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Protein

Cyclin-dependent kinase 4 inhibitor B

Gene

CDKN2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • cyclin-dependent protein serine/threonine kinase inhibitor activity Source: BHF-UCL
  • protein kinase binding Source: BHF-UCL

GO - Biological processi

  • cell cycle arrest Source: BHF-UCL
  • cellular response to extracellular stimulus Source: BHF-UCL
  • cellular response to nutrient Source: BHF-UCL
  • G2/M transition of mitotic cell cycle Source: BHF-UCL
  • megakaryocyte differentiation Source: UniProtKB
  • mitotic cell cycle checkpoint Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: Reactome
  • negative regulation of epithelial cell proliferation Source: BHF-UCL
  • negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
  • negative regulation of phosphorylation Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: Reactome
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • spleen development Source: Ensembl

Keywordsi

Biological processCell cycle

Enzyme and pathway databases

ReactomeiR-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-69231 Cyclin D associated events in G1
SIGNORiP42772

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
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000147883.10
HGNCiHGNC:1788 CDKN2B
MIMi600431 gene
neXtProtiNX_P42772

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi1030
MalaCardsiCDKN2B
OpenTargetsiENSG00000147883
Orphaneti618 Familial melanoma
652 Multiple endocrine neoplasia type 1
PharmGKBiPA26321

Polymorphism and mutation databases

BioMutaiCDKN2B
DMDMi1168869

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001441841 – 138Cyclin-dependent kinase 4 inhibitor BAdd BLAST138

Proteomic databases

MaxQBiP42772
PaxDbiP42772
PeptideAtlasiP42772
PRIDEiP42772
ProteomicsDBi55555
55556 [P42772-2]

PTM databases

iPTMnetiP42772
PhosphoSitePlusiP42772

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000147883
CleanExiHS_CDKN2B
ExpressionAtlasiP42772 baseline and differential
GenevisibleiP42772 HS

Organism-specific databases

HPAiCAB000349
HPA052838
HPA063327

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107464, 16 interactors
IntActiP42772, 25 interactors
MINTiP42772
STRINGi9606.ENSP00000276925

Structurei

3D structure databases

ProteinModelPortaliP42772
SMRiP42772
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati13 – 39ANK 1; truncatedAdd BLAST27
Repeati46 – 74ANK 2Add BLAST29
Repeati79 – 108ANK 3Add BLAST30
Repeati112 – 138ANK 4Add BLAST27

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00390000004527
HOGENOMiHOG000290191
HOVERGENiHBG050870
InParanoidiP42772
KOiK04685
OMAiVNCYGRR
OrthoDBiEOG091G0WSF
PhylomeDBiP42772
TreeFamiTF352389

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
SUPFAMiSSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti20 – 22SAA → TP in AAA50282 (PubMed:8078588).Curated3
Sequence conflicti32 – 34QLL → HSW in AAA50282 (PubMed:8078588).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00148847G → E in lung adenocarcinoma. 1 Publication1
Natural variantiVAR_00148950A → V in lung adenocarcinoma. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04389854 – 138MMMGS…TATGD → AGAPGPRRQGARERGARPRR IGAGT in isoform 2. 1 PublicationAdd BLAST85

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 No translation available.
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.4 human [P42772-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCDN2B_HUMAN
AccessioniPrimary (citable) accession number: P42772
Secondary accession number(s): O15125, Q6FI09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 18, 2018
This is version 166 of the entry and version 1 of the sequence. See 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

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