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Q8WWN8 (ARAP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1544 AA.
Sequence statusComplete.
Protein existenceEvidence 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 (via SAM domain) with INPPL1/SHIP2. Ref.1 Ref.5 Ref.9

Subcellular location

Cytoplasm By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane; Peripheral membrane protein By similarity. Cell projectionlamellipodium By similarity. Cell projectionruffle 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 componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionGTPase activation
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcytoskeleton organization

Traceable author statement Ref.4. Source: UniProtKB

negative regulation of Rac protein signal transduction

Inferred from electronic annotation. Source: Ensembl

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

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

vesicle-mediated transport

Traceable author statement Ref.4. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

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_functionARF 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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SH3KBP1Q96B972EBI-4402732,EBI-346595

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15441544Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
PRO_0000074215

Regions

Domain4 – 6865SAM
Domain287 – 37993PH 1
Domain394 – 48390PH 2
Domain480 – 611132Arf-GAP
Domain907 – 1088182Rho-GAP
Domain1117 – 121094Ras-associating
Domain1223 – 1325103PH 3
Zinc finger504 – 52724C4-type
Compositional bias81 – 13959Pro-rich
Compositional bias1462 – 154281Pro-rich

Amino acid modifications

Modified residue14031Phosphotyrosine By similarity
Modified residue14081Phosphotyrosine By similarity
Modified residue14441Phosphoserine Ref.6 Ref.7
Modified residue14801Phosphoserine Ref.7

Natural variations

Natural variant2181D → H.
Corresponds to variant rs1031904 [ dbSNP | Ensembl ].
VAR_048330
Natural variant4711R → W in a colorectal cancer sample; somatic mutation. Ref.10
VAR_036180
Natural variant10851I → M in a breast cancer sample; somatic mutation. Ref.10
VAR_036181
Natural variant14281T → P in a breast cancer sample; somatic mutation. Ref.10
VAR_036182

Experimental info

Mutagenesis307 – 3082RR → AA: Loss of PtdIns(3,4,5)P3 binding. Ref.1

Secondary structure

.............. 1544
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8WWN8 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 40C03A22591B2B6F

FASTA1,544169,844
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1444, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1444 AND SER-1480, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam."
Leone M., Cellitti J., Pellecchia M.
BMC Struct. Biol. 9:59-59(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-80, INTERACTION WITH INPPL1.
[10]"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. expand/collapse author list , 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] [Europe PMC] [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.
PIRE59431.
RefSeqNP_071926.4. NM_022481.5.
UniGeneHs.726187.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KG5NMR-A1-80[»]
2LNWNMR-B1404-1412[»]
ProteinModelPortalQ8WWN8.
SMRQ8WWN8. Positions 1-80, 293-392, 394-482, 489-653, 675-786, 906-1080, 1224-1323.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122163. 3 interactions.
IntActQ8WWN8. 1 interaction.
MINTMINT-8098880.
STRING9606.ENSP00000239440.

PTM databases

PhosphoSiteQ8WWN8.

Polymorphism databases

DMDM73619965.

Proteomic databases

PaxDbQ8WWN8.
PeptideAtlasQ8WWN8.
PRIDEQ8WWN8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000239440; ENSP00000239440; ENSG00000120318.
GeneID64411.
KEGGhsa:64411.
UCSCuc003llm.3. human.

Organism-specific databases

CTD64411.
GeneCardsGC05M141032.
HGNCHGNC:24097. ARAP3.
HPAHPA042887.
MIM606647. gene.
neXtProtNX_Q8WWN8.
PharmGKBPA164715983.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5347.
HOGENOMHOG000246988.
HOVERGENHBG069114.
InParanoidQ8WWN8.
KOK12490.
OMATQLLCVE.
PhylomeDBQ8WWN8.
TreeFamTF105769.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ8WWN8.
BgeeQ8WWN8.
CleanExHS_ARAP3.
GenevestigatorQ8WWN8.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
1.10.555.10. 1 hit.
2.30.29.30. 3 hits.
InterProIPR001164. ArfGAP.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000159. Ras-assoc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
[Graphical view]
PfamPF01412. ArfGap. 1 hit.
PF00169. PH. 2 hits.
PF00788. RA. 1 hit.
PF00620. RhoGAP. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
PRINTSPR00405. REVINTRACTNG.
SMARTSM00105. ArfGap. 1 hit.
SM00233. PH. 5 hits.
SM00324. RhoGAP. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF48350. SSF48350. 1 hit.
PROSITEPS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 3 hits.
PS50200. RA. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSARAP3. human.
EvolutionaryTraceQ8WWN8.
GeneWikiCENTD3.
GenomeRNAi64411.
NextBio66374.
PROQ8WWN8.
SOURCESearch...

Entry information

Entry nameARAP3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM