This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting ... See more...

Aliases for GSKIP Gene

Aliases for GSKIP Gene

  • GSK3B Interacting Protein 2 3 5
  • GSK3beta Interaction Protein 2 4
  • GSK3B-Interacting Protein 3 4
  • C14orf129 3 4
  • Chromosome 14 Open Reading Frame 129 2
  • GSK3-Beta Interaction Protein 3
  • HSPC210 3

External Ids for GSKIP Gene

Previous HGNC Symbols for GSKIP Gene

  • C14orf129

Previous GeneCards Identifiers for GSKIP Gene

  • GC14P096831

Summaries for GSKIP Gene

Entrez Gene Summary for GSKIP Gene

  • This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting domain (GID) in its C-terminus, which is similar to the GID of Axin. The protein also contains an evolutionarily conserved RII-binding domain, which facilitates binding with protein kinase-A and GSK3-beta, enabling its role as an A-kinase anchoring protein. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

GeneCards Summary for GSKIP Gene

GSKIP (GSK3B Interacting Protein) is a Protein Coding gene.

UniProtKB/Swiss-Prot Summary for GSKIP Gene

  • 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).

Additional gene information for GSKIP Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GSKIP Gene

Genomics for GSKIP Gene

GeneHancer (GH) Regulatory Elements for GSKIP Gene

Promoters and enhancers for GSKIP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J096361 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 555.2 +0.1 55 5 ZBTB40 EP300 SIN3A POLR2G USF1 PHF8 ZFX ZNF10 POLR2A CLOCK GSKIP ATG2B lnc-AK7-2-001 lnc-AK7-2-002 lnc-AK7-1 lnc-ATG2B-4
GH14J096272 Enhancer 1.5 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 45.6 -88.9 -88875 3.3 CTCF JUND FOS ZIC2 REST RAD21 EP300 TRIM22 SMC3 GATA3 GSKIP ENSG00000258729 lnc-ATG2B-13
GH14J096307 Enhancer 0.7 Ensembl ENCODE 67 -53.7 -53709 3.9 CTCF FOXA2 RXRA MAX RAD21 HNF4A REST HNRNPK YY1 TAF1 GSKIP RNU2-33P PAPOLA lnc-TCL1A-7 lnc-TCL1A-8 ATG2B
GH14J096390 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 15.7 +28.5 28549 2.8 SIN3A TCF12 NRF1 MYC POLR2G SP1 PHF8 ZNF639 ZIC2 POLR2A AK7 lnc-ATG2B-11 GSKIP
GH14J096279 Enhancer 0.5 Ensembl ENCODE 53.4 -83.6 -83551 0.6 ZNF24 CTCF GSKIP ENSG00000258729 lnc-TCL1A-6 ATG2B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSKIP on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GSKIP

Genomic Locations for GSKIP Gene

Genomic Locations for GSKIP Gene
chr14:96,363,452-96,387,290
(GRCh38/hg38)
Size:
23,839 bases
Orientation:
Plus strand
chr14:96,829,814-96,853,625
(GRCh37/hg19)
Size:
23,812 bases
Orientation:
Plus strand

Genomic View for GSKIP Gene

Genes around GSKIP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GSKIP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GSKIP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GSKIP Gene

Proteins for GSKIP Gene

  • Protein details for GSKIP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P0R6-GSKIP_HUMAN
    Recommended name:
    GSK3B-interacting protein
    Protein Accession:
    Q9P0R6
    Secondary Accessions:
    • B3KSZ0
    • Q9BST1
    • Q9NWK0

    Protein attributes for GSKIP Gene

    Size:
    139 amino acids
    Molecular mass:
    15648 Da
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=AAF36130.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for GSKIP Gene

neXtProt entry for GSKIP Gene

Post-translational modifications for GSKIP Gene

No data available for DME Specific Peptides for GSKIP Gene

Domains & Families for GSKIP Gene

Gene Families for GSKIP Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GSKIP Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GSKIP Gene

GenScript: Design optimal peptide antigens:
  • GSK3-beta interaction protein (GSKIP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P0R6

UniProtKB/Swiss-Prot:

GSKIP_HUMAN :
  • Belongs to the GSKIP family.
Family:
  • Belongs to the GSKIP family.
genes like me logo Genes that share domains with GSKIP: view

Function for GSKIP Gene

Molecular function for GSKIP Gene

UniProtKB/Swiss-Prot Function:
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).

Phenotypes From GWAS Catalog for GSKIP Gene

Gene Ontology (GO) - Molecular Function for GSKIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004860 protein kinase inhibitor activity IMP 16981698
GO:0005515 protein binding IPI 20007971
GO:0008013 NOT beta-catenin binding IDA 27484798
GO:0019901 protein kinase binding IPI 16981698
GO:0034237 protein kinase A regulatory subunit binding IPI 27484798
genes like me logo Genes that share ontologies with GSKIP: view
genes like me logo Genes that share phenotypes with GSKIP: view

Animal Models for GSKIP Gene

MGI Knock Outs for GSKIP:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSKIP

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GSKIP Gene

Localization for GSKIP Gene

Subcellular locations from UniProtKB/Swiss-Prot for GSKIP Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GSKIP gene
Compartment Confidence
nucleus 5
extracellular 2
cytosol 2
golgi apparatus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Nucleoli (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GSKIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 20007971
GO:0005737 cytoplasm IEA,IDA 16981698
genes like me logo Genes that share ontologies with GSKIP: view

Pathways & Interactions for GSKIP Gene

PathCards logo

SuperPathways for GSKIP Gene

No Data Available

Interacting Proteins for GSKIP Gene

;

Gene Ontology (GO) - Biological Process for GSKIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006469 negative regulation of protein kinase activity IMP 16981698
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress IMP 25920809
GO:0030111 regulation of Wnt signaling pathway IMP 16981698
GO:0060828 regulation of canonical Wnt signaling pathway IEA --
GO:0090263 positive regulation of canonical Wnt signaling pathway IDA 27484798
genes like me logo Genes that share ontologies with GSKIP: view

No data available for Pathways by source and SIGNOR curated interactions for GSKIP Gene

Drugs & Compounds for GSKIP Gene

(1) Drugs for GSKIP Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
AT9283 Investigational Pharma inhibitor Aurora kinase/JAK inhibitor, Kinase Inhibitors, Inhibitors of mitosis Aurora kinase inhibitors 0
genes like me logo Genes that share compounds with GSKIP: view

Transcripts for GSKIP Gene

mRNA/cDNA for GSKIP Gene

4 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSKIP

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GSKIP Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b ^ 6a · 6b · 6c · 6d
SP1: - - -
SP2: - -
SP3: -
SP4: -
SP5: - -
SP6: - - - - - -

Relevant External Links for GSKIP Gene

GeneLoc Exon Structure for
GSKIP

Expression for GSKIP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GSKIP Gene

Protein differential expression in normal tissues from HIPED for GSKIP Gene

This gene is overexpressed in Bone (17.3), Colon (7.1), and Rectum (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GSKIP Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GSKIP

SOURCE GeneReport for Unigene cluster for GSKIP Gene:

Hs.4104

mRNA Expression by UniProt/SwissProt for GSKIP Gene:

Q9P0R6-GSKIP_HUMAN
Tissue specificity: Detected in heart, brain, placenta, liver, skeletal muscle, kidney, testis, lung and pancreas.

Evidence on tissue expression from TISSUES for GSKIP Gene

  • Nervous system(4.7)
  • Intestine(4.2)
  • Blood(4.1)
genes like me logo Genes that share expression patterns with GSKIP: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for GSKIP Gene

Orthologs for GSKIP Gene

This gene was present in the common ancestor of animals.

Orthologs for GSKIP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia C14H14ORF129 31
  • 100 (a)
OneToOne
C14H14orf129 30
  • 99.52 (n)
cow
(Bos Taurus)
Mammalia GSKIP 31 30
  • 89.93 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GSKIP 31 30
  • 89.54 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Gskip 17 31 30
  • 87.77 (n)
rat
(Rattus norvegicus)
Mammalia Gskip 30
  • 87.77 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GSKIP 31
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 81 (a)
OneToMany
-- 31
  • 77 (a)
OneToMany
chicken
(Gallus gallus)
Aves GSKIP 31
  • 77 (a)
OneToOne
C5H14ORF129 30
  • 75.3 (n)
lizard
(Anolis carolinensis)
Reptilia GSKIP 31
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gskip 30
  • 72.18 (n)
Str.17150 30
zebrafish
(Danio rerio)
Actinopterygii gskip 31 30
  • 65.66 (n)
OneToOne
wufc74a11 30
fruit fly
(Drosophila melanogaster)
Insecta CG11523 31
  • 25 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea T24H7.3 31
  • 28 (a)
OneToMany
C06A12.3 31
  • 14 (a)
OneToMany
Y43F8B.2 31
  • 13 (a)
OneToMany
Species where no ortholog for GSKIP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GSKIP Gene

ENSEMBL:
Gene Tree for GSKIP (if available)
TreeFam:
Gene Tree for GSKIP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSKIP: view image

Paralogs for GSKIP Gene

No data available for Paralogs for GSKIP Gene

Variants for GSKIP Gene

Additional dbSNP identifiers (rs#s) for GSKIP Gene

Structural Variations from Database of Genomic Variants (DGV) for GSKIP Gene

Variant ID Type Subtype PubMed ID
esv2660133 CNV deletion 23128226
esv28071 CNV loss 19812545
esv3552010 CNV deletion 23714750
esv3635422 CNV loss 21293372
esv3635423 CNV gain 21293372
nsv565649 CNV gain 21841781

Variation tolerance for GSKIP Gene

Residual Variation Intolerance Score: 42.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.10; 2.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSKIP Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSKIP

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GSKIP Gene

Disorders for GSKIP Gene

Additional Disease Information for GSKIP

No disorders were found for GSKIP Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for GSKIP Gene

Publications for GSKIP Gene

  1. GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta. (PMID: 16981698) Chou HY … Hong YR (Biochemistry 2006) 2 3 4 54
  2. The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3β Interaction Protein (GSKIP) Regulates β-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3β. (PMID: 27484798) Dema A … Klussmann E (The Journal of biological chemistry 2016) 3 4 54
  3. GSKIP- and GSK3-mediated anchoring strengthens cAMP/PKA/Drp1 axis signaling in the regulation of mitochondrial elongation. (PMID: 25920809) Loh JK … Hong YR (Biochimica et biophysica acta 2015) 3 4 54
  4. Prediction of the binding mode between GSK3β and a peptide derived from GSKIP using molecular dynamics simulation. (PMID: 21328310) Tang XN … Yang CN (Biopolymers 2011) 2 3 54
  5. Glycogen synthase kinase 3beta interaction protein functions as an A-kinase anchoring protein. (PMID: 20007971) Hundsrucker C … Klussmann E (The Journal of biological chemistry 2010) 3 4 54

Products for GSKIP Gene

Sources for GSKIP Gene