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P42772

- CDN2B_HUMAN

UniProt

P42772 - CDN2B_HUMAN

Protein

Cyclin-dependent kinase 4 inhibitor B

Gene

CDKN2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.

    GO - Molecular functioni

    1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: UniProtKB
    2. protein binding Source: IntAct
    3. protein kinase binding Source: BHF-UCL

    GO - Biological processi

    1. aging Source: Ensembl
    2. cell cycle arrest Source: BHF-UCL
    3. cellular response to extracellular stimulus Source: BHF-UCL
    4. cellular response to nutrient Source: BHF-UCL
    5. G2/M transition of mitotic cell cycle Source: BHF-UCL
    6. gene expression Source: Reactome
    7. liver development Source: Ensembl
    8. megakaryocyte differentiation Source: UniProtKB
    9. mitotic cell cycle Source: Reactome
    10. mitotic cell cycle checkpoint Source: BHF-UCL
    11. negative regulation of cell proliferation Source: BHF-UCL
    12. negative regulation of epithelial cell proliferation Source: BHF-UCL
    13. negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
    14. negative regulation of phosphorylation Source: BHF-UCL
    15. negative regulation of protein serine/threonine kinase activity Source: GOC
    16. positive regulation of epithelial cell differentiation Source: Ensembl
    17. positive regulation of transcription from RNA polymerase II promoter Source: Reactome
    18. positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    19. regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
    20. response to cytokine Source: Ensembl
    21. response to organic cyclic compound Source: Ensembl
    22. spleen development Source: Ensembl
    23. transcription, DNA-templated Source: Reactome
    24. transcription initiation from RNA polymerase II promoter Source: Reactome
    25. transforming growth factor beta receptor signaling pathway Source: Reactome

    Keywords - Biological processi

    Cell cycle

    Enzyme and pathway databases

    ReactomeiREACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 4 inhibitor B
    Alternative name(s):
    Multiple tumor suppressor 2
    Short name:
    MTS-2
    p14-INK4b
    p15-INK4b
    Short name:
    p15INK4B
    Gene namesi
    Name:CDKN2B
    Synonyms:MTS2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:1788. CDKN2B.

    Subcellular locationi

    Cytoplasm 1 Publication
    Note: Also found in the nucleus.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    Orphaneti618. Familial melanoma.
    652. Multiple endocrine neoplasia type 1.
    PharmGKBiPA26321.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 138138Cyclin-dependent kinase 4 inhibitor BPRO_0000144184Add
    BLAST

    Proteomic databases

    MaxQBiP42772.
    PaxDbiP42772.
    PRIDEiP42772.

    PTM databases

    PhosphoSiteiP42772.

    Expressioni

    Tissue specificityi

    Isoform 2 is expressed in normal (keratinocytes, fibroblasts) and tumor cell lines.1 Publication

    Gene expression databases

    ArrayExpressiP42772.
    BgeeiP42772.
    CleanExiHS_CDKN2B.
    GenevestigatoriP42772.

    Organism-specific databases

    HPAiCAB000349.
    HPA052838.

    Interactioni

    Subunit structurei

    Heterodimer of CDKN2B with CDK4 or CDK6. Isoform 2 does not interact with CDK4 nor CDK6.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDK4P118028EBI-711280,EBI-295644
    CDK6Q005343EBI-711280,EBI-295663

    Protein-protein interaction databases

    BioGridi107464. 13 interactions.
    IntActiP42772. 11 interactions.
    MINTiMINT-1377924.
    STRINGi9606.ENSP00000276925.

    Structurei

    3D structure databases

    ProteinModelPortaliP42772.
    SMRiP42772. Positions 11-138.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati13 – 3927ANK 1; truncatedAdd
    BLAST
    Repeati46 – 7429ANK 2Add
    BLAST
    Repeati79 – 10830ANK 3Add
    BLAST
    Repeati112 – 13827ANK 4Add
    BLAST

    Sequence similaritiesi

    Contains 4 ANK repeats.Curated

    Keywords - Domaini

    ANK repeat, Repeat

    Phylogenomic databases

    eggNOGiNOG287192.
    HOGENOMiHOG000290191.
    HOVERGENiHBG050870.
    InParanoidiP42772.
    KOiK04685.
    OMAiEPNCADE.
    OrthoDBiEOG7TTQ94.
    PhylomeDBiP42772.
    TreeFamiTF352389.

    Family and domain databases

    Gene3Di1.25.40.20. 1 hit.
    InterProiIPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view]
    PfamiPF12796. Ank_2. 1 hit.
    [Graphical view]
    SMARTiSM00248. ANK. 3 hits.
    [Graphical view]
    SUPFAMiSSF48403. SSF48403. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P42772-1) [UniParc]FASTAAdd to Basket

    Also known as: p15

    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.

    « Hide

    MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA    50
    IQVMMMGSAR VAELLLLHGA EPNCADPATL TRPVHDAARE GFLDTLVVLH 100
    RAGARLDVRD AWGRLPVDLA EERGHRDVAG YLRTATGD 138
    Length:138
    Mass (Da):14,722
    Last modified:November 1, 1995 - v1
    Checksum:i0D6FFBDFA6FEAD21
    GO
    Isoform 2 (identifier: P42772-2) [UniParc]FASTAAdd to Basket

    Also known as: p10

    The sequence of this isoform differs from the canonical sequence as follows:
         54-138: MMMGSARVAE...AGYLRTATGD → AGAPGPRRQGARERGARPRRIGAGT

    Show »
    Length:78
    Mass (Da):8,078
    Checksum:i3EB74DDEC36E674D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti20 – 223SAA → TP in AAA50282. (PubMed:8078588)Curated
    Sequence conflicti32 – 343QLL → HSW in AAA50282. (PubMed:8078588)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti47 – 471G → E in lung adenocarcinoma. 1 Publication
    VAR_001488
    Natural varianti50 – 501A → V in lung adenocarcinoma. 1 Publication
    VAR_001489

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei54 – 13885MMMGS…TATGD → AGAPGPRRQGARERGARPRR IGAGT in isoform 2. 1 PublicationVSP_043898Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17075 mRNA. Translation: AAC50075.1.
    L36844 mRNA. Translation: AAA50282.1.
    AF004819 mRNA. Translation: AAB69989.1.
    CR536529 mRNA. Translation: CAG38766.1.
    AF513858 Genomic DNA. Translation: AAM44859.1.
    AL449423 Genomic DNA. Translation: CAH70602.1.
    AL449423 Genomic DNA. Translation: CAH70603.1.
    BC014469 mRNA. Translation: AAH14469.1.
    S69805 Genomic DNA. Translation: AAD14049.1.
    CCDSiCCDS6512.1. [P42772-1]
    CCDS6513.1. [P42772-2]
    PIRiB55479.
    RefSeqiNP_004927.2. NM_004936.3. [P42772-1]
    NP_511042.1. NM_078487.2. [P42772-2]
    UniGeneiHs.72901.

    Genome annotation databases

    EnsembliENST00000276925; ENSP00000276925; ENSG00000147883. [P42772-1]
    ENST00000380142; ENSP00000369487; ENSG00000147883. [P42772-2]
    GeneIDi1030.
    KEGGihsa:1030.
    UCSCiuc003zpn.3. human. [P42772-2]
    uc003zpo.3. human. [P42772-1]

    Polymorphism databases

    DMDMi1168869.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

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

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17075 mRNA. Translation: AAC50075.1 .
    L36844 mRNA. Translation: AAA50282.1 .
    AF004819 mRNA. Translation: AAB69989.1 .
    CR536529 mRNA. Translation: CAG38766.1 .
    AF513858 Genomic DNA. Translation: AAM44859.1 .
    AL449423 Genomic DNA. Translation: CAH70602.1 .
    AL449423 Genomic DNA. Translation: CAH70603.1 .
    BC014469 mRNA. Translation: AAH14469.1 .
    S69805 Genomic DNA. Translation: AAD14049.1 .
    CCDSi CCDS6512.1. [P42772-1 ]
    CCDS6513.1. [P42772-2 ]
    PIRi B55479.
    RefSeqi NP_004927.2. NM_004936.3. [P42772-1 ]
    NP_511042.1. NM_078487.2. [P42772-2 ]
    UniGenei Hs.72901.

    3D structure databases

    ProteinModelPortali P42772.
    SMRi P42772. Positions 11-138.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107464. 13 interactions.
    IntActi P42772. 11 interactions.
    MINTi MINT-1377924.
    STRINGi 9606.ENSP00000276925.

    PTM databases

    PhosphoSitei P42772.

    Polymorphism databases

    DMDMi 1168869.

    Proteomic databases

    MaxQBi P42772.
    PaxDbi P42772.
    PRIDEi P42772.

    Protocols and materials databases

    DNASUi 1030.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000276925 ; ENSP00000276925 ; ENSG00000147883 . [P42772-1 ]
    ENST00000380142 ; ENSP00000369487 ; ENSG00000147883 . [P42772-2 ]
    GeneIDi 1030.
    KEGGi hsa:1030.
    UCSCi uc003zpn.3. human. [P42772-2 ]
    uc003zpo.3. human. [P42772-1 ]

    Organism-specific databases

    CTDi 1030.
    GeneCardsi GC09M021992.
    HGNCi HGNC:1788. CDKN2B.
    HPAi CAB000349.
    HPA052838.
    MIMi 600431. gene.
    neXtProti NX_P42772.
    Orphaneti 618. Familial melanoma.
    652. Multiple endocrine neoplasia type 1.
    PharmGKBi PA26321.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG287192.
    HOGENOMi HOG000290191.
    HOVERGENi HBG050870.
    InParanoidi P42772.
    KOi K04685.
    OMAi EPNCADE.
    OrthoDBi EOG7TTQ94.
    PhylomeDBi P42772.
    TreeFami TF352389.

    Enzyme and pathway databases

    Reactomei REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.

    Miscellaneous databases

    GeneWikii CDKN2B.
    GenomeRNAii 1030.
    NextBioi 4331.
    PROi P42772.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42772.
    Bgeei P42772.
    CleanExi HS_CDKN2B.
    Genevestigatori P42772.

    Family and domain databases

    Gene3Di 1.25.40.20. 1 hit.
    InterProi IPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view ]
    Pfami PF12796. Ank_2. 1 hit.
    [Graphical view ]
    SMARTi SM00248. ANK. 3 hits.
    [Graphical view ]
    SUPFAMi SSF48403. SSF48403. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function."
      Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L., Matera G.A., Xiong Y.
      Genes Dev. 8:2939-2952(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest."
      Hannon G.J., Beach D.
      Nature 371:257-261(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Cloning and characterization of p10, an alternatively spliced form of p15 cyclin-dependent kinase inhibitor."
      Tsubari M., Tiihonen E., Laiho M.
      Cancer Res. 57:2966-2973(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. NIEHS SNPs program
      Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "DNA sequence and analysis of human chromosome 9."
      Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
      , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
      Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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 1).
      Tissue: Skin.
    8. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-138.
    9. "Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data."
      Yuan C., Selby T.L., Li J., Byeon I.J., Tsai M.D.
      Protein Sci. 9:1120-1128(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    10. "Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer."
      Okamoto A., Hussain S.P., Hagiwara K., Spillare E.A., Rusin M.R., Demetrick D.J., Serrano M., Hannon G.J., Shiseki M., Zariwala M., Xiong Y., Beach D.H., Yokota J., Harris C.C.
      Cancer Res. 55:1448-1451(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LUNG ADENOCARCINOMA GLU-47 AND VAL-50.

    Entry informationi

    Entry nameiCDN2B_HUMAN
    AccessioniPrimary (citable) accession number: P42772
    Secondary accession number(s): O15125, Q6FI09
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 132 of the entry and version 1 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3