P42773 (CDN2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	168 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cell cycle
Coding sequence diversity	Polymorphism
Domain	ANK repeat Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/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_component	cytoplasm 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_function	cyclin-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

With	Entry	#Exp.	IntAct	Notes
CDK4	P11802	3	EBI-711290,EBI-295644
CDK6	Q00534	3	EBI-711290,EBI-295663

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 168

168

Cyclin-dependent kinase 4 inhibitor C

PRO_0000144186

Regions

Repeat

4 – 33

30

ANK 1

Repeat

37 – 65

29

ANK 2

Repeat

69 – 98

30

ANK 3

Repeat

102 – 132

31

ANK 4

Natural variations

Natural variant

72

1

A → P in breast cancer; loss of CDK6 interaction. Ref.2 Ref.8

VAR_001490

Natural variant

126

1

T → M. Ref.4
Corresponds to variant rs17851380 [ dbSNP | Ensembl ].

VAR_038604

Secondary structure

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168

Helix Strand Turn

Details...

Helix

6 – 15

10

Helix

18 – 24

7

Turn

36 – 38

3

Helix

41 – 44

4

Turn

45 – 48

4

Helix

50 – 58

9

Helix

73 – 80

8

Helix

83 – 91

9

Beta strand

101 – 103

3

Helix

106 – 112

7

Helix

116 – 125

10

Beta strand

135 – 137

3

Helix

140 – 146

7

Helix

150 – 158

9

Sequences

	Sequence		Length	Mass (Da)
	P42773 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 5D66AFA715186E9A	FASTA	168	18,127
	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

References

	« Hide 'large scale' referencesShow '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

NIEHS-SNPs

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.

CCDS

CCDS555.1.

PIR

A55479.

RefSeq

NP_001253.1. NM_001262.2.
NP_523240.1. NM_078626.2.

UniGene

Hs.525324.

3D structure databases

PDBe
RCSB-PDB
PDBj

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	[»]

ProteinModelPortal

P42773.

SMR

P42773. Positions 5-160.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

107465. 22 interactions.

IntAct

P42773. 16 interactions.

MINT

MINT-1372629.

STRING

9606.ENSP00000262662.

PTM databases

PhosphoSite

P42773.

Polymorphism databases

DMDM

1168870.

Proteomic databases

MaxQB

P42773.

PaxDb

P42773.

PRIDE

P42773.

Protocols and materials databases

DNASU

1031.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262662; ENSP00000262662; ENSG00000123080.
ENST00000371761; ENSP00000360826; ENSG00000123080.
ENST00000396148; ENSP00000379452; ENSG00000123080.

GeneID

1031.

KEGG

hsa:1031.

UCSC

uc001csf.3. human.

Organism-specific databases

CTD

1031.

GeneCards

GC01P051427.

HGNC

HGNC:1789. CDKN2C.

HPA

CAB005303.
CAB018398.
HPA019057.
HPA019764.

MIM

603369. gene.

neXtProt

NX_P42773.

Orphanet

652. Multiple endocrine neoplasia type 1.

PharmGKB

PA26322.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0666.

HOGENOM

HOG000290191.

HOVERGEN

HBG050870.

InParanoid

P42773.

KO

K06622.

OMA

KDQTGFA.

OrthoDB

EOG7ZSHVC.

PhylomeDB

P42773.

TreeFam

TF333311.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpress

P42773.

Bgee

P42773.

CleanEx

HS_CDKN2C.

Genevestigator

P42773.

Family and domain databases

Gene3D

1.25.40.20. 2 hits.

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]

Pfam

PF00023. Ank. 3 hits.
[Graphical view]

SMART

SM00248. ANK. 4 hits.
[Graphical view]

SUPFAM

SSF48403. SSF48403. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P42773.

GeneWiki

CDKN2C.

GenomeRNAi

1031.

NextBio

4337.

PRO

P42773.

SOURCE

Search...

Entry information

Entry name

CDN2C_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.