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Symbol CCDC88A contributors: mct/npt/pgu - updated : 06-09-2016
HGNC name coiled-coil domain containing 88A
HGNC id 25523
Corresponding disease
PEHO progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy
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
     nerve   highly
    Reproductivemale systemtestis  highly
    Urinarykidney   lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Muscular   moderately
    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
  • 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
  • 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)
  • 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
  • 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) PEHO
    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