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Protein

Cyclin-dependent kinase 4 inhibitor B

Gene

CDKN2B

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

  • cyclin-dependent protein serine/threonine kinase inhibitor activity Source: UniProtKB
  • 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 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 from RNA polymerase II promoter 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
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Enzyme and pathway databases

BioCyciZFISH:HS07479-MONOMER.
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

HGNCiHGNC:1788. CDKN2B.

Subcellular locationi

  • Cytoplasm 1 Publication

  • Note: Also found in the nucleus.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

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.

PTM databases

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

WithEntry#Exp.IntActNotes
CDK4P118029EBI-711280,EBI-295644
CDK6Q0053410EBI-711280,EBI-295663
NIF3L1Q9GZT83EBI-711280,EBI-740897
TRAF1Q130775EBI-711280,EBI-359224

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107464. 16 interactors.
IntActiP42772. 16 interactors.
MINTiMINT-1377924.
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

Contains 4 ANK repeats.Curated

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
[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. 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. 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.4. human. [P42772-1]

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:
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. 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.

3D structure databases

ProteinModelPortaliP42772.
SMRiP42772.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107464. 16 interactors.
IntActiP42772. 16 interactors.
MINTiMINT-1377924.
STRINGi9606.ENSP00000276925.

PTM databases

PhosphoSitePlusiP42772.

Polymorphism and mutation databases

BioMutaiCDKN2B.
DMDMi1168869.

Proteomic databases

MaxQBiP42772.
PaxDbiP42772.
PeptideAtlasiP42772.
PRIDEiP42772.

Protocols and materials databases

DNASUi1030.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276925; ENSP00000276925; ENSG00000147883. [P42772-1]
ENST00000380142; ENSP00000369487; ENSG00000147883. [P42772-2]
GeneIDi1030.
KEGGihsa:1030.
UCSCiuc003zpn.4. human. [P42772-1]

Organism-specific databases

CTDi1030.
DisGeNETi1030.
GeneCardsiCDKN2B.
HGNCiHGNC:1788. CDKN2B.
HPAiCAB000349.
HPA052838.
HPA063327.
MalaCardsiCDKN2B.
MIMi600431. gene.
neXtProtiNX_P42772.
OpenTargetsiENSG00000147883.
Orphaneti618. Familial melanoma.
652. Multiple endocrine neoplasia type 1.
PharmGKBiPA26321.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS07479-MONOMER.
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.

Miscellaneous databases

GeneWikiiCDKN2B.
GenomeRNAii1030.
PROiP42772.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147883.
CleanExiHS_CDKN2B.
ExpressionAtlasiP42772. baseline and differential.
GenevisibleiP42772. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 152 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.