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Protein

GSK3B-interacting protein

Gene

GSKIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets (PubMed:27484798, PubMed:25920809, PubMed:16981698). 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:27484798, PubMed:16981698). 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).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei130Required for GSK3B interaction; contributes to a protective effect against H(2)O(2)-induced apoptosis3 Publications1

GO - Molecular functioni

  • protein kinase A binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB
  • protein kinase inhibitor activity Source: UniProtKB

GO - Biological processi

  • intrinsic apoptotic signaling pathway in response to oxidative stress Source: UniProtKB
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB

Names & Taxonomyi

Protein namesi
Recommended name:
GSK3B-interacting proteinImported
Short name:
GSKIP1 Publication
Alternative name(s):
GSK3beta interaction proteinImported
Gene namesi
Name:GSKIP1 PublicationImported
Synonyms:C14orf129Imported
ORF Names:HSPC210
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100744.14.
HGNCiHGNC:20343. GSKIP.

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41 – 45VNDVL → PNDVP: Abolishes interaction with PRKAR2A and PRKAR2B. Abolishes acquired resistance against oxidative stress-induced apoptosis under activated cAMP signaling. Decreases PKA-mediated DNM1L phosphorylation. 1 Publication5
Mutagenesisi42N → I: Abolishes interaction with PRKAR2A. Prevents the Wnt-induced transcription. Does not alter the phosphorylation of CTNNB1 in the presence of Wnt. 1 Publication1
Mutagenesisi109S → A: 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. 1 Publication1
Mutagenesisi113T → A: 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. 1 Publication1
Mutagenesisi115S → A: 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. 1 Publication1
Mutagenesisi130L → P: 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. 3 Publications1

Organism-specific databases

DisGeNETi51527.
OpenTargetsiENSG00000100744.
PharmGKBiPA134987554.

Polymorphism and mutation databases

DMDMi34582343.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002209511 – 139GSK3B-interacting proteinAdd BLAST139

Post-translational modificationi

Phosphorylated by GSK3B.1 Publication

Proteomic databases

EPDiQ9P0R6.
MaxQBiQ9P0R6.
PaxDbiQ9P0R6.
PeptideAtlasiQ9P0R6.
PRIDEiQ9P0R6.

Expressioni

Tissue specificityi

Detected in heart, brain, placenta, liver, skeletal muscle, kidney, testis, lung and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000100744.
CleanExiHS_C14orf129.
ExpressionAtlasiQ9P0R6. baseline and differential.
GenevisibleiQ9P0R6. HS.

Organism-specific databases

HPAiHPA043054.
HPA046782.

Interactioni

Subunit structurei

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).4 Publications

GO - Molecular functioni

  • protein kinase A binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119589. 6 interactors.
IntActiQ9P0R6. 4 interactors.
STRINGi9606.ENSP00000412315.

Structurei

Secondary structure

1139
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 13Combined sources4
Helixi33 – 44Combined sources12
Helixi45 – 47Combined sources3
Beta strandi48 – 53Combined sources6
Beta strandi63 – 69Combined sources7
Beta strandi75 – 81Combined sources7
Beta strandi84 – 91Combined sources8
Beta strandi103 – 107Combined sources5
Helixi108 – 114Combined sources7
Helixi116 – 135Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SGONMR-A1-139[»]
ProteinModelPortaliQ9P0R6.
SMRiQ9P0R6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9P0R6.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 45Required for PRKAR2A interaction; contributes to a protective effect against H(2)O(2)-induced apoptosis1 Publication5
Regioni115 – 139Interaction with GSK3B and acts as GSK3B inhibitor1 PublicationAdd BLAST25

Sequence similaritiesi

Belongs to the GSKIP family.Curated

Phylogenomic databases

eggNOGiKOG3965. Eukaryota.
ENOG4111QBG. LUCA.
GeneTreeiENSGT00390000009517.
HOGENOMiHOG000007951.
HOVERGENiHBG051028.
InParanoidiQ9P0R6.
OMAiNDVKAHV.
OrthoDBiEOG091G15HV.
PhylomeDBiQ9P0R6.
TreeFamiTF313906.

Family and domain databases

Gene3Di3.30.2280.10. 1 hit.
InterProiView protein in InterPro
IPR007967. DUF727.
IPR023231. GSKIP_dom_sf.
PANTHERiPTHR12490. PTHR12490. 1 hit.
PfamiView protein in Pfam
PF05303. DUF727. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD080843. DUF727. 1 hit.
SUPFAMiSSF103107. SSF103107. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9P0R6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METDCNPMEL SSMSGFEEGS ELNGFEGTDM KDMRLEAEAV VNDVLFAVNN
60 70 80 90 100
MFVSKSLRCA DDVAYINVET KERNRYCLEL TEAGLKVVGY AFDQVDDHLQ
110 120 130
TPYHETVYSL LDTLSPAYRE AFGNALLQRL EALKRDGQS
Length:139
Mass (Da):15,648
Last modified:September 9, 2003 - v2
Checksum:iA2D8BAF4B458B316
GO

Sequence cautioni

The sequence AAF36130 differs from that shown. Reason: Frameshift at position 132.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46F → S in BAA91380 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151044 mRNA. Translation: AAF36130.1. Frameshift.
AK000796 mRNA. Translation: BAA91380.1.
AK094654 mRNA. Translation: BAG52902.1.
AL359240 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81634.1.
BC004818 mRNA. Translation: AAH04818.1.
CCDSiCCDS32153.1.
RefSeqiNP_001258833.1. NM_001271904.1.
NP_001258834.1. NM_001271905.1.
NP_001258835.1. NM_001271906.1.
NP_057556.2. NM_016472.4.
XP_016876854.1. XM_017021365.1.
UniGeneiHs.4104.
Hs.745067.

Genome annotation databases

EnsembliENST00000438650; ENSP00000412315; ENSG00000100744.
ENST00000554182; ENSP00000451384; ENSG00000100744.
ENST00000555181; ENSP00000450420; ENSG00000100744.
ENST00000556095; ENSP00000451188; ENSG00000100744.
GeneIDi51527.
KEGGihsa:51527.
UCSCiuc001yfj.6. human.

Similar proteinsi

Entry informationi

Entry nameiGSKIP_HUMAN
AccessioniPrimary (citable) accession number: Q9P0R6
Secondary accession number(s): B3KSZ0, Q9BST1, Q9NWK0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 9, 2003
Last sequence update: September 9, 2003
Last modified: November 22, 2017
This is version 125 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
  5. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries