Reactome | UniProt:Q96P48 ARAP1

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UniProt:Q96P48 ARAP1 Show undefined attributes

chain	chain:1-1450
checksum	A4B6CCC28EC4CD0D
comment	FUNCTION Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members (PubMed:11804590, PubMed:19666464). Activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding and, to a lesser extent, by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) binding (PubMed:11804590). Has a preference for ARF1 and ARF5 (PubMed:11804590, PubMed:19666464). Positively regulates the ring size of circular dorsal ruffles and promotes macropinocytosis (PubMed:22573888). Acts as a bridging factor in osteoclasts to control actin and membrane dynamics (By similarity). Regulates the condensing of osteoclast podosomes into sealing zones which segregate the bone-facing membrane from other membrane domains and are required for osteoclast resorption activity (By similarity). Also regulates recruitment of the AP-3 complex to endosomal membranes and trafficking of lysosomal membrane proteins to the ruffled membrane border of osteoclasts to modulate bone resorption (By similarity). Regulates the endocytic trafficking of EGFR (PubMed:18764928, PubMed:18939958, PubMed:21275903). Regulates the incorporation of CD63 and CD9 into multivesicular bodies (PubMed:38682696). Required in the retinal pigment epithelium (RPE) for photoreceptor survival due to its role in promoting RPE phagocytosis (By similarity).SUBUNIT Interacts with SH3KBP1/CIN85 (via SH3 domains) (PubMed:21275903). The interaction is independent of EGF and does not affect ARAP1 GTPase-activating activity but is involved in regulating ubiquitination and endocytic trafficking of EGFR (PubMed:21275903). ARAP1 competes with E3 ubiquitin-protein ligase CBL for binding to SH3KBP1, preventing interaction of CBL with SH3KBP1; this is likely to regulate SH3KBP1-mediated internalization of EGFR (By similarity). Interacts with TNFRSF10A (PubMed:18165900).INTERACTION Associated with Golgi stacks in resting cells (PubMed:11804590). Throughout the cytoplasm and in surface protrusions in cells that are in the process of attaching to a surface and spreading (PubMed:11804590). Localizes to actin-rich podosomes, sealing zones and early endosomes in osteoclasts (By similarity).ALTERNATIVE PRODUCTS Detected in heart, skeletal muscle, spleen, kidney, liver, placenta, lung, peripheral blood leukocytes, adrenal gland, bone marrow, brain, lymph node, mammary gland, prostate, spinal cord, stomach, thyroid and trachea.DOMAIN The first PH domain, PH 1, interacts with PtdIns(3,4,5)P3 which stimulates ARAP1 GTPase-activating activity and is also required for ARAP1-mediated regulation of endocytic trafficking of EGFR (PubMed:18939958, PubMed:19666464). It does not mediate PtdIns(3,4,5)P3-dependent recruitment of ARAP1 to membranes although this may be mediated by other PH domains (PubMed:19666464).PTM Phosphorylated by PTK6 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation; the interaction is mediated by the SH2 domain of PTK6 (PubMed:20554524). Phosphorylation promotes association with the Golgi apparatus and endosomes (PubMed:18939958).
created	[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
crossReference	[DatabaseIdentifier:12399790] RefSeq:NP_001035207.1 [DatabaseIdentifier:11486381] ENSEMBL:ENSG00000186635 [DatabaseIdentifier:11590387] ENSEMBL:ENSP00000352332 [DatabaseIdentifier:11590388] ENSEMBL:ENSP00000335506 [DatabaseIdentifier:11590390] ENSEMBL:ENSP00000377233 [DatabaseIdentifier:11590391] ENSEMBL:ENSP00000377230 [DatabaseIdentifier:11590389] ENSEMBL:ENSP00000403127 [DatabaseIdentifier:11713089] ENSEMBL:ENST00000334211 [DatabaseIdentifier:11713087] ENSEMBL:ENST00000359373 [DatabaseIdentifier:11713088] ENSEMBL:ENST00000393605 [DatabaseIdentifier:11713086] ENSEMBL:ENST00000393609 [DatabaseIdentifier:11713090] ENSEMBL:ENST00000429686 [DatabaseIdentifier:11783053] GeneCards:ARAP1 [DatabaseIdentifier:11798678] GlyGen:Q96P48 [DatabaseIdentifier:11830531] HMDB Protein:HMDBP14131 [DatabaseIdentifier:11836163] HPA:ENSG00000186635-ARAP1 [DatabaseIdentifier:12120633] OpenTargets:ENSG00000186635 [DatabaseIdentifier:12146686] PDB:4X1V [DatabaseIdentifier:12238214] PRO:Q96P48 [DatabaseIdentifier:12280969] Pharos - Targets:Q96P48 [DatabaseIdentifier:12399791] RefSeq:NP_056057.2 [DatabaseIdentifier:12399789] RefSeq:NP_001128662.1
databaseName	UniProt
dbId	412998
description	recommendedName: Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 alternativeName: Centaurin-delta-2 shortName: Cnt-d2
displayName	UniProt:Q96P48 ARAP1
geneName	ARAP1 CENTD2 KIAA0782
identifier	Q96P48
isSequenceChanged	false
keyword	3D-structure Alternative splicing Cell junction Cell membrane Cell projection Cytoplasm Endosome Golgi apparatus GTPase activation Membrane Metal-binding Phosphoprotein Proteomics identification Reference proteome Repeat Zinc Zinc-finger
modified	[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType	Protein
name	ARAP1
otherIdentifier	116985 11719038_a_at 11740162_a_at 11758732_at 16741779 212516_3p_at 212516_PM_at 212516_at 238911_PM_at 238911_at 3381235 3381237 3381238 3381239 3381240 3381242 3381243 3381244 3381245 3381246 3381247 3381248 3381249 3381250 3381251 3381252 3381253 3381254 3381255 3381256 3381259 3381260 3381261 3381262 3381263 3381264 3381265 3381266 3381267 3381268 3381269 3381270 3381271 3381272 3381273 3381274 3381275 3381276 3381277 3381278 3381279 3381280 3381281 3381284 3381285 3381286 3381288 3381290 3381291 3381292 3381293 3381294 3381295 3381296 3381297 3381298 3381299 3381300 3381301 3381302 3381303 3381304 3381306 3381308 3381309 3381310 3381314 3381361 3381362 3381363 3381364 34206_PM_at 34206_at 7950197 85926_at 92043_at A_23_P105184 A_24_P398432 A_33_P3416583 GE53485 GO:0001726 GO:0001921 GO:0002090 GO:0002102 GO:0005096 GO:0005515 GO:0005547 GO:0005654 GO:0005737 GO:0005768 GO:0005769 GO:0005771 GO:0005794 GO:0005795 GO:0005802 GO:0005829 GO:0005886 GO:0007015 GO:0007165 GO:0008270 GO:0008360 GO:0016020 GO:0019897 GO:0030100 GO:0031344 GO:0031702 GO:0032956 GO:0042995 GO:0043226 GO:0043547 GO:0045124 GO:0045494 GO:0046872 GO:0050766 GO:0051056 GO:0051130 GO:0051491 GO:0051497 GO:0070161 GO:0098772 HMNXSV003030070 Hs.132760.0.S1_3p_at Hs.21264.0.S1_3p_at Hs.21264.0.S1_3p_s_at ILMN_1772233 ILMN_1786357 PH_hs_0022925 TC11003491.hg
physicalEntity	[EntityWithAccessionedSequence:R-HSA-3211582] ARAP1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8848869] p-Y231-ARAP1 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000186635] ENSEMBL:ENSG00000186635 ARAP1 [ReferenceDNASequence:12696296] UCSC:Q96P48 ARAP1 [ReferenceDNASequence:11351660] BioGPS Gene:116985 ARAP1 [ReferenceDNASequence:11393794] COSMIC - genes:ARAP1 ARAP1 [ReferenceDNASequence:11406628] CTD Gene:116985 ARAP1 [ReferenceDNASequence:11429792] dbSNP Gene:116985 ARAP1 [ReferenceDNASequence:11814665] HGNC:16925 ARAP1 [ReferenceDNASequence:11891410] KEGG:hsa:116985 ARAP1 [ReferenceDNASequence:11981449] Monarch:116985 ARAP1 [ReferenceDNASequence:12065542] NCBI Gene:116985 ARAP1 [ReferenceDNASequence:12106421] OMIM:606646 ARAP1
referenceTranscript	[ReferenceRNASequence:12581499] RefSeq:NM_015242.5 ARAP1 [ReferenceRNASequence:12581497] RefSeq:NM_001135190.2 ARAP1 [ReferenceRNASequence:12581498] RefSeq:NM_001040118.3 ARAP1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ARAP1_HUMAN A3KLL7 B2RTS2 O94879 Q4LDD5 Q59FI7 Q6PHS3 Q8WU51 Q96HP6 Q96L71
sequenceLength	1450
species	[Species:48887] Homo sapiens
stId	uniprot:Q96P48
url	http://purl.uniprot.org/uniprot/Q96P48

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-3211582] ARAP1 [cytosol] [EntityWithAccessionedSequence:R-HSA-8848869] p-Y231-ARAP1 [cytosol]
(referenceSequence)	[ModifiedResidue:8848871] O4'-phospho-L-tyrosine at 231
(interactor)	[UndirectedInteraction:11164043] UniProt:P46108 <-> UniProt:Q96P48 (IntAct) [UndirectedInteraction:11169959] UniProt:Q96B97 <-> UniProt:Q96P48 (IntAct) [UndirectedInteraction:11183621] UniProt:Q96P48 <-> UniProt:P62993 (IntAct) [UndirectedInteraction:11183623] UniProt:Q96P48 <-> UniProt:O43639 (IntAct) [UndirectedInteraction:11183625] UniProt:Q96P48 <-> UniProt:P47756 (IntAct) [UndirectedInteraction:11183627] UniProt:Q96P48 <-> UniProt:P47755 (IntAct) [UndirectedInteraction:11183629] UniProt:Q96P48 <-> UniProt:O00220 (IntAct) [UndirectedInteraction:11183631] UniProt:Q96P48 <-> UniProt:P16333 (IntAct) [UndirectedInteraction:11183633] UniProt:Q96P48 <-> UniProt:O60504 (IntAct) [UndirectedInteraction:11183635] UniProt:Q96P48 <-> UniProt:P25090 (IntAct) [UndirectedInteraction:11183637] UniProt:Q96P48 <-> UniProt:P12956 (IntAct) [UndirectedInteraction:11183639] UniProt:Q96P48 <-> UniProt:P27958-PRO_0000037576 (IntAct)

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