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Protein

Cyclin-dependent kinase inhibitor 3

Gene

CDKN3

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

Functioni

May play a role in cell cycle regulation. Dual specificity phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues. Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner.3 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei140Phosphocysteine intermediateBy similarity1

GO - Molecular functioni

  • protein serine/threonine phosphatase activity Source: MGI
  • protein tyrosine/serine/threonine phosphatase activity Source: ProtInc
  • protein tyrosine phosphatase activity Source: MGI

GO - Biological processi

  • cell cycle arrest Source: MGI
  • G1/S transition of mitotic cell cycle Source: ProtInc
  • negative regulation of cell proliferation Source: ProtInc
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Cell cycle

Enzyme and pathway databases

BioCyciZFISH:HS02104-MONOMER.
SIGNORiQ16667.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 3 (EC:3.1.3.16, EC:3.1.3.48)
Alternative name(s):
CDK2-associated dual-specificity phosphatase
Cyclin-dependent kinase interactor 1
Cyclin-dependent kinase-interacting protein 2
Kinase-associated phosphatase
Gene namesi
Name:CDKN3
Synonyms:CDI1, CIP2, KAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:1791. CDKN3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleus Source: GO_Central
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Hepatocellular carcinoma (HCC)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.
See also OMIM:114550
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01384231W → R in HCC; patient BX-01. 1 Publication1
Natural variantiVAR_01384378F → L in HCC; patient T9. 1 Publication1
Natural variantiVAR_01384479C → Y in HCC; patient BX-01. 1 Publication1
Natural variantiVAR_01384591N → K in HCC; patient BX-10. 1 PublicationCorresponds to variant rs760687800dbSNPEnsembl.1
Natural variantiVAR_01384694D → V in HCC; patient NT1. 1 Publication1
Natural variantiVAR_01384795L → F in HCC; patient BX-05. 1 Publication1
Natural variantiVAR_013848108I → V in HCC; patient T9. 1 PublicationCorresponds to variant rs144479038dbSNPEnsembl.1
Natural variantiVAR_013849187N → S in HCC; patient NT4. 1 Publication1
Natural variantiVAR_013850195K → I in HCC; patient NT4. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1033.
MalaCardsiCDKN3.
MIMi114550. phenotype.
OpenTargetsiENSG00000100526.
PharmGKBiPA26324.

Polymorphism and mutation databases

BioMutaiCDKN3.
DMDMi2499769.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000949491 – 212Cyclin-dependent kinase inhibitor 3Add BLAST212

Proteomic databases

EPDiQ16667.
MaxQBiQ16667.
PaxDbiQ16667.
PeptideAtlasiQ16667.
PRIDEiQ16667.

PTM databases

DEPODiQ16667.
iPTMnetiQ16667.
PhosphoSitePlusiQ16667.

Expressioni

Inductioni

Up-regulated in breast and prostate cancer cells.1 Publication

Gene expression databases

BgeeiENSG00000100526.
ExpressionAtlasiQ16667. baseline and differential.
GenevisibleiQ16667. HS.

Organism-specific databases

HPAiCAB005285.
HPA039311.
HPA058874.

Interactioni

Subunit structurei

Interacts with cyclin-dependent kinases such as CDK1, CDK2 and CDK3. Does not interact with CDK4. Interacts (via C-terminus) with phosphorylated CDK2 (via C-terminal helix). Interacts with MS4A3 (via C-terminus); the interaction enhances CDKN3 enzymatic activity.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK2P249416EBI-1031527,EBI-375096

Protein-protein interaction databases

BioGridi107467. 4 interactors.
DIPiDIP-24231N.
DIP-245N.
IntActiQ16667. 4 interactors.
MINTiMINT-204916.
STRINGi9606.ENSP00000335357.

Structurei

Secondary structure

1212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 33Combined sources4
Helixi35 – 37Combined sources3
Beta strandi42 – 47Combined sources6
Helixi60 – 70Combined sources11
Beta strandi74 – 77Combined sources4
Helixi81 – 86Combined sources6
Helixi92 – 98Combined sources7
Beta strandi102 – 105Combined sources4
Helixi116 – 131Combined sources16
Beta strandi136 – 139Combined sources4
Beta strandi141 – 145Combined sources5
Helixi146 – 158Combined sources13
Beta strandi160 – 162Combined sources3
Helixi164 – 175Combined sources12
Helixi183 – 189Combined sources7
Helixi192 – 197Combined sources6
Turni198 – 200Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FPZX-ray2.00A/B/C/D/E/F1-212[»]
1FQ1X-ray3.00A1-212[»]
ProteinModelPortaliQ16667.
SMRiQ16667.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16667.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 34Interaction with CDK2Add BLAST34

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1720. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00390000004717.
HOVERGENiHBG075798.
InParanoidiQ16667.
KOiK14167.
OMAiTVKQYNF.
OrthoDBiEOG091G0MIF.
PhylomeDBiQ16667.
TreeFamiTF101040.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR008425. CDK_inhib_3.
IPR022778. CDKN3.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF05706. CDKN3. 1 hit.
[Graphical view]
PIRSFiPIRSF037322. CDKN3. 1 hit.
SMARTiSM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q16667-1) [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
MKPPSSIQTS EFDSSDEEPI EDEQTPIHIS WLSLSRVNCS QFLGLCALPG
60 70 80 90 100
CKFKDVRRNV QKDTEELKSC GIQDIFVFCT RGELSKYRVP NLLDLYQQCG
110 120 130 140 150
IITHHHPIAD GGTPDIASCC EIMEELTTCL KNYRKTLIHC YGGLGRSCLV
160 170 180 190 200
AACLLLYLSD TISPEQAIDS LRDLRGSGAI QTIKQYNYLH EFRDKLAAHL
210
SSRDSQSRSV SR
Length:212
Mass (Da):23,805
Last modified:November 1, 1996 - v1
Checksum:iD87FAC8E28F6525F
GO
Isoform 2 (identifier: Q16667-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     11-50: Missing.

Show »
Length:172
Mass (Da):19,359
Checksum:iE1F3AA29AAABE3DE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2K → E in AAC04932 (PubMed:8242750).Curated1
Sequence conflicti2K → E in AAV38258 (Ref. 8) Curated1
Sequence conflicti10S → G in AAK06380 (PubMed:10987270).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01384231W → R in HCC; patient BX-01. 1 Publication1
Natural variantiVAR_01384378F → L in HCC; patient T9. 1 Publication1
Natural variantiVAR_01384479C → Y in HCC; patient BX-01. 1 Publication1
Natural variantiVAR_01384591N → K in HCC; patient BX-10. 1 PublicationCorresponds to variant rs760687800dbSNPEnsembl.1
Natural variantiVAR_01384694D → V in HCC; patient NT1. 1 Publication1
Natural variantiVAR_01384795L → F in HCC; patient BX-05. 1 Publication1
Natural variantiVAR_013848108I → V in HCC; patient T9. 1 PublicationCorresponds to variant rs144479038dbSNPEnsembl.1
Natural variantiVAR_051769159S → F.Corresponds to variant rs1803843dbSNPEnsembl.1
Natural variantiVAR_013849187N → S in HCC; patient NT4. 1 Publication1
Natural variantiVAR_013850195K → I in HCC; patient NT4. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03661311 – 50Missing in isoform 2. 2 PublicationsAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02681 mRNA. Translation: AAC04932.1.
L27711 mRNA. Translation: AAA66496.1.
AF213033 mRNA. Translation: AAK06365.1.
AF213036 mRNA. Translation: AAK06368.1.
AF213038 mRNA. Translation: AAK06370.1.
AF213039 mRNA. Translation: AAK06371.1.
AF213041 mRNA. Translation: AAK06373.1.
AF213042 mRNA. Translation: AAK06374.1.
AF213046 mRNA. Translation: AAK06377.1.
AF213047 mRNA. Translation: AAK06378.1.
AF213049 mRNA. Translation: AAK06380.1.
AF213053 mRNA. Translation: AAK06384.1.
AY257474 mRNA. Translation: AAP13062.1.
L25876 mRNA. Translation: AAA60222.1.
EF560750 mRNA. Translation: ABQ59060.1.
CR407666 mRNA. Translation: CAG28594.1.
BT019451 mRNA. Translation: AAV38258.1.
AY194117 Genomic DNA. Translation: AAN86348.1.
CH471061 Genomic DNA. Translation: EAW80632.1.
CH471061 Genomic DNA. Translation: EAW80634.1.
BC064965 mRNA. Translation: AAH64965.1.
CCDSiCCDS45109.1. [Q16667-2]
CCDS9716.1. [Q16667-1]
PIRiA49436.
RefSeqiNP_001124323.1. NM_001130851.1. [Q16667-2]
NP_005183.2. NM_005192.3. [Q16667-1]
UniGeneiHs.84113.

Genome annotation databases

EnsembliENST00000335183; ENSP00000335357; ENSG00000100526. [Q16667-1]
ENST00000442975; ENSP00000415333; ENSG00000100526. [Q16667-2]
GeneIDi1033.
KEGGihsa:1033.
UCSCiuc001xap.4. human. [Q16667-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02681 mRNA. Translation: AAC04932.1.
L27711 mRNA. Translation: AAA66496.1.
AF213033 mRNA. Translation: AAK06365.1.
AF213036 mRNA. Translation: AAK06368.1.
AF213038 mRNA. Translation: AAK06370.1.
AF213039 mRNA. Translation: AAK06371.1.
AF213041 mRNA. Translation: AAK06373.1.
AF213042 mRNA. Translation: AAK06374.1.
AF213046 mRNA. Translation: AAK06377.1.
AF213047 mRNA. Translation: AAK06378.1.
AF213049 mRNA. Translation: AAK06380.1.
AF213053 mRNA. Translation: AAK06384.1.
AY257474 mRNA. Translation: AAP13062.1.
L25876 mRNA. Translation: AAA60222.1.
EF560750 mRNA. Translation: ABQ59060.1.
CR407666 mRNA. Translation: CAG28594.1.
BT019451 mRNA. Translation: AAV38258.1.
AY194117 Genomic DNA. Translation: AAN86348.1.
CH471061 Genomic DNA. Translation: EAW80632.1.
CH471061 Genomic DNA. Translation: EAW80634.1.
BC064965 mRNA. Translation: AAH64965.1.
CCDSiCCDS45109.1. [Q16667-2]
CCDS9716.1. [Q16667-1]
PIRiA49436.
RefSeqiNP_001124323.1. NM_001130851.1. [Q16667-2]
NP_005183.2. NM_005192.3. [Q16667-1]
UniGeneiHs.84113.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FPZX-ray2.00A/B/C/D/E/F1-212[»]
1FQ1X-ray3.00A1-212[»]
ProteinModelPortaliQ16667.
SMRiQ16667.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107467. 4 interactors.
DIPiDIP-24231N.
DIP-245N.
IntActiQ16667. 4 interactors.
MINTiMINT-204916.
STRINGi9606.ENSP00000335357.

PTM databases

DEPODiQ16667.
iPTMnetiQ16667.
PhosphoSitePlusiQ16667.

Polymorphism and mutation databases

BioMutaiCDKN3.
DMDMi2499769.

Proteomic databases

EPDiQ16667.
MaxQBiQ16667.
PaxDbiQ16667.
PeptideAtlasiQ16667.
PRIDEiQ16667.

Protocols and materials databases

DNASUi1033.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000335183; ENSP00000335357; ENSG00000100526. [Q16667-1]
ENST00000442975; ENSP00000415333; ENSG00000100526. [Q16667-2]
GeneIDi1033.
KEGGihsa:1033.
UCSCiuc001xap.4. human. [Q16667-1]

Organism-specific databases

CTDi1033.
DisGeNETi1033.
GeneCardsiCDKN3.
HGNCiHGNC:1791. CDKN3.
HPAiCAB005285.
HPA039311.
HPA058874.
MalaCardsiCDKN3.
MIMi114550. phenotype.
123832. gene.
neXtProtiNX_Q16667.
OpenTargetsiENSG00000100526.
PharmGKBiPA26324.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1720. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00390000004717.
HOVERGENiHBG075798.
InParanoidiQ16667.
KOiK14167.
OMAiTVKQYNF.
OrthoDBiEOG091G0MIF.
PhylomeDBiQ16667.
TreeFamiTF101040.

Enzyme and pathway databases

BioCyciZFISH:HS02104-MONOMER.
SIGNORiQ16667.

Miscellaneous databases

ChiTaRSiCDKN3. human.
EvolutionaryTraceiQ16667.
GeneWikiiCDKN3.
GenomeRNAii1033.
PROiQ16667.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100526.
ExpressionAtlasiQ16667. baseline and differential.
GenevisibleiQ16667. HS.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR008425. CDK_inhib_3.
IPR022778. CDKN3.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR003595. Tyr_Pase_cat.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF05706. CDKN3. 1 hit.
[Graphical view]
PIRSFiPIRSF037322. CDKN3. 1 hit.
SMARTiSM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
PROSITEiPS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDKN3_HUMAN
AccessioniPrimary (citable) accession number: Q16667
Secondary accession number(s): Q53ZU6
, Q5U0M4, Q6P1N8, Q99585, Q9BPW7, Q9BY36, Q9C042, Q9C046, Q9C047, Q9C049, Q9C051, Q9C053
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 161 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 14
    Human chromosome 14: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.