Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P42772

- CDN2B_HUMAN

UniProt

P42772 - CDN2B_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

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

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 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP42772.
CleanExiHS_CDKN2B.
ExpressionAtlasiP42772. baseline and differential.
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.
GeneTreeiENSGT00390000004527.
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

        10         20         30         40         50
MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA
60 70 80 90 100
IQVMMMGSAR VAELLLLHGA EPNCADPATL TRPVHDAARE GFLDTLVVLH
110 120 130
RAGARLDVRD AWGRLPVDLA EERGHRDVAG YLRTATGD
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.
GeneTreei ENSGT00390000004527.
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

Bgeei P42772.
CleanExi HS_CDKN2B.
ExpressionAtlasi P42772. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 133 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