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Protein

Cyclin-dependent kinase inhibitor 2A

Gene

Cdkn2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

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 (By similarity).By similarity

Miscellaneous

Down-regulated in a number of tumor cell lines in response to methylation of the CpG island in exon 1.1 Publication

Caution

The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in term of sequence and function to tumor suppressor ARF (AC Q8QZZ9) which is encoded by the same gene.Curated

GO - Biological processi

  • aging Source: RGD
  • cell cycle Source: UniProtKB-KW
  • cellular response to glucose stimulus Source: RGD
  • cerebellum development Source: RGD
  • negative regulation of hepatocyte proliferation Source: RGD
  • neurogenesis Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • response to caloric restriction Source: RGD
  • response to drug Source: RGD
  • response to fatty acid Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to salt stress Source: RGD

Keywordsi

Biological processCell cycle

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 2AImported
Alternative name(s):
Cyclin-dependent kinase 4 inhibitor A
Short name:
CDK4I
p16-INK4a
Short name:
p16
Short name:
p16-INK4
Gene namesi
Name:Cdkn2aImported
Synonyms:P16ink4aBy similarity
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2323 Cdkn2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001441791 – 159Cyclin-dependent kinase inhibitor 2AAdd BLAST159

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei143PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation seems to increase interaction with CDK4.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R0Z3
PRIDEiQ9R0Z3

Expressioni

Tissue specificityi

Expressed in spleen, liver and lung. Not detected in kidney, colon, stomach or brain.1 Publication

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 similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000061040

Structurei

3D structure databases

ProteinModelPortaliQ9R0Z3
SMRiQ9R0Z3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati3 – 35ANK 1Sequence analysisAdd BLAST33
Repeati36 – 64ANK 2Sequence analysisAdd BLAST29
Repeati69 – 98ANK 3Sequence analysisAdd BLAST30
Repeati102 – 134ANK 4Sequence analysisAdd BLAST33

Sequence similaritiesi

Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.Sequence analysis

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
HOGENOMiHOG000290191
HOVERGENiHBG050870
KOiK06621

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 4 hits
SUPFAMiSSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: 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.By similarity
Isoform 11 Publication (identifier: Q9R0Z3-1) [UniParc]FASTAAdd to basket
Also known as: p16INK4aBy similarity

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MESSADRLAR AAALGREHEV RALLEAGASP NAPNTFGRTP IQVMMMGNVK
60 70 80 90 100
VAALLLSYGA DSNCEDPTTL SRPVHDAARE GFLDTLVVLH QAGARLDVRD
110 120 130 140 150
AWGRLPLDLA LERGHHDVVR YLRYLLSSAG NVSRVTDRHN FCSSTPRCLG

LRGQPPKQR
Length:159
Mass (Da):17,366
Last modified:May 1, 2000 - v1
Checksum:i3C4CA920A1FEAEB6
GO
Isoform tumor suppressor ARFCurated (identifier: Q8QZZ9-1) [UniParc]FASTAAdd to basket
Also known as: p19ARFCurated
The sequence of this isoform can be found in the external entry Q8QZZ9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:160
Mass (Da):17,307
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L81167 mRNA Translation: AAD48924.1
AF474976 mRNA Translation: AAL76338.1
AF474977 mRNA Translation: AAL76339.1
AY679728 mRNA Translation: AAT92510.1
RefSeqiNP_113738.1, NM_031550.1 [Q9R0Z3-1]
UniGeneiRn.48717

Genome annotation databases

GeneIDi25163
KEGGirno:25163

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCDN2A_RAT
AccessioniPrimary (citable) accession number: Q9R0Z3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 109 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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