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P42773 (CDN2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 4 inhibitor C
Alternative name(s):
Cyclin-dependent kinase 6 inhibitor
p18-INK4c
p18-INK6
Gene names
Name:CDKN2C
Synonyms:CDKN6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length168 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB.

Subunit structure

Heterodimer of p18 with CDK6.

Tissue specificity

Highest levels found in skeletal muscle. Also found in pancreas and heart.

Sequence similarities

Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.

Contains 4 ANK repeats.

Ontologies

Keywords
   Biological processCell cycle
   Coding sequence diversityPolymorphism
   DomainANK repeat
Repeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

cell cycle arrest

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of cell growth

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of phosphorylation

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: GOC

oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11800646. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 11800646. Source: BHF-UCL

   Molecular_functioncyclin-dependent protein serine/threonine kinase inhibitor activity

Inferred from direct assay Ref.1. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 18394558PubMed 21988832PubMed 23455922PubMed 23602568Ref.8. Source: IntAct

protein kinase binding

Inferred from physical interaction Ref.1. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 168168Cyclin-dependent kinase 4 inhibitor C
PRO_0000144186

Regions

Repeat4 – 3330ANK 1
Repeat37 – 6529ANK 2
Repeat69 – 9830ANK 3
Repeat102 – 13231ANK 4

Natural variations

Natural variant721A → P in breast cancer; loss of CDK6 interaction. Ref.2 Ref.8
VAR_001490
Natural variant1261T → M. Ref.4
Corresponds to variant rs17851380 [ dbSNP | Ensembl ].
VAR_038604

Secondary structure

............................ 168
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42773 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 5D66AFA715186E9A

FASTA16818,127
        10         20         30         40         50         60 
MAEPWGNELA SAAARGDLEQ LTSLLQNNVN VNAQNGFGRT ALQVMKLGNP EIARRLLLRG 

        70         80         90        100        110        120 
ANPDLKDRTG FAVIHDAARA GFLDTLQTLL EFQADVNIED NEGNLPLHLA AKEGHLRVVE 

       130        140        150        160 
FLVKHTASNV GHRNHKGDTA CDLARLYGRN EVVSLMQANG AGGATNLQ 

« Hide

References

« Hide 'large scale' references
[1]"Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function."
Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L., Matera G.A., Xiong Y.
Genes Dev. 8:2939-2952(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer."
Blais A., Labrie Y., Pouliot F., Lachance Y., Labrie C.
Biochem. Biophys. Res. Commun. 247:146-153(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT BREAST CANCER PRO-72.
Tissue: Mammary gland.
[3]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-126.
Tissue: Brain, Kidney and Uterus.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations."
Venkataramani R., Swaminathan K., Marmorstein R.
Nat. Struct. Biol. 5:74-81(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[7]"Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A."
Li J., Byeon I.-J.L., Ericson K., Poi M.-J., O'Maille P., Selby T., Tsai M.-D.
Biochemistry 38:2930-2940(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[8]"A p18 mutant defective in CDK6 binding in human breast cancer cells."
Lapointe J., Lachance Y., Labrie Y., Labrie C.
Cancer Res. 56:4586-4589(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BREAST CANCER PRO-72.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U17074 mRNA. Translation: AAC50074.1.
AF041248 mRNA. Translation: AAC39782.1.
AF041250, AF041249 Genomic DNA. Translation: AAC39783.1.
AY094608 Genomic DNA. Translation: AAM11873.1.
BC000598 mRNA. Translation: AAH00598.1.
BC005041 mRNA. Translation: AAH05041.1.
BC016173 mRNA. Translation: AAH16173.1.
CCDSCCDS555.1.
PIRA55479.
RefSeqNP_001253.1. NM_001262.2.
NP_523240.1. NM_078626.2.
UniGeneHs.525324.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BU9NMR-A1-168[»]
1G3NX-ray2.90B/F1-168[»]
1IHBX-ray1.95A/B1-162[»]
1MX2X-ray2.25A/B1-168[»]
1MX4X-ray2.00A/B1-168[»]
1MX6X-ray2.00A/B1-168[»]
ProteinModelPortalP42773.
SMRP42773. Positions 5-160.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107465. 22 interactions.
IntActP42773. 16 interactions.
MINTMINT-1372629.
STRING9606.ENSP00000262662.

PTM databases

PhosphoSiteP42773.

Polymorphism databases

DMDM1168870.

Proteomic databases

MaxQBP42773.
PaxDbP42773.
PRIDEP42773.

Protocols and materials databases

DNASU1031.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262662; ENSP00000262662; ENSG00000123080.
ENST00000371761; ENSP00000360826; ENSG00000123080.
ENST00000396148; ENSP00000379452; ENSG00000123080.
GeneID1031.
KEGGhsa:1031.
UCSCuc001csf.3. human.

Organism-specific databases

CTD1031.
GeneCardsGC01P051427.
HGNCHGNC:1789. CDKN2C.
HPACAB005303.
CAB018398.
HPA019057.
HPA019764.
MIM603369. gene.
neXtProtNX_P42773.
Orphanet652. Multiple endocrine neoplasia type 1.
PharmGKBPA26322.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000290191.
HOVERGENHBG050870.
InParanoidP42773.
KOK06622.
OMAKDQTGFA.
OrthoDBEOG7ZSHVC.
PhylomeDBP42773.
TreeFamTF333311.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressP42773.
BgeeP42773.
CleanExHS_CDKN2C.
GenevestigatorP42773.

Family and domain databases

Gene3D1.25.40.20. 2 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamPF00023. Ank. 3 hits.
[Graphical view]
SMARTSM00248. ANK. 4 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP42773.
GeneWikiCDKN2C.
GenomeRNAi1031.
NextBio4337.
PROP42773.
SOURCESearch...

Entry information

Entry nameCDN2C_HUMAN
AccessionPrimary (citable) accession number: P42773
Secondary accession number(s): Q8TB83
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM