CDKN1A Gene Summary [Human]
This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]
Details
| Type | Processed Transcript |
| Official Symbol | CDKN1A |
| Official Name | cyclin dependent kinase inhibitor 1A [Source:HGNC Symbol;Acc:HGNC:1784] |
| Ensembl ID | ENSG00000124762 |
| Bio databases IDs | |
| Aliases | cyclin dependent kinase inhibitor 1A |
| Synonyms | CAP20, CDKI, CDKN1, CDKNA1, CIP1, cyclin-dependent kinase inhibitor 1A, MDA-6, P21, p21Cip, p21CIP1, p21WAF, p21WAF1, Pzl Cyclin-Dependent Kinase Inhibitor, SDI1, UV96, WAF1 |
| Species | Human, Homo sapiens |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in human CDKN1A often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- ubiquitin protein ligase binding
- PCNA binding domain
- 3-10 helix
- protein kinase binding
- protein kinase inhibitor activity
- nuclear localization sequence
- cyclin recognition motif
- cyclin-dependent protein kinase activating kinase
- PIP degron
- protein binding
- cyclin-dependent kinase binding domain
- cyclin dependent kinase site
- phosphorylation site
- cyclin-CDK binding domain
- cyclin binding
- kinase
- cdk2 binding domain
- cyclin-dependent protein kinase inhibitor activity
- binding protein
- cyclin-binding domain
- C-terminal extension
- Cyclin-dependent kinase inhibitor
- Jnk phosphorylation site
Pathways
Biological processes and signaling networks where the CDKN1A gene in human plays a role, providing insight into its function and relevance in health or disease.
- Antiproliferative Role of Somatostatin Receptor 2
- Aryl Hydrocarbon Receptor Signaling
- ATM Signaling
- Bladder Cancer Signaling
- Cyclins and Cell Cycle Regulation
- DNA damage-induced 14-3-3σ Signaling
- Endocannabinoid Cancer Inhibition Pathway
- Estrogen-mediated S-phase Entry
- GADD45 Signaling
- Glioma Signaling
- Glucocorticoid Receptor Signaling
- HER-2 Signaling in Breast Cancer
- Hereditary Breast Cancer Signaling
- HGF Signaling
- JAK/Stat Signaling
- Melanoma Signaling
- p53 Signaling
- Pancreatic Adenocarcinoma Signaling
- Prostate Cancer Signaling
- PTEN Signaling
- Role of BRCA1 in DNA Damage Response
- Role of CHK Proteins in Cell Cycle Checkpoint Control
- VDR/RXR Activation
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- non-insulin-dependent diabetes mellitus
- heart failure
- diabetic nephropathy
- bladder cancer
- epithelial cancer
- abdominal cancer
- epithelial neoplasia
- cancer
- neoplasia
- breast cancer
role in cell
- quantity
- size
- cell viability
- phosphorylation in
- apoptosis
- expression in
- replication in
- molecular cleavage in
- binding
- accumulation
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Nucleus
- nuclear fraction
- soluble fraction
- primary granule fractions
- insoluble fractions
- Cytoplasm
- perinuclear region
- centrosome
- cytosol
- nucleoplasm
- nucleoli
- nuclear bodies
- plasma
- detergent-soluble fraction
- cytoskeletal fraction
- cytoplasmic fraction
- cytosolic fraction
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human CDKN1A gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- response to hyperoxia
- mitotic cell cycle G2/M transition DNA damage checkpoint
- cellular response to amino acid starvation
- positive regulation of programmed cell death
- DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis
- negative regulation of protein binding
- response to toxin
- cellular response to UV-B
- wound healing
- in utero embryonic development
- negative regulation of cell growth
- regulation of cell cycle
- negative regulation of DNA biosynthetic process
- Ras protein signal transduction
- response to DNA damage stimulus
- negative regulation of cyclin-dependent protein kinase activity
- negative regulation of gene expression
- keratinocyte differentiation
- response to corticosterone stimulus
- cellular response to gamma radiation
- positive regulation of protein kinase activity
- protein import into nucleus
- positive regulation of B cell proliferation
- regulation of G1/S transition of mitotic cell cycle
- organ regeneration
- regulation of G2/M transition of mitotic cell cycle
- response to X-ray
- replicative senescence
- negative regulation of cell proliferation
- cellular senescence
- intrinsic apoptotic signaling pathway
- positive regulation of DNA replication
- response to xenobiotic stimulus
- regulation of cyclin-dependent protein kinase activity
- fibroblast proliferation
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
- heart development
- cellular response to heat
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
- response to arsenic-containing substance
- positive regulation of fibroblast proliferation
- G1/S transition of mitotic cell cycle
- cellular response to ionizing radiation
- negative regulation of G1/S transition of mitotic cell cycle
- positive regulation of reactive oxygen species metabolic process
- intestinal epithelial cell maturation
- oncogene-induced senescence
- keratinocyte proliferation
- stress-induced premature senescence
- tissue regeneration
- negative regulation of phosphorylation
- cellular response to cell-matrix adhesion
- negative regulation of protein phosphorylation
- negative regulation of apoptotic process
- positive regulation of protein phosphorylation
- response to organic nitrogen
Cellular Component
Where in the cell the gene product is active
- nucleus
- nuclear body
- perinuclear region of cytoplasm
- cyclin-dependent protein kinase holoenzyme complex
- cytosol
- macromolecular complex
- nucleolus
- PCNA-p21 complex
- nucleoplasm
Molecular Function
What the gene product does at the molecular level
- protein kinase binding
- cyclin-dependent protein kinase activating kinase activity
- protein binding
- ubiquitin protein ligase binding
- metal ion binding
- cyclin binding
- cyclin-dependent protein kinase inhibitor activity
- protein kinase inhibitor activity