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P49918 (CDN1C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase inhibitor 1C
Alternative name(s):
Cyclin-dependent kinase inhibitor p57
p57Kip2
Gene names
Name:CDKN1C
Synonyms:KIP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length316 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processCell cycle
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Tumor suppressor
   DomainRepeat
   Molecular functionProtein kinase inhibitor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle arrest

Traceable author statement Ref.1. Source: ProtInc

mitotic G1 phase

Traceable author statement Ref.1. Source: ProtInc

negative regulation of cell proliferation

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 kinase activity

Inferred from direct assay PubMed 19170105. Source: UniProtKB

negative regulation of phosphorylation

Inferred from direct assay PubMed 19170105. Source: UniProtKB

negative regulation of protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: GOC

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19170105. Source: UniProtKB

neuron maturation

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

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_componentcytoplasm

Inferred from direct assay PubMed 16943770. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 16943770. Source: BHF-UCL

   Molecular_functioncyclin-dependent protein serine/threonine kinase inhibitor activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 19170105Ref.7. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FBXL12Q9NXK86EBI-519256,EBI-719790
MCM7P339932EBI-519256,EBI-355924

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 316316Cyclin-dependent kinase inhibitor 1C
PRO_0000190087

Regions

Repeat156 – 15941
Repeat160 – 16342
Repeat180 – 18343
Repeat184 – 18744
Repeat188 – 19145
Repeat198 – 20146
Repeat202 – 20547
Repeat206 – 20948
Repeat210 – 21349
Region156 – 213589 X 4 AA repeats of P-A-P-A
Motif278 – 2814Nuclear localization signal Potential

Amino acid modifications

Modified residue2681Phosphoserine Ref.6

Natural variations

Alternative sequence1 – 1111Missing in isoform Short.
VSP_000867
Natural variant171 – 1744Missing in several cancers.
VAR_001404
Natural variant181 – 1844Missing in hepatocellular carcinomas.
VAR_001405
Natural variant200 – 2034Missing in a bladder cancer.
VAR_001406
Natural variant206 – 2094Missing in a breast cancer.
VAR_001407
Natural variant2741D → N in IMAGE. Ref.7
VAR_068848
Natural variant2761F → S in IMAGE; PCNA binding is disrupted. Ref.7
VAR_068849
Natural variant2761F → V in IMAGE. Ref.7
VAR_068850
Natural variant2781K → E in IMAGE; PCNA binding is disrupted. Ref.7
VAR_068851
Natural variant2791R → P in IMAGE. Ref.7
VAR_068852

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: A94CCBF09F8CB3E4

FASTA31632,177
        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 

« Hide

Isoform Short [UniParc].

Checksum: C4C82AF45384A1CC
Show »

FASTA30531,040

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.

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.
CCDSCCDS44519.1. [P49918-2]
CCDS7738.1. [P49918-1]
PIRG02424.
RefSeqNP_000067.1. NM_000076.2. [P49918-1]
NP_001116102.1. NM_001122630.1. [P49918-2]
NP_001116103.1. NM_001122631.1. [P49918-2]
XP_005252788.1. XM_005252731.1. [P49918-1]
UniGeneHs.106070.

3D structure databases

DisProtDP00017.
ProteinModelPortalP49918.
SMRP49918. Positions 26-91.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107462. 15 interactions.
IntActP49918. 7 interactions.
MINTMINT-128985.
STRING9606.ENSP00000413720.

PTM databases

PhosphoSiteP49918.

Polymorphism databases

DMDM1705731.

Proteomic databases

MaxQBP49918.
PaxDbP49918.
PRIDEP49918.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000313407; ENSP00000321019; ENSG00000129757. [P49918-2]
ENST00000414822; ENSP00000413720; ENSG00000129757. [P49918-1]
ENST00000430149; ENSP00000411552; ENSG00000129757. [P49918-1]
ENST00000440480; ENSP00000411257; ENSG00000129757. [P49918-2]
GeneID1028.
KEGGhsa:1028.
UCSCuc001lwr.4. human. [P49918-1]

Organism-specific databases

CTD1028.
GeneCardsGC11M002904.
GeneReviewsCDKN1C.
HGNCHGNC:1786. CDKN1C.
HPAHPA002924.
MIM130650. phenotype.
600856. gene.
614732. phenotype.
neXtProtNX_P49918.
Orphanet231120. Beckwith-Wiedemann syndrome due to CDKN1C mutation.
85173. IMAGe syndrome.
397590. Silver-Russell syndrome due to a point mutation.
PharmGKBPA26320.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245842.
HOGENOMHOG000294081.
HOVERGENHBG107407.
InParanoidP49918.
KOK09993.
OMAEQGANQG.
OrthoDBEOG7GJ6HD.
PhylomeDBP49918.
TreeFamTF101111.

Enzyme and pathway databases

SignaLinkP49918.

Gene expression databases

ArrayExpressP49918.
BgeeP49918.
CleanExHS_CDKN1C.
GenevestigatorP49918.

Family and domain databases

InterProIPR003175. CDI.
[Graphical view]
PANTHERPTHR10265. PTHR10265. 1 hit.
PfamPF02234. CDI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCyclin-dependent_kinase_inhibitor_1C.
GenomeRNAi1028.
NextBio4319.
PROP49918.
SOURCESearch...

Entry information

Entry nameCDN1C_HUMAN
AccessionPrimary (citable) accession number: P49918
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 130 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

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 11

Human chromosome 11: entries, gene names and cross-references to MIM