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Q16667 (CDKN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CDKN3
Synonyms:CDI1, CIP2, KAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length212 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.12

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

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

Subunit structure

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. Ref.1 Ref.2 Ref.4 Ref.14 Ref.15

Subcellular location

Cytoplasmperinuclear region Ref.13.

Induction

Up-regulated in breast and prostate cancer cells. Ref.13

Involvement in disease

Hepatocellular carcinoma (HCC) [MIM:114550]: A 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.
Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.3

Sequence similarities

Belongs to the protein-tyrosine phosphatase family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDK2P249413EBI-1031527,EBI-375096

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16667-1)

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 2 (identifier: Q16667-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 212212Cyclin-dependent kinase inhibitor 3
PRO_0000094949

Regions

Region1 – 3434Interaction with CDK2

Sites

Active site1401Phosphocysteine intermediate By similarity

Natural variations

Alternative sequence11 – 5040Missing in isoform 2.
VSP_036613
Natural variant311W → R in HCC; patient BX-01. Ref.3
VAR_013842
Natural variant781F → L in HCC; patient T9. Ref.3
VAR_013843
Natural variant791C → Y in HCC; patient BX-01. Ref.3
VAR_013844
Natural variant911N → K in HCC; patient BX-10. Ref.3
VAR_013845
Natural variant941D → V in HCC; patient NT1. Ref.3
VAR_013846
Natural variant951L → F in HCC; patient BX-05. Ref.3
VAR_013847
Natural variant1081I → V in HCC; patient T9. Ref.3
Corresponds to variant rs144479038 [ dbSNP | Ensembl ].
VAR_013848
Natural variant1591S → F.
Corresponds to variant rs1803843 [ dbSNP | Ensembl ].
VAR_051769
Natural variant1871N → S in HCC; patient NT4. Ref.3
VAR_013849
Natural variant1951K → I in HCC; patient NT4. Ref.3
VAR_013850

Experimental info

Sequence conflict21K → E in AAC04932. Ref.1
Sequence conflict21K → E in AAV38258. Ref.8
Sequence conflict101S → G in AAK06380. Ref.3

Secondary structure

................................. 212
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: D87FAC8E28F6525F

FASTA21223,805
        10         20         30         40         50         60 
MKPPSSIQTS EFDSSDEEPI EDEQTPIHIS WLSLSRVNCS QFLGLCALPG CKFKDVRRNV 

        70         80         90        100        110        120 
QKDTEELKSC GIQDIFVFCT RGELSKYRVP NLLDLYQQCG IITHHHPIAD GGTPDIASCC 

       130        140        150        160        170        180 
EIMEELTTCL KNYRKTLIHC YGGLGRSCLV AACLLLYLSD TISPEQAIDS LRDLRGSGAI 

       190        200        210 
QTIKQYNYLH EFRDKLAAHL SSRDSQSRSV SR 

« Hide

Isoform 2 [UniParc].

Checksum: E1F3AA29AAABE3DE
Show »

FASTA17219,359

References

« Hide 'large scale' references
[1]"Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2."
Gyuris J., Golemis E., Chertkov H., Brent R.
Cell 75:791-803(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDK1; CDK2 AND CDK3.
[2]"KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases."
Hannon G.J., Casso D., Beach D.
Proc. Natl. Acad. Sci. U.S.A. 91:1731-1735(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDK1 AND CDK2.
[3]"Aberrant transcripts of the cyclin-dependent kinase-associated protein phosphatase in hepatocellular carcinoma."
Yeh C.-T., Lu S.-C., Chen T.-C., Peng C.-Y., Liaw Y.-F.
Cancer Res. 60:4697-4700(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS HCC ARG-31; LEU-78; TYR-79; LYS-91; VAL-94; PHE-95; VAL-108; SER-187 AND ILE-195.
[4]"Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a truncated KAP mutant."
Yeh C.-T., Lu S.-C., Chao C.-H., Chao M.-L.
Biochem. Biophys. Res. Commun. 305:311-314(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CDK2.
[5]Harper W., Elledge S.J.
Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]Schupp I.
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]NIEHS SNPs program
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"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 2).
Tissue: Retinoblastoma.
[12]"Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin."
Poon R.Y.C., Hunter T.
Science 270:90-93(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Overexpression of kinase-associated phosphatase (KAP) in breast and prostate cancer and inhibition of the transformed phenotype by antisense KAP expression."
Lee S.W., Reimer C.L., Fang L., Iruela-Arispe M.L., Aaronson S.A.
Mol. Cell. Biol. 20:1723-1732(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INDUCTION.
[14]"Human HTm4 is a hematopoietic cell cycle regulator."
Donato J.-L., Ko J., Kutok J.L., Cheng T., Shirakawa T., Mao X.-Q., Beach D., Scadden D.T., Sayegh M.H., Adra C.N.
J. Clin. Invest. 109:51-58(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MS4A3.
[15]"Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2."
Chinami M., Yano Y., Yang X., Salahuddin S., Moriyama K., Shiroishi M., Turner H., Shirakawa T., Adra C.N.
J. Biol. Chem. 280:17235-17242(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MS4A3.
[16]"Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2."
Song H., Hanlon N., Brown N.R., Noble M.E.M., Johnson L.N., Barford D.
Mol. Cell 7:615-626(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH THR-160 PHOSPHORYLATED CDK2.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA49436.
RefSeqNP_001124323.1. NM_001130851.1.
NP_005183.2. NM_005192.3.
UniGeneHs.84113.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FPZX-ray2.00A/B/C/D/E/F1-212[»]
1FQ1X-ray3.00A1-212[»]
ProteinModelPortalQ16667.
SMRQ16667. Positions 21-203.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107467. 5 interactions.
DIPDIP-24231N.
DIP-245N.
IntActQ16667. 4 interactions.
MINTMINT-204916.

PTM databases

PhosphoSiteQ16667.

Polymorphism databases

DMDM2499769.

Proteomic databases

PaxDbQ16667.
PRIDEQ16667.

Protocols and materials databases

DNASU1033.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335183; ENSP00000335357; ENSG00000100526. [Q16667-1]
ENST00000442975; ENSP00000415333; ENSG00000100526. [Q16667-2]
GeneID1033.
KEGGhsa:1033.
UCSCuc001xap.3. human. [Q16667-1]
uc001xar.3. human. [Q16667-2]

Organism-specific databases

CTD1033.
GeneCardsGC14P054863.
HGNCHGNC:1791. CDKN3.
HPACAB005285.
HPA039311.
MIM114550. phenotype.
123832. gene.
neXtProtNX_Q16667.
PharmGKBPA26324.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2453.
HOVERGENHBG075798.
InParanoidQ16667.
KOK14167.
OMATVKQYNF.
OrthoDBEOG7M0NSV.
PhylomeDBQ16667.
TreeFamTF101040.

Gene expression databases

ArrayExpressQ16667.
BgeeQ16667.
GenevestigatorQ16667.

Family and domain databases

InterProIPR008425. CDK_inhib_3.
IPR022778. CDKN3.
IPR000387. Tyr/Dual-sp_Pase.
[Graphical view]
PANTHERPTHR23339:SF24. PTHR23339:SF24. 1 hit.
PfamPF05706. CDKN3. 1 hit.
[Graphical view]
PIRSFPIRSF037322. CDKN3. 1 hit.
PROSITEPS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16667.
GeneWikiCDKN3.
GenomeRNAi1033.
NextBio4349.
PROQ16667.
SOURCESearch...

Entry information

Entry nameCDKN3_HUMAN
AccessionPrimary (citable) accession number: Q16667
Secondary accession number(s): Q53ZU6 expand/collapse secondary AC list , Q5U0M4, Q6P1N8, Q99585, Q9BPW7, Q9BY36, Q9C042, Q9C046, Q9C047, Q9C049, Q9C051, Q9C053
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 136 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 14

Human chromosome 14: entries, gene names and cross-references to MIM