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P42773

- CDN2C_HUMAN

UniProt

P42773 - CDN2C_HUMAN

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Protein

Cyclin-dependent kinase 4 inhibitor C

Gene

CDKN2C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: BHF-UCL
  2. protein kinase binding Source: BHF-UCL

GO - Biological processi

  1. cell cycle arrest Source: BHF-UCL
  2. G1/S transition of mitotic cell cycle Source: BHF-UCL
  3. mitotic cell cycle Source: Reactome
  4. negative regulation of cell growth Source: BHF-UCL
  5. negative regulation of cell proliferation Source: BHF-UCL
  6. negative regulation of phosphorylation Source: BHF-UCL
  7. negative regulation of protein serine/threonine kinase activity Source: GOC
  8. oligodendrocyte differentiation Source: Ensembl
  9. regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Enzyme and pathway databases

ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_821. Cyclin D associated events in G1.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 4 inhibitor C
Alternative name(s):
Cyclin-dependent kinase 6 inhibitor
p18-INK4c
p18-INK6
Gene namesi
Name:CDKN2C
Synonyms:CDKN6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:1789. CDKN2C.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. cytosol Source: Reactome
  3. nucleus Source: BHF-UCL
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

Orphaneti652. Multiple endocrine neoplasia type 1.
PharmGKBiPA26322.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 168168Cyclin-dependent kinase 4 inhibitor CPRO_0000144186Add
BLAST

Proteomic databases

MaxQBiP42773.
PaxDbiP42773.
PRIDEiP42773.

PTM databases

PhosphoSiteiP42773.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP42773.
CleanExiHS_CDKN2C.
ExpressionAtlasiP42773. baseline and differential.
GenevestigatoriP42773.

Organism-specific databases

HPAiCAB005303.
CAB018398.
HPA019057.
HPA019764.

Interactioni

Subunit structurei

Heterodimer of p18 with CDK6.

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK4P118023EBI-711290,EBI-295644
CDK6Q005343EBI-711290,EBI-295663

Protein-protein interaction databases

BioGridi107465. 25 interactions.
IntActiP42773. 16 interactions.
MINTiMINT-1372629.
STRINGi9606.ENSP00000262662.

Structurei

Secondary structure

1
168
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 1510Combined sources
Helixi18 – 247Combined sources
Turni36 – 383Combined sources
Helixi41 – 444Combined sources
Turni45 – 484Combined sources
Helixi50 – 589Combined sources
Helixi73 – 808Combined sources
Helixi83 – 919Combined sources
Beta strandi101 – 1033Combined sources
Helixi106 – 1127Combined sources
Helixi116 – 12510Combined sources
Beta strandi135 – 1373Combined sources
Helixi140 – 1467Combined sources
Helixi150 – 1589Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP42773.
SMRiP42773. Positions 5-160.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42773.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati4 – 3330ANK 1Add
BLAST
Repeati37 – 6529ANK 2Add
BLAST
Repeati69 – 9830ANK 3Add
BLAST
Repeati102 – 13231ANK 4Add
BLAST

Sequence similaritiesi

Contains 4 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiCOG0666.
HOGENOMiHOG000290191.
HOVERGENiHBG050870.
InParanoidiP42773.
KOiK06622.
OMAiKDQTGFA.
OrthoDBiEOG7ZSHVC.
PhylomeDBiP42773.
TreeFamiTF333311.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 3 hits.
[Graphical view]
SMARTiSM00248. ANK. 4 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P42773-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEPWGNELA SAAARGDLEQ LTSLLQNNVN VNAQNGFGRT ALQVMKLGNP
60 70 80 90 100
EIARRLLLRG ANPDLKDRTG FAVIHDAARA GFLDTLQTLL EFQADVNIED
110 120 130 140 150
NEGNLPLHLA AKEGHLRVVE FLVKHTASNV GHRNHKGDTA CDLARLYGRN
160
EVVSLMQANG AGGATNLQ
Length:168
Mass (Da):18,127
Last modified:November 1, 1995 - v1
Checksum:i5D66AFA715186E9A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti72 – 721A → P in breast cancer; loss of CDK6 interaction. 2 Publications
VAR_001490
Natural varianti126 – 1261T → M.1 Publication
Corresponds to variant rs17851380 [ dbSNP | Ensembl ].
VAR_038604

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS555.1.
PIRiA55479.
RefSeqiNP_001253.1. NM_001262.2.
NP_523240.1. NM_078626.2.
UniGeneiHs.525324.

Genome annotation databases

EnsembliENST00000262662; ENSP00000262662; ENSG00000123080.
ENST00000371761; ENSP00000360826; ENSG00000123080.
ENST00000396148; ENSP00000379452; ENSG00000123080.
GeneIDi1031.
KEGGihsa:1031.
UCSCiuc001csf.3. human.

Polymorphism databases

DMDMi1168870.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS555.1.
PIRi A55479.
RefSeqi NP_001253.1. NM_001262.2.
NP_523240.1. NM_078626.2.
UniGenei Hs.525324.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1BU9 NMR - A 1-168 [» ]
1G3N X-ray 2.90 B/F 1-168 [» ]
1IHB X-ray 1.95 A/B 1-162 [» ]
1MX2 X-ray 2.25 A/B 1-168 [» ]
1MX4 X-ray 2.00 A/B 1-168 [» ]
1MX6 X-ray 2.00 A/B 1-168 [» ]
ProteinModelPortali P42773.
SMRi P42773. Positions 5-160.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107465. 25 interactions.
IntActi P42773. 16 interactions.
MINTi MINT-1372629.
STRINGi 9606.ENSP00000262662.

PTM databases

PhosphoSitei P42773.

Polymorphism databases

DMDMi 1168870.

Proteomic databases

MaxQBi P42773.
PaxDbi P42773.
PRIDEi P42773.

Protocols and materials databases

DNASUi 1031.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262662 ; ENSP00000262662 ; ENSG00000123080 .
ENST00000371761 ; ENSP00000360826 ; ENSG00000123080 .
ENST00000396148 ; ENSP00000379452 ; ENSG00000123080 .
GeneIDi 1031.
KEGGi hsa:1031.
UCSCi uc001csf.3. human.

Organism-specific databases

CTDi 1031.
GeneCardsi GC01P051427.
HGNCi HGNC:1789. CDKN2C.
HPAi CAB005303.
CAB018398.
HPA019057.
HPA019764.
MIMi 603369. gene.
neXtProti NX_P42773.
Orphaneti 652. Multiple endocrine neoplasia type 1.
PharmGKBi PA26322.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0666.
HOGENOMi HOG000290191.
HOVERGENi HBG050870.
InParanoidi P42773.
KOi K06622.
OMAi KDQTGFA.
OrthoDBi EOG7ZSHVC.
PhylomeDBi P42773.
TreeFami TF333311.

Enzyme and pathway databases

Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_821. Cyclin D associated events in G1.

Miscellaneous databases

EvolutionaryTracei P42773.
GeneWikii CDKN2C.
GenomeRNAii 1031.
NextBioi 4337.
PROi P42773.
SOURCEi Search...

Gene expression databases

Bgeei P42773.
CleanExi HS_CDKN2C.
ExpressionAtlasi P42773. baseline and differential.
Genevestigatori P42773.

Family and domain databases

Gene3Di 1.25.40.20. 2 hits.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view ]
Pfami PF00023. Ank. 3 hits.
[Graphical view ]
SMARTi SM00248. ANK. 4 hits.
[Graphical view ]
SUPFAMi SSF48403. SSF48403. 1 hit.
PROSITEi PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCDN2C_HUMAN
AccessioniPrimary (citable) accession number: P42773
Secondary accession number(s): Q8TB83
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 26, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3