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P38936

- CDN1A_HUMAN

UniProt

P38936 - CDN1A_HUMAN

Protein

Cyclin-dependent kinase inhibitor 1

Gene

CDKN1A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 168 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex.2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri13 – 4129C4-typeSequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. cyclin-dependent protein kinase activating kinase activity Source: UniProtKB
    2. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: BHF-UCL
    3. metal ion binding Source: UniProtKB-KW
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle arrest Source: BHF-UCL
    2. cellular response to DNA damage stimulus Source: BHF-UCL
    3. cellular response to extracellular stimulus Source: BHF-UCL
    4. cellular response to ionizing radiation Source: BHF-UCL
    5. cellular senescence Source: BHF-UCL
    6. DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: BHF-UCL
    7. epidermal growth factor receptor signaling pathway Source: Reactome
    8. Fc-epsilon receptor signaling pathway Source: Reactome
    9. fibroblast growth factor receptor signaling pathway Source: Reactome
    10. G1/S transition of mitotic cell cycle Source: BHF-UCL
    11. G2/M transition of mitotic cell cycle Source: BHF-UCL
    12. innate immune response Source: Reactome
    13. intrinsic apoptotic signaling pathway Source: ProtInc
    14. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
    15. mitotic cell cycle Source: Reactome
    16. mitotic cell cycle arrest Source: Ensembl
    17. negative regulation of apoptotic process Source: Ensembl
    18. negative regulation of cell growth Source: BHF-UCL
    19. negative regulation of cell proliferation Source: BHF-UCL
    20. negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
    21. negative regulation of gene expression Source: Ensembl
    22. negative regulation of phosphorylation Source: BHF-UCL
    23. neurotrophin TRK receptor signaling pathway Source: Reactome
    24. organ regeneration Source: Ensembl
    25. phosphatidylinositol-mediated signaling Source: Reactome
    26. positive regulation of B cell proliferation Source: Ensembl
    27. positive regulation of fibroblast proliferation Source: BHF-UCL
    28. positive regulation of programmed cell death Source: Ensembl
    29. positive regulation of protein kinase activity Source: GOC
    30. positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
    31. protein phosphorylation Source: GOC
    32. Ras protein signal transduction Source: BHF-UCL
    33. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
    34. regulation of DNA biosynthetic process Source: Ensembl
    35. regulation of protein import into nucleus, translocation Source: Ensembl
    36. response to arsenic-containing substance Source: Ensembl
    37. response to corticosterone Source: Ensembl
    38. response to drug Source: Ensembl
    39. response to hyperoxia Source: Ensembl
    40. response to organonitrogen compound Source: Ensembl
    41. response to toxic substance Source: Ensembl
    42. response to UV Source: Ensembl
    43. stress-induced premature senescence Source: BHF-UCL

    Keywords - Molecular functioni

    Protein kinase inhibitor

    Keywords - Biological processi

    Cell cycle

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_1156. Orc1 removal from chromatin.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_1625. p53-Dependent G1 DNA Damage Response.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9029. Cyclin A:Cdk2-associated events at S phase entry.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase inhibitor 1
    Alternative name(s):
    CDK-interacting protein 1
    Melanoma differentiation-associated protein 6
    Short name:
    MDA-6
    p21
    Gene namesi
    Name:CDKN1A
    Synonyms:CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:1784. CDKN1A.

    Subcellular locationi

    GO - Cellular componenti

    1. cyclin-dependent protein kinase holoenzyme complex Source: BHF-UCL
    2. cytosol Source: Reactome
    3. intracellular membrane-bounded organelle Source: HPA
    4. nucleoplasm Source: Reactome
    5. nucleus Source: BHF-UCL
    6. PCNA-p21 complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi114 – 1141S → E: Phosphomimetic mutant, increases ubiquitination by the DCX(DTL) complex. 2 Publications
    Mutagenesisi144 – 1507QTSMTDF → ATSATDA: Abolishes interaction with PCNA and subsequent degradation by the proteasome. 1 Publication
    Mutagenesisi145 – 1451T → A: Reduces phosphorylation by Akt; no change in interaction with PCNA, CDK2 or CDK4; no change in subcellular location. 2 Publications
    Mutagenesisi145 – 1451T → D: No interaction with PCNA; 59% inhibition of CDK2 binding; modest inhibition of CDK4 binding; no change in subcellular location. 2 Publications
    Mutagenesisi146 – 1461S → A: No change in interaction with PCNA. 2 Publications
    Mutagenesisi146 – 1461S → D: Reduces interaction with PCNA. 2 Publications
    Mutagenesisi147 – 1515MTDFY → ATDAAA: Abolishes interaction with PCNA and subsequent degradation by the proteasome. 1 Publication
    Mutagenesisi154 – 1563KRR → AAA: Abolishes degradation by the proteasome without affecting the interaction with PCNA. 1 Publication

    Organism-specific databases

    Orphaneti652. Multiple endocrine neoplasia type 1.
    PharmGKBiPA104.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 164163Cyclin-dependent kinase inhibitor 1PRO_0000190079Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    Cross-linki2 – 2Glycyl serine ester (Ser-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei114 – 1141Phosphoserine; by GSK3-beta1 Publication
    Modified residuei130 – 1301Phosphoserine2 Publications
    Modified residuei145 – 1451Phosphothreonine; by PKA; PKB/AKT1, PIM1 and PIM25 Publications
    Modified residuei146 – 1461Phosphoserine; by PKC1 Publication
    Modified residuei160 – 1601Phosphoserine; by PKC; in vitro1 Publication

    Post-translational modificationi

    Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell proliferation. Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability.8 Publications
    Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation.1 Publication
    Acetylation leads to protein stability. Acetylated in vitro on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1 By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP38936.
    PaxDbiP38936.
    PRIDEiP38936.

    2D gel databases

    SWISS-2DPAGEP38936.

    PTM databases

    PhosphoSiteiP38936.

    Expressioni

    Tissue specificityi

    Expressed in all adult tissues, with 5-fold lower levels observed in the brain.

    Inductioni

    Activated by p53/TP53, mezerein (antileukemic compound) and IFNB1. Repressed by HDAC1.2 Publications

    Gene expression databases

    ArrayExpressiP38936.
    BgeeiP38936.
    CleanExiHS_CDKN1A.
    GenevestigatoriP38936.

    Organism-specific databases

    HPAiCAB000064.
    HPA051359.

    Interactioni

    Subunit structurei

    Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 By similarity. Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Interacts with PIM1.By similarity8 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    P279583EBI-375077,EBI-6377335From a different organism.
    CCNA1P783963EBI-375077,EBI-375065
    CCNA2P202482EBI-375077,EBI-457097
    CCND1P243856EBI-375077,EBI-375001
    CCND2P302793EBI-375077,EBI-748789
    CCND3P302814EBI-375077,EBI-375013
    CCNE1P248649EBI-375077,EBI-519526
    CCNE2O960202EBI-375077,EBI-375033
    CDC45O754192EBI-375077,EBI-374969
    CDC6Q997412EBI-375077,EBI-374862
    CDK14O949218EBI-375077,EBI-1043945
    CDK2P2494114EBI-375077,EBI-375096
    CDK4P118025EBI-375077,EBI-295644
    CDK5Q005354EBI-375077,EBI-1041567
    MKRN1Q9UHC75EBI-375077,EBI-373524
    NABP2Q9BQ157EBI-375077,EBI-2120336
    PCNAP120046EBI-375077,EBI-358311
    PCNAQ6FI352EBI-375077,EBI-8469539
    SIPA1Q96FS42EBI-375077,EBI-1054981
    SKP1P632083EBI-375077,EBI-307486
    SKP2Q133092EBI-375077,EBI-456291
    TP53P046373EBI-375077,EBI-366083

    Protein-protein interaction databases

    BioGridi107460. 197 interactions.
    DIPiDIP-246N.
    IntActiP38936. 152 interactions.
    MINTiMINT-104203.
    STRINGi9606.ENSP00000244741.

    Structurei

    Secondary structure

    1
    164
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi147 – 1493
    Beta strandi151 – 1588

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AXCX-ray2.60B/D/F139-160[»]
    2ZVVX-ray2.00X/Y139-160[»]
    2ZVWX-ray2.50I/J/K/L/M/N/O/P139-160[»]
    DisProtiDP00016.
    ProteinModelPortaliP38936.
    SMRiP38936. Positions 17-77.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP38936.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni17 – 248Required for binding cyclins
    Regioni53 – 586Required for binding CDKs

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi140 – 16425PIP-box K+4 motifAdd
    BLAST
    Motifi141 – 15616Nuclear localization signalSequence AnalysisAdd
    BLAST

    Domaini

    The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.
    The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex.

    Sequence similaritiesi

    Belongs to the CDI family.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri13 – 4129C4-typeSequence AnalysisAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG290902.
    HOGENOMiHOG000285999.
    HOVERGENiHBG050868.
    InParanoidiP38936.
    KOiK06625.
    OrthoDBiEOG7GJ6HD.
    PhylomeDBiP38936.
    TreeFamiTF101038.

    Family and domain databases

    InterProiIPR003175. CDI.
    [Graphical view]
    PANTHERiPTHR10265. PTHR10265. 1 hit.
    PfamiPF02234. CDI. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P38936-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSEPAGDVRQ NPCGSKACRR LFGPVDSEQL SRDCDALMAG CIQEARERWN    50
    FDFVTETPLE GDFAWERVRG LGLPKLYLPT GPRRGRDELG GGRRPGTSPA 100
    LLQGTAEEDH VDLSLSCTLV PRSGEQAEGS PGGPGDSQGR KRRQTSMTDF 150
    YHSKRRLIFS KRKP 164
    Length:164
    Mass (Da):18,119
    Last modified:January 23, 2007 - v3
    Checksum:i98D1E7C519ADFCA9
    GO

    Sequence cautioni

    The sequence AAB59559.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
    The sequence AAB59560.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti4 – 41P → L.
    Corresponds to variant rs4986866 [ dbSNP | Ensembl ].
    VAR_048686
    Natural varianti31 – 311S → R.3 Publications
    Corresponds to variant rs1801270 [ dbSNP | Ensembl ].
    VAR_011870
    Natural varianti63 – 631F → L.
    Corresponds to variant rs4986867 [ dbSNP | Ensembl ].
    VAR_048687
    Natural varianti149 – 1491D → G.
    Corresponds to variant rs1801724 [ dbSNP | Ensembl ].
    VAR_014875

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L25610 mRNA. Translation: AAA16109.1.
    S67388 mRNA. Translation: AAB29246.1.
    U09579 mRNA. Translation: AAA85641.1.
    U03106 mRNA. Translation: AAC04313.1.
    L26165 mRNA. Translation: AAA19811.1.
    L47232 mRNA. Translation: AAB59559.1. Different initiation.
    L47233 mRNA. Translation: AAB59560.1. Different initiation.
    AF497972 Genomic DNA. Translation: AAM11787.1.
    BT006719 mRNA. Translation: AAP35365.1.
    AB451290 mRNA. Translation: BAG70104.1.
    AB451422 mRNA. Translation: BAG70236.1.
    CR536533 mRNA. Translation: CAG38770.1.
    Z85996 Genomic DNA. Translation: CAB06656.1.
    CH471081 Genomic DNA. Translation: EAX03904.1.
    BC000275 mRNA. Translation: AAH00275.1.
    BC000312 mRNA. Translation: AAH00312.1.
    BC001935 mRNA. Translation: AAH01935.1.
    BC013967 mRNA. Translation: AAH13967.1.
    CCDSiCCDS4824.1.
    PIRiI54380.
    I68674.
    RefSeqiNP_000380.1. NM_000389.4.
    NP_001207706.1. NM_001220777.1.
    NP_001207707.1. NM_001220778.1.
    NP_001278478.1. NM_001291549.1.
    NP_510867.1. NM_078467.2.
    UniGeneiHs.370771.
    Hs.732576.

    Genome annotation databases

    EnsembliENST00000244741; ENSP00000244741; ENSG00000124762.
    ENST00000373711; ENSP00000362815; ENSG00000124762.
    ENST00000405375; ENSP00000384849; ENSG00000124762.
    GeneIDi1026.
    KEGGihsa:1026.
    UCSCiuc003omm.4. human.

    Polymorphism databases

    DMDMi729143.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L25610 mRNA. Translation: AAA16109.1 .
    S67388 mRNA. Translation: AAB29246.1 .
    U09579 mRNA. Translation: AAA85641.1 .
    U03106 mRNA. Translation: AAC04313.1 .
    L26165 mRNA. Translation: AAA19811.1 .
    L47232 mRNA. Translation: AAB59559.1 . Different initiation.
    L47233 mRNA. Translation: AAB59560.1 . Different initiation.
    AF497972 Genomic DNA. Translation: AAM11787.1 .
    BT006719 mRNA. Translation: AAP35365.1 .
    AB451290 mRNA. Translation: BAG70104.1 .
    AB451422 mRNA. Translation: BAG70236.1 .
    CR536533 mRNA. Translation: CAG38770.1 .
    Z85996 Genomic DNA. Translation: CAB06656.1 .
    CH471081 Genomic DNA. Translation: EAX03904.1 .
    BC000275 mRNA. Translation: AAH00275.1 .
    BC000312 mRNA. Translation: AAH00312.1 .
    BC001935 mRNA. Translation: AAH01935.1 .
    BC013967 mRNA. Translation: AAH13967.1 .
    CCDSi CCDS4824.1.
    PIRi I54380.
    I68674.
    RefSeqi NP_000380.1. NM_000389.4.
    NP_001207706.1. NM_001220777.1.
    NP_001207707.1. NM_001220778.1.
    NP_001278478.1. NM_001291549.1.
    NP_510867.1. NM_078467.2.
    UniGenei Hs.370771.
    Hs.732576.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AXC X-ray 2.60 B/D/F 139-160 [» ]
    2ZVV X-ray 2.00 X/Y 139-160 [» ]
    2ZVW X-ray 2.50 I/J/K/L/M/N/O/P 139-160 [» ]
    DisProti DP00016.
    ProteinModelPortali P38936.
    SMRi P38936. Positions 17-77.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107460. 197 interactions.
    DIPi DIP-246N.
    IntActi P38936. 152 interactions.
    MINTi MINT-104203.
    STRINGi 9606.ENSP00000244741.

    Chemistry

    ChEMBLi CHEMBL3038463.

    PTM databases

    PhosphoSitei P38936.

    Polymorphism databases

    DMDMi 729143.

    2D gel databases

    SWISS-2DPAGE P38936.

    Proteomic databases

    MaxQBi P38936.
    PaxDbi P38936.
    PRIDEi P38936.

    Protocols and materials databases

    DNASUi 1026.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000244741 ; ENSP00000244741 ; ENSG00000124762 .
    ENST00000373711 ; ENSP00000362815 ; ENSG00000124762 .
    ENST00000405375 ; ENSP00000384849 ; ENSG00000124762 .
    GeneIDi 1026.
    KEGGi hsa:1026.
    UCSCi uc003omm.4. human.

    Organism-specific databases

    CTDi 1026.
    GeneCardsi GC06P036761.
    HGNCi HGNC:1784. CDKN1A.
    HPAi CAB000064.
    HPA051359.
    MIMi 116899. gene.
    neXtProti NX_P38936.
    Orphaneti 652. Multiple endocrine neoplasia type 1.
    PharmGKBi PA104.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG290902.
    HOGENOMi HOG000285999.
    HOVERGENi HBG050868.
    InParanoidi P38936.
    KOi K06625.
    OrthoDBi EOG7GJ6HD.
    PhylomeDBi P38936.
    TreeFami TF101038.

    Enzyme and pathway databases

    Reactomei REACT_1156. Orc1 removal from chromatin.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_1625. p53-Dependent G1 DNA Damage Response.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9029. Cyclin A:Cdk2-associated events at S phase entry.

    Miscellaneous databases

    ChiTaRSi CDKN1A. human.
    EvolutionaryTracei P38936.
    GeneWikii P21.
    GenomeRNAii 1026.
    NextBioi 4309.
    PROi P38936.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P38936.
    Bgeei P38936.
    CleanExi HS_CDKN1A.
    Genevestigatori P38936.

    Family and domain databases

    InterProi IPR003175. CDI.
    [Graphical view ]
    PANTHERi PTHR10265. PTHR10265. 1 hit.
    Pfami PF02234. CDI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases."
      Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J.
      Cell 75:805-816(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Use of a sensitive and efficient subtraction hybridization protocol for the identification of genes differentially regulated during the induction of differentiation in human melanoma cells."
      Jiang H., Fisher P.B.
      Mol. Cell. Differ. 1:285-299(1993)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "The melanoma differentiation-associated gene mda-6, which encodes the cyclin-dependent kinase inhibitor p21, is differentially expressed during growth, differentiation and progression in human melanoma cells."
      Jiang H., Lin J., Su Z.Z., Herlyn M., Kerbel R.S., Weissman B.E., Welch D.R., Fisher P.B.
      Oncogene 10:1855-1864(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen."
      Noda A., Ning Y., Venable S.F., Pereira-Smith O.M., Smith J.R.
      Exp. Cell Res. 211:90-98(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    7. "Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer."
      Mousses S., Oezcelik H., Lee P.D., Malkin D., Bull S.B., Andrulis I.L.
      Hum. Mol. Genet. 4:1089-1092(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-31.
    8. NIEHS SNPs program
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-31.
    9. "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 (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    10. "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 (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    11. "Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
      Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.
      , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
      Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    12. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    13. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    14. "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], VARIANT ARG-31.
      Tissue: Eye and Lung.
    15. "N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1)."
      Chen X., Chi Y., Bloecher A., Aebersold R., Clurman B.E., Roberts J.M.
      Mol. Cell 16:839-847(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-16, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
    16. "Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding."
      Scott M.T., Morrice N., Ball K.L.
      J. Biol. Chem. 275:11529-11537(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND SER-160, IDENTIFICATION BY MASS SPECTROMETRY.
    17. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDK4 AND CCND1 IN THE CYCLIN D-CDK4-CDKN1A COMPLEX.
    18. "A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 alpha-subunit of the 20S proteasome."
      Touitou R., Richardson J., Bose S., Nakanishi M., Rivett J., Allday M.J.
      EMBO J. 20:2367-2375(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PSMA3.
    19. "Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells."
      Roessig L., Jadidi A.S., Urbich C., Badorff C., Zeiher A.M., Dimmeler S.
      Mol. Cell. Biol. 21:5644-5657(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, SUBCELLULAR LOCATION.
    20. "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase."
      Wang Z., Bhattacharya N., Mixter P.F., Wei W., Sedivy J., Magnuson N.S.
      Biochim. Biophys. Acta 1593:45-55(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-145 BY PIM1, SUBCELLULAR LOCATION, INTERACTION WITH PIM1.
    21. "N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome."
      Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.
      Mol. Cell. Biol. 24:6140-6150(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT SER-2.
    22. "Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding."
      Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D., Hemmings B.A., Fernandez A., Lamb N.J.
      Mol. Cell. Biol. 26:8267-8280(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-145.
    23. "A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
      Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
      Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    24. "PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex."
      Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.
      Genes Dev. 22:2496-2506(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, INTERACTION WITH PCNA, MUTAGENESIS OF SER-114 AND 144-GLN--PHE-150, PHOSPHORYLATION AT SER-114.
    25. "The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing."
      Kim Y., Starostina N.G., Kipreos E.T.
      Genes Dev. 22:2507-2519(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    26. "CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation."
      Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.
      J. Biol. Chem. 283:29045-29052(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, MUTAGENESIS OF 147-MET--TYR-151 AND 154-LYS--ARG-156, INTERACTION WITH PCNA.
    27. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    28. "A dual role of Cdk2 in DNA damage response."
      Satyanarayana A., Kaldis P.
      Cell Div. 4:9-9(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON DNA REPAIR, INTERACTION WITH CDK2.
    29. "Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis."
      Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C., Lane D.P., Song J.
      EMBO J. 28:2100-2113(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, INTERACTION WITH MKRN1.
    30. "Ionizing radiation induces ATM-independent degradation of p21Cip1 in transformed cells."
      Stuart S.A., Wang J.Y.
      J. Biol. Chem. 284:15061-15070(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    31. "Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells."
      Wang Z., Zhang Y., Gu J.J., Davitt C., Reeves R., Magnuson N.S.
      Int. J. Biochem. Cell Biol. 42:1030-1038(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-145 BY PIM2.
    32. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    33. "ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.)."
      Han J., Kim Y.L., Lee K.W., Her N.G., Ha T.K., Yoon S., Jeong S.I., Lee J.H., Kang M.J., Lee M.G., Ryu B.K., Baik J.H., Chi S.G.
      Cell Death Differ. 20:1055-1067(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY RNF114.
    34. "Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA."
      Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.
      Cell 87:297-306(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160 IN COMPLEX WITH PCNA.

    Entry informationi

    Entry nameiCDN1A_HUMAN
    AccessioniPrimary (citable) accession number: P38936
    Secondary accession number(s): Q14010, Q6FI05, Q9BUT4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 168 of the entry and version 3 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: 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

    External Data

    Dasty 3