1; NbExp=3; IntAct=EBI-745859, EBI-12012124;
CC P55273; Q86W67: FAM228A; NbExp=3; IntAct=EBI-745859, EBI-12958227;
CC P55273; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-745859, EBI-12845222;
CC P55273; Q8WXI9: GATAD2B; NbExp=3; IntAct=EBI-745859, EBI-923440;
CC P55273; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-745859, EBI-12143817;
CC P55273; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-745859, EBI-739467;
CC P55273; O15499: GSC2; NbExp=3; IntAct=EBI-745859, EBI-19954058;
CC P55273; Q9BPX1: HSD17B14; NbExp=8; IntAct=EBI-745859, EBI-742664;
CC P55273; Q9UKT9: IKZF3; NbExp=5; IntAct=EBI-745859, EBI-747204;
CC P55273; Q0VD86: INCA1; NbExp=9; IntAct=EBI-745859, EBI-6509505;
CC P55273; O95678: KRT75; NbExp=3; IntAct=EBI-745859, EBI-2949715;
CC P55273; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-745859, EBI-739832;
CC P55273; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-745859, EBI-2341787;
CC P55273; A8MW99: MEI4; NbExp=3; IntAct=EBI-745859, EBI-19944212;
CC P55273; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-745859, EBI-16439278;
CC P55273; Q4VC12: MSS51; NbExp=3; IntAct=EBI-745859, EBI-11599933;
CC P55273; Q9Y483-4: MTF2; NbExp=3; IntAct=EBI-745859, EBI-10698053;
CC P55273; P17568: NDUFB7; NbExp=3; IntAct=EBI-745859, EBI-1246238;
CC P55273; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-745859, EBI-740897;
CC P55273; O00746: NME4; NbExp=3; IntAct=EBI-745859, EBI-744871;
CC P55273; P22736: NR4A1; NbExp=4; IntAct=EBI-745859, EBI-721550;
CC P55273; F1D8N6: NR4A2; NbExp=3; IntAct=EBI-745859, EBI-10214997;
CC P55273; P43354: NR4A2; NbExp=4; IntAct=EBI-745859, EBI-2681738;
CC P55273; Q92570: NR4A3; NbExp=3; IntAct=EBI-745859, EBI-13644623;
CC P55273; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-745859, EBI-79165;
CC P55273; P30044: PRDX5; NbExp=3; IntAct=EBI-745859, EBI-722161;
CC P55273; Q96LW4: PRIMPOL; NbExp=3; IntAct=EBI-745859, EBI-10044038;
CC P55273; P25786: PSMA1; NbExp=3; IntAct=EBI-745859, EBI-359352;
CC P55273; Q04864-2: REL; NbExp=3; IntAct=EBI-745859, EBI-10829018;
CC P55273; Q6ZNE9: RUFY4; NbExp=3; IntAct=EBI-745859, EBI-10181525;
CC P55273; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-745859, EBI-3957636;
CC P55273; O00560: SDCBP; NbExp=3; IntAct=EBI-745859, EBI-727004;
CC P55273; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-745859, EBI-741515;
CC P55273; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-745859, EBI-10241197;
CC P55273; Q9BRT2: UQCC2; NbExp=3; IntAct=EBI-745859, EBI-1054584;
CC P55273; Q99990: VGLL1; NbExp=3; IntAct=EBI-745859, EBI-11983165;
CC P55273; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-745859, EBI-10188476;
CC P55273; Q96N95-3: ZNF396; NbExp=3; IntAct=EBI-745859, EBI-12328453;
CC P55273; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-745859, EBI-4395669;
CC P55273; P0C7X2: ZNF688; NbExp=3; IntAct=EBI-745859, EBI-4395732;
CC P55273; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-745859, EBI-10251462;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9482106}. Cytoplasm
CC {ECO:0000269|PubMed:9482106}.
CC -!- SIMILARITY: Belongs to the CDKN2 cyclin-dependent kinase inhibitor
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdkn2d/";
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DR EMBL; U49399; AAB03772.1; -; mRNA.
DR EMBL; U20498; AAA85436.1; -; mRNA.
DR EMBL; U40343; AAB18139.1; -; mRNA.
DR EMBL; AF061327; AAC27450.1; -; Genomic_DNA.
DR EMBL; CR542158; CAG46955.1; -; mRNA.
DR EMBL; AF518878; AAM54045.1; -; Genomic_DNA.
DR EMBL; BC001822; AAH01822.1; -; mRNA.
DR EMBL; AF044171; AAD02320.1; -; Genomic_DNA.
DR CCDS; CCDS12244.1; -.
DR PIR; A57378; A57378.
DR RefSeq; NP_001791.1; NM_001800.3.
DR RefSeq; NP_524145.1; NM_079421.2.
DR PDB; 1BD8; X-ray; 1.80 A; A=7-162.
DR PDB; 1BI8; X-ray; 2.80 A; B/D=1-166.
DR PDBsum; 1BD8; -.
DR PDBsum; 1BI8; -.
DR AlphaFoldDB; P55273; -.
DR SMR; P55273; -.
DR BioGRID; 107466; 79.
DR DIP; DIP-6109N; -.
DR IntAct; P55273; 53.
DR MINT; P55273; -.
DR STRING; 9606.ENSP00000377224; -.
DR iPTMnet; P55273; -.
DR PhosphoSitePlus; P55273; -.
DR BioMuta; CDKN2D; -.
DR DMDM; 1705730; -.
DR MassIVE; P55273; -.
DR MaxQB; P55273; -.
DR PaxDb; P55273; -.
DR PeptideAtlas; P55273; -.
DR PRIDE; P55273; -.
DR ProteomicsDB; 56832; -.
DR Antibodypedia; 4404; 301 antibodies from 34 providers.
DR DNASU; 1032; -.
DR Ensembl; ENST00000335766.2; ENSP00000337056.1; ENSG00000129355.7.
DR Ensembl; ENST00000393599.3; ENSP00000377224.1; ENSG00000129355.7.
DR GeneID; 1032; -.
DR KEGG; hsa:1032; -.
DR MANE-Select; ENST00000393599.3; ENSP00000377224.1; NM_001800.4; NP_001791.1.
DR UCSC; uc002mpa.4; human.
DR CTD; 1032; -.
DR DisGeNET; 1032; -.
DR GeneCards; CDKN2D; -.
DR HGNC; HGNC:1790; CDKN2D.
DR HPA; ENSG00000129355; Tissue enhanced (bone).
DR MIM; 600927; gene.
DR neXtProt; NX_P55273; -.
DR OpenTargets; ENSG00000129355; -.
DR PharmGKB; PA26323; -.
DR VEuPathDB; HostDB:ENSG00000129355; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000159801; -.
DR HOGENOM; CLU_000134_37_0_1; -.
DR InParanoid; P55273; -.
DR OMA; LHQEFVH; -.
DR OrthoDB; 1453965at2759; -.
DR PhylomeDB; P55273; -.
DR TreeFam; TF333311; -.
DR PathwayCommons; P55273; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR SignaLink; P55273; -.
DR SIGNOR; P55273; -.
DR BioGRID-ORCS; 1032; 15 hits in 1086 CRISPR screens.
DR EvolutionaryTrace; P55273; -.
DR GeneWiki; CDKN2D; -.
DR GenomeRNAi; 1032; -.
DR Pharos; P55273; Tbio.
DR PRO; PR:P55273; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P55273; protein.
DR Bgee; ENSG00000129355; Expressed in monocyte and 127 other tissues.
DR ExpressionAtlas; P55273; baseline and differential.
DR Genevisible; P55273; HS.
DR GO; GO:0097129; C:cyclin D2-CDK4 complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0048102; P:autophagic cell death; IMP:BHF-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IMP:BHF-UCL.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:BHF-UCL.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
DR GO; GO:0032526; P:response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0009411; P:response to UV; IMP:BHF-UCL.
DR GO; GO:0033280; P:response to vitamin D; IMP:BHF-UCL.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 2.
DR SMART; SM00248; ANK; 4.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ANK repeat; Cell cycle; Cytoplasm;
KW Direct protein sequencing; Nucleus; Reference proteome; Repeat;
KW Tumor suppressor.
FT CHAIN 1..166
FT /note="Cyclin-dependent kinase 4 inhibitor D"
FT /id="PRO_0000144188"
FT REPEAT 41..69
FT /note="ANK 1"
FT REPEAT 73..102
FT /note="ANK 2"
FT REPEAT 106..135
FT /note="ANK 3"
FT REPEAT 138..166
FT /note="ANK 4"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CONFLICT 159
FT /note="Q -> P (in Ref. 2; AAA85436)"
FT /evidence="ECO:0000305"
FT HELIX 8..18
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 21..29
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 54..62
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 77..83
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 87..95
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 110..117
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 120..127
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 142..148
FT /evidence="ECO:0007829|PDB:1BD8"
FT HELIX 152..159
FT /evidence="ECO:0007829|PDB:1BD8"
SQ SEQUENCE 166 AA; 17700 MW; 2FACD11CF56340DC CRC64;
MLLEEVRAGD RLSGAAARGD VQEVRRLLHR ELVHPDALNR FGKTALQVMM FGSTAIALEL
LKQGASPNVQ DTSGTSPVHD AARTGFLDTL KVLVEHGADV NVPDGTGALP IHLAVQEGHT
AVVSFLAAES DLHRRDARGL TPLELALQRG AQDLVDILQG HMVAPL
