CDN2A_MONDO
ID CDN2A_MONDO Reviewed; 171 AA.
AC O77617; Q548V3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Cyclin-dependent kinase inhibitor 2A {ECO:0000305|PubMed:9839807};
DE AltName: Full=Cyclin-dependent kinase 4 inhibitor A;
DE Short=CDK4I;
DE AltName: Full=Tumor suppressor CDKN2A;
DE AltName: Full=p16-INK4a;
DE Short=p16-INK4;
GN Name=CDKN2A {ECO:0000303|PubMed:9839807};
OS Monodelphis domestica (Gray short-tailed opossum).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Monodelphis.
OX NCBI_TaxID=13616;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE INITIATION.
RX PubMed=9839807; DOI=10.1089/dna.1998.17.975;
RA Sherburn T.E., Gale J.M., Ley R.D.;
RT "Cloning and characterization of the CDKN2A and p19ARF genes from
RT Monodelphis domestica.";
RL DNA Cell Biol. 17:975-981(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT PHE-151.
RX PubMed=11398194; DOI=10.1002/mc.1033;
RA Chan J., Robinson E.S., Atencio J., Wang Z., Kazianis S., Coletta L.D.,
RA Nairn R.S., McCarrey J.R.;
RT "Characterization of the CDKN2A and ARF genes in UV-induced melanocytic
RT hyperplasias and melanomas of an opossum (Monodelphis domestica).";
RL Mol. Carcinog. 31:16-26(2001).
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}.
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, Alternative initiation; Named isoforms=3;
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.;
CC Name=1; Synonyms=CDKN2A, p16INK4a;
CC IsoId=O77617-1; Sequence=Displayed;
CC Name=3;
CC IsoId=O77617-2; Sequence=VSP_018701;
CC Name=tumor suppressor ARF; Synonyms=p19ARF;
CC IsoId=O77618-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in lung and testis. In the
CC testis, restricted to germ cells in the seminiferous epithelium. Not
CC detected in premeiotic spermatogonia but high levels found in
CC postmeiotic spermatids. In primary tumors, low levels detected in
CC melanocytic hyperplasias. Higher levels found in non-metastatic and
CC metastatic melanomas. {ECO:0000269|PubMed:11398194}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation at Met-
CC 35 of isoform 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CDKN2 cyclin-dependent kinase inhibitor
CC family. {ECO:0000305}.
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 O77618) which is encoded by the same gene.
CC {ECO:0000305}.
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DR EMBL; AF064808; AAC23669.1; -; mRNA.
DR EMBL; AF064808; AAC23670.1; -; mRNA.
DR EMBL; AF236861; AAF65222.1; -; mRNA.
DR RefSeq; NP_001029248.1; NM_001034076.1. [O77617-1]
DR AlphaFoldDB; O77617; -.
DR SMR; O77617; -.
DR STRING; 13616.ENSMODP00000004687; -.
DR Ensembl; ENSMODT00000004787; ENSMODP00000004687; ENSMODG00000003820. [O77617-1]
DR GeneID; 554242; -.
DR CTD; 1029; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000165099; -.
DR HOGENOM; CLU_000134_37_1_1; -.
DR InParanoid; O77617; -.
DR OMA; RDEDKGM; -.
DR OrthoDB; 1435166at2759; -.
DR TreeFam; TF352389; -.
DR Proteomes; UP000002280; Chromosome 6.
DR Bgee; ENSMODG00000003820; Expressed in testis and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 2: Evidence at transcript level;
KW Alternative initiation; Alternative splicing; ANK repeat; Cell cycle;
KW Cytoplasm; Nucleus; Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..171
FT /note="Cyclin-dependent kinase inhibitor 2A"
FT /id="PRO_0000004804"
FT REPEAT 45..74
FT /note="ANK 1"
FT REPEAT 78..106
FT /note="ANK 2"
FT REPEAT 111..140
FT /note="ANK 3"
FT REGION 33..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_018701"
FT VARIANT 151
FT /note="L -> F (in some primary melanomas and melanoma cell
FT lines)"
FT /evidence="ECO:0000269|PubMed:11398194"
SQ SEQUENCE 171 AA; 18707 MW; 694264F5D0F4F6CC CRC64;
MGIVEKKEGG LERNRALFNS EGSCEGAKCG KEASMHTKHE SEESFSGEKL TEAAARGRTE
VVTELLELGT NPNAVNRFGR SAIQVMMMGN VRLAAILLQY GAEPNTPDPT TLTLPVHDAA
REGFLDTLML LHRAGARLDV RDSWGRLPVD LAEEQGHHLV VAYLREVVRD A
