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Symbol CCDC88A contributors: mct/npt/pgu - updated : 06-09-2017
HGNC name coiled-coil domain containing 88A
HGNC id 25523
Corresponding disease
PEHOL progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy, like-syndrome
Location 2p16.1      Physical location : 55.514.977 - 55.647.057
Synonym name
  • hook-related protein 1
  • girders of actin filament
  • girdin
  • Akt phosphorylation enhancer
  • G alpha-interacting vesicle-associated protein
  • Synonym symbol(s) APE, GIV, GRDN, HkRP1, GIRDIN, KIAA1212, FLJ10392, DKFZp686D0630
    TYPE functioning gene
    STRUCTURE 132.08 kb     32 Exon(s)
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    32 splicing 9746 212.5 1843 - 2005 15749703
  • lacking an alternate segment in the 3' coding region compared to variant 1
  • 33 splicing 9827 215.8 1870 - 2005 15749703
    34 - 9605 - 1796 - 2005 15749703
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   moderately
     pancreas exocrine   lowly
     pharynx   moderately
     salivary gland   moderately
    Lymphoid/Immunelymph node   predominantly
    Nervousbrain   highly Mus musculus
     nerve   highly Mus musculus
     spinal cord     Mus musculus
    Reproductivemale systemtestis  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Muscular   moderately
    Nervousautonomous    Mus musculus
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Mus musculus
    cell lineage
    cell lines
    at STAGE
  • N-terminus containing a putative microtubule-binding domain that can bind microtubules in the Hook protein
  • the central region of each protein is comprised of an extensive coiled-coil domain
  • several conserved domains, including a unique C-terminal HkRP domain, that causes an accumulation of internal membranes with an electron-dense coat
  • NUCB1 and NUCB2, two highly homologous calcium-binding proteins, share a common motif with CCDC88A for Galpha(i) binding and activation
  • conjugated PhosphoP
    mono polymer homomer , dimer
    interspecies homolog to rattus Ccdc88a (93.2 pc)
    homolog to murine Ccdc88a (94.9 pc)
  • Hook-related protein (HkRP) family
  • CCDC88 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • lamellipodium
  • localized to the cell membrane through interaction with phosphoinositides
  • GNAS and CCDC88A localize to EEA1 early endosomes
  • basic FUNCTION
  • enhancing phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB
  • being essential for the integrity of the actin cytoskeleton and for cell migration
  • required for formation of actin stress fibers and lamellipodia
  • may be involved in membrane sorting in the early endosome
  • involved in the process of tubulation of sorting nexin-1 positive membranes from early endosome subdomains
  • important role in tumor progression in which the Akt signaling pathway is aberrantly activated
  • may play a role in Galpha-mediated effects on vesicle trafficking within the Golgi and/or between the ER and the Golgi
  • CCDC88A/GNAI3 coupling is essential for cell migration during wound healing, macrophage chemotaxis, and tumor cell migration
  • serves as a nonreceptor guanine nucleotide exchange factors for G alpha i through an evolutionarily conserved motif
  • metastasis-related protein and an independent adverse prognosticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma
  • CCDC88A and its AKT-mediated phosphorylation have major roles in the migration and proliferation of vascular smooth muscle cells (VSMCs) and vascular remodeling
  • important intrinsic factor that specifically governs neuroblast chain migration along the rostral migratory stream
  • enhances AKT activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5prime -triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion
  • actin-binding protein identified as a novel substrate of AKT1, that regulates the sprouting of axons and the migration of neural progenitor cells during early postnatal-stage neurogenesis in the hippocampus
  • required for Glioblastoma (GBM)-initiating stem cells to sustain the stemness and invasive properties
  • played an important role in cell migration and also regulates cell division
  • multidomain signal transducing protein CCDC88A influences EGFR trafficking and signaling
  • CCDC88A and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina
  • is a new and major regulator of the insulin signal in myoblasts and skeletal muscle
  • links vascular endothelial growth factor signaling to AKT1 survival signaling in podocytes independent of NPHS1
  • interacts with several key molecules such as actin, and it functions as a regulator of the cytoskeleton
  • transcriptional upregulation of CCDC88A expression and CCDC88A-GNAI3 signaling play crucial roles in regulating epithelial apicobasal polarity through the PAR complex
  • enhances integrin-dependent cell responses upon extracellular matrix stimulation and makes tumor cells more invasive
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, replication
    cell organization/biogenesis
    cell migration & motility
  • lamellipodium biogenesis
  • regulation of actin cytoskeleton organization and biogenesis
  • regulation of cell proliferation
    a component
    small molecule
  • non-phosphorylated form interacting with phosphatidylinositol 4-phosphate and weakly with phosphatidylinositol 3-phosphate
  • interacting with microtubules
  • interacting with actin through its C-terminal domain
  • interacting with the C-terminus of AKT1/PKB
  • binds members of the Galpha(i) and Galpha subfamilies of heterotrimeric G proteins
  • is a GNAI3 binding partner
  • interacting with G alpha(i3) (activation of G alpha(i3) by CCDC88A is essential for biological functions associated with G alpha(i3) activation)
  • tyrosine phosphoprotein that directly binds to and activates phosphoinositide 3-kinase (PI3K)
  • is an AKT1 substrate and actin-binding protein
  • AKT1/CCDC88A signaling in cancer-associated fibroblasts contributes to tumor progression
  • regulates transendothelial permeability in synergy with RRAS and CDH5 in an endothelial monolayer
  • PARD3 physically interacts with CCDC88A, and together with GNAI3, CCDC88A controls tight junction formation, apical domain development and actin organization downstream of PARD3
  • CDK5 activates CCDC88A to orchestrate migration-proliferation dichotomy
  • GNAS and CCDC88A functionally interact to facilitate endosome maturation, EGFR degradation, and down-regulation of EGFR proliferative signaling
  • cell & other
    Phosphorylated by CDK5, that binds and phosphorylates CCDC88A at Ser1674 near its GEF motif
    Other phosphorylation induced by epidermal growth factor (EGF) in a phosphoinositide 3-kinase (PI3K)-dependent manner
    phosphorylation by AKT1/PKB is necessary for the delocalization from the cell membrane and for cell migration
    phosphorylated by the stimulation of insulin-like growth factor (IGF-I)
    corresponding disease(s) PEHOL
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in glioblastoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
    AKT/CCDC88A signaling pathway is a potential target for the development of new therapeutics for vascular diseases
    because of its important role in promoting podocyte survival, GIV may represent a novel target for therapeutic intervention in the nephrotic syndrome and other proteinuric diseases
  • mice with germ-line deletions of Girdin exhibit complete postnatal lethality accompanied by growth retardation and neuronal cell migration defects, which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyrus