UniProtKB - P51480 (CDN2A_MOUSE)
Protein
Cyclin-dependent kinase inhibitor 2A
Gene
Cdkn2a
Organism
Mus musculus (Mouse)
Status
Functioni
Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
Caution
The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to tumor suppressor ARF (AC Q64364) which is encoded by the same gene.Curated
GO - Molecular functioni
- cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGI
- disordered domain specific binding Source: MGI
- MDM2/MDM4 family protein binding Source: MGI
- NF-kappaB binding Source: MGI
- p53 binding Source: MGI
- protein kinase binding Source: MGI
- protein N-terminus binding Source: MGI
- SUMO transferase activity Source: MGI
- transcription factor binding Source: MGI
- ubiquitin ligase inhibitor activity Source: MGI
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- aging Source: MGI
- amyloid fibril formation Source: MGI
- apoptotic mitochondrial changes Source: MGI
- autophagy of mitochondrion Source: MGI
- cell aging Source: MGI
- cell cycle arrest Source: MGI
- cellular response to hydrogen peroxide Source: MGI
- cellular senescence Source: MGI
- epidermis development Source: MGI
- G1/S transition of mitotic cell cycle Source: MGI
- glucose homeostasis Source: MGI
- mitochondrial depolarization Source: MGI
- negative regulation of cell cycle Source: MGI
- negative regulation of cell growth Source: MGI
- negative regulation of cell-matrix adhesion Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
- negative regulation of hepatocyte proliferation Source: MGI
- negative regulation of mammary gland epithelial cell proliferation Source: MGI
- negative regulation of NF-kappaB transcription factor activity Source: MGI
- negative regulation of phosphorylation Source: MGI
- negative regulation of protein binding Source: MGI
- negative regulation of protein kinase activity Source: MGI
- negative regulation of protein neddylation Source: MGI
- negative regulation of proteolysis involved in cellular protein catabolic process Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- negative regulation of ubiquitin-dependent protein catabolic process Source: MGI
- negative regulation of ubiquitin protein ligase activity Source: MGI
- positive regulation of apoptotic process Source: MGI
- positive regulation of apoptotic process involved in mammary gland involution Source: MGI
- positive regulation of cell cycle arrest Source: MGI
- positive regulation of cellular senescence Source: MGI
- positive regulation of DNA damage response, signal transduction by p53 class mediator Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of macrophage apoptotic process Source: BHF-UCL
- positive regulation of protein localization to nucleus Source: MGI
- positive regulation of protein sumoylation Source: MGI
- positive regulation of signal transduction by p53 class mediator Source: MGI
- positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- protein destabilization Source: MGI
- protein K63-linked ubiquitination Source: MGI
- protein polyubiquitination Source: MGI
- protein stabilization Source: MGI
- regulation of apoptotic DNA fragmentation Source: MGI
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
- regulation of DNA-binding transcription factor activity Source: MGI
- regulation of G2/M transition of mitotic cell cycle Source: MGI
- regulation of gene expression Source: MGI
- regulation of nucleocytoplasmic transport Source: MGI
- regulation of protein export from nucleus Source: MGI
- regulation of protein targeting to mitochondrion Source: MGI
- replicative senescence Source: MGI
- response to drug Source: MGI
- response to organic cyclic compound Source: MGI
- response to organonitrogen compound Source: MGI
- rRNA transcription Source: MGI
- senescence-associated heterochromatin focus assembly Source: MGI
- somatic stem cell population maintenance Source: MGI
Keywordsi
Biological process | Cell cycle |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclin-dependent kinase inhibitor 2AImportedAlternative name(s): Cyclin-dependent kinase 4 inhibitor A Short name: CDK4I p16-INK4a Short name: p16-INK4 |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104738, Cdkn2a |
Subcellular locationi
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- nucleolus Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
- protein-containing complex Source: MGI
- senescence-associated heterochromatin focus Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 64 | C → G or R: No effect on activity. 1 Publication | 1 | |
Mutagenesisi | 76 | D → N: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 84 – 85 | Missing : Loss of activity. 1 Publication | 2 |
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144178 | 1 – 168 | Cyclin-dependent kinase inhibitor 2AAdd BLAST | 168 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 152 | PhosphoserineBy similarity | 1 | |
Modified residuei | 164 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylation seems to increase interaction with CDK4.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PeptideAtlasi | P51480 |
PRIDEi | P51480 |
PTM databases
iPTMneti | P51480 |
PhosphoSitePlusi | P51480 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000044303, Expressed in spinal cord and 72 other tissues |
ExpressionAtlasi | P51480, baseline and differential |
Genevisiblei | P51480, MM |
Interactioni
Subunit structurei
Heterodimer with CDK4 or CDK6. Predominamt P16 complexes contained CDK6.
Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity.
Interacts with ISCO2 (By similarity).
By similarityGO - Molecular functioni
- disordered domain specific binding Source: MGI
- MDM2/MDM4 family protein binding Source: MGI
- NF-kappaB binding Source: MGI
- p53 binding Source: MGI
- protein kinase binding Source: MGI
- protein N-terminus binding Source: MGI
- transcription factor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198654, 37 interactors |
CORUMi | P51480 |
DIPi | DIP-60251N |
IntActi | P51480, 1 interactor |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 3 – 32 | ANK 1Add BLAST | 30 | |
Repeati | 36 – 64 | ANK 2Add BLAST | 29 | |
Repeati | 69 – 98 | ANK 3Add BLAST | 30 | |
Repeati | 102 – 131 | ANK 4Add BLAST | 30 |
Sequence similaritiesi
Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.Curated
Keywords - Domaini
ANK repeat, RepeatPhylogenomic databases
GeneTreei | ENSGT00940000168083 |
HOGENOMi | CLU_000134_37_1_1 |
OMAi | APNRYGR |
TreeFami | TF352389 |
Family and domain databases
Gene3Di | 1.25.40.20, 1 hit |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf |
Pfami | View protein in Pfam PF12796, Ank_2, 1 hit |
SMARTi | View protein in SMART SM00248, ANK, 4 hits |
SUPFAMi | SSF48403, SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketNote: Isoform 1 and isoform tumor suppressor ARF arise due to the use of two alternative first exons joined to a common exon 2 at the same acceptor site but in different reading frames, resulting in two completely different isoforms.
Isoform 1 (identifier: P51480-1) [UniParc]FASTAAdd to basket
Also known as: p16INK4a
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MESAADRLAR AAAQGRVHDV RALLEAGVSP NAPNSFGRTP IQVMMMGNVH
60 70 80 90 100
VAALLLNYGA DSNCEDPTTF SRPVHDAARE GFLDTLVVLH GSGARLDVRD
110 120 130 140 150
AWGRLPLDLA QERGHQDIVR YLRSAGCSLC SAGWSLCTAG NVAQTDGHSF
160
SSSTPRALEL RGQSQEQS
Isoform tumor suppressor ARF (identifier: Q64364-1) [UniParc]FASTAAdd to basket
Also known as: p19ARF
The sequence of this isoform can be found in the external entry Q64364.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoform smARF (identifier: Q64364-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q64364.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 11 | Missing in AAA85453 (PubMed:7651726).Curated | 1 |
Polymorphismi
Strain BALB/c displays a significantly reduced ability to inhibit phosphorylation of the retinoblastoma protein.
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 12 | A → V in some liver tumors. 1 Publication | 1 | |
Natural varianti | 18 | H → P in strain: 020, BALB/c, BALB/cJ, C3H/21BG, C3H/HeJ, CBA/J, MA/M4J and PL/J. 3 Publications | 1 | |
Natural varianti | 27 | G → E in some liver tumors. 1 Publication | 1 | |
Natural varianti | 51 | V → I in strain: BALB/c and BALB/cJ. 2 Publications | 1 | |
Natural varianti | 73 | P → L in some liver tumors. 1 Publication | 1 | |
Natural varianti | 74 | V → M in plasmacytoma cell lines. 1 Publication | 1 | |
Natural varianti | 75 | H → Y in plasmacytoma cell lines. 1 Publication | 1 | |
Natural varianti | 90 | H → Q in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication | 1 | |
Natural varianti | 90 | H → R in plasmacytoma cell lines. 1 Publication | 1 | |
Natural varianti | 127 | C → S in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015867 | 1 – 43 | Missing in isoform 2. CuratedAdd BLAST | 43 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76150 mRNA Translation: AAA85453.1 AF044335 mRNA Translation: AAC08962.1 AF044336 mRNA Translation: AAC08963.1 AF332190 Genomic DNA Translation: AAK83159.1 AK155307 mRNA Translation: BAE33180.1 AL831719 Genomic DNA No translation available. U66087, U66086 Genomic DNA Translation: AAB39600.1 U79625 Genomic DNA Translation: AAD00223.1 U79626 Genomic DNA Translation: AAD00224.1 U79627 Genomic DNA Translation: AAD00225.1 U79628 Genomic DNA Translation: AAD00226.1 U79630 Genomic DNA Translation: AAD00227.1 U79631 Genomic DNA Translation: AAD00228.1 U79632 Genomic DNA Translation: AAD00229.1 U49279 Genomic DNA Translation: AAC00051.1 U49280 Genomic DNA Translation: AAC00052.1 AF004588 Genomic DNA Translation: AAB61416.1 |
CCDSi | CCDS38812.1 [P51480-1] |
RefSeqi | NP_001035744.1, NM_001040654.1 [P51480-1] |
Genome annotation databases
Ensembli | ENSMUST00000060501; ENSMUSP00000061847; ENSMUSG00000044303 [P51480-1] |
GeneIDi | 12578 |
KEGGi | mmu:12578 |
UCSCi | uc008toh.1, mouse [P51480-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76150 mRNA Translation: AAA85453.1 AF044335 mRNA Translation: AAC08962.1 AF044336 mRNA Translation: AAC08963.1 AF332190 Genomic DNA Translation: AAK83159.1 AK155307 mRNA Translation: BAE33180.1 AL831719 Genomic DNA No translation available. U66087, U66086 Genomic DNA Translation: AAB39600.1 U79625 Genomic DNA Translation: AAD00223.1 U79626 Genomic DNA Translation: AAD00224.1 U79627 Genomic DNA Translation: AAD00225.1 U79628 Genomic DNA Translation: AAD00226.1 U79630 Genomic DNA Translation: AAD00227.1 U79631 Genomic DNA Translation: AAD00228.1 U79632 Genomic DNA Translation: AAD00229.1 U49279 Genomic DNA Translation: AAC00051.1 U49280 Genomic DNA Translation: AAC00052.1 AF004588 Genomic DNA Translation: AAB61416.1 |
CCDSi | CCDS38812.1 [P51480-1] |
RefSeqi | NP_001035744.1, NM_001040654.1 [P51480-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1LNN | model | - | A | 12-159 | [»] | |
SMRi | P51480 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 198654, 37 interactors |
CORUMi | P51480 |
DIPi | DIP-60251N |
IntActi | P51480, 1 interactor |
PTM databases
iPTMneti | P51480 |
PhosphoSitePlusi | P51480 |
Proteomic databases
PeptideAtlasi | P51480 |
PRIDEi | P51480 |
Genome annotation databases
Ensembli | ENSMUST00000060501; ENSMUSP00000061847; ENSMUSG00000044303 [P51480-1] |
GeneIDi | 12578 |
KEGGi | mmu:12578 |
UCSCi | uc008toh.1, mouse [P51480-1] |
Organism-specific databases
CTDi | 1029 |
MGIi | MGI:104738, Cdkn2a |
Phylogenomic databases
GeneTreei | ENSGT00940000168083 |
HOGENOMi | CLU_000134_37_1_1 |
OMAi | APNRYGR |
TreeFami | TF352389 |
Miscellaneous databases
BioGRID-ORCSi | 12578, 1 hit in 17 CRISPR screens |
ChiTaRSi | Cdkn2a, mouse |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000044303, Expressed in spinal cord and 72 other tissues |
ExpressionAtlasi | P51480, baseline and differential |
Genevisiblei | P51480, MM |
Family and domain databases
Gene3Di | 1.25.40.20, 1 hit |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf |
Pfami | View protein in Pfam PF12796, Ank_2, 1 hit |
SMARTi | View protein in SMART SM00248, ANK, 4 hits |
SUPFAMi | SSF48403, SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CDN2A_MOUSE | |
Accessioni | P51480Primary (citable) accession number: P51480 Secondary accession number(s): A2ANM1 Q9QWH8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 25, 2005 | |
Last modified: | December 2, 2020 | |
This is version 176 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families