Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
ACAPs are arf6 GTPase-activating proteins that function in the cell periphery.
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ACAP1 and ACAP2 are ARF6 GTPase-activating proteins.
"Here, we report the identification and characterization of two Arf6 GAPs, ACAP1 and ACAP2."
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The GAP activity has genuine substrate preference for ARF6 over ARF1 and ARF5.
"In vitro, ACAP1 and ACAP2 preferred Arf6 as a substrate, rather than Arf1 and Arf5, more so than did ASAP1."
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GAP activity requires PIP2 together with phosphatidic acid.
"ACAP1 and ACAP2 showed similar phospholipid dependencies when Arf6 was used as a substrate."
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The conserved arginine of the ArfGAP domain is essential; R442Q abolishes ACAP2 activity.
"[R448Q]ACAP1 and [R442Q]ACAP2 had no detectable activity using Arf6 as a substrate"
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ACAP2 overexpression suppresses PDGF-induced dorsal ruffles, and the protein is recruited to the ruffles that do form even when GAP-dead.
"The mutant ACAPs, like mutant ASAP1, were efficiently recruited to the actin-rich ruffles"
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In human HeLa cells ACAP2 suppresses ARF6-dependent actin-rich protrusions, GAP-dependently.
"Coexpression of Arf6 with either ACAP inhibited the formation of protrusions in response to AlF4 treatment"
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ACAP2 is largely cytosolic at steady state with a pool on tubular ARF6 endosomes.
"In untreated cells, although ACAP1 and ACAP2 were primarily cytosolic, they could be observed on tubular portions of the Arf6 endosomal compartment"
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The ARF6 tubules ACAP2 occupies are the route for recycling back to the plasma membrane.
"In addition, ACAP1 and ACAP2 were recruited to peripheral, tubular membranes, where activation of Arf6 occurs to allow membrane recycling back to the plasma membrane."
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The effect is confined to the cell periphery; the Golgi is unaffected.
"Neither ACAP1, ACAP2, nor ASAP1 (Brown et al. 1998) caused changes in the morphology of the Golgi apparatus"
Defining the membrane proteome of NK cells.
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The protocol was designed to remove peripheral membrane proteins before analysis, which is the class ACAP2 belongs to.
"Isolated membranes were treated with reagents that have been reported to remove peripheral membrane proteins."
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Only about 40% of the 1843 identifications were judged plausible membrane proteins.
"approximately 40% of the identified proteins were predicted as plausible membrane proteins"
Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.
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Crystal structures of RAB35 bound to its specific effectors ACAP2 and RUSC2.
"Here, we provide the high-resolution crystal structures of Rab35 in complex with its two specific effectors ACAP2 and RUSC2, respectively."
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RAB35 engages the terminal ankyrin repeat of ACAP2 plus a following extended helix, a binding mode not previously seen for either Rabs or ankyrin repeats.
"In the Rab35/ACAP2 complex structure, Rab35 binds to the terminal ankyrin repeat and a C-terminal extended"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 affinity-purification interactome; the source of one of the two ACAP2-ACAP3 protein binding annotations.
"Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks."
OpenCell: Endogenous tagging for the cartography of human cellular organization.
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Endogenous-tagging interactome and localisation atlas, measuring protein at near-native abundance; independently recovers the ACAP2-ACAP3 interaction.
"Genome-edited cells enable to examine protein function at near-native expression levels"
Rab35 regulates phagosome formation through recruitment of ACAP2 in macrophages during FcγR-mediated phagocytosis.
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GTP-RAB35 recruits ACAP2, an ARF6 GAP, to the forming phagocytic cup.
"Furthermore, GTP-Rab35-dependent recruitment of ACAP2, an ARF6 GTPase-activating protein, was shown in the phagocytic cup formation."
Rab35 regulates Arf6 activity through centaurin-β2 (ACAP2) during neurite outgrowth.
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ACAP2 acts both as a RAB35 effector and as an ARF6 GAP during neurite outgrowth of PC12 cells.
"Here we show that centaurin-β2 (also known as ACAP2) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells."
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NGF drives RAB35 onto ARF6-positive endosomes, and ACAP2 follows in a RAB35-dependent manner.
"We found that Rab35 accumulates at Arf6-positive endosomes in response to nerve growth factor (NGF) stimulation and that centaurin-β2 is recruited to the same compartment in a Rab35-dependent manner."
Rab35, acting through ACAP2 switching off Arf6, negatively regulates oligodendrocyte differentiation and myelination.
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ACAP2 is the RAB35 effector that switches ARF6 off, and the pair acts as a brake on oligodendrocyte differentiation.
"We show that Rab35 and its effector, ACAP2, a GTPase-activating protein that switches off Arf6 activity, negatively regulate oligodendrocyte morphological differentiation."
Structure-function analyses of the small GTPase Rab35 and its effector protein centaurin-β2/ACAP2 during neurite outgrowth of PC12 cells.
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ACAP2 recognises RAB35 exclusively, and none of the other 59 mammalian Rabs.
"Centaurin-β2 is the only Rab35-binding protein reported thus far that exclusively recognizes Rab35 and does not recognize any of the other 59 Rabs identified in mammals"
Human ACAP2 is a homolog of C. elegans CNT-1 that promotes apoptosis in cancer cells.
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ACAP2 has a pro-apoptotic function and the same phosphoinositide-binding pattern as tCNT-1, but is not itself a caspase substrate.
"We report here that ACAP2, a homolog of C. elegans CNT-1, has a pro-apoptotic function and an identical phosphoinositide-binding pattern to that of tCNT-1, despite not being an apparent target of caspase cleavage."
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Knockdown of ACAP2 in human cancer cells blocks 5-fluorouracil-induced apoptosis.
"We show that knockdown of ACAP2 blocks apoptosis in cancer cells in response to the chemotherapeutic antimetabolite 5-fluorouracil"
Vaccinia virus K1L protein supports viral replication in human and rabbit cells through a cell-type-specific set of its ankyrin repeat residues that are distinct from its binding site for ACAP2.
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The ankyrin-repeat residues K1L needs for host-range function are distinct from those it uses to bind ACAP2, so ACAP2 binding is separable from the host-range activity.
"These substitutions, however, did not affect K1L's ability to bind ACAP2, a GTPase-activating protein for ARF6."
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The authors conclude that the host-range function of K1L is mediated by factors distinct from ACAP2.
"Our data support the hypothesis that surface residues of a few consecutive K1L ANKs mediate the host-range function by interacting with protein factors that are distinct from ACAP2."
RNF126 Promotes Ovarian Cancer Progression by Reprogramming Lipid Metabolism Through Degradation of ACAP2.
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ACAP2 is a ubiquitination substrate of RNF126, and its abundance is negatively regulated by RNF126.
"Mechanistically, ACAP2 was identified as a ubiquitination substrate of RNF126, and its expression was negatively regulated by RNF126."
The PI(3)P interactome from a colon cancer cell.
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A PI(3)P affinity-proteomics screen recovered 681 proteins, ACAP2 among them.
"Affinity/LC/MS/MS experiments allowed the identification of 681 proteins/protein complexes which interact with PI(3)P."
ACAP2 WITH/FROM resolution and domain-architecture check
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Every one of the 22 WITH/FROM identifiers in ACAP2-goa.tsv resolves; the three ISS/IEA ortholog transfers come from rat and mouse Acap2, while MGI:MGI:2153589 is mouse Acap3, a paralog.
"| `MGI:MGI:2153589` | Q6NXL5 Q6NXL5_MOUSE (Acap3) | Mus musculus | 833 | yes | GO:0005096 (IBA) |"
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Drosophila blow carries only a PH domain on all four of its UniProt entries and no PANTHER cross-reference, yet PANTHER places it in PTHR23180:SF399.
"- `A1Z714` A1Z714_DROME, 644 aa, domains: PH 204-307, PANTHER xrefs in UniProt: NONE"
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SF399 is a real ACAP subfamily rather than a domain-less outlier group - its other reviewed member is C. elegans cnt-1, a bona fide Arf-GAP with ANK and PH domains.
"- `Q9XXH8` cnt-1 (Caenorhabditis elegans), 826 aa - Arf-GAP with ANK repeat and PH domain-containing protein cnt-1"
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Every source with a resolvable UniProt accession holds its own experimental evidence for the term it donates, so none of these transfers is an inference recycling another inference.
"| `dictyBase:DDB_G0279649` | Q54WI0 | GO:0030036 | IBAx1, IGIx1, IMPx1 (n=3) | **yes** |"
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PANTHER node PTN001142372 is pan-eukaryotic, propagating the same four terms across plants, a charophyte alga, fungi and vertebrates.
"- QuickGO reports 1000 annotations citing this node."
Affinage mechanistic annotation for ACAP2 (human)