CCDC88A
entrez
55704
canonical
uniprot
Q3V6T2
canonical
ensembl
ENSG00000115355
resolver
ensp
ENSP00000263630
resolver
ensp
ENSP00000338728
resolver
ensp
ENSP00000410608
resolver
ensp
ENSP00000493703
resolver
genesymbol
CCDC88A
resolver
genesymbol_syn
APE
resolver
genesymbol_syn
GRDN
resolver
genesymbol_syn
KIAA1212
resolver
hgnc
HGNC:25523
resolver
uniprot
A1IGE7
resolver
uniprot
B7ZM78
resolver
uniprot
C9JG83
resolver
uniprot
O14997
resolver
uniprot
Q53SF1
resolver
uniprot
Q581G3
resolver
uniprot
Q5HYD0
resolver
uniprot
Q7Z339
resolver
uniprot
Q7Z3C5
resolver
uniprot_entry
GRDN_HUMAN
resolver
uniprot_entry
O14997_HUMAN
resolver
uniprot_sec
A1IGE7
resolver
uniprot_sec
B7ZM78
resolver
uniprot_sec
C9JG83
resolver
uniprot_sec
Q53SF1
resolver
uniprot_sec
Q581G3
resolver
uniprot_sec
Q5HYD0
resolver
uniprot_sec
Q7Z339
resolver
uniprot_sec
Q7Z3C5
resolver
amino_acid_sequence
MENEIFTPLLEQFMTSPLVTWVKTFGPLAAGNGTNLDEYVALVDGVFLNQVMLQINPKLESQRVNKKVNNDASLRMHNLSILVRQIKFYYQETLQQLIMMSLPNVLIIGKNPFSEQGTEEVKKLLLLLLGCAVQCQKKEEFIERIQGLDFDTKAAVAAHIQEVTHNQENVFDLQWMEVTDMSQEDIEPLLKNMALHLKRLIDERDEHSETIIELSEERDGLHFLPHASSSAQSPCGSPGMKRTESRQHLSVELADAKAKIRRLRQELEEKTEQLLDCKQELEQMEIELKRLQQENMNLLSDARSARMYRDELDALREKAVRVDKLESEVSRYKERLHDIEFYKARVEELKEDNQVLLETKTMLEDQLEGTRARSDKLHELEKENLQLKAKLHDMEMERDMDRKKIEELMEENMTLEMAQKQSMDESLHLGWELEQISRTSELSEAPQKSLGHEVNELTSSRLLKLEMENQSLTKTVEELRTTVDSVEGNASKILKMEKENQRLSKKVEILENEIVQEKQSLQNCQNLSKDLMKEKAQLEKTIETLRENSERQIKILEQENEHLNQTVSSLRQRSQISAEARVKDIEKENKILHESIKETSSKLSKIEFEKRQIKKELEHYKEKGERAEELENELHHLEKENELLQKKITNLKITCEKIEALEQENSELERENRKLKKTLDSFKNLTFQLESLEKENSQLDEENLELRRNVESLKCASMKMAQLQLENKELESEKEQLKKGLELLKASFKKTERLEVSYQGLDIENQRLQKTLENSNKKIQQLESELQDLEMENQTLQKNLEELKISSKRLEQLEKENKSLEQETSQLEKDKKQLEKENKRLRQQAEIKDTTLEENNVKIGNLEKENKTLSKEIGIYKESCVRLKELEKENKELVKRATIDIKTLVTLREDLVSEKLKTQQMNNDLEKLTHELEKIGLNKERLLHDEQSTDDSRYKLLESKLESTLKKSLEIKEEKIAALEARLEESTNYNQQLRQELKTVKKNYEALKQRQDEERMVQSSPPISGEDNKWERESQETTRELLKVKDRLIEVERNNATLQAEKQALKTQLKQLETQNNNLQAQILALQRQTVSLQEQNTTLQTQNAKLQVENSTLNSQSTSLMNQNAQLLIQQSSLENENESVIKEREDLKSLYDSLIKDHEKLELLHERQASEYESLISKHGTLKSAHKNLEVEHRDLEDRYNQLLKQKGQLEDLEKMLKVEQEKMLLENKNHETVAAEYKKLCGENDRLNHTYSQLLKETEVLQTDHKNLKSLLNNSKLEQTRLEAEFSKLKEQYQQLDITSTKLNNQCELLSQLKGNLEEENRHLLDQIQTLMLQNRTLLEQNMESKDLFHVEQRQYIDKLNELRRQKEKLEEKIMDQYKFYDPSPPRRRGNWITLKMRKLIKSKKDINRERQKSLTLTPTRSDSSEGFLQLPHQDSQDSSSVGSNSLEDGQTLGTKKSSMVALKRLPFLRNRPKDKDKMKACYRRSMSMNDLVQSMVLAGQWTGSTENLEVPDDISTGKRRKELGAMAFSTTAINFSTVNSSAGFRSKQLVNNKDTTSFEDISPQGVSDDSSTGSRVHASRPASLDSGRTSTSNSNNNASLHEVKAGAVNNQSRPQSHSSGEFSLLHDHEAWSSSGSSPIQYLKRQTRSSPVLQHKISETLESRHHKIKTGSPGSEVVTLQQFLEESNKLTSVQIKSSSQENLLDEVMKSLSVSSDFLGKDKPVSCGLARSVSGKTPGDFYDRRTTKPEFLRPGPRKTEDTYFISSAGKPTPGTQGKIKLVKESSLSRQSKDSNPYATLPRASSVISTAEGTTRRTSIHDFLTKDSRLPISVDSPPAAADSNTTAASNVDKVQESRNSKSRSREQQSS
uniprot
proteins
disease_involvement
DISEASE: PEHO-like syndrome (PEHOL) [MIM:617507]: An autosomal recessive syndrome characterized by microcephaly and moderately severe hypotonia manifesting at birth, seizures that progress into infantile spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria and pachygyria, thin corpus callosum, and mild reduction in cerebellar vermis volume. Patients also display optic atrophy, severe cognitive delay, puffiness of the maxillary region of the face, and edema of the dorsum of the hands and feet. {ECO:0000269|PubMed:26917597}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}.
uniprot
proteins
mass_dalton
216042
uniprot
proteins
mutagenesis
MUTAGEN 1417; /note="S->A: Phosphorylation-deficient mutant which disrupts actin organization, cell migration and lamellipodia formation but has no effect on tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:21954290"; MUTAGEN 1417; /note="S->D: Phosphomimetic mutant which has no effect on tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:21954290"; MUTAGEN 1675; /note="S->A: Phosphorylation-deficient mutant which disrupts binding to GNAI3 and GNAS."; /evidence="ECO:0000269|PubMed:27621449"; MUTAGEN 1675; /note="S->D: Phosphomimetic mutant which results in slight increase in binding to GNAI3 and GNAS. Increased inhibition of GNAS; when associated with D-1690."; /evidence="ECO:0000269|PubMed:27621449"; MUTAGEN 1684; /note="Q->A: No effect on guanine nucleotide exchange factor activity."; /evidence="ECO:0000269|PubMed:31363053"; MUTAGEN 1686; /note="F->A: Abolishes interaction with and activation of GNAI3 and also abolishes recruitment of GNAI3 to EGFR. Reduced EGFR autophosphorylation and SH2 adapter recruitment, reduced localization of EGFR at the cell membrane following ligand stimulation with increased endosomal localization, reduced cell migration and increased cell proliferation. Abolishes enhancement of AKT signaling. Abolishes interaction with GNAS."; /evidence="ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:27621449"; MUTAGEN 1689; /note="E->A: Abolishes interaction with GNAI3."; /evidence="ECO:0000269|PubMed:19211784"; MUTAGEN 1690; /note="S->A: Phosphorylation-deficient mutant which retains the ability to bind GNAI3."; /evidence="ECO:0000269|PubMed:23509302"; MUTAGEN 1690; /note="S->D: Phosphomimetic mutant which abolishes interaction with GNAI3, inhibits guanine nucleotide exchange factor activity, inhibits cell migration and triggers cell proliferation. Retains ability to bind to GNAS. Increased inhibition of GNAS; when associated with D-1675."; /evidence="ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:27621449"; MUTAGEN 1723; /note="K->E: Abolishes binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1725; /note="K->E: Does not affect binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1746; /note="R->K,L: Abolishes binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1750; /note="K->E: Abolishes binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1765; /note="Y->F: Abolishes phosphorylation and leads to reduced AKT phosphorylation, impaired formation of actin stress fibers and impaired cell migration abolishes interaction with PIK3R1 and activation of PI3K, reduces phosphorylation of Ser-1417 but does not affect interaction with or activation of GNAI3; when associated with F-1799."; /evidence="ECO:0000269|PubMed:21954290"; MUTAGEN 1766; /note="F->T: Increases binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1778; /note="Q->E: Abolishes binding to phosphorylated EGFR."; /evidence="ECO:0000269|PubMed:25187647"; MUTAGEN 1799; /note="Y->F: Abolishes phosphorylation and leads to reduced AKT phosphorylation, impaired formation of actin stress fibers and impaired cell migration, abolishes interaction with PIK3R1 and activation of PI3K activity, reduces phosphorylation of Ser-1417 but does not affect interaction with or activation of GNAI3; when associated with F-1765."; /evidence="ECO:0000269|PubMed:21954290
uniprot
proteins
post_translational_modification
PTM: Phosphorylation is induced by epidermal growth factor (EGF) in a phosphoinositide 3-kinase (PI3K)-dependent manner (PubMed:16139227). Phosphorylation by AKT1/PKB is necessary for delocalization from the cell membrane and for cell migration (PubMed:16139227). Phosphorylated on tyrosine residues which promotes binding to phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a and enhances PI3K activity (PubMed:21954290). Tyrosine-phosphorylated by both receptor and non-receptor tyrosine kinases in vitro (PubMed:21954290). Tyrosine phosphorylation is required for AKT1-dependent phosphorylation of Ser-1417 (PubMed:21954290). Phosphorylation at Ser-1690 by PRKCQ disrupts interaction with GNAI3 and inhibits guanine nucleotide exchange factor activity (PubMed:23509302). {ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302}.
uniprot
proteins
protein_family
CCDC88 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15749703
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15882442
uniprot
proteins
pubmed
16139227
uniprot
proteins
pubmed
17185515
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19211784
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20462955
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21954290
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23509302
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25187647
uniprot
proteins
pubmed
26917597
uniprot
proteins
pubmed
27621449
uniprot
proteins
pubmed
27623382
uniprot
proteins
pubmed
27864364
uniprot
proteins
pubmed
30194280
uniprot
proteins
pubmed
31363053
uniprot
proteins
pubmed
31570568
uniprot
proteins
sequence_length
1871
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:27864364}; Peripheral membrane protein {ECO:0000305}. Cytoplasm, cytosol {ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:27864364}. Cytoplasmic vesicle {ECO:0000269|PubMed:15749703, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227}. Cell projection, lamellipodium {ECO:0000269|PubMed:15882442}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:27623382}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000269|PubMed:27623382}. Note=Localizes to the cytosol in unstimulated cells while EGF stimulation promotes membrane localization and guanine nucleotide exchange factor activity (PubMed:27864364). Localizes to the cell membrane through interaction with phosphoinositides (PubMed:15882442, PubMed:16139227). {ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:27864364}.
uniprot
proteins