ARAP3_MOUSE
ID ARAP3_MOUSE Reviewed; 1538 AA.
AC Q8R5G7; E9QMK7; Q5DTN4; Q6NVF1; Q8R5G6;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3;
DE AltName: Full=Centaurin-delta-3;
DE Short=Cnt-d3;
DE AltName: Full=Dual specificity Rho- and Arf-GTPase-activating protein 1;
GN Name=Arap3; Synonyms=Centd3, Drag1, Kiaa4097;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, MUTAGENESIS OF
RP ARG-938; TYR-1399 AND TYR-1404, PHOSPHORYLATION AT TYR-1399 AND TYR-1404,
RP AND SUBCELLULAR LOCATION.
RC STRAIN=NIH Swiss; TISSUE=Embryo;
RX PubMed=15546919; DOI=10.1242/jcs.01526;
RA Stacey T.T.I., Nie Z., Stewart A., Najdovska M., Hall N.E., He H.,
RA Randazzo P.A., Lock P.;
RT "ARAP3 is transiently tyrosine phosphorylated in cells attaching to
RT fibronectin and inhibits cell spreading in a RhoGAP-dependent manner.";
RL J. Cell Sci. 117:6071-6084(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 619-1538 (ISOFORM 3).
RC TISSUE=Brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1404, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1344, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Acts preferentially on ARF5 and
CC on RHOA. {ECO:0000269|PubMed:15546919}.
CC -!- SUBUNIT: Interacts (via SAM domain) with INPPL1/SHIP2. {ECO:0000250}.
CC -!- INTERACTION:
CC Q8R5G7; P07948: LYN; Xeno; NbExp=2; IntAct=EBI-621463, EBI-79452;
CC Q8R5G7; P12931: SRC; Xeno; NbExp=3; IntAct=EBI-621463, EBI-621482;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15546919}. Cell
CC membrane {ECO:0000269|PubMed:15546919}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15546919}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15546919}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:15546919}. Cell projection, ruffle
CC {ECO:0000269|PubMed:15546919}. Note=Cytoplasmic, and associated with F-
CC actin-rich membrane ruffles and lamellipodia.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8R5G7-1; Sequence=Displayed;
CC Name=2; Synonyms=ARAP3 delta-SAM;
CC IsoId=Q8R5G7-2; Sequence=VSP_015003;
CC Name=3;
CC IsoId=Q8R5G7-3; Sequence=VSP_015002, VSP_015004;
CC -!- PTM: Tyrosine phosphorylated at a low basal level. PDGF treatment
CC stimulates phosphorylation. Tyrosine phosphorylation is increased in
CC cells that are in the process of becoming attached to a substrate and
CC that start spreading and flattening. {ECO:0000269|PubMed:15546919}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL78678.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD90507.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF469621; AAL78677.1; -; mRNA.
DR EMBL; AF469622; AAL78678.1; ALT_INIT; mRNA.
DR EMBL; AC121886; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC129315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC068145; AAH68145.1; -; mRNA.
DR EMBL; AK220486; BAD90507.1; ALT_INIT; mRNA.
DR CCDS; CCDS29196.1; -. [Q8R5G7-1]
DR CCDS; CCDS89225.1; -. [Q8R5G7-2]
DR RefSeq; NP_001192265.1; NM_001205336.1. [Q8R5G7-2]
DR RefSeq; NP_631945.2; NM_139206.2. [Q8R5G7-1]
DR RefSeq; XP_006525552.1; XM_006525489.1. [Q8R5G7-1]
DR AlphaFoldDB; Q8R5G7; -.
DR SMR; Q8R5G7; -.
DR BioGRID; 223164; 6.
DR IntAct; Q8R5G7; 5.
DR STRING; 10090.ENSMUSP00000035662; -.
DR iPTMnet; Q8R5G7; -.
DR PhosphoSitePlus; Q8R5G7; -.
DR MaxQB; Q8R5G7; -.
DR PaxDb; Q8R5G7; -.
DR PRIDE; Q8R5G7; -.
DR ProteomicsDB; 296280; -. [Q8R5G7-1]
DR ProteomicsDB; 296281; -. [Q8R5G7-2]
DR ProteomicsDB; 296282; -. [Q8R5G7-3]
DR Antibodypedia; 27363; 118 antibodies from 30 providers.
DR DNASU; 106952; -.
DR Ensembl; ENSMUST00000042944; ENSMUSP00000035662; ENSMUSG00000024451. [Q8R5G7-1]
DR Ensembl; ENSMUST00000237272; ENSMUSP00000157868; ENSMUSG00000024451. [Q8R5G7-2]
DR GeneID; 106952; -.
DR KEGG; mmu:106952; -.
DR UCSC; uc008erq.2; mouse. [Q8R5G7-1]
DR CTD; 64411; -.
DR MGI; MGI:2147274; Arap3.
DR VEuPathDB; HostDB:ENSMUSG00000024451; -.
DR eggNOG; KOG1117; Eukaryota.
DR GeneTree; ENSGT00940000158869; -.
DR HOGENOM; CLU_002900_1_0_1; -.
DR InParanoid; Q8R5G7; -.
DR OMA; CETVFQS; -.
DR OrthoDB; 98944at2759; -.
DR PhylomeDB; Q8R5G7; -.
DR TreeFam; TF105769; -.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 106952; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Arap3; mouse.
DR PRO; PR:Q8R5G7; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8R5G7; protein.
DR Bgee; ENSMUSG00000024451; Expressed in granulocyte and 131 other tissues.
DR ExpressionAtlas; Q8R5G7; baseline and differential.
DR Genevisible; Q8R5G7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IDA:MGI.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:MGI.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:MGI.
DR GO; GO:0035021; P:negative regulation of Rac protein signal transduction; IBA:GO_Central.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
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; -; 3.
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 InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF07647; SAM_2; 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; SSF54236; SSF54236; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50115; ARFGAP; 1.
DR PROSITE; PS50003; PH_DOMAIN; 3.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; GTPase activation; Membrane; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1538
FT /note="Arf-GAP with Rho-GAP domain, ANK repeat and PH
FT domain-containing protein 3"
FT /id="PRO_0000074216"
FT DOMAIN 4..68
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 282..374
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 389..478
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 479..606
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT DOMAIN 671..785
FT /note="PH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 795..901
FT /note="PH 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 903..1084
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 1113..1206
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 1219..1321
FT /note="PH 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 72..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 125..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1425..1538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 220..241
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1425..1443
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1467..1481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1508..1538
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1344
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1399
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15546919"
FT MOD_RES 1404
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15546919,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 1438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WWN8"
FT MOD_RES 1474
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WWN8"
FT VAR_SEQ 1..618
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_015002"
FT VAR_SEQ 1..78
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15546919"
FT /id="VSP_015003"
FT VAR_SEQ 1446..1538
FT /note="KASMLGHEERIPDPPPGPPSKSSSQARGSLEEQLLQELNNLILRKGEPASCP
FT ESSSQPTSPQAPSPTSLPTPTPSLPTQPPCTSNPPSSQPLT -> GPSPFVCTMKSLKE
FT GEG (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_015004"
FT MUTAGEN 938
FT /note="R->L: Loss of Rho GAP activity. Enhances cell
FT spreading."
FT /evidence="ECO:0000269|PubMed:15546919"
FT MUTAGEN 1399
FT /note="Y->F: Strongly reduces phosphorylation by CSK; when
FT associated with F-1404."
FT /evidence="ECO:0000269|PubMed:15546919"
FT MUTAGEN 1404
FT /note="Y->F: Strongly reduces phosphorylation by CSK; when
FT associated with F-1399."
FT /evidence="ECO:0000269|PubMed:15546919"
FT CONFLICT 144
FT /note="Q -> H (in Ref. 3; AAH68145)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="R -> Q (in Ref. 1; AAL78677/AAL78678)"
FT /evidence="ECO:0000305"
FT CONFLICT 1304
FT /note="M -> T (in Ref. 1; AAL78677/AAL78678)"
FT /evidence="ECO:0000305"
FT CONFLICT 1500
FT /note="S -> P (in Ref. 1; AAL78677/AAL78678)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1538 AA; 169741 MW; D7E55C57FD4B83ED CRC64;
MAAPQDLDIA VWLALVHLEQ YADTFRRHGL ATAGAAQHLG HEELRHLGIS ATGHRKRILR
LLRAGSAEGF LDSHLDNTME PTPSPAPDAQ PPKPVPKPRT VFGLSNPATA QRPGLSPIFW
DPEVSRNSEC TQRSSPLLPS SSEQPSVPNT MEMMPNAIYF GLDLRGRAQA AQDVTPDSSQ
ATVPTPAFRP TTGTVHIMDP GCLYYGVQPV GIPGASDRRD GRGVCQERAE HRQDLETRED
AGYASLELPG DSILSLPTQD AETSDDLISP YASFSSTADR PVPLLSGWLD KLSPQGNYVF
QRRFVQFNGR SLMYFGSDKD PFPKGVIPLT AIEMTRSSKD NKFQVITGQR VFVFRTESEA
QRDLWCSTLQ SCLKEQRLLG HPRPPHPPRP LRTGTLELRG HKAKVFAALI PGELALYKSE
QAFSLGIGIC FIELQGCSVR ETKSRSFDLL TPHRCFSFTA ESGGARQSWA AALQEAVTET
LSDYEVAEKV WSNPANRHCA DCRASRPDWA AVNLGVVICK QCAGQHRALG SGISKVQSLK
LDTSVWSNEI VQLFIVLGND RANCFWAGAL PPGEGLHPDS APGPRGEFIS RKYKLGLFRK
PHPRHPDHSQ LLQALCAAMA GPNLLKNMAQ LLCVETSEGE EPLSPSALNG SLLSLLPSDS
PGVYNEVVVP ATYRGFLYCG SISNKAGAPP LRRGRDAPPR LWCVLGAALE MFASESSPEP
LSLLQPQDIV CLGVSPPPAD PGDLDRFPFS FELILTGGRI QHFATDGADS LEAWISAVGK
WFSPLSCHQL LGPGLLRMGR LWLRSPSHAG LAPGLWLSGF GLLRGDHLFL CPAPGPGPPA
PEDMVHLRRL QEISVVSAAD TPDKKEHLVL VETGRTLYLQ GEGRLDFAAW NTAIGGAAGG
GGTGLQEQQM SRGDIPIIVD ACISFVTQHG LRLEGVYRKG GARARSLRLL AEFRRDARSV
KLRPREHFVE DVTDTLKRFF RELDDPVTSA RLLPRWREAA ELSQKNQRLE KYKEVISCLP
RVNRRTLATL IGHLYRVQKC ASLNQMCTRN LALLFAPSVF QTDGRGEHEV RVLQELIDGY
ISVFDIDSDQ AAQIDLEVSL ITTWKDVQLS QAGDLIMEVY IEQQLPDNCV TLKVSPTLTA
EELTNQVLEM RGAASGTDLW VTFEILEHGE LERPLHPKEK VLEQALQWCQ LPEPCSASLL
LRKVSMAHAG CLFTGVRRES PRVGLLRCRE EPPRLLGNRF QERFFLVRGR CLLLLKEKKS
SKPEREWSLE GAKVYLGIRK KLKPPTLWGF TLILEKMHLC LSCMDEEEMW DWTTSILKAQ
HDDQQSVVLR RRSSSDLARQ KFGTMPLLPI RGDDSGATLL SANQTLRRLH NRRTLSMFFP
MKSPQGSVEE QDELEEPVYE EPVYEEVGAF PELTKDTTFS STWEWSAKSD PSLTSQRSFD
QPPLSKASML GHEERIPDPP PGPPSKSSSQ ARGSLEEQLL QELNNLILRK GEPASCPESS
SQPTSPQAPS PTSLPTPTPS LPTQPPCTSN PPSSQPLT
