ASAP2_HUMAN
ID ASAP2_HUMAN Reviewed; 1006 AA.
AC O43150; D6W4Y8;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2004, sequence version 3.
DT 03-AUG-2022, entry version 200.
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, KIAA0400;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ASP-748.
RC TISSUE=Placenta;
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 FUNCTION, PHOSPHORYLATION, INTERACTION WITH ARF1; ARF5; ARF6; PTK2B AND
RP SRC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
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 [5]
RP FUNCTION, MUTAGENESIS OF CYS-436, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH PXN.
RX PubMed=10749932; DOI=10.1091/mbc.11.4.1315;
RA Kondo A., Hashimoto S., Yano H., Nagayama K., Mazaki Y., Sabe H.;
RT "A new paxillin-binding protein, PAG3/Papalpha/KIAA0400, bearing an ADP-
RT ribosylation factor GTPase-activating protein activity, is involved in
RT paxillin recruitment to focal adhesions and cell migration.";
RL Mol. Biol. Cell 11:1315-1327(2000).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-822, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701 AND THR-903, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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 {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:10749932,
CC ECO:0000269|PubMed:11304556}.
CC -!- SUBUNIT: Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.
CC -!- INTERACTION:
CC O43150; P46108: CRK; NbExp=2; IntAct=EBI-310968, EBI-886;
CC O43150; P62993: GRB2; NbExp=3; IntAct=EBI-310968, EBI-401755;
CC O43150; P19174: PLCG1; NbExp=3; IntAct=EBI-310968, EBI-79387;
CC O43150; Q96B97: SH3KBP1; NbExp=3; IntAct=EBI-310968, EBI-346595;
CC O43150; P0CG48: UBC; NbExp=2; IntAct=EBI-310968, EBI-3390054;
CC O43150; Q5JPT6; NbExp=3; IntAct=EBI-310968, EBI-10244213;
CC O43150; P70039: apc; Xeno; NbExp=4; IntAct=EBI-310968, EBI-8069633;
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; Synonyms=PAPalpha;
CC IsoId=O43150-1; Sequence=Displayed;
CC Name=2; Synonyms=PAPbeta;
CC IsoId=O43150-2; Sequence=VSP_009722;
CC -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, kidney,
CC monocytes and pancreas. {ECO:0000269|PubMed:10022920}.
CC -!- INDUCTION: Up-regulated during monocytic maturation.
CC -!- DOMAIN: The conserved Arg-464 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:0000269|PubMed:10022920}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23696.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB007860; BAA23696.2; ALT_INIT; mRNA.
DR EMBL; CH471053; EAX01004.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX01006.1; -; Genomic_DNA.
DR EMBL; BC063308; AAH63308.1; -; mRNA.
DR CCDS; CCDS1661.1; -. [O43150-1]
DR CCDS; CCDS46224.1; -. [O43150-2]
DR PIR; T00050; T00050.
DR RefSeq; NP_001128663.1; NM_001135191.1. [O43150-2]
DR RefSeq; NP_003878.1; NM_003887.2. [O43150-1]
DR AlphaFoldDB; O43150; -.
DR SMR; O43150; -.
DR BioGRID; 114378; 29.
DR IntAct; O43150; 24.
DR MINT; O43150; -.
DR STRING; 9606.ENSP00000281419; -.
DR iPTMnet; O43150; -.
DR PhosphoSitePlus; O43150; -.
DR BioMuta; ASAP2; -.
DR EPD; O43150; -.
DR jPOST; O43150; -.
DR MassIVE; O43150; -.
DR MaxQB; O43150; -.
DR PaxDb; O43150; -.
DR PeptideAtlas; O43150; -.
DR PRIDE; O43150; -.
DR ProteomicsDB; 48770; -. [O43150-1]
DR ProteomicsDB; 48771; -. [O43150-2]
DR ABCD; O43150; 1 sequenced antibody.
DR Antibodypedia; 4352; 108 antibodies from 28 providers.
DR DNASU; 8853; -.
DR Ensembl; ENST00000281419.8; ENSP00000281419.3; ENSG00000151693.11. [O43150-1]
DR Ensembl; ENST00000315273.4; ENSP00000316404.4; ENSG00000151693.11. [O43150-2]
DR GeneID; 8853; -.
DR KEGG; hsa:8853; -.
DR MANE-Select; ENST00000281419.8; ENSP00000281419.3; NM_003887.3; NP_003878.1.
DR UCSC; uc002qzh.3; human. [O43150-1]
DR CTD; 8853; -.
DR DisGeNET; 8853; -.
DR GeneCards; ASAP2; -.
DR HGNC; HGNC:2721; ASAP2.
DR HPA; ENSG00000151693; Tissue enhanced (testis).
DR MIM; 603817; gene.
DR neXtProt; NX_O43150; -.
DR OpenTargets; ENSG00000151693; -.
DR PharmGKB; PA164716118; -.
DR VEuPathDB; HostDB:ENSG00000151693; -.
DR eggNOG; KOG0521; Eukaryota.
DR GeneTree; ENSGT00940000155623; -.
DR HOGENOM; CLU_006942_0_0_1; -.
DR InParanoid; O43150; -.
DR OMA; MKMECHI; -.
DR OrthoDB; 751525at2759; -.
DR PhylomeDB; O43150; -.
DR TreeFam; TF325156; -.
DR PathwayCommons; O43150; -.
DR SignaLink; O43150; -.
DR BioGRID-ORCS; 8853; 12 hits in 1089 CRISPR screens.
DR ChiTaRS; ASAP2; human.
DR GeneWiki; DDEF2; -.
DR GenomeRNAi; 8853; -.
DR Pharos; O43150; Tbio.
DR PRO; PR:O43150; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43150; protein.
DR Bgee; ENSG00000151693; Expressed in secondary oocyte and 209 other tissues.
DR ExpressionAtlas; O43150; baseline and differential.
DR Genevisible; O43150; HS.
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; 1.
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 Alternative splicing; ANK repeat; Cell membrane; Coiled coil; Cytoplasm;
KW Golgi apparatus; GTPase activation; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; SH3 domain; Zinc.
FT CHAIN 1..1006
FT /note="Arf-GAP with SH3 domain, ANK repeat and PH domain-
FT containing protein 2"
FT /id="PRO_0000074198"
FT DOMAIN 305..397
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 421..543
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 584..616
FT /note="ANK 1"
FT REPEAT 620..649
FT /note="ANK 2"
FT DOMAIN 944..1006
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 288..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..916
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 256..283
FT /evidence="ECO:0000255"
FT COILED 729..752
FT /evidence="ECO:0000255"
FT COMPBIAS 772..786
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 793..823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 825..853
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 869..890
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 822
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 903
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 795..840
FT /note="VQTASSANTLWKTNSVSVDGGSRQRSSSDPPAVHPPLPPLRVTSTN -> D
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009722"
FT VARIANT 748
FT /note="E -> D (in dbSNP:rs2715860)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_020307"
FT MUTAGEN 436
FT /note="C->A: Loss of Arf-GAP activity."
FT /evidence="ECO:0000269|PubMed:10749932"
FT CONFLICT 86
FT /note="C -> R (in Ref. 3; AAH63308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1006 AA; 111651 MW; 6A213517DCD99E1B CRC64;
MPDQISVSEF VAETHEDYKA PTASSFTTRT AQCRNTVAAI EEALDVDRMV LYKMKKSVKA
INSSGLAHVE NEEQYTQALE KFGGNCVCRD DPDLGSAFLK FSVFTKELTA LFKNLIQNMN
NIISFPLDSL LKGDLKGVKG DLKKPFDKAW KDYETKITKI EKEKKEHAKL HGMIRTEISG
AEIAEEMEKE RRFFQLQMCE YLLKVNEIKI KKGVDLLQNL IKYFHAQCNF FQDGLKAVES
LKPSIETLST DLHTIKQAQD EERRQLIQLR DILKSALQVE QKEDSQIRQS TAYSLHQPQG
NKEHGTERNG SLYKKSDGIR KVWQKRKCSV KNGFLTISHG TANRPPAKLN LLTCQVKTNP
EEKKCFDLIS HDRTYHFQAE DEQECQIWMS VLQNSKEEAL NNAFKGDDNT GENNIVQELT
KEIISEVQRM TGNDVCCDCG APDPTWLSTN LGILTCIECS GIHRELGVHY SRMQSLTLDV
LGTSELLLAK NIGNAGFNEI MECCLPAEDS VKPNPGSDMN ARKDYITAKY IERRYARKKH
ADNAAKLHSL CEAVKTRDIF GLLQAYADGV DLTEKIPLAN GHEPDETALH LAVRSVDRTS
LHIVDFLVQN SGNLDKQTGK GSTALHYCCL TDNAECLKLL LRGKASIEIA NESGETPLDI
AKRLKHEHCE ELLTQALSGR FNSHVHVEYE WRLLHEDLDE SDDDMDEKLQ PSPNRREDRP
ISFYQLGSNQ LQSNAVSLAR DAANLAKEKQ RAFMPSILQN ETYGALLSGS PPPAQPAAPS
TTSAPPLPPR NVGKVQTASS ANTLWKTNSV SVDGGSRQRS SSDPPAVHPP LPPLRVTSTN
PLTPTPPPPV AKTPSVMEAL SQPSKPAPPG ISQIRPPPLP PQPPSRLPQK KPAPGADKST
PLTNKGQPRG PVDLSATEAL GPLSNAMVLQ PPAPMPRKSQ ATKLKPKRVK ALYNCVADNP
DELTFSEGDV IIVDGEEDQE WWIGHIDGDP GRKGAFPVSF VHFIAD
