ARAP2_HUMAN
ID ARAP2_HUMAN Reviewed; 1704 AA.
AC Q8WZ64; Q4W5D2; Q7Z2L5; Q96L70; Q96P49; Q9Y4E4;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2;
DE AltName: Full=Centaurin-delta-1;
DE Short=Cnt-d1;
DE AltName: Full=Protein PARX;
GN Name=ARAP2; Synonyms=CENTD1, KIAA0580;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT GLN-1523.
RX PubMed=11804590; DOI=10.1016/s1097-2765(02)00428-8;
RA Miura K., Jacques K.M., Stauffer S., Kubosaki A., Zhu K., Hirsch D.S.,
RA Resau J., Zheng Y., Randazzo P.A.;
RT "ARAP1: a point of convergence for Arf and Rho signaling.";
RL Mol. Cell 9:109-119(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-1523.
RA Wong J.A., Chen Z., Marignani P.A., Yu M., Zhao Y., Vallis K.A.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 74-1704, AND VARIANT GLN-1523.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [5]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Ishikawa K.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 742-1605.
RA Hong W.;
RT "KIAA0580 as a member (centaurin delta1) of ArfGAP-domain centaurin
RT family.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP STRUCTURE BY NMR OF 1-78 AND 483-584.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the N-terminal PH domain and of the SAM domain of
RT human ARAP2.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-
CC activating protein that modulates actin cytoskeleton remodeling by
CC regulating ARF and RHO family members. Is activated by
CC phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can
CC be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2)
CC binding, albeit with lower efficiency (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in brain, thymus, lymph node, thyroid,
CC spinal cord, trachea, heart, skeletal muscle, spleen, kidney, liver,
CC placenta, lung and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:11804590}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL04166.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY049733; AAL12170.1; -; mRNA.
DR EMBL; AF439781; AAL32459.1; -; mRNA.
DR EMBL; AC098827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108033; AAY40927.1; -; Genomic_DNA.
DR EMBL; AC109818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB011152; BAA25506.2; -; mRNA.
DR EMBL; AF411982; AAL04166.1; ALT_FRAME; mRNA.
DR CCDS; CCDS3441.1; -.
DR PIR; T00342; T00342.
DR RefSeq; NP_056045.2; NM_015230.3.
DR RefSeq; XP_016863188.1; XM_017007699.1.
DR PDB; 1X40; NMR; -; A=1-78.
DR PDB; 2COD; NMR; -; A=483-584.
DR PDBsum; 1X40; -.
DR PDBsum; 2COD; -.
DR AlphaFoldDB; Q8WZ64; -.
DR BMRB; Q8WZ64; -.
DR SMR; Q8WZ64; -.
DR BioGRID; 125547; 21.
DR IntAct; Q8WZ64; 10.
DR MINT; Q8WZ64; -.
DR STRING; 9606.ENSP00000302895; -.
DR iPTMnet; Q8WZ64; -.
DR PhosphoSitePlus; Q8WZ64; -.
DR BioMuta; ARAP2; -.
DR DMDM; 308153629; -.
DR EPD; Q8WZ64; -.
DR jPOST; Q8WZ64; -.
DR MassIVE; Q8WZ64; -.
DR MaxQB; Q8WZ64; -.
DR PaxDb; Q8WZ64; -.
DR PeptideAtlas; Q8WZ64; -.
DR PRIDE; Q8WZ64; -.
DR ProteomicsDB; 75223; -.
DR Antibodypedia; 23290; 100 antibodies from 19 providers.
DR DNASU; 116984; -.
DR Ensembl; ENST00000303965.9; ENSP00000302895.4; ENSG00000047365.13.
DR GeneID; 116984; -.
DR KEGG; hsa:116984; -.
DR MANE-Select; ENST00000303965.9; ENSP00000302895.4; NM_015230.4; NP_056045.2.
DR UCSC; uc003gsq.3; human.
DR CTD; 116984; -.
DR DisGeNET; 116984; -.
DR GeneCards; ARAP2; -.
DR HGNC; HGNC:16924; ARAP2.
DR HPA; ENSG00000047365; Tissue enhanced (bone marrow, brain).
DR MIM; 606645; gene.
DR neXtProt; NX_Q8WZ64; -.
DR OpenTargets; ENSG00000047365; -.
DR PharmGKB; PA164715938; -.
DR VEuPathDB; HostDB:ENSG00000047365; -.
DR eggNOG; KOG1117; Eukaryota.
DR GeneTree; ENSGT00940000160197; -.
DR HOGENOM; CLU_002900_1_0_1; -.
DR InParanoid; Q8WZ64; -.
DR OMA; VTDIIRM; -.
DR OrthoDB; 98944at2759; -.
DR PhylomeDB; Q8WZ64; -.
DR TreeFam; TF105769; -.
DR PathwayCommons; Q8WZ64; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q8WZ64; -.
DR SIGNOR; Q8WZ64; -.
DR BioGRID-ORCS; 116984; 14 hits in 1066 CRISPR screens.
DR ChiTaRS; ARAP2; human.
DR EvolutionaryTrace; Q8WZ64; -.
DR GeneWiki; CENTD1; -.
DR GenomeRNAi; 116984; -.
DR Pharos; Q8WZ64; Tbio.
DR PRO; PR:Q8WZ64; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8WZ64; protein.
DR Bgee; ENSG00000047365; Expressed in endothelial cell and 188 other tissues.
DR ExpressionAtlas; Q8WZ64; baseline and differential.
DR Genevisible; Q8WZ64; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd04385; RhoGAP_ARAP; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 2.30.29.30; -; 4.
DR InterPro; IPR037278; ARFGAP/RecO.
DR InterPro; IPR001164; ArfGAP_dom.
DR InterPro; IPR038508; ArfGAP_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR037858; RhoGAP_ARAP.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF00169; PH; 4.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00233; PH; 5.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50115; ARFGAP; 1.
DR PROSITE; PS50003; PH_DOMAIN; 4.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; GTPase activation; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..1704
FT /note="Arf-GAP with Rho-GAP domain, ANK repeat and PH
FT domain-containing protein 2"
FT /id="PRO_0000074212"
FT DOMAIN 6..70
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 482..574
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 587..679
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 676..811
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT DOMAIN 878..1003
FT /note="PH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1014..1114
FT /note="PH 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1116..1297
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 1326..1420
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 1434..1537
FT /note="PH 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 700..723
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REGION 126..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1636..1675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1654..1675
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 77
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZ05"
FT MOD_RES 1632
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZ05"
FT VARIANT 384
FT /note="K -> N (in dbSNP:rs35468501)"
FT /id="VAR_055530"
FT VARIANT 1006
FT /note="F -> L (in dbSNP:rs35218548)"
FT /id="VAR_055531"
FT VARIANT 1523
FT /note="R -> Q (in dbSNP:rs4833069)"
FT /evidence="ECO:0000269|PubMed:11804590,
FT ECO:0000269|PubMed:9628581, ECO:0000269|Ref.2"
FT /id="VAR_027952"
FT CONFLICT 227
FT /note="T -> I (in Ref. 2; AAL32459)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="I -> V (in Ref. 2; AAL32459)"
FT /evidence="ECO:0000305"
FT HELIX 11..16
FT /evidence="ECO:0007829|PDB:1X40"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:1X40"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:1X40"
FT HELIX 24..30
FT /evidence="ECO:0007829|PDB:1X40"
FT HELIX 36..40
FT /evidence="ECO:0007829|PDB:1X40"
FT HELIX 43..49
FT /evidence="ECO:0007829|PDB:1X40"
FT HELIX 54..70
FT /evidence="ECO:0007829|PDB:1X40"
FT STRAND 485..491
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 501..507
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 509..518
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:2COD"
FT TURN 529..531
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 532..538
FT /evidence="ECO:0007829|PDB:2COD"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 542..549
FT /evidence="ECO:0007829|PDB:2COD"
FT STRAND 552..555
FT /evidence="ECO:0007829|PDB:2COD"
FT HELIX 559..576
FT /evidence="ECO:0007829|PDB:2COD"
SQ SEQUENCE 1704 AA; 193452 MW; A5A13EE08D43A9A0 CRC64;
MSSVSEVNVD IKDFLMSINL EQYLLHFHES GFTTVKDCAA INDSLLQKIG ISPTGHRRRI
LKQLQIILSK MQDIPIYANV HKTKKNDDPS KDYHVPSSDQ NICIELSNSG SVQTSSPPQL
ETVRKNLEDS DASVERSQYP QSDDKLSPPK RDFPTAEEPH LNLGSLNDSL FGSDNIKIES
LITKKTVDHT VEEQQTEKVK LITENLSKLP NADSECLSFV GCSTSGTNSG NGTNGLLEGS
PPSPFFKFQG EMIVNDLYVP SSPILAPVRS RSKLVSRPSR SFLLRHRPVP EIPGSTKGVS
GSYFRERRNV ATSTEKSVAW QNSNEENSSS IFPYGETFLF QRLENSKKRS IKNEFLTQGE
ALKGEAATAT NSFIIKSSIY DNRKEKISED KVEDIWIPRE DKNNFLIDTA SESEYSTVEE
CFQSLRRKNS KASKSRTQKA LILDSVNRHS YPLSSTSGNA DSSAVSSQAI SPYACFYGAS
AKKVKSGWLD KLSPQGKRMF QKRWVKFDGL SISYYNNEKE MYSKGIIPLS AISTVRVQGD
NKFEVVTTQR TFVFRVEKEE ERNDWISILL NALKSQSLTS QSQAVVTPEK CGYLELRGYK
AKIFTVLSGN SVWLCKNEQD FKSGLGITII PMNVANVKQV DRTVKQSFEI ITPYRSFSFT
AETEKEKQDW IEAVQQSIAE TLSDYEVAEK IWFNESNRSC ADCKAPDPDW ASINLCVVIC
KKCAGQHRSL GPKDSKVRSL KMDASIWSNE LIELFIVIGN KRANDFWAGN LQKDEELHMD
SPVEKRKNFI TQKYKEGKFR KTLLASLTKE ELNKALCAAV VKPDVLETMA LLFSGADVMC
ATGDPVHSTP YLLAKKAGQS LQMEFLYHNK FSDFPQHDIH SEGVLSQESS QSTFLCDFLY
QAPSAASKLS SEKKLLEETN KKWCVLEGGF LSYYENDKST TPNGTININE VICLAIHKED
FYLNTGPIFI FEIYLPSERV FLFGAETSQA QRKWTEAIAK HFVPLFAENL TEADYDLIGQ
LFYKDCHALD QWRKGWFAMD KSSLHFCLQM QEVQGDRMHL RRLQELTIST MVQNGEKLDV
LLLVEKGRTL YIHGHTKLDF TVWHTAIEKA AGTDGNALQD QQLSKNDVPI IVNSCIAFVT
QYGLGCKYIY QKNGDPLHIS ELLESFKKDA RSFKLRAGKH QLEDVTAVLK SFLSDIDDAL
LTKELYPYWI SALDTQDDKE RIKKYGAFIR SLPGVNRATL AAIIEHLYRV QKCSEINHMN
AHNLALVFSS CLFQTKGQTS EEVNVIEDLI NNYVEIFEVK EDQVKQMDIE NSFITKWKDT
QVSQAGDLLI EVYVERKEPD CSIIIRISPV MEAEELTNDI LAIKNIIPTK GDIWATFEVI
ENEELERPLH YKENVLEQVL RWSSLAEPGS AYLVVKRFLT ADTIKHCSDR STLGSIKEGI
LKIKEEPSKI LSGNKFQDRY FVLRDGFLFL YKDVKSSKHD KMFSLSSMKF YRGVKKKMKP
PTSWGLTAYS EKHHWHLCCD SSRTQTEWMT SIFIAQHEYD IWPPAGKERK RSITKNPKIG
GLPLIPIQHE GNATLARKNI ESARAELERL RLSEKCDKES VDSSLKERAS MVAHCLEHKD
DKLRNRPRKH RSFNCLEDTE PEAPLGQPKG HKGLKTLRKT EDRNSKATLD SDHKLPSRVI
EELNVVLQRS RTLPKELQDE QILK
