Q8WWN8 (ARAP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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)

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.
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.4
Subunit structure	Interacts with INPPL1/SHIP2. Ref.1 Ref.5
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. Ref.6
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cytoskeleton organization Traceable author statement Ref.4. 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 small GTPase mediated signal transduction Traceable author statement. Source: Reactome vesicle-mediated transport Traceable author statement Ref.4. Source: UniProtKB
Cellular component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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 Inferred from direct assay Ref.1. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate binding Inferred from direct assay Ref.1. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
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.6

Natural variations

Natural variant

218

1

D → H.
Corresponds to variant rs1031904 [ dbSNP | Ensembl ].

VAR_048330

Natural variant

471

1

R → W in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036180

Natural variant

1085

1

I → M in a breast cancer sample; somatic mutation. Ref.7

VAR_036181

Natural variant

1428

1

T → P in a breast cancer sample; somatic mutation. Ref.7

VAR_036182

Experimental info

Mutagenesis

307 – 308

2

RR → AA: Loss of PtdIns(3,4,5)P3 binding. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

1544

Helix Strand Turn

Details...

Helix

9 – 13

5

Helix

14 – 16

3

Helix

19 – 21

3

Helix

22 – 27

6

Helix

42 – 46

5

Helix

55 – 62

8

Sequences

	Sequence		Length	Mass (Da)
	Q8WWN8 [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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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.
[4]	"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.
[5]	"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.
[6]	"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. Tissue: Cervix carcinoma.
[7]	"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

EMBL
GenBank
DDBJ

AJ310567 mRNA. Translation: CAC83946.1.
CH471062 Genomic DNA. Translation: EAW61904.1.
CH471062 Genomic DNA. Translation: EAW61905.1.

IPI

IPI00103380.

PIR

E59431.

RefSeq

NP_071926.4. NM_022481.5.

UniGene

Hs.726187.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KG5	NMR	-	A	1-80	[»]

ProteinModelPortal

Q8WWN8.

SMR

Q8WWN8. Positions 1-80, 287-390, 396-483, 489-638, 675-786, 801-903, 906-1091, 1223-1322.

ModBase

Search...

Protein-protein interaction databases

STRING

Q8WWN8.

PTM databases

PhosphoSite

Q8WWN8.

Polymorphism databases

DMDM

73619965.

Proteomic databases

PeptideAtlas

Q8WWN8.

PRIDE

Q8WWN8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000239440; ENSP00000239440; ENSG00000120318.

GeneID

64411.

KEGG

hsa:64411.

UCSC

uc003llm.1. human.

Organism-specific databases

CTD

64411.

GeneCards

GC05M141013.

H-InvDB

HIX0005258.

HGNC

HGNC:24097. ARAP3.

HPA

HPA042887.

MIM

606647. gene.

neXtProt

NX_Q8WWN8.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG446850.

HOVERGEN

HBG069114.

InParanoid

Q8WWN8.

OMA

GEFISRK.

PhylomeDB

Q8WWN8.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.

Reactome

REACT_111102. Signal Transduction.

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_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
[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.

KO

K12490.

Pfam

PF01412. ArfGap. 1 hit.
PF00169. PH. 2 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]

SUPFAM

SSF57863. ArfGAP. 1 hit.
SSF48350. Rho_GAP. 1 hit.
SSF47769. SAM_homology. 1 hit.

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

NextBio

66374.

SOURCE

Search...

Entry information

Entry name

ARAP3_HUMAN

Accession

Primary (citable) accession number: Q8WWN8
Secondary accession number(s): D3DQE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	March 1, 2002
Last modified:	January 25, 2012
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.