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 27-MAR-2024, entry version 197. 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; 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; A4QMS7: CFAP90; NbExp=3; IntAct=EBI-745859, EBI-12039847; 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9606-ENSP00000377224; -. DR PeptideAtlas; P55273; -. DR ProteomicsDB; 56832; -. DR Antibodypedia; 4404; 330 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 AGR; HGNC:1790; -. DR CTD; 1032; -. DR DisGeNET; 1032; -. DR GeneCards; CDKN2D; -. DR HGNC; HGNC:1790; CDKN2D. DR HPA; ENSG00000129355; Group enriched (bone marrow, brain, lymphoid tissue). 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; QVMMFGN; -. DR OrthoDB; 2321802at2759; -. 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; 16 hits in 1167 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 129 other cell types or tissues. DR ExpressionAtlas; P55273; baseline and differential. 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; Ankyrin repeat-containing domain; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR PANTHER; PTHR24201; ANK_REP_REGION DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24201:SF7; CYCLIN-DEPENDENT KINASE 4 INHIBITOR D; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR SMART; SM00248; ANK; 4. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 1. DR Genevisible; P55273; HS. 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 //