Q8WZ64 (ARAP2_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 2

Alternative name(s):
Centaurin-delta-1
Short name=Cnt-d1
Protein PARX

Gene names

Name:	ARAP2
Synonyms:	CENTD1, KIAA0580

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1704 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 By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Detected in brain, thymus, lymph node, thyroid, spinal cord, trachea, heart, skeletal muscle, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes. Ref.1
Sequence similarities	Contains 1 Arf-GAP domain. Contains 5 PH domains. Contains 1 Ras-associating domain. Contains 1 Rho-GAP domain. Contains 1 SAM (sterile alpha motif) domain.
Sequence caution	The sequence AAL04166.1 differs from that shown. Reason: Frameshift at position 1579.

Ontologies

Keywords
Cellular component	Cytoplasm
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	positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro phosphatidylinositol-3,4,5-trisphosphate binding Inferred from direct assay PubMed 11804589. 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 – 1704

1704

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2

PRO_0000074212

Regions

Domain

6 – 70

65

SAM

Domain

482 – 574

93

PH 1

Domain

587 – 679

93

PH 2

Domain

676 – 811

136

Arf-GAP

Domain

878 – 1003

126

PH 3

Domain

1014 – 1114

101

PH 4

Domain

1116 – 1297

182

Rho-GAP

Domain

1326 – 1420

95

Ras-associating

Domain

1434 – 1537

104

PH 5

Zinc finger

700 – 723

24

C4-type

Amino acid modifications

Modified residue

77

1

Phosphotyrosine By similarity

Modified residue

473

1

Phosphotyrosine By similarity

Natural variations

Natural variant

384

1

K → N.
Corresponds to variant rs35468501 [ dbSNP | Ensembl ].

VAR_055530

Natural variant

1006

1

F → L.
Corresponds to variant rs35218548 [ dbSNP | Ensembl ].

VAR_055531

Natural variant

1523

1

R → Q. Ref.1 Ref.2 Ref.4
Corresponds to variant rs4833069 [ dbSNP | Ensembl ].

VAR_027952

Experimental info

Sequence conflict

227

1

T → I in AAL32459. Ref.2

Sequence conflict

532

1

I → V in AAL32459. Ref.2

Secondary structure

1

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1704

Helix Strand Turn

Details...

Helix

11 – 16

6

Turn

17 – 19

3

Helix

21 – 23

3

Helix

24 – 30

7

Helix

36 – 40

5

Helix

43 – 49

7

Helix

54 – 70

17

Beta strand

485 – 491

7

Beta strand

494 – 498

5

Beta strand

501 – 507

7

Beta strand

509 – 518

10

Beta strand

526 – 528

3

Turn

529 – 531

3

Beta strand

532 – 538

7

Turn

539 – 541

3

Beta strand

542 – 549

8

Beta strand

552 – 555

4

Helix

559 – 576

18

Sequences

	Sequence		Length	Mass (Da)
	Q8WZ64 [UniParc]. Last modified October 5, 2010. Version 3. Checksum: A5A13EE08D43A9A0	FASTA	1,704	193,452
	10 20 30 40 50 60 MSSVSEVNVD IKDFLMSINL EQYLLHFHES GFTTVKDCAA INDSLLQKIG ISPTGHRRRI 70 80 90 100 110 120 LKQLQIILSK MQDIPIYANV HKTKKNDDPS KDYHVPSSDQ NICIELSNSG SVQTSSPPQL 130 140 150 160 170 180 ETVRKNLEDS DASVERSQYP QSDDKLSPPK RDFPTAEEPH LNLGSLNDSL FGSDNIKIES 190 200 210 220 230 240 LITKKTVDHT VEEQQTEKVK LITENLSKLP NADSECLSFV GCSTSGTNSG NGTNGLLEGS 250 260 270 280 290 300 PPSPFFKFQG EMIVNDLYVP SSPILAPVRS RSKLVSRPSR SFLLRHRPVP EIPGSTKGVS 310 320 330 340 350 360 GSYFRERRNV ATSTEKSVAW QNSNEENSSS IFPYGETFLF QRLENSKKRS IKNEFLTQGE 370 380 390 400 410 420 ALKGEAATAT NSFIIKSSIY DNRKEKISED KVEDIWIPRE DKNNFLIDTA SESEYSTVEE 430 440 450 460 470 480 CFQSLRRKNS KASKSRTQKA LILDSVNRHS YPLSSTSGNA DSSAVSSQAI SPYACFYGAS 490 500 510 520 530 540 AKKVKSGWLD KLSPQGKRMF QKRWVKFDGL SISYYNNEKE MYSKGIIPLS AISTVRVQGD 550 560 570 580 590 600 NKFEVVTTQR TFVFRVEKEE ERNDWISILL NALKSQSLTS QSQAVVTPEK CGYLELRGYK 610 620 630 640 650 660 AKIFTVLSGN SVWLCKNEQD FKSGLGITII PMNVANVKQV DRTVKQSFEI ITPYRSFSFT 670 680 690 700 710 720 AETEKEKQDW IEAVQQSIAE TLSDYEVAEK IWFNESNRSC ADCKAPDPDW ASINLCVVIC 730 740 750 760 770 780 KKCAGQHRSL GPKDSKVRSL KMDASIWSNE LIELFIVIGN KRANDFWAGN LQKDEELHMD 790 800 810 820 830 840 SPVEKRKNFI TQKYKEGKFR KTLLASLTKE ELNKALCAAV VKPDVLETMA LLFSGADVMC 850 860 870 880 890 900 ATGDPVHSTP YLLAKKAGQS LQMEFLYHNK FSDFPQHDIH SEGVLSQESS QSTFLCDFLY 910 920 930 940 950 960 QAPSAASKLS SEKKLLEETN KKWCVLEGGF LSYYENDKST TPNGTININE VICLAIHKED 970 980 990 1000 1010 1020 FYLNTGPIFI FEIYLPSERV FLFGAETSQA QRKWTEAIAK HFVPLFAENL TEADYDLIGQ 1030 1040 1050 1060 1070 1080 LFYKDCHALD QWRKGWFAMD KSSLHFCLQM QEVQGDRMHL RRLQELTIST MVQNGEKLDV 1090 1100 1110 1120 1130 1140 LLLVEKGRTL YIHGHTKLDF TVWHTAIEKA AGTDGNALQD QQLSKNDVPI IVNSCIAFVT 1150 1160 1170 1180 1190 1200 QYGLGCKYIY QKNGDPLHIS ELLESFKKDA RSFKLRAGKH QLEDVTAVLK SFLSDIDDAL 1210 1220 1230 1240 1250 1260 LTKELYPYWI SALDTQDDKE RIKKYGAFIR SLPGVNRATL AAIIEHLYRV QKCSEINHMN 1270 1280 1290 1300 1310 1320 AHNLALVFSS CLFQTKGQTS EEVNVIEDLI NNYVEIFEVK EDQVKQMDIE NSFITKWKDT 1330 1340 1350 1360 1370 1380 QVSQAGDLLI EVYVERKEPD CSIIIRISPV MEAEELTNDI LAIKNIIPTK GDIWATFEVI 1390 1400 1410 1420 1430 1440 ENEELERPLH YKENVLEQVL RWSSLAEPGS AYLVVKRFLT ADTIKHCSDR STLGSIKEGI 1450 1460 1470 1480 1490 1500 LKIKEEPSKI LSGNKFQDRY FVLRDGFLFL YKDVKSSKHD KMFSLSSMKF YRGVKKKMKP 1510 1520 1530 1540 1550 1560 PTSWGLTAYS EKHHWHLCCD SSRTQTEWMT SIFIAQHEYD IWPPAGKERK RSITKNPKIG 1570 1580 1590 1600 1610 1620 GLPLIPIQHE GNATLARKNI ESARAELERL RLSEKCDKES VDSSLKERAS MVAHCLEHKD 1630 1640 1650 1660 1670 1680 DKLRNRPRKH RSFNCLEDTE PEAPLGQPKG HKGLKTLRKT EDRNSKATLD SDHKLPSRVI 1690 1700 EELNVVLQRS RTLPKELQDE QILK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ARAP1: a point of convergence for Arf and Rho signaling." Miura K., Jacques K.M., Stauffer S., Kubosaki A., Zhu K., Hirsch D.S., Resau J., Zheng Y., Randazzo P.A. Mol. Cell 9:109-119(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT GLN-1523.
[2]	Wong J.A., Chen Z., Marignani P.A., Yu M., Zhao Y., Vallis K.A. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-1523.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 74-1704, VARIANT GLN-1523. Tissue: Brain.
[5]	Ohara O., Nagase T., Ishikawa K. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[6]	"KIAA0580 as a member (centaurin delta1) of ArfGAP-domain centaurin family." Hong W. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 742-1605.
[7]	"Solution structure of the N-terminal PH domain and of the SAM domain of human ARAP2." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-78 AND 483-584.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY049733 mRNA. Translation: AAL12170.1.
AF439781 mRNA. Translation: AAL32459.1.
AC098827 Genomic DNA. No translation available.
AC104078 Genomic DNA. No translation available.
AC108033 Genomic DNA. Translation: AAY40927.1.
AC109818 Genomic DNA. No translation available.
AC116623 Genomic DNA. No translation available.
AB011152 mRNA. Translation: BAA25506.2.
AF411982 mRNA. Translation: AAL04166.1. Frameshift.

IPI

IPI00292471.

PIR

T00342.

RefSeq

NP_056045.2. NM_015230.3.

UniGene

Hs.479451.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X40	NMR	-	A	1-78	[»]
2COD	NMR	-	A	483-584	[»]

ProteinModelPortal

Q8WZ64.

SMR

Q8WZ64. Positions 6-79, 488-584, 588-679, 687-916, 1128-1289.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8WZ64. 2 interactions.

STRING

9606.ENSP00000302895.

PTM databases

PhosphoSite

Q8WZ64.

Polymorphism databases

DMDM

308153629.

Proteomic databases

PaxDb

Q8WZ64.

PRIDE

Q8WZ64.

Protocols and materials databases

DNASU

116984.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000303965; ENSP00000302895; ENSG00000047365.

GeneID

116984.

KEGG

hsa:116984.

UCSC

uc003gsq.2. human.

Organism-specific databases

CTD

116984.

GeneCards

GC04M036067.

H-InvDB

HIX0004149.

HGNC

HGNC:16924. ARAP2.

HPA

HPA035925.

MIM

606645. gene.

neXtProt

NX_Q8WZ64.

PharmGKB

PA164715938.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5347.

HOGENOM

HOG000246988.

HOVERGEN

HBG095947.

InParanoid

Q8WZ64.

KO

K12490.

OMA

EQDFKSG.

OrthoDB

EOG4C2H8M.

PhylomeDB

Q8WZ64.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6cyclingpathway. Arf6 signaling events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q8WZ64.

Bgee

Q8WZ64.

CleanEx

HS_ARAP2.

Genevestigator

Q8WZ64.

GermOnline

ENSG00000047365. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
1.10.555.10. 1 hit.
2.30.29.30. 4 hits.

InterPro

IPR001164. ArfGAP.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000159. Ras-assoc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
[Graphical view]

Pfam

PF01412. ArfGap. 1 hit.
PF00169. PH. 4 hits.
PF00788. RA. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00536. SAM_1. 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

SSF48350. Rho_GAP. 1 hit.
SSF47769. SAM_homology. 1 hit.

PROSITE

PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 4 hits.
PS50200. RA. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8WZ64.

GenomeRNAi

116984.

NextBio

80056.

SOURCE

Search...

Entry information

Entry name

ARAP2_HUMAN

Accession

Primary (citable) accession number: Q8WZ64
Secondary accession number(s): Q4W5D2 , Q7Z2L5, Q96L70, Q96P49, Q9Y4E4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 106 of the entry and version 3 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.