CDN2A_RAT
ID CDN2A_RAT Reviewed; 159 AA.
AC Q9R0Z3;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Cyclin-dependent kinase inhibitor 2A {ECO:0000312|RGD:2323};
DE AltName: Full=Cyclin-dependent kinase 4 inhibitor A;
DE Short=CDK4I;
DE AltName: Full=p16-INK4a;
DE Short=p16;
DE Short=p16-INK4;
GN Name=Cdkn2a {ECO:0000312|EMBL:AAL76338.1, ECO:0000312|RGD:2323};
GN Synonyms=P16ink4a {ECO:0000250|UniProtKB:P51480};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD48924.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Fischer 344/N; TISSUE=Lung {ECO:0000312|EMBL:AAD48924.1};
RX PubMed=9032263; DOI=10.1128/mcb.17.3.1366;
RA Swafford D.S., Middleton S.K., Palmisano W.A., Nikula K.J., Tesfaigzi J.,
RA Baylin S.B., Herman J.G., Belinsky S.A.;
RT "Frequent aberrant methylation of p16INK4a in primary rat lung tumors.";
RL Mol. Cell. Biol. 17:1366-1374(1997).
RN [2] {ECO:0000312|EMBL:AAL76338.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ACI/SegHsd {ECO:0000312|EMBL:AAL76338.1},
RC Brown Norway/SsNHsd {ECO:0000312|EMBL:AAT92510.1}, and
RC COP {ECO:0000312|EMBL:AAL76339.1};
RC TISSUE=Spleen {ECO:0000312|EMBL:AAL76338.1};
RA Buckles L.K., Shull J.D.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Acts as a negative regulator of the proliferation of normal
CC cells by interacting strongly with CDK4 and CDK6. This inhibits their
CC ability to interact with cyclins D and to phosphorylate the
CC retinoblastoma protein (By similarity). {ECO:0000250|UniProtKB:P51480}.
CC -!- SUBUNIT: Heterodimer with CDK4 or CDK6. Predominamt P16 complexes
CC contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and
CC non-phosphorylated forms); the interaction inhibits cyclin D-CDK4
CC kinase activity. Interacts with ISCO2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Isoform 1 and isoform tumor suppressor ARF arise due to the
CC use of two alternative first exons joined to a common exon 2 at the
CC same acceptor site but in different reading frames, resulting in two
CC completely different isoforms. {ECO:0000250|UniProtKB:P51480};
CC Name=1 {ECO:0000269|PubMed:9032263}; Synonyms=p16INK4a
CC {ECO:0000250|UniProtKB:P51480};
CC IsoId=Q9R0Z3-1; Sequence=Displayed;
CC Name=tumor suppressor ARF {ECO:0000305}; Synonyms=p19ARF {ECO:0000305};
CC IsoId=Q8QZZ9-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, liver and lung. Not detected
CC in kidney, colon, stomach or brain. {ECO:0000269|PubMed:9032263}.
CC -!- PTM: Phosphorylation seems to increase interaction with CDK4.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Down-regulated in a number of tumor cell lines in
CC response to methylation of the CpG island in exon 1.
CC {ECO:0000269|PubMed:9032263}.
CC -!- SIMILARITY: Belongs to the CDKN2 cyclin-dependent kinase inhibitor
CC family. {ECO:0000255}.
CC -!- CAUTION: The proteins described here are encoded by the gene CDKN2A,
CC but are completely unrelated in terms of sequence and function to tumor
CC suppressor ARF (AC Q8QZZ9) which is encoded by the same gene.
CC {ECO:0000305}.
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; L81167; AAD48924.1; -; mRNA.
DR EMBL; AF474976; AAL76338.1; -; mRNA.
DR EMBL; AF474977; AAL76339.1; -; mRNA.
DR EMBL; AY679728; AAT92510.1; -; mRNA.
DR RefSeq; NP_113738.1; NM_031550.1. [Q9R0Z3-1]
DR AlphaFoldDB; Q9R0Z3; -.
DR SMR; Q9R0Z3; -.
DR STRING; 10116.ENSRNOP00000061040; -.
DR PaxDb; Q9R0Z3; -.
DR Ensembl; ENSRNOT00000103638; ENSRNOP00000087870; ENSRNOG00000059837. [Q9R0Z3-1]
DR GeneID; 25163; -.
DR KEGG; rno:25163; -.
DR CTD; 1029; -.
DR RGD; 2323; Cdkn2a.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000165099; -.
DR OrthoDB; 1435166at2759; -.
DR Proteomes; UP000002494; Chromosome 5.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0001652; C:granular component; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0035985; C:senescence-associated heterochromatin focus; ISO:RGD.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISO:RGD.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; ISO:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:RGD.
DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; ISO:RGD.
DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:1990000; P:amyloid fibril formation; ISO:RGD.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0090398; P:cellular senescence; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0008544; P:epidermis development; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IMP:RGD.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISO:RGD.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; ISO:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:RGD.
DR GO; GO:2000435; P:negative regulation of protein neddylation; ISO:RGD.
DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; ISO:RGD.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0022008; P:neurogenesis; IEP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISO:RGD.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:RGD.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISO:RGD.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0007265; P:Ras protein signal transduction; ISO:RGD.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; ISO:RGD.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0090399; P:replicative senescence; ISO:RGD.
DR GO; GO:0061771; P:response to caloric restriction; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IDA:RGD.
DR GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0009303; P:rRNA transcription; ISO:RGD.
DR GO; GO:0048103; P:somatic stem cell division; ISO:RGD.
DR GO; GO:0035019; P:somatic stem cell population maintenance; ISO:RGD.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF13637; Ank_4; 1.
DR SMART; SM00248; ANK; 4.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ANK repeat; Cell cycle; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..159
FT /note="Cyclin-dependent kinase inhibitor 2A"
FT /id="PRO_0000144179"
FT REPEAT 3..35
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 36..64
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 69..98
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 102..134
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42771"
SQ SEQUENCE 159 AA; 17366 MW; 3C4CA920A1FEAEB6 CRC64;
MESSADRLAR AAALGREHEV RALLEAGASP NAPNTFGRTP IQVMMMGNVK VAALLLSYGA
DSNCEDPTTL SRPVHDAARE GFLDTLVVLH QAGARLDVRD AWGRLPLDLA LERGHHDVVR
YLRYLLSSAG NVSRVTDRHN FCSSTPRCLG LRGQPPKQR
