ASAP2_MOUSE
ID ASAP2_MOUSE Reviewed; 958 AA.
AC Q7SIG6; Q501K1; Q66JN2;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2;
DE AltName: Full=Development and differentiation-enhancing factor 2;
DE AltName: Full=Paxillin-associated protein with ARF GAP activity 3;
DE Short=PAG3;
DE AltName: Full=Pyk2 C-terminus-associated protein;
DE Short=PAP;
GN Name=Asap2; Synonyms=Ddef2, Gm1523, Gm592;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [2]
RP PROTEIN SEQUENCE OF 425-432, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [3]
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH PTK2B AND SRC, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10022920; DOI=10.1128/mcb.19.3.2338;
RA Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A.,
RA Schlessinger J.;
RT "Identification of a new Pyk2 target protein with Arf-GAP activity.";
RL Mol. Cell. Biol. 19:2338-2350(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARF6 AND ACTIN
RP FILAMENTS.
RX PubMed=11304556; DOI=10.1084/jem.193.8.955;
RA Uchida H., Kondo A., Yoshimura Y., Mazaki Y., Sabe H.;
RT "PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation
RT factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of
RT macrophages.";
RL J. Exp. Med. 193:955-966(2001).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 421-679 IN COMPLEX WITH A ZINC
RP ION, AND MUTAGENESIS OF TRP-449; ILE-460; ARG-467; LEU-481 AND ASP-482.
RX PubMed=10601011; DOI=10.1093/emboj/18.24.6890;
RA Mandiyan V., Andreev J., Schlessinger J., Hubbard S.R.;
RT "Crystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-
RT associated protein beta.";
RL EMBO J. 18:6890-6898(1999).
CC -!- FUNCTION: Activates the small GTPases ARF1, ARF5 and ARF6. Regulates
CC the formation of post-Golgi vesicles and modulates constitutive
CC secretion. Modulates phagocytosis mediated by Fc gamma receptor and
CC ARF6. Modulates PXN recruitment to focal contacts and cell migration
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:10022920,
CC ECO:0000269|PubMed:11304556}.
CC -!- SUBUNIT: Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.
CC {ECO:0000269|PubMed:10601011}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus, Golgi stack membrane;
CC Peripheral membrane protein. Cell membrane; Peripheral membrane
CC protein. Note=Colocalizes with F-actin and ARF6 in phagocytic cups.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7SIG6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7SIG6-2; Sequence=VSP_014776, VSP_014777;
CC -!- DOMAIN: The conserved Arg-467 in the Arf-GAP domain probably becomes
CC part of the active site of bound small GTPases and is necessary for GTP
CC hydrolysis.
CC -!- PTM: Phosphorylated on tyrosine residues by SRC and PTK2B.
CC {ECO:0000250}.
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DR EMBL; BC096022; AAH96022.1; -; mRNA.
DR EMBL; BC080847; AAH80847.1; -; mRNA.
DR CCDS; CCDS56832.1; -. [Q7SIG6-1]
DR RefSeq; NP_001004364.2; NM_001004364.2.
DR RefSeq; NP_001091637.1; NM_001098168.1. [Q7SIG6-1]
DR RefSeq; NP_001128664.1; NM_001135192.1.
DR PDB; 1DCQ; X-ray; 2.10 A; A=421-697.
DR PDBsum; 1DCQ; -.
DR AlphaFoldDB; Q7SIG6; -.
DR SMR; Q7SIG6; -.
DR BioGRID; 229271; 15.
DR IntAct; Q7SIG6; 2.
DR MINT; Q7SIG6; -.
DR STRING; 10090.ENSMUSP00000063217; -.
DR iPTMnet; Q7SIG6; -.
DR PhosphoSitePlus; Q7SIG6; -.
DR jPOST; Q7SIG6; -.
DR MaxQB; Q7SIG6; -.
DR PeptideAtlas; Q7SIG6; -.
DR PRIDE; Q7SIG6; -.
DR ProteomicsDB; 283178; -. [Q7SIG6-1]
DR ProteomicsDB; 283179; -. [Q7SIG6-2]
DR Antibodypedia; 4352; 108 antibodies from 28 providers.
DR DNASU; 211914; -.
DR Ensembl; ENSMUST00000090834; ENSMUSP00000088344; ENSMUSG00000052632. [Q7SIG6-2]
DR Ensembl; ENSMUST00000101562; ENSMUSP00000099098; ENSMUSG00000052632. [Q7SIG6-1]
DR GeneID; 211914; -.
DR KEGG; mmu:211914; -.
DR UCSC; uc007ndi.1; mouse. [Q7SIG6-1]
DR UCSC; uc011ykr.1; mouse. [Q7SIG6-2]
DR CTD; 8853; -.
DR MGI; MGI:2685438; Asap2.
DR VEuPathDB; HostDB:ENSMUSG00000052632; -.
DR eggNOG; KOG0521; Eukaryota.
DR GeneTree; ENSGT00940000155623; -.
DR InParanoid; Q7SIG6; -.
DR OrthoDB; 751525at2759; -.
DR BioGRID-ORCS; 211914; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Asap2; mouse.
DR EvolutionaryTrace; Q7SIG6; -.
DR PRO; PR:Q7SIG6; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q7SIG6; protein.
DR Bgee; ENSMUSG00000052632; Expressed in lumbar subsegment of spinal cord and 190 other tissues.
DR ExpressionAtlas; Q7SIG6; baseline and differential.
DR Genevisible; Q7SIG6; MM.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR CDD; cd13251; PH_ASAP; 1.
DR CDD; cd11966; SH3_ASAP2; 1.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR037278; ARFGAP/RecO.
DR InterPro; IPR001164; ArfGAP_dom.
DR InterPro; IPR038508; ArfGAP_dom_sf.
DR InterPro; IPR043593; ASAP.
DR InterPro; IPR035677; ASAP2_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR037844; PH_ASAP.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR45854; PTHR45854; 2.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS50115; ARFGAP; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Cell membrane; Coiled coil;
KW Cytoplasm; Direct protein sequencing; Golgi apparatus; GTPase activation;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW SH3 domain; Zinc.
FT CHAIN 1..958
FT /note="Arf-GAP with SH3 domain, ANK repeat and PH domain-
FT containing protein 2"
FT /id="PRO_0000074199"
FT DOMAIN 308..400
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 424..546
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 587..619
FT /note="ANK 1"
FT REPEAT 623..655
FT /note="ANK 2"
FT DOMAIN 896..958
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 283..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 703..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 767..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 259..286
FT /evidence="ECO:0000255"
FT COMPBIAS 781..806
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 807..830
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 831..846
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 704
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 861
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43150"
FT VAR_SEQ 284..286
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014776"
FT VAR_SEQ 345..490
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014777"
FT MUTAGEN 449
FT /note="W->A: Strongly reduces Arf-GAP mediated stimulation
FT of GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:10601011"
FT MUTAGEN 460
FT /note="I->A: Reduces Arf-GAP mediated stimulation of GTP
FT hydrolysis 100-fold and abolishes Arf-GAP mediated
FT stimulation of GTP hydrolysis; when associated with A-306."
FT /evidence="ECO:0000269|PubMed:10601011"
FT MUTAGEN 467
FT /note="R->A: Abolishes Arf-GAP mediated stimulation of GTP
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:10601011"
FT MUTAGEN 467
FT /note="R->K: Reduces Arf-GAP mediated stimulation of GTP
FT hydrolysis more than 10000-fold."
FT /evidence="ECO:0000269|PubMed:10601011"
FT MUTAGEN 481
FT /note="L->A: Reduces Arf-GAP mediated stimulation of GTP
FT hydrolysis 100-fold and abolishes Arf-GAP mediated
FT stimulation of GTP hydrolysis; when associated with A-285."
FT /evidence="ECO:0000269|PubMed:10601011"
FT MUTAGEN 482
FT /note="D->A: Reduces Arf-GAP mediated stimulation of GTP
FT hydrolysis 1000-fold."
FT /evidence="ECO:0000269|PubMed:10601011"
FT HELIX 423..432
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 434..437
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 440..442
FT /evidence="ECO:0007829|PDB:1DCQ"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 460..469
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:1DCQ"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 479..481
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 486..489
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 497..504
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:1DCQ"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 522..533
FT /evidence="ECO:0007829|PDB:1DCQ"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 546..558
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 562..570
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 591..598
FT /evidence="ECO:0007829|PDB:1DCQ"
FT TURN 601..603
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 604..613
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 627..633
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 637..645
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 660..666
FT /evidence="ECO:0007829|PDB:1DCQ"
FT HELIX 670..680
FT /evidence="ECO:0007829|PDB:1DCQ"
SQ SEQUENCE 958 AA; 106805 MW; 2CA0056C2AD14D7E CRC64;
MPDQISVSEF VAETHEDYKA PTASSFTTRT AQCRNTVAAI EEALDVDRMV LYKMKKSVKA
INISGLAHVE NEEQYTQALE KFGGNCVCRD DPDLGSAFLK FSVFTKELTA LFKNLIQNMN
NIISFPLDSL LKGDLKGVKG DLKKPFDKAW KDYETKITKI EKEKKEHAKL HGMIRTEISG
AEIAEEMEKE RRFFQLQMCE YLLKVNEIKV KKGVDLLQNL IKYFHAQCNF FQDGLKAVES
LKPSIETLST DLHTIKQAQD EERRQLIQLR DILKSALQVE QKESRRDSQL RQSTAYSLHQ
PQGNKEHGTE RNGNLYKKSD GIRKVWQKRK CSVKNGFLTI SHGTANRPPA KLNLLTCQVK
TNPEEKKCFD LISHDRTYHF QAEDEQECQI WMSVLQNSKE EALNNAFKGD DNTGENNIVQ
ELTKEIISEV QRMTGNDVCC DCGAPDPTWL STNLGILTCI ECSGIHRELG VHYSRMQSLT
LDVLGTSELL LAKNIGNAGF NEIMECCLPS EDPVKPNPGS DMIARKDYIT AKYMERRYAR
KKHADTAAKL HSLCEAVKTR DIFGLLQAYA DGVDLTEKIP LANGHEPDET ALHLAVRSVD
RTSLHIVDFL VQNSGNLDKQ TGKGSTALHY CCLTDNAECL KLLLRGKASI EIANESGETP
LDIAKRLKHE HCEELLTQAL SGRFNSHVHV EYEWRLLHED LDESDDDVDE KLQPSPNRRE
DRPVSFYQLG SSQFQSNAVS LARDTANLTK DKQRGFGPSI LQNETYGAIL SGSPPSSQSI
PPSTTSAPPL PPRNVGKDPL TTTPPPPVAK TSGTLEAMNQ PSKSSQPGTS QSKPPPLPPQ
PPSRLPQKKP ASGTDKPTPL TNKGQPRGPE ASGPLSNAMA LQPPAPMPRK SQATKSKPKR
VKALYNCVAD NPDELTFSEG DVIIVDGEED QEWWIGHIDG EPSRKGAFPV SFVHFIAD
