CDN2C_HUMAN
ID CDN2C_HUMAN Reviewed; 168 AA.
AC P42773; Q8TB83;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Cyclin-dependent kinase 4 inhibitor C;
DE AltName: Full=Cyclin-dependent kinase 6 inhibitor;
DE AltName: Full=p18-INK4c;
DE AltName: Full=p18-INK6;
GN Name=CDKN2C; Synonyms=CDKN6;
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].
RX PubMed=8001816; DOI=10.1101/gad.8.24.2939;
RA Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L.,
RA Matera G.A., Xiong Y.;
RT "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6
RT inhibitor, correlates with wild-type pRb function.";
RL Genes Dev. 8:2939-2952(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT BREAST CANCER PRO-72.
RC TISSUE=Mammary gland;
RX PubMed=9636670; DOI=10.1006/bbrc.1998.8497;
RA Blais A., Labrie Y., Pouliot F., Lachance Y., Labrie C.;
RT "Structure of the gene encoding the human cyclin-dependent kinase inhibitor
RT p18 and mutational analysis in breast cancer.";
RL Biochem. Biophys. Res. Commun. 247:146-153(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-126.
RC TISSUE=Brain, Kidney, and Uterus;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
RX PubMed=9437433; DOI=10.1038/nsb0198-74;
RA Venkataramani R., Swaminathan K., Marmorstein R.;
RT "Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides
RT insights into ankyrin-like repeat structure/function and tumor-derived
RT p16INK4 mutations.";
RL Nat. Struct. Biol. 5:74-81(1998).
RN [7]
RP STRUCTURE BY NMR.
RX PubMed=10074345; DOI=10.1021/bi982286e;
RA Li J., Byeon I.-J.L., Ericson K., Poi M.-J., O'Maille P., Selby T.,
RA Tsai M.-D.;
RT "Tumor suppressor INK4: determination of the solution structure of p18INK4C
RT and demonstration of the functional significance of loops in p18INK4C and
RT p16INK4A.";
RL Biochemistry 38:2930-2940(1999).
RN [8]
RP VARIANT BREAST CANCER PRO-72.
RX PubMed=8840966;
RA Lapointe J., Lachance Y., Labrie Y., Labrie C.;
RT "A p18 mutant defective in CDK6 binding in human breast cancer cells.";
RL Cancer Res. 56:4586-4589(1996).
CC -!- FUNCTION: Interacts strongly with CDK6, weakly with CDK4. Inhibits cell
CC growth and proliferation with a correlated dependence on endogenous
CC retinoblastoma protein RB.
CC -!- SUBUNIT: Heterodimer of p18 with CDK6.
CC -!- INTERACTION:
CC P42773; O43865: AHCYL1; NbExp=10; IntAct=EBI-711290, EBI-2371423;
CC P42773; P05067: APP; NbExp=3; IntAct=EBI-711290, EBI-77613;
CC P42773; P55212: CASP6; NbExp=3; IntAct=EBI-711290, EBI-718729;
CC P42773; P11802: CDK4; NbExp=23; IntAct=EBI-711290, EBI-295644;
CC P42773; Q00534: CDK6; NbExp=25; IntAct=EBI-711290, EBI-295663;
CC P42773; O43186: CRX; NbExp=3; IntAct=EBI-711290, EBI-748171;
CC P42773; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-711290, EBI-751587;
CC P42773; O00291: HIP1; NbExp=3; IntAct=EBI-711290, EBI-473886;
CC P42773; Q15323: KRT31; NbExp=3; IntAct=EBI-711290, EBI-948001;
CC P42773; P13473-2: LAMP2; NbExp=3; IntAct=EBI-711290, EBI-21591415;
CC P42773; Q9UJ70: NAGK; NbExp=4; IntAct=EBI-711290, EBI-372578;
CC P42773; Q9UJ70-2: NAGK; NbExp=3; IntAct=EBI-711290, EBI-11526455;
CC P42773; Q9GZT8: NIF3L1; NbExp=6; IntAct=EBI-711290, EBI-740897;
CC P42773; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-711290, EBI-10302990;
CC P42773; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-711290, EBI-949255;
CC P42773; P78424: POU6F2; NbExp=3; IntAct=EBI-711290, EBI-12029004;
CC P42773; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-711290, EBI-5280197;
CC P42773; Q04864: REL; NbExp=4; IntAct=EBI-711290, EBI-307352;
CC P42773; Q04864-2: REL; NbExp=3; IntAct=EBI-711290, EBI-10829018;
CC P42773; O60504: SORBS3; NbExp=3; IntAct=EBI-711290, EBI-741237;
CC P42773; Q99081: TCF12; NbExp=5; IntAct=EBI-711290, EBI-722877;
CC P42773; Q99081-3: TCF12; NbExp=4; IntAct=EBI-711290, EBI-11952764;
CC P42773; P15884: TCF4; NbExp=4; IntAct=EBI-711290, EBI-533224;
CC P42773; P15884-3: TCF4; NbExp=3; IntAct=EBI-711290, EBI-13636688;
CC -!- TISSUE SPECIFICITY: Highest levels found in skeletal muscle. Also found
CC in pancreas and heart.
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/cdkn2c/";
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DR EMBL; U17074; AAC50074.1; -; mRNA.
DR EMBL; AF041248; AAC39782.1; -; mRNA.
DR EMBL; AF041250; AAC39783.1; -; Genomic_DNA.
DR EMBL; AF041249; AAC39783.1; JOINED; Genomic_DNA.
DR EMBL; AY094608; AAM11873.1; -; Genomic_DNA.
DR EMBL; BC000598; AAH00598.1; -; mRNA.
DR EMBL; BC005041; AAH05041.1; -; mRNA.
DR EMBL; BC016173; AAH16173.1; -; mRNA.
DR CCDS; CCDS555.1; -.
DR PIR; A55479; A55479.
DR RefSeq; NP_001253.1; NM_001262.2.
DR RefSeq; NP_523240.1; NM_078626.2.
DR PDB; 1BU9; NMR; -; A=1-168.
DR PDB; 1G3N; X-ray; 2.90 A; B/F=1-168.
DR PDB; 1IHB; X-ray; 1.95 A; A/B=1-162.
DR PDB; 1MX2; X-ray; 2.25 A; A/B=1-168.
DR PDB; 1MX4; X-ray; 2.00 A; A/B=1-168.
DR PDB; 1MX6; X-ray; 2.00 A; A/B=1-168.
DR PDBsum; 1BU9; -.
DR PDBsum; 1G3N; -.
DR PDBsum; 1IHB; -.
DR PDBsum; 1MX2; -.
DR PDBsum; 1MX4; -.
DR PDBsum; 1MX6; -.
DR AlphaFoldDB; P42773; -.
DR SMR; P42773; -.
DR BioGRID; 107465; 90.
DR IntAct; P42773; 54.
DR MINT; P42773; -.
DR STRING; 9606.ENSP00000262662; -.
DR iPTMnet; P42773; -.
DR PhosphoSitePlus; P42773; -.
DR BioMuta; CDKN2C; -.
DR DMDM; 1168870; -.
DR EPD; P42773; -.
DR jPOST; P42773; -.
DR MassIVE; P42773; -.
DR PaxDb; P42773; -.
DR PeptideAtlas; P42773; -.
DR PRIDE; P42773; -.
DR ProteomicsDB; 55557; -.
DR Antibodypedia; 3941; 567 antibodies from 36 providers.
DR DNASU; 1031; -.
DR Ensembl; ENST00000262662.5; ENSP00000262662.1; ENSG00000123080.12.
DR Ensembl; ENST00000371761.4; ENSP00000360826.3; ENSG00000123080.12.
DR Ensembl; ENST00000396148.2; ENSP00000379452.1; ENSG00000123080.12.
DR GeneID; 1031; -.
DR KEGG; hsa:1031; -.
DR MANE-Select; ENST00000371761.4; ENSP00000360826.3; NM_078626.3; NP_523240.1.
DR CTD; 1031; -.
DR DisGeNET; 1031; -.
DR GeneCards; CDKN2C; -.
DR HGNC; HGNC:1789; CDKN2C.
DR HPA; ENSG00000123080; Tissue enhanced (adipose tissue, lymphoid tissue).
DR MalaCards; CDKN2C; -.
DR MIM; 603369; gene.
DR neXtProt; NX_P42773; -.
DR OpenTargets; ENSG00000123080; -.
DR Orphanet; 652; Multiple endocrine neoplasia type 1.
DR PharmGKB; PA26322; -.
DR VEuPathDB; HostDB:ENSG00000123080; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000160194; -.
DR HOGENOM; CLU_000134_37_0_1; -.
DR InParanoid; P42773; -.
DR OMA; MAEPLGN; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; P42773; -.
DR TreeFam; TF333311; -.
DR PathwayCommons; P42773; -.
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; P42773; -.
DR SIGNOR; P42773; -.
DR BioGRID-ORCS; 1031; 26 hits in 1113 CRISPR screens.
DR ChiTaRS; CDKN2C; human.
DR EvolutionaryTrace; P42773; -.
DR GeneWiki; CDKN2C; -.
DR GenomeRNAi; 1031; -.
DR Pharos; P42773; Tbio.
DR PRO; PR:P42773; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P42773; protein.
DR Bgee; ENSG00000123080; Expressed in ventricular zone and 209 other tissues.
DR ExpressionAtlas; P42773; baseline and differential.
DR Genevisible; P42773; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
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:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
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:0072089; P:stem cell proliferation; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF13637; Ank_4; 2.
DR SMART; SM00248; ANK; 4.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cell cycle; Reference proteome; Repeat.
FT CHAIN 1..168
FT /note="Cyclin-dependent kinase 4 inhibitor C"
FT /id="PRO_0000144186"
FT REPEAT 4..33
FT /note="ANK 1"
FT REPEAT 37..65
FT /note="ANK 2"
FT REPEAT 69..98
FT /note="ANK 3"
FT REPEAT 102..132
FT /note="ANK 4"
FT VARIANT 72
FT /note="A -> P (in breast cancer; loss of CDK6 interaction;
FT dbSNP:rs771853517)"
FT /evidence="ECO:0000269|PubMed:8840966,
FT ECO:0000269|PubMed:9636670"
FT /id="VAR_001490"
FT VARIANT 126
FT /note="T -> M (in dbSNP:rs17851380)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038604"
FT HELIX 6..15
FT /evidence="ECO:0007829|PDB:1IHB"
FT HELIX 18..24
FT /evidence="ECO:0007829|PDB:1IHB"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:1BU9"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1IHB"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:1BU9"
FT HELIX 50..58
FT /evidence="ECO:0007829|PDB:1IHB"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:1IHB"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:1IHB"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1BU9"
FT HELIX 106..112
FT /evidence="ECO:0007829|PDB:1IHB"
FT HELIX 116..125
FT /evidence="ECO:0007829|PDB:1IHB"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1BU9"
FT HELIX 140..146
FT /evidence="ECO:0007829|PDB:1IHB"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:1IHB"
SQ SEQUENCE 168 AA; 18127 MW; 5D66AFA715186E9A CRC64;
MAEPWGNELA SAAARGDLEQ LTSLLQNNVN VNAQNGFGRT ALQVMKLGNP EIARRLLLRG
ANPDLKDRTG FAVIHDAARA GFLDTLQTLL EFQADVNIED NEGNLPLHLA AKEGHLRVVE
FLVKHTASNV GHRNHKGDTA CDLARLYGRN EVVSLMQANG AGGATNLQ
