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Symbol CDKN1A contributors: npt/mct - updated : 01-12-2010
HGNC name cyclin-dependent kinase inhibitor 1A (p21, Cip1)
HGNC id 1784
Location 6p21.2      Physical location : 36.646.458 - 36.655.108
Synonym name
  • cyclin-dependent kinase inhibitor, p21
  • wild-type p53-activated fragment 1
  • DNA synthesis inhibitor
  • CDK-interacting protein 1
  • melanoma differentiation-associated protein 6
  • Synonym symbol(s) CDKN1, CIP1, WAF1, P21, SDI1, CAP20, MDA6, p21CIP1, p21Cip1/Waf1
    TYPE functioning gene
    STRUCTURE 8.65 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer   transcription factor
    text structure
  • BCL11B is recruited to the gene promoter, silenced CDKN1A gene transcription through interactions with histone deacetylases and methyltransferases
  • a novel AP-2 binding site within the proximal promoter of the CDKN1A gene, required for optimal, TP53-independent expression of CDKN1A
  • three putative ARID3A binding sites were found in the CDKN1A promoter region
  • MAPPING cloned Y linked N status confirmed
    Physical map
    DEF6 6p21.33-p21.1 differentially expressed in FDCP 6 homolog (mouse) PPARD 6p21.2-p21.1 peroxisome proliferative activated receptor, delta MKRNP2 6p21.1 makorin, ring finger protein, pseudogene 2 FANCE 6p22-p21 Fanconi anemia, complementation group E RPL10A 6p21.3 ribosomal protein L10a TEAD3 6p21.2 TEA domain family member 3 TULP1 6p21.3 tubby like protein 1 LOC389382 6 similar to Rps15a protein FKBP5 6p21.3-p21.2 FK506 binding protein 5 C6orf81 6p21.31 chromosome 6 open reading frame 81 LOC389383 6 similar to AAAL3045 LOC340204 6p21.31 similar to precursor peptide CLPS 6p22-p21.1 colipase, pancreatic MGC33835 6p21.31 hypothetical protein MGC33835 SRPK1 6p213-p21.2 SFRS protein kinase 1 SLC26A8 6p21 solute carrier family 26, member 8 MAPK14 6p21.2 mitogen-activated protein kinase 14 MAPK13 6p21.1 mitogen-activated protein kinase 13 BRPF3 6p21 bromodomain and PHD finger containing, 3 PNPLA1 6p21.31 patatin-like phospholipase domain containing 1 LOC389384 6 similar to RIKEN cDNA 4930539E08 ETV7 6p21 ets variant gene 7 (TEL2 oncogene ) STEPP 6p21.31 small testis-specific peroxisomal protein C6orf69 6p21.31 chromosome 6 open reading frame 69 STK38 6p21 serine/threonine kinase 38 SFRS3 11p15.1 splicing factor, arginine/serine-rich 3 LOC389385 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) LOC389386 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) CDKN1A 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) LOC346190 6p21.31 similar to hypothetical protein FLJ31614 LOC391917 6 similar to putative G-protein coupled receptor CPNE5 6p21.1 copine V PPIL1 6p21.1 peptidylprolyl isomerase (cyclophilin)-like 1 C6orf89 6p21.31 chromosome 6 open reading frame 89 PI16 6p21.31 protease inhibitor 16 MTCH1 6pter-p24.1 mitochondrial carrier homolog 1 (C. elegans) FGD2 6p21.2 FGD1 family, member 2 LOC285849 6p21.31 similar to cytochrome c oxidase subunit VIa polypeptide 1 precursor; cytochrome C oxidase subunit VIa homolog LOC389387 6 similar to 60S ribosomal protein L12 PIM1 6p21.2 pim-1 oncogene C6orf128 6p21.31-p21.2 chromosome 6 open reading frame 128 C6orf197 6p21.2 chromosome 6 open reading frame 197 RNF8 6p21.3 ring finger protein (C3HC4 type) 8 KIAA0082 6p21.2 ring finger protein (C3HC4 type) 8 C6orf129 6p21.2 chromosome 6 open reading frame 129 MDGA1 6p21 MAM domain containing glycosylphosphatidylinositol anchor 1 TEX27 6pter-p22.3 testis expressed sequence 27
    TRANSCRIPTS type messenger
  • two transcripts encoding for the same product
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 2168 18.12 164 - 1999 9925645
    lacking an internal sequence segment in the 5' UTR
    3 splicing 2281 18.12 164 - 1999 9925645
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestivemouth   moderately
     salivary gland   moderately
     stomach   highly
    Endocrinepancreas   moderately
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunethymus   moderately
    Nervousnerve   highly
    Reproductivefemale systemuteruscervix moderately
    Respiratorylung   predominantly
    Skin/Tegumentskin   highly
    Visualeye   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    cell cycle     cell cycle, interphase, G1
    Text embryonic tissue
  • a CDK inhibitory domain
  • a proline-rich domain
  • an acidic repeat region
  • a conserved C terminal domain hybridizing with WI-7311, WI-10190
    interspecies homolog to rattus Cdkn1a (76.54 pc)
    homolog to murine Cdkn1a (79.25 pc)
  • CDK inhibitor family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    text apoptosis
    basic FUNCTION
  • wild type p53-activated fragment 1 mediating the cell cycle G1 phase arrest in response of various stress stimuli
  • involved in an age-dependent increase in cell cycle negative regulation of the Human Corneal Endothelial Cells (HCEC)
  • may be responsible, at least in part, for the reduced proliferative response observed in HCECs from older donors
  • upstream regulator of DNMT1 expression, and negatively regulates DNMT1 expression in mammalian cells
  • major cell cycle regulator of the response to DNA damage, senescence and tumor suppression
  • plays an essential role in promoting cell cycle exit in endocrine progenitors downstream of NEUROG3)
  • CELLULAR PROCESS cell cycle
  • CDK inhibitor controlling differentiation of skeletal muscle and alveoli in the lung in parallel with P21 and myogenin
  • suppressor of malignant skin tumor formation and as a determinant of keratinocyte stem-cell potential
  • regulator at G1 cell cylce exit in megacaryocytes
    CDKN1A-EP300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division
    a component
    small molecule
  • TYMS
  • inhibiting CDK2, CDK4 complexes
  • inhibiting cycle progression by interacting with G1 cyclin/CDK complexes and PCNA
  • CCNE2
  • TFAP2A binds CDKN1A to two regions of the promoter: the proximal region where the AP-2 site lies and upstream near the major TP53 binding site
  • SSBP1 directly binds CDKN1A and this interaction may prevent CDKN1A from ubiquitin-mediated degradation
  • new function of SRSF2 in the process of cellular senescence and CDKN1A is a key target of SRSF2 in this setting
  • acted in part to mediate growth suppression by ARID1A
  • cooperative and interdependent roles for ARID3A and TP53 in the transcriptional activation of CDKN1A in response to DNA damage
  • RNF144B is a potentially critical component of epithelial homeostasis, acting downstream of TP63 to regulate cellular levels of CDKN1A and TP63
  • HIC1 is a direct transcriptional repressor of CDKN1A and is a key player in the regulation of the DNA damage response
  • FMN2 is a crucial protein involved in the control of CDKN1A (
  • has dual effects under HSPA9-depleted conditions, i.e., mediating cell cycle arrest while limiting cell death
  • RASSF6 triggers CDKN1A accumulation to induce G 1 cell cycle arrest and promote apoptosis upon exposure to pro-apoptotic agents
  • cell & other
    activated by TP53
    KLF1 (directly activates CDKN1A by proximal promoter and novel intronic regulatory regions during erythroid differentiation)
    induced by chimeric oncoprotein SS18-SSX1 for suppression of cell growth
    low concentration of Cl-
    inhibited by AMPHL in early stage of muscle differentiation program
    repressed by TYMS
    ZBTB2 by a direct interaction with TP53 and SP1
    Phosphorylated by PIM2, that phosphorylates CDKN1A on Thr145
    Other cleaved by caspase 3 in the earlier stage of apoptosis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    papillary thyroid carcinoma
    tumoral     --low  
    in adult T-cell leukemia/lymphoma (ATLL) cells may be a key player in ATLL leukemogenesis, and the abnormal genomic methylation may influence the expression of not only HTLV-1 TAX but also CDKN1A during long-term development of ATLL from the HTLV-1-infected T lymphocytes
  • esophageal cancer, cervical cancer
  • to advanced prostate carcinoma
  • Variant & Polymorphism other
  • variant of the codon 31 increasing in primary cervical cancer (Japanese)
  • genotype CT and TT strongly associated with advanced prostate carcinoma
  • Candidate gene
    Therapy target
  • being a novel, unique therapeutic strategy for gastric cancer treatment via control of decreased the intracellular chloride concentration