Q16667 · CDKN3_HUMAN
- ProteinCyclin-dependent kinase inhibitor 3
- GeneCDKN3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids212 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
May play a role in cell cycle regulation. Dual specificity CC phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues (PubMed:8127873, PubMed:8242750).
Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner (PubMed:7569954).
Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner (PubMed:7569954).
Catalytic activity
- H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphateThis reaction proceeds in the forward direction.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 140 | Phosphocysteine intermediate | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Cellular Component | perinuclear region of cytoplasm | |
Molecular Function | myosin phosphatase activity | |
Molecular Function | protein serine/threonine phosphatase activity | |
Molecular Function | protein tyrosine phosphatase activity | |
Molecular Function | protein tyrosine/serine/threonine phosphatase activity | |
Biological Process | G1/S transition of mitotic cell cycle | |
Biological Process | negative regulation of cell population proliferation | |
Biological Process | regulation of cell cycle | |
Biological Process | regulation of cyclin-dependent protein serine/threonine kinase activity |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCyclin-dependent kinase inhibitor 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ16667
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Hepatocellular carcinoma (HCC)
- Note
- 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 alsoMIM:114550
Natural variants in HCC
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_013842 | 31 | W>R | in HCC; patient BX-01 | |
VAR_013843 | 78 | F>L | in HCC; patient T9 | |
VAR_013844 | 79 | C>Y | in HCC; patient BX-01; dbSNP:rs2030352101 | |
VAR_013845 | 91 | N>K | in HCC; patient BX-10; dbSNP:rs760687800 | |
VAR_013846 | 94 | D>V | in HCC; patient NT1 | |
VAR_013847 | 95 | L>F | in HCC; patient BX-05 | |
VAR_013848 | 108 | I>V | in HCC; patient T9; dbSNP:rs144479038 | |
VAR_013849 | 187 | N>S | in HCC; patient NT4 | |
VAR_013850 | 195 | K>I | in HCC; patient NT4 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_013842 | 31 | in HCC; patient BX-01 | |||
Sequence: W → R | ||||||
Natural variant | VAR_013843 | 78 | in HCC; patient T9 | |||
Sequence: F → L | ||||||
Natural variant | VAR_013844 | 79 | in HCC; patient BX-01; dbSNP:rs2030352101 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_013845 | 91 | in HCC; patient BX-10; dbSNP:rs760687800 | |||
Sequence: N → K | ||||||
Natural variant | VAR_013846 | 94 | in HCC; patient NT1 | |||
Sequence: D → V | ||||||
Natural variant | VAR_013847 | 95 | in HCC; patient BX-05 | |||
Sequence: L → F | ||||||
Natural variant | VAR_013848 | 108 | in HCC; patient T9; dbSNP:rs144479038 | |||
Sequence: I → V | ||||||
Natural variant | VAR_051769 | 159 | in dbSNP:rs1803843 | |||
Sequence: S → F | ||||||
Natural variant | VAR_013849 | 187 | in HCC; patient NT4 | |||
Sequence: N → S | ||||||
Natural variant | VAR_013850 | 195 | in HCC; patient NT4 | |||
Sequence: K → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 213 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000094949 | 1-212 | UniProt | Cyclin-dependent kinase inhibitor 3 | |||
Sequence: MKPPSSIQTSEFDSSDEEPIEDEQTPIHISWLSLSRVNCSQFLGLCALPGCKFKDVRRNVQKDTEELKSCGIQDIFVFCTRGELSKYRVPNLLDLYQQCGIITHHHPIADGGTPDIASCCEIMEELTTCLKNYRKTLIHCYGGLGRSCLVAACLLLYLSDTISPEQAIDSLRDLRGSGAIQTIKQYNYLHEFRDKLAAHLSSRDSQSRSVSR | |||||||
Modified residue (large scale data) | 14 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 80 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Proteomic databases
PTM databases
Expression
Induction
Up-regulated in breast and prostate cancer cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q16667 | ARK2N Q96B23 | 2 | EBI-1031527, EBI-742108 | |
BINARY | Q16667 | CDK2 P24941 | 9 | EBI-1031527, EBI-375096 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-20 | Disordered | ||||
Sequence: MKPPSSIQTSEFDSSDEEPI | ||||||
Region | 1-34 | Interaction with CDK2 | ||||
Sequence: MKPPSSIQTSEFDSSDEEPIEDEQTPIHISWLSL | ||||||
Domain | 33-201 | Tyrosine-protein phosphatase | ||||
Sequence: SLSRVNCSQFLGLCALPGCKFKDVRRNVQKDTEELKSCGIQDIFVFCTRGELSKYRVPNLLDLYQQCGIITHHHPIADGGTPDIASCCEIMEELTTCLKNYRKTLIHCYGGLGRSCLVAACLLLYLSDTISPEQAIDSLRDLRGSGAIQTIKQYNYLHEFRDKLAAHLS |
Sequence similarities
Belongs to the protein-tyrosine phosphatase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
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.
- Name1
- Length212
- Mass (Da)23,805
- Last updated1996-11-01 v1
- ChecksumD87FAC8E28F6525F
Q16667-2
- Name2
- Differences from canonical
- 11-50: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 1; AAC04932 and 8; AAV38258 | ||||
Sequence: K → E | ||||||
Sequence conflict | 10 | in Ref. 3; AAK06380 | ||||
Sequence: S → G | ||||||
Alternative sequence | VSP_036613 | 11-50 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U02681 EMBL· GenBank· DDBJ | AAC04932.1 EMBL· GenBank· DDBJ | mRNA | ||
L27711 EMBL· GenBank· DDBJ | AAA66496.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213033 EMBL· GenBank· DDBJ | AAK06365.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213036 EMBL· GenBank· DDBJ | AAK06368.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213038 EMBL· GenBank· DDBJ | AAK06370.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213039 EMBL· GenBank· DDBJ | AAK06371.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213041 EMBL· GenBank· DDBJ | AAK06373.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213042 EMBL· GenBank· DDBJ | AAK06374.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213046 EMBL· GenBank· DDBJ | AAK06377.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213047 EMBL· GenBank· DDBJ | AAK06378.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213049 EMBL· GenBank· DDBJ | AAK06380.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213053 EMBL· GenBank· DDBJ | AAK06384.1 EMBL· GenBank· DDBJ | mRNA | ||
AY257474 EMBL· GenBank· DDBJ | AAP13062.1 EMBL· GenBank· DDBJ | mRNA | ||
L25876 EMBL· GenBank· DDBJ | AAA60222.1 EMBL· GenBank· DDBJ | mRNA | ||
EF560750 EMBL· GenBank· DDBJ | ABQ59060.1 EMBL· GenBank· DDBJ | mRNA | ||
CR407666 EMBL· GenBank· DDBJ | CAG28594.1 EMBL· GenBank· DDBJ | mRNA | ||
BT019451 EMBL· GenBank· DDBJ | AAV38258.1 EMBL· GenBank· DDBJ | mRNA | ||
AY194117 EMBL· GenBank· DDBJ | AAN86348.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471061 EMBL· GenBank· DDBJ | EAW80632.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471061 EMBL· GenBank· DDBJ | EAW80634.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC064965 EMBL· GenBank· DDBJ | AAH64965.1 EMBL· GenBank· DDBJ | mRNA |