P49918 (CDN1C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase inhibitor 1C

Alternative name(s):
Cyclin-dependent kinase inhibitor p57
p57Kip2

Gene names

Name:	CDKN1C
Synonyms:	KIP2

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	316 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non-proliferative state throughout life.
Subunit structure	Interacts with PCNA. Ref.7
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. Expressed in the eye. High levels are seen in the placenta while low levels are seen in the liver. Ref.7
Developmental stage	Expressed within a subset of cells in the subcapsular or developing definitive zone of the adrenal gland. Ref.7
Involvement in disease	Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies (IMAGE) [MIM:614732]: A rare condition characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Defects in CDKN1C are involved in tumor formation.
Sequence similarities	Belongs to the CDI family.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Tumor suppressor
Domain	Repeat
Molecular function	Protein kinase inhibitor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 phase of mitotic cell cycle Traceable author statement Ref.1. Source: ProtInc cell cycle arrest Traceable author statement Ref.1. Source: ProtInc negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 19170105. Source: UniProtKB neuron maturation Inferred from electronic annotation. Source: Compara placenta development Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from genetic interaction PubMed 19170105. Source: UniProtKB positive regulation of transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL regulation of cyclin-dependent protein serine/threonine kinase activity Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay PubMed 16943770. Source: BHF-UCL nucleus Inferred from direct assay PubMed 16943770. Source: BHF-UCL
Molecular_function	cyclin-dependent protein serine/threonine kinase inhibitor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P49918-1)

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.

Isoform Short (identifier: P49918-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 316	316	Cyclin-dependent kinase inhibitor 1C		PRO_0000190087
Regions
	Repeat	156 – 159	4	1
	Repeat	160 – 163	4	2
	Repeat	180 – 183	4	3
	Repeat	184 – 187	4	4
	Repeat	188 – 191	4	5
	Repeat	198 – 201	4	6
	Repeat	202 – 205	4	7
	Repeat	206 – 209	4	8
	Repeat	210 – 213	4	9
	Region	156 – 213	58	9 X 4 AA repeats of P-A-P-A
	Motif	278 – 281	4	Nuclear localization signal Potential
Amino acid modifications
	Modified residue	268	1	Phosphoserine Ref.6
Natural variations
	Alternative sequence	1 – 11	11	Missing in isoform Short.		VSP_000867
	Natural variant	171 – 174	4	Missing in several cancers.		VAR_001404
	Natural variant	181 – 184	4	Missing in hepatocellular carcinomas.		VAR_001405
	Natural variant	200 – 203	4	Missing in a bladder cancer.		VAR_001406
	Natural variant	206 – 209	4	Missing in a breast cancer.		VAR_001407
	Natural variant	274	1	D → N in IMAGE. Ref.7		VAR_068848
	Natural variant	276	1	F → S in IMAGE; PCNA binding is disrupted. Ref.7		VAR_068849
	Natural variant	276	1	F → V in IMAGE. Ref.7		VAR_068850
	Natural variant	278	1	K → E in IMAGE; PCNA binding is disrupted. Ref.7		VAR_068851
	Natural variant	279	1	R → P in IMAGE. Ref.7		VAR_068852

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 1, 1996. Version 1. Checksum: A94CCBF09F8CB3E4	FASTA	316	32,177
	10 20 30 40 50 60 MSDASLRSTS TMERLVARGT FPVLVRTSAC RSLFGPVDHE ELSRELQARL AELNAEDQNR 70 80 90 100 110 120 WDYDFQQDMP LRGPGRLQWT EVDSDSVPAF YRETVQVGRC RLLLAPRPVA VAVAVSPPLE 130 140 150 160 170 180 PAAESLDGLE EAPEQLPSVP VPAPASTPPP VPVLAPAPAP APAPVAAPVA APVAVAVLAP 190 200 210 220 230 240 APAPAPAPAP APAPVAAPAP APAPAPAPAP APAPAPDAAP QESAEQGANQ GQRGQEPLAD 250 260 270 280 290 300 QLHSGISGRP AAGTAAASAN GAAIKKLSGP LISDFFAKRK RSAPEKSSGD VPAPCPSPSA 310 APGVGSVEQT PRKRLR
	Isoform Short [UniParc]. Checksum: C4C82AF45384A1CC	FASTA	305	31,040
	10 20 30 40 50 60 MERLVARGTF PVLVRTSACR SLFGPVDHEE LSRELQARLA ELNAEDQNRW DYDFQQDMPL 70 80 90 100 110 120 RGPGRLQWTE VDSDSVPAFY RETVQVGRCR LLLAPRPVAV AVAVSPPLEP AAESLDGLEE 130 140 150 160 170 180 APEQLPSVPV PAPASTPPPV PVLAPAPAPA PAPVAAPVAA PVAVAVLAPA PAPAPAPAPA 190 200 210 220 230 240 PAPVAAPAPA PAPAPAPAPA PAPAPDAAPQ ESAEQGANQG QRGQEPLADQ LHSGISGRPA 250 260 270 280 290 300 AGTAAASANG AAIKKLSGPL ISDFFAKRKR SAPEKSSGDV PAPCPSPSAA PGVGSVEQTP RKRLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene." Matsuoka S., Edwards M.C., Bai C., Parker S., Zhang P., Baldini A., Harper J.W., Elledge S.J. Genes Dev. 9:650-662(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Embryo.
[2]	"Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay." Reid L.H., Crider-Miller S.J., West A., Lee M.H., Massague J., Weissman B.E. Cancer Res. 56:1214-1218(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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] (ISOFORM LONG). Tissue: Placenta.
[4]	"Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis." Tokino T., Urano T., Furuhata T., Matsushima M., Miyatsu T., Sasaki S., Nakamura Y. Hum. Genet. 97:625-631(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-316, VARIANTS.
[5]	"Analysis of germline CDKN1C (p57-KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation." Lam W.W.K., Hatada I., Ohishi S., Mukai T., Joyce J.A., Cole T.R.P., Donnai D., Reik W., Schofield P.N., Maher E.R. J. Med. Genet. 36:518-523(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BWS.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome." Arboleda V.A., Lee H., Parnaik R., Fleming A., Banerjee A., Ferraz-de-Souza B., Delot E.C., Rodriguez-Fernandez I.A., Braslavsky D., Bergada I., Dell'Angelica E.C., Nelson S.F., Martinez-Agosto J.A., Achermann J.C., Vilain E. Nat. Genet. 44:788-792(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH PCNA, VARIANTS IMAGE ASN-274; SER-276; VAL-276; GLU-278 AND PRO-279, CHARACTERIZATION OF VARIANTS IMAGE SER-276 AND GLU-278.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U22398 mRNA. Translation: AAA85095.1. U48869 Genomic DNA. Translation: AAB05896.1. BC067842 mRNA. Translation: AAH67842.1. D64137 Genomic DNA. Translation: BAA11014.1. D64137 Genomic DNA. Translation: BAA11015.1.
IPI	IPI00029086. IPI00216615.
PIR	G02424.
RefSeq	NP_000067.1. NM_000076.2. NP_001116102.1. NM_001122630.1. NP_001116103.1. NM_001122631.1.
UniGene	Hs.106070.
3D structure databases
DisProt	DP00017.
ProteinModelPortal	P49918.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49918. 4 interactions.
MINT	MINT-128985.
STRING	9606.ENSP00000413720.
PTM databases
PhosphoSite	P49918.
Polymorphism databases
DMDM	1705731.
Proteomic databases
PaxDb	P49918.
PRIDE	P49918.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313407; ENSP00000321019; ENSG00000129757. ENST00000414822; ENSP00000413720; ENSG00000129757. ENST00000430149; ENSP00000411552; ENSG00000129757. ENST00000440480; ENSP00000411257; ENSG00000129757.
GeneID	1028.
KEGG	hsa:1028.
UCSC	uc001lwr.4. human.
Organism-specific databases
CTD	1028.
GeneCards	GC11M002904.
HGNC	HGNC:1786. CDKN1C.
HPA	HPA002924.
MIM	130650. phenotype. 600856. gene. 614732. phenotype.
neXtProt	NX_P49918.
Orphanet	231120. Beckwith-Wiedemann syndrome due to CDKN1C mutation. 85173. IMAGe syndrome.
PharmGKB	PA26320.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245842.
HOGENOM	HOG000294081.
HOVERGEN	HBG107407.
InParanoid	P49918.
KO	K09993.
OMA	EQGANQG.
OrthoDB	EOG4ZS94X.
Enzyme and pathway databases
SignaLink	P49918.
Gene expression databases
ArrayExpress	P49918.
Bgee	P49918.
CleanEx	HS_CDKN1C.
Genevestigator	P49918.
GermOnline	ENSG00000129757. Homo sapiens.
Family and domain databases
InterPro	IPR003175. CDI. [Graphical view]
PANTHER	PTHR10265. PTHR10265. 1 hit.
Pfam	PF02234. CDI. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1028.
NextBio	4319.
SOURCE	Search...

Entry information

Entry name

CDN1C_HUMAN

Accession

Primary (citable) accession number: P49918

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 119 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.