Linked Life Data

CPATH-364

Source:http://cbio.mskcc.org/cpath#CPATH-364

Statements in which the resource exists.
SubjectPredicateObjectContext
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cpath:CPATH-364http://www.biopax.org/relea...Melanoma differentiation-associated protein 6lld:biogrid
cpath:CPATH-364http://www.biopax.org/relea...Melanoma differentiation-associated protein 6lld:cellmap
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cpath:CPATH-364http://www.biopax.org/relea...FUNCTION: May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin- dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D- CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. SUBUNIT: Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Expressed in all adult human tissues, with 5- fold lower levels observed in the brain. INDUCTION: By p53/TP53, mezerein (antileukemic compound) and IFNB1. DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination. DOMAIN: The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex. PTM: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. SIMILARITY: Belongs to the CDI family. SEQUENCE CAUTION: Sequence=AAB59559.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAB59560.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDKN1AID139.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdkn1a/"; GENE SYNONYMS: CAP20 CDKN1 CIP1 MDA6 PIC1 SDI1 WAF1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:biogrid
cpath:CPATH-364http://www.biopax.org/relea...FUNCTION: May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin- dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D- CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. SUBUNIT: Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Expressed in all adult human tissues, with 5- fold lower levels observed in the brain. INDUCTION: By p53/TP53, mezerein (antileukemic compound) and IFNB1. DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination. DOMAIN: The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex. PTM: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. SIMILARITY: Belongs to the CDI family. SEQUENCE CAUTION: Sequence=AAB59559.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAB59560.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDKN1AID139.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdkn1a/"; GENE SYNONYMS: CAP20 CDKN1 CIP1 MDA6 PIC1 SDI1 WAF1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:cellmap
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