Reviewed, UniProtKB/Swiss-Prot Q8WWN8 (ARAP3_HUMAN)

Names and origin

Protein names

Recommended name:
    Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
Alternative name(s):
    Centaurin-delta-3
      Short name=Cnt-d3

Gene names

Name:	ARAP3
Synonyms:	CENTD3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1544 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin. Ref.1 Ref.3
Subunit structure	Interacts with INPPL1/SHIP2. Ref.1 Ref.4
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein By similarity. Cell projection › lamellipodium By similarity. Cell projection › ruffle By similarity. Note: Cytoplasmic, and associated with F-actin-rich membrane ruffles and lamellipodia By similarity.
Post-translational modification	Tyrosine phosphorylated at a low basal level. PDGF treatment stimulates phosphorylation. Tyrosine phosphorylation is increased in cells that are in the process of becoming attached to a substrate and that start spreading and flattening By similarity.
Sequence similarities	Contains 1 Arf-GAP domain. Contains 3 PH domains. Contains 1 Ras-associating domain. Contains 1 Rho-GAP domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cytoskeleton organization Ref.3 Traceable author statement. Source: UniProtKB negative regulation of Rho protein signal transduction Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro vesicle-mediated transport Ref.3 Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Inferred by curator. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW ruffle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ARF GTPase activator activity Inferred from sequence or structural similarity. Source: UniProtKB Rho GTPase activator activity Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-3,4,5-trisphosphate binding Ref.1 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate binding Ref.1 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1544	1544	Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3		PRO_0000074215
Regions
	Domain	4 – 68	65	SAM
	Domain	287 – 379	93	PH 1
	Domain	394 – 483	90	PH 2
	Domain	480 – 611	132	Arf-GAP
	Domain	907 – 1088	182	Rho-GAP
	Domain	1117 – 1210	94	Ras-associating
	Domain	1223 – 1325	103	PH 3
	Zinc finger	504 – 527	24	C4-type
	Compositional bias	81 – 139	59	Pro-rich
	Compositional bias	1462 – 1542	81	Pro-rich
Amino acid modifications
	Modified residue	1403	1	Phosphotyrosine By similarity
	Modified residue	1408	1	Phosphotyrosine By similarity
	Modified residue	1444	1	Phosphoserine Ref.5
Natural variations
	Natural variant	218	1	D → H: dbSNP rs1031904.		VAR_048330
	Natural variant	471	1	R → W in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036180
	Natural variant	1085	1	I → M in a breast cancer sample; somatic mutation. Ref.6		VAR_036181
	Natural variant	1428	1	T → P in a breast cancer sample; somatic mutation. Ref.6		VAR_036182
Experimental info
	Mutagenesis	307 – 308	2	RR → AA: Loss of PtdIns(3,4,5)P3 binding. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8WWN8-1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 40C03A22591B2B6F	FASTA	1,544	169,844
	10 20 30 40 50 60 MAAPQDLDIA VWLATVHLEQ YADTFRRHGL ATAGAARGLG HEELKQLGIS ATGHRKRILR 70 80 90 100 110 120 LLQTGTEEGS LDPKSDSAME PSPSPAPQAQ PPKPVPKPRT VFGGLSGPAT TQRPGLSPAL 130 140 150 160 170 180 GGPGVSRSPE PSPRPPPLPT SSSEQSSALN TVEMMPNSIY FGLDSRGRAQ AAQDKAPDSS 190 200 210 220 230 240 QISAPTPALR PTTGTVHIMD PGCLYYGVQP VGTPGAPDRR ESRGVCQGRA EHRLSRQDLE 250 260 270 280 290 300 AREDAGYASL ELPGDSTLLS PTLETEETSD DLISPYASFS FTADRLTPLL SGWLDKLSPQ 310 320 330 340 350 360 GNYVFQRRFV QFNGRSLMYF GSDKDPFPKG VIPLTAIEMT RSSKDNKFQV ITGQRVFVFR 370 380 390 400 410 420 TESEAQRDMW CSTLQSCLKE QRLLGHPRPP QPPRPLRTGM LELRGHKAKV FAALSPGELA 430 440 450 460 470 480 LYKSEQAFSL GIGICFIELQ GCSVRETKSR SFDLLTPHRC FSFTAESGGA RQSWAAALQE 490 500 510 520 530 540 AVTETLSDYE VAEKIWSNRA NRQCADCGSS RPDWAAVNLG VVICKQCAGQ HRALGSGISK 550 560 570 580 590 600 VQSLKLDTSV WSNEIVQLFI VLGNDRANRF WAGTLPPGEG LHPDATPGPR GEFISRKYRL 610 620 630 640 650 660 GLFRKPHPQY PDHSQLLQAL CAAVARPNLL KNMTQLLCVE AFEGEEPWFP PAPDGSCPGL 670 680 690 700 710 720 LPSDPSPGVY NEVVVRATYS GFLYCSPVSN KAGPSPPRRG RDAPPRLWCV LGAALEMFAS 730 740 750 760 770 780 ENSPEPLSLI QPQDIVCLGV SPPPTDPGDR FPFSFELILA GGRIQHFGTD GADSLEAWTS 790 800 810 820 830 840 AVGKWFSPLS CHQLLGPGLL RLGRLWLRSP SHTAPAPGLW LSGFGLLRGD HLFLCSAPGP 850 860 870 880 890 900 GPPAPEDMVH LRRLQEISVV SAADTPDKKE HLVLVETGRT LYLQGEGRLD FTAWNAAIGG 910 920 930 940 950 960 AAGGGGTGLQ EQQMSRGDIP IIVDACISFV TQHGLRLEGV YRKGGARARS LRLLAEFRRD 970 980 990 1000 1010 1020 ARSVKLRPGE HFVEDVTDTL KRFFRELDDP VTSARLLPRW REAAELPQKN QRLEKYKDVI 1030 1040 1050 1060 1070 1080 GCLPRVNRRT LATLIGHLYR VQKCAALNQM CTRNLALLFA PSVFQTDGRG EHEVRVLQEL 1090 1100 1110 1120 1130 1140 IDGYISVFDI DSDQVAQIDL EVSLITTWKD VQLSQAGDLI MEVYIEQQLP DNCVTLKVSP 1150 1160 1170 1180 1190 1200 TLTAEELTNQ VLEMRGTAAG MDLWVTFEIR EHGELERPLH PKEKVLEQAL QWCQLPEPCS 1210 1220 1230 1240 1250 1260 ASLLLKKVPL AQAGCLFTGI RRESPRVGLL RCREEPPRLL GSRFQERFFL LRGRCLLLLK 1270 1280 1290 1300 1310 1320 EKKSSKPERE WPLEGAKVYL GIRKKLKPPT PWGFTLILEK MHLYLSCTDE DEMWDWTTSI 1330 1340 1350 1360 1370 1380 LKAQHDDQQP VVLRRHSSSD LARQKFGTMP LLPIRGDDSG ATLLSANQTL RRLHNRRTLS 1390 1400 1410 1420 1430 1440 MFFPMKSSQG SVEEQEELEE PVYEEPVYEE VGAFPELIQD TSTSFSTTRE WTVKPENPLT 1450 1460 1470 1480 1490 1500 SQKSLDQPFL SKSSTLGQEE RPPEPPPGPP SKSSPQARGS LEEQLLQELS SLILRKGETT 1510 1520 1530 1540 AGLGSPSQPS SPQSPSPTGL PTQTPGFPTQ PPCTSSPPSS QPLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices." Krugmann S., Anderson K.E., Ridley S.H., Risso N., McGregor A., Coadwell J., Davidson K., Eguinoa A., Ellson C.D., Lipp P., Manifava M., Ktistakis N., Painter G., Thuring J.W., Cooper M.A., Lim Z.-Y., Holmes A.B., Dove S.K. , Michell R.H., Grewal A., Nazarian A., Erdjument-Bromage H., Tempst P., Stephens L.R., Hawkins P.T. Mol. Cell 9:95-108(2002) [PubMed: 11804589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF 307-ARG-ARG-308, FUNCTION, INTERACTION WITH PHOSPHATIDYLINOSITOL 3-PHOSPHATE.
[2]	"GTPase signaling: bridging the GAP between ARF and Rho." Santy L.C., Casanova J.E. Curr. Biol. 12:R360-R362(2002) [PubMed: 12015138] [Abstract] Cited for: REVIEW.
[3]	"EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin." Lu Q., Wei W., Kowalski P.E., Chang A.C.Y., Cohen S.N. Proc. Natl. Acad. Sci. U.S.A. 101:17246-17251(2004) [PubMed: 15569923] [Abstract] Cited for: ROLE IN THE INTERNALIZATION OF ANTHRAX TOXIN.
[4]	"The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner." Raaijmakers J.H., Deneubourg L., Rehmann H., de Koning J., Zhang Z., Krugmann S., Erneux C., Bos J.L. Cell. Signal. 19:1249-1257(2007) [PubMed: 17314030] [Abstract] Cited for: INTERACTION WITH INPPL1.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1444, MASS SPECTROMETRY.
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TRP-471; MET-1085 AND PRO-1428.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ310567 mRNA. Translation: CAC83946.1.
IPI	IPI00103380.
PIR	E59431.
RefSeq	NP_071926.4.
UniGene	Hs.25277
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8WWN8.
PTM databases
PhosphoSite	Q8WWN8.
Proteomic databases
PeptideAtlas	Q8WWN8.
PRIDE	Q8WWN8.
Genome annotation databases
Ensembl	ENST00000239440; ENSP00000239440; ENSG00000120318; Homo sapiens. [Genome view]
GeneID	64411.
KEGG	hsa:64411.
UCSC	uc003llm.1. human.
Organism-specific databases
CTD	64411.
GeneCards	GC05M141013.
H-InvDB	HIX0005258.
HGNC	HGNC:24097. ARAP3.
MIM	606647. gene.
PharmGKB	PA134981095.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8WWN8.
HOVERGEN	Q8WWN8.
OMA	GARQSWA
OrthoDB	EOG9RBT3X
Enzyme and pathway databases
BioCyc	CATTLE:ENSBTAG00000015938-MON.
Pathway_Interaction_DB	pi3kcipathway. Class I PI3K signaling events.
Reactome	REACT_11044. Signaling by Rho GTPases.
Gene expression databases
ArrayExpress	Q8WWN8.
Bgee	Q8WWN8.
CleanEx	HS_ARAP3.
Genevestigator	Q8WWN8.
GermOnline	ENSG00000120318. Homo sapiens.
Family and domain databases
InterPro	IPR001164. ArfGAP. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR000159. Ras-assoc. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP. IPR001660. SAM. IPR011510. SAM_2. IPR010993. SAM_homology. IPR013761. SAM_type. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 3 hits. G3DSA:1.10.555.10. RhoGAP. 1 hit. G3DSA:1.10.150.50. SAM_type. 1 hit.
Pfam	PF01412. ArfGap. 1 hit. PF00169. PH. 3 hits. PF00788. RA. 1 hit. PF00620. RhoGAP. 1 hit. PF07647. SAM_2. 1 hit. [Graphical view]
PRINTS	PR00405. REVINTRACTNG.
SMART	SM00105. ArfGap. 1 hit. SM00233. PH. 5 hits. SM00324. RhoGAP. 1 hit. SM00454. SAM. 1 hit. [Graphical view]
PROSITE	PS50115. ARFGAP. 1 hit. PS50003. PH_DOMAIN. 3 hits. PS50200. RA. 1 hit. PS50238. RHOGAP. 1 hit. PS50105. SAM_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	66374.
SOURCE	Search...

Entry information

Entry name

ARAP3_HUMAN

Accession

Primary (citable) accession number: Q8WWN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	March 1, 2002
Last modified:	November 24, 2009
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.