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P42772 (CDN2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CDKN2B
Synonyms:MTS2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length138 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

Cytoplasm. Note: Also found in the nucleus. Ref.3

Tissue specificity

Isoform 2 is expressed in normal (keratinocytes, fibroblasts) and tumor cell lines. Ref.3

Sequence similarities

Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.

Contains 4 ANK repeats.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseTumor suppressor
   DomainANK repeat
Repeat
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

aging

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

cellular response to extracellular stimulus

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

cellular response to nutrient

Inferred from mutant phenotype PubMed 17597576. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

liver development

Inferred from electronic annotation. Source: Ensembl

megakaryocyte differentiation

Inferred from expression pattern PubMed 10812241. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic cell cycle checkpoint

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

negative regulation of G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL

negative regulation of phosphorylation

Inferred from direct assay Ref.2. Source: BHF-UCL

negative regulation of protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: GOC

positive regulation of epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL

regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: BHF-UCL

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

spleen development

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.3. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 18564286Ref.3. Source: UniProtKB

   Molecular_functioncyclin-dependent protein serine/threonine kinase inhibitor activity

Non-traceable author statement Ref.3. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P42772-1)

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.
Isoform 2 (identifier: P42772-2)

Also known as: p10;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 138138Cyclin-dependent kinase 4 inhibitor B
PRO_0000144184

Regions

Repeat13 – 3927ANK 1; truncated
Repeat46 – 7429ANK 2
Repeat79 – 10830ANK 3
Repeat112 – 13827ANK 4

Natural variations

Alternative sequence54 – 13885MMMGS…TATGD → AGAPGPRRQGARERGARPRR IGAGT in isoform 2.
VSP_043898
Natural variant471G → E in lung adenocarcinoma. Ref.10
VAR_001488
Natural variant501A → V in lung adenocarcinoma. Ref.10
VAR_001489

Experimental info

Sequence conflict20 – 223SAA → TP in AAA50282. Ref.2
Sequence conflict32 – 343QLL → HSW in AAA50282. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (p15) [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 0D6FFBDFA6FEAD21

FASTA13814,722
        10         20         30         40         50         60 
MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA IQVMMMGSAR 

        70         80         90        100        110        120 
VAELLLLHGA EPNCADPATL TRPVHDAARE GFLDTLVVLH RAGARLDVRD AWGRLPVDLA 

       130 
EERGHRDVAG YLRTATGD 

« Hide

Isoform 2 (p10) [UniParc].

Checksum: 3EB74DDEC36E674D
Show »

FASTA788,078

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"A cell cycle regulator potentially involved in genesis of many tumor types."
Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnick M.H.
Science 264:436-440(1994) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRB55479.
RefSeqNP_004927.2. NM_004936.3.
NP_511042.1. NM_078487.2.
UniGeneHs.72901.

3D structure databases

ProteinModelPortalP42772.
SMRP42772. Positions 11-138.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107464. 13 interactions.
IntActP42772. 10 interactions.
MINTMINT-1377924.
STRING9606.ENSP00000276925.

PTM databases

PhosphoSiteP42772.

Polymorphism databases

DMDM1168869.

Proteomic databases

PaxDbP42772.
PRIDEP42772.

Protocols and materials databases

DNASU1030.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276925; ENSP00000276925; ENSG00000147883. [P42772-1]
ENST00000380142; ENSP00000369487; ENSG00000147883. [P42772-2]
ENST00000539462; ENSP00000445136; ENSG00000147883. [P42772-2]
GeneID1030.
KEGGhsa:1030.
UCSCuc003zpn.3. human. [P42772-2]
uc003zpo.3. human. [P42772-1]

Organism-specific databases

CTD1030.
GeneCardsGC09M021992.
HGNCHGNC:1788. CDKN2B.
HPACAB000349.
HPA052838.
MIM600431. gene.
neXtProtNX_P42772.
Orphanet618. Familial melanoma.
652. Multiple endocrine neoplasia type 1.
PharmGKBPA26321.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG287192.
HOGENOMHOG000290191.
HOVERGENHBG050870.
InParanoidP42772.
KOK04685.
OMAMMGSTSV.
OrthoDBEOG7TTQ94.
PhylomeDBP42772.
TreeFamTF352389.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressP42772.
BgeeP42772.
CleanExHS_CDKN2B.
GenevestigatorP42772.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamPF12796. Ank_2. 1 hit.
[Graphical view]
SMARTSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCDKN2B.
GenomeRNAi1030.
NextBio4331.
PROP42772.
SOURCESearch...

Entry information

Entry nameCDN2B_HUMAN
AccessionPrimary (citable) accession number: P42772
Secondary accession number(s): O15125, Q6FI09
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM