Q9P0R6 · GSKIP_HUMAN
- ProteinGSK3B-interacting protein
- GeneGSKIP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids139 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets (PubMed:16981698, PubMed:25920809, PubMed:27484798).
The ternary complex enhances Wnt-induced signaling by facilitating the GSK3B- and PKA-induced phosphorylation of beta-catenin leading to beta-catenin degradation and stabilization respectively (PubMed:16981698, PubMed:27484798).
Upon cAMP activation, the ternary complex contributes to neuroprotection against oxidative stress-induced apoptosis by facilitating the PKA-induced phosphorylation of DML1 and PKA-induced inactivation of GSK3B (PubMed:25920809).
During neurite outgrowth promotes neuron proliferation; while increases beta-catenin-induced transcriptional activity through GSK3B kinase activity inhibition, reduces N-cadherin level to promote cell cycle progression (PubMed:19830702).
The ternary complex enhances Wnt-induced signaling by facilitating the GSK3B- and PKA-induced phosphorylation of beta-catenin leading to beta-catenin degradation and stabilization respectively (PubMed:16981698, PubMed:27484798).
Upon cAMP activation, the ternary complex contributes to neuroprotection against oxidative stress-induced apoptosis by facilitating the PKA-induced phosphorylation of DML1 and PKA-induced inactivation of GSK3B (PubMed:25920809).
During neurite outgrowth promotes neuron proliferation; while increases beta-catenin-induced transcriptional activity through GSK3B kinase activity inhibition, reduces N-cadherin level to promote cell cycle progression (PubMed:19830702).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 130 | Required for GSK3B interaction; contributes to a protective effect against H2O2-induced apoptosis | ||||
Sequence: L |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | kinase regulator activity | |
Molecular Function | protein kinase A binding | |
Molecular Function | protein kinase A regulatory subunit binding | |
Molecular Function | protein kinase binding | |
Molecular Function | protein kinase inhibitor activity | |
Biological Process | intrinsic apoptotic signaling pathway in response to oxidative stress | |
Biological Process | negative regulation of protein kinase activity | |
Biological Process | positive regulation of canonical Wnt signaling pathway | |
Biological Process | regulation of Wnt signaling pathway |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGSK3B-interacting protein
- Short namesGSKIP
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9P0R6
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 41-45 | Abolishes interaction with PRKAR2A and PRKAR2B. Abolishes acquired resistance against oxidative stress-induced apoptosis under activated cAMP signaling. Decreases PKA-mediated DNM1L phosphorylation. | ||||
Sequence: VNDVL → PNDVP | ||||||
Mutagenesis | 42 | Abolishes interaction with PRKAR2A. Prevents the Wnt-induced transcription. Does not alter the phosphorylation of CTNNB1 in the presence of Wnt. | ||||
Sequence: N → I | ||||||
Mutagenesis | 109 | No effect on GSK3B-mediated phosphorylation. Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A-113. Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A-113 and A-115. | ||||
Sequence: S → A | ||||||
Mutagenesis | 113 | No effect on GSK3B-mediated phosphorylation. Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A-109.Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A-113 and A-115. | ||||
Sequence: T → A | ||||||
Mutagenesis | 115 | No effect on GSK3B-mediated phosphorylation. Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A-109.Reduces to 30 % GSK3B-mediated phosphorylation; when associated with A109 and A-113. | ||||
Sequence: S → A | ||||||
Mutagenesis | 130 | Loss of interaction with GSK3B. Abolishes GSK3B-mediated phosphorylation. Prevents beta-catenin accumulation in the cytoplasm and nucleus. Prevents the Wnt-induced transcription. Decreases PKA-mediated phosphorylation of GSK3B. Abolishes acquired resistance against oxidative stress-induced apoptosis under activated cAMP signaling. Decreases PKA-mediated DNM1L phosphorylation. | ||||
Sequence: L → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 135 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000220951 | 1-139 | GSK3B-interacting protein | |||
Sequence: METDCNPMELSSMSGFEEGSELNGFEGTDMKDMRLEAEAVVNDVLFAVNNMFVSKSLRCADDVAYINVETKERNRYCLELTEAGLKVVGYAFDQVDDHLQTPYHETVYSLLDTLSPAYREAFGNALLQRLEALKRDGQS |
Post-translational modification
Phosphorylated by GSK3B.
Proteomic databases
Expression
Tissue specificity
Detected in heart, brain, placenta, liver, skeletal muscle, kidney, testis, lung and pancreas.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation of GSK3B leading to GSK3B inactivation; recruits DNM1L through GSK3B for PKA-mediated phosphorylation of DNM1L; promotes beta-catenin degradation through GSK3B-induced phosphorylation of beta-catenin; stabilizes beta-catenin and enhances Wnt-induced signaling through PKA-induced phosphorylation of beta-catenin (PubMed:20007971, PubMed:25920809, PubMed:27484798).
Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP and inhibits GSK3B kinase activity (PubMed:16981698, PubMed:25920809).
Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP and inhibits GSK3B kinase activity (PubMed:16981698, PubMed:25920809).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9P0R6 | GSK3A P49840 | 5 | EBI-1052580, EBI-1044067 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-22 | Disordered | ||||
Sequence: METDCNPMELSSMSGFEEGSEL | ||||||
Region | 41-45 | Required for PRKAR2A interaction; contributes to a protective effect against H2O2-induced apoptosis | ||||
Sequence: VNDVL | ||||||
Region | 115-139 | Interaction with GSK3B and acts as a GSK3B inhibitor | ||||
Sequence: SPAYREAFGNALLQRLEALKRDGQS |
Sequence similarities
Belongs to the GSKIP family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length139
- Mass (Da)15,648
- Last updated2003-09-09 v2
- ChecksumA2D8BAF4B458B316
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 46 | in Ref. 2; BAA91380 | ||||
Sequence: F → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF151044 EMBL· GenBank· DDBJ | AAF36130.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK000796 EMBL· GenBank· DDBJ | BAA91380.1 EMBL· GenBank· DDBJ | mRNA | ||
AK094654 EMBL· GenBank· DDBJ | BAG52902.1 EMBL· GenBank· DDBJ | mRNA | ||
AL359240 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471061 EMBL· GenBank· DDBJ | EAW81634.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC004818 EMBL· GenBank· DDBJ | AAH04818.1 EMBL· GenBank· DDBJ | mRNA |