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Protein

Cyclin-dependent kinase inhibitor 1C

Gene

CDKN1C

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

Functioni

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.

Miscellaneous

Paternally imprinted, therefore most expression comes from the maternal allele.1 Publication

GO - Molecular functioni

  • cyclin-dependent protein serine/threonine kinase inhibitor activity Source: InterPro
  • protein complex binding Source: CAFA
  • protein kinase inhibitor activity Source: CAFA

GO - Biological processi

Keywordsi

Molecular functionProtein kinase inhibitor
Biological processCell cycle

Enzyme and pathway databases

ReactomeiR-HSA-69231. Cyclin D associated events in G1.
SignaLinkiP49918.
SIGNORiP49918.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 1C
Alternative name(s):
Cyclin-dependent kinase inhibitor p57
p57Kip2
Gene namesi
Name:CDKN1C
Synonyms:KIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000129757.12.
HGNCiHGNC:1786. CDKN1C.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Beckwith-Wiedemann syndrome (BWS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:130650
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07520012M → L in BWS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs483352966Ensembl.1
Natural variantiVAR_07520153L → P in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352968Ensembl.1
Natural variantiVAR_07520264Missing in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352969Ensembl.1
Natural variantiVAR_07520370P → L in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352970Ensembl.1
Natural variantiVAR_075204158P → A in BWS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs483352981Ensembl.1
Natural variantiVAR_075205215A → APA in BWS. 1 PublicationCorresponds to variant dbSNP:rs772704243Ensembl.1
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies (IMAGE)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614732
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068848274D → N in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs387907225Ensembl.1
Natural variantiVAR_068849276F → S in IMAGE; PCNA binding is disrupted. 1 PublicationCorresponds to variant dbSNP:rs387907224Ensembl.1
Natural variantiVAR_068850276F → V in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs387907223Ensembl.1
Natural variantiVAR_068851278K → E in IMAGE; PCNA binding is disrupted. 1 PublicationCorresponds to variant dbSNP:rs387907226Ensembl.1
Natural variantiVAR_068852279R → P in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs318240750Ensembl.1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi1028.
GeneReviewsiCDKN1C.
MalaCardsiCDKN1C.
MIMi130650. phenotype.
614732. phenotype.
OpenTargetsiENSG00000129757.
Orphaneti231120. Beckwith-Wiedemann syndrome due to CDKN1C mutation.
85173. IMAGe syndrome.
397590. Silver-Russell syndrome due to a point mutation.
PharmGKBiPA26320.

Polymorphism and mutation databases

BioMutaiCDKN1C.
DMDMi1705731.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001900871 – 316Cyclin-dependent kinase inhibitor 1CAdd BLAST316

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei107Omega-N-methylarginineBy similarity1
Modified residuei268PhosphoserineCombined sources1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP49918.
MaxQBiP49918.
PaxDbiP49918.
PeptideAtlasiP49918.
PRIDEiP49918.

PTM databases

iPTMnetiP49918.
PhosphoSitePlusiP49918.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

Expressed within a subset of cells in the subcapsular or developing definitive zone of the adrenal gland.1 Publication

Gene expression databases

BgeeiENSG00000129757.
CleanExiHS_CDKN1C.
ExpressionAtlasiP49918. baseline and differential.
GenevisibleiP49918. HS.

Organism-specific databases

HPAiHPA002924.

Interactioni

Subunit structurei

Interacts with PCNA.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein complex binding Source: CAFA

Protein-protein interaction databases

BioGridi107462. 21 interactors.
ELMiP49918.
IntActiP49918. 8 interactors.
MINTiMINT-128985.
STRINGi9606.ENSP00000411552.

Structurei

3D structure databases

DisProtiDP00017.
ProteinModelPortaliP49918.
SMRiP49918.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati156 – 15914
Repeati160 – 16324
Repeati180 – 18334
Repeati184 – 18744
Repeati188 – 19154
Repeati198 – 20164
Repeati202 – 20574
Repeati206 – 20984
Repeati210 – 21394

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni156 – 2139 X 4 AA repeats of P-A-P-AAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi278 – 281Nuclear localization signalSequence analysis4

Sequence similaritiesi

Belongs to the CDI family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4743. Eukaryota.
ENOG410XXN5. LUCA.
GeneTreeiENSGT00530000063588.
HOGENOMiHOG000294081.
HOVERGENiHBG107407.
InParanoidiP49918.
KOiK09993.
OMAiQWTEVDS.
OrthoDBiEOG091G19PZ.
PhylomeDBiP49918.
TreeFamiTF101111.

Family and domain databases

InterProiView protein in InterPro
IPR003175. CDI.
IPR029842. CDKN1C.
PANTHERiPTHR10265. PTHR10265. 1 hit.
PTHR10265:SF7. PTHR10265:SF7. 1 hit.
PfamiView protein in Pfam
PF02234. CDI. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P49918-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSDASLRSTS TMERLVARGT FPVLVRTSAC RSLFGPVDHE ELSRELQARL
60 70 80 90 100
AELNAEDQNR WDYDFQQDMP LRGPGRLQWT EVDSDSVPAF YRETVQVGRC
110 120 130 140 150
RLLLAPRPVA VAVAVSPPLE PAAESLDGLE EAPEQLPSVP VPAPASTPPP
160 170 180 190 200
VPVLAPAPAP APAPVAAPVA APVAVAVLAP APAPAPAPAP APAPVAAPAP
210 220 230 240 250
APAPAPAPAP APAPAPDAAP QESAEQGANQ GQRGQEPLAD QLHSGISGRP
260 270 280 290 300
AAGTAAASAN GAAIKKLSGP LISDFFAKRK RSAPEKSSGD VPAPCPSPSA
310
APGVGSVEQT PRKRLR
Length:316
Mass (Da):32,177
Last modified:October 1, 1996 - v1
Checksum:iA94CCBF09F8CB3E4
GO
Isoform Short (identifier: P49918-2) [UniParc]FASTAAdd to basket

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

Show »
Length:305
Mass (Da):31,040
Checksum:iC4C82AF45384A1CC
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07520012M → L in BWS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs483352966Ensembl.1
Natural variantiVAR_07520153L → P in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352968Ensembl.1
Natural variantiVAR_07520264Missing in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352969Ensembl.1
Natural variantiVAR_07520370P → L in BWS. 1 PublicationCorresponds to variant dbSNP:rs483352970Ensembl.1
Natural variantiVAR_075204158P → A in BWS; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs483352981Ensembl.1
Natural variantiVAR_001404171 – 174Missing in several cancers. 4
Natural variantiVAR_001405181 – 184Missing in hepatocellular carcinomas. 4
Natural variantiVAR_001406200 – 203Missing in a bladder cancer. 4
Natural variantiVAR_001407206 – 209Missing in a breast cancer. 4
Natural variantiVAR_075205215A → APA in BWS. 1 PublicationCorresponds to variant dbSNP:rs772704243Ensembl.1
Natural variantiVAR_068848274D → N in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs387907225Ensembl.1
Natural variantiVAR_068849276F → S in IMAGE; PCNA binding is disrupted. 1 PublicationCorresponds to variant dbSNP:rs387907224Ensembl.1
Natural variantiVAR_068850276F → V in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs387907223Ensembl.1
Natural variantiVAR_068851278K → E in IMAGE; PCNA binding is disrupted. 1 PublicationCorresponds to variant dbSNP:rs387907226Ensembl.1
Natural variantiVAR_068852279R → P in IMAGE. 1 PublicationCorresponds to variant dbSNP:rs318240750Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0008671 – 11Missing in isoform Short. CuratedAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44519.1. [P49918-2]
CCDS7738.1. [P49918-1]
PIRiG02424.
RefSeqiNP_000067.1. NM_000076.2. [P49918-1]
NP_001116102.1. NM_001122630.1. [P49918-2]
NP_001116103.1. NM_001122631.1. [P49918-2]
XP_016872577.1. XM_017017088.1. [P49918-1]
UniGeneiHs.106070.

Genome annotation databases

EnsembliENST00000414822; ENSP00000413720; ENSG00000129757. [P49918-1]
ENST00000430149; ENSP00000411552; ENSG00000129757. [P49918-1]
ENST00000440480; ENSP00000411257; ENSG00000129757. [P49918-2]
GeneIDi1028.
KEGGihsa:1028.
UCSCiuc001lwr.5. human. [P49918-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCDN1C_HUMAN
AccessioniPrimary (citable) accession number: P49918
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 25, 2017
This is version 158 of the entry and version 1 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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. SIMILARITY comments
    Index of protein domains and families