ID AGAP2_HUMAN Reviewed; 1192 AA.
AC Q99490; A8K9F7; O00578; Q548E0; Q8IWU3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 24-JAN-2024, entry version 221.
DE RecName: Full=Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2;
DE Short=AGAP-2;
DE AltName: Full=Centaurin-gamma-1;
DE Short=Cnt-g1;
DE AltName: Full=GTP-binding and GTPase-activating protein 2;
DE Short=GGAP2;
DE AltName: Full=Phosphatidylinositol 3-kinase enhancer;
DE Short=PIKE;
GN Name=AGAP2; Synonyms=CENTG1, KIAA0167;
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 [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), AND
RP VARIANT VAL-1124.
RX PubMed=9192850; DOI=10.1006/geno.1997.4727;
RA Elkahloun A.G., Krizman D.B., Wang Z., Hofmann T.A., Roe B.A.,
RA Meltzer P.S.;
RT "Transcript mapping in a 46-kb sequenced region at the core of 12q13.3
RT amplification in human cancers.";
RL Genomics 42:295-301(1997).
RN [2]
RP SEQUENCE REVISION TO 389; 768-769; 1124; 1137 AND 1147 (ISOFORM 2).
RA Roe B.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RC TISSUE=Heart;
RX PubMed=12640130; DOI=10.1128/mcb.23.7.2476-2488.2003;
RA Xia C., Ma W., Stafford L.J., Liu C., Gong L., Martin J.F., Liu M.;
RT "GGAPs, a new family of bifunctional GTP-binding and GTPase-activating
RT proteins.";
RL Mol. Cell. Biol. 23:2476-2488(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=14528310; DOI=10.1038/nn1134;
RA Rong R., Ahn J.-Y., Huang H., Nagata E., Kalman D., Kapp J.A., Tu J.,
RA Worley P.F., Snyder S.H., Ye K.;
RT "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing
RT neuronal apoptosis.";
RL Nat. Neurosci. 6:1153-1161(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Hong W.;
RT "Kiaa0167 as a member (centaurin gamma1) of centaurin ArfGAP family.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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 [10]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH AKT1, AND
RP FUNCTION.
RX PubMed=14761976; DOI=10.1074/jbc.m312175200;
RA Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.;
RT "PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt
RT activity and mediates cellular invasion.";
RL J. Biol. Chem. 279:16441-16451(2004).
RN [11]
RP TISSUE SPECIFICITY, INTERACTION WITH AKT1, AND FUNCTION.
RX PubMed=15118108; DOI=10.1073/pnas.0400921101;
RA Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.;
RT "PIKE-A is amplified in human cancers and prevents apoptosis by up-
RT regulating Akt.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004).
RN [12]
RP TISSUE SPECIFICITY, INTERACTION WITH THE AP-1 COMPLEX, AND FUNCTION.
RX PubMed=16079295; DOI=10.1242/jcs.02486;
RA Nie Z., Fei J., Premont R.T., Randazzo P.A.;
RT "The Arf GAPs AGAP1 and AGAP2 distinguish between the adaptor protein
RT complexes AP-1 and AP-3.";
RL J. Cell Sci. 118:3555-3566(2005).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=16150119; DOI=10.1111/j.1365-2990.2005.00660.x;
RA Knobbe C.B., Trampe-Kieslich A., Reifenberger G.;
RT "Genetic alteration and expression of the phosphoinositol-3-kinase/Akt
RT pathway genes PIK3CA and PIKE in human glioblastomas.";
RL Neuropathol. Appl. Neurobiol. 31:486-490(2005).
RN [14]
RP PHOSPHORYLATION AT TYR-682 AND TYR-774 (ISOFORM 2) BY FYN.
RX PubMed=16841086; DOI=10.1038/sj.cdd.4402011;
RA Tang X., Feng Y., Ye K.;
RT "Src-family tyrosine kinase fyn phosphorylates phosphatidylinositol 3-
RT kinase enhancer-activating Akt, preventing its apoptotic cleavage and
RT promoting cell survival.";
RL Cell Death Differ. 14:368-377(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-638, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 402-577.
RX PubMed=17037982; DOI=10.1042/bj20060555;
RA Soundararajan M., Yang X., Elkins J.M., Sobott F., Doyle D.A.;
RT "The centaurin gamma-1 GTPase-like domain functions as an NTPase.";
RL Biochem. J. 401:679-688(2007).
RN [17]
RP STRUCTURE BY NMR OF 674-914.
RX PubMed=18371979; DOI=10.1016/j.jmb.2008.02.052;
RA Yan J., Wen W., Chan L.N., Zhang M.;
RT "Split pleckstrin homology domain-mediated cytoplasmic-nuclear localization
RT of PI3-kinase enhancer GTPase.";
RL J. Mol. Biol. 378:425-435(2008).
RN [18]
RP VARIANTS ALA-455; GLY-518; ILE-568; VAL-651; VAL-767; ASP-939; MET-947 AND
RP PRO-1022, AND SUBCELLULAR LOCATION.
RX PubMed=16263930; DOI=10.1073/pnas.0507365102;
RA Hu Y., Liu Z., Ye K.;
RT "Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase
RT enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt
RT signalings.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16853-16858(2005).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] ALA-339 AND TYR-816.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: GTPase-activating protein (GAP) for ARF1 and ARF5, which also
CC shows strong GTPase activity. Isoform 1 participates in the prevention
CC of neuronal apoptosis by enhancing PI3 kinase activity. It aids the
CC coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3
CC kinase by interacting with Homer scaffolding proteins, and also seems
CC to mediate anti-apoptotic effects of NGF by activating nuclear PI3
CC kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells
CC from apoptosis by stimulating Akt. It also regulates the adapter
CC protein 1 (AP-1)-dependent trafficking of proteins in the endosomal
CC system. It seems to be oncogenic. It is overexpressed in cancer cells,
CC prevents apoptosis and promotes cancer cell invasion.
CC {ECO:0000269|PubMed:12640130, ECO:0000269|PubMed:14761976,
CC ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16079295}.
CC -!- ACTIVITY REGULATION: GAP activity is stimulated by phosphatidylinositol
CC 4,5-bisphosphate (PIP2) and, to a lesser extent, by
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid
CC potentiates PIP2 stimulation.
CC -!- SUBUNIT: Isoform 1 interacts with EPB41L1, PLCG1, NF2, HOMER1 and
CC HOMER2 (By similarity). Isoform 2 interacts with activated AKT1 in the
CC presence of guanine nucleotides, and with the AP-1 complex.
CC {ECO:0000250, ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15118108,
CC ECO:0000269|PubMed:16079295}.
CC -!- INTERACTION:
CC Q99490; P06213: INSR; NbExp=2; IntAct=EBI-2361824, EBI-475899;
CC Q99490-2; P42229: STAT5A; NbExp=3; IntAct=EBI-7737644, EBI-749537;
CC Q99490-2; Q08501: Prlr; Xeno; NbExp=2; IntAct=EBI-7737644, EBI-7737664;
CC Q99490-2; P42230: Stat5a; Xeno; NbExp=2; IntAct=EBI-7737644, EBI-617434;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PIKE-L;
CC IsoId=Q99490-1; Sequence=Displayed;
CC Name=2; Synonyms=PIKE-A;
CC IsoId=Q99490-2; Sequence=VSP_018531, VSP_018532, VSP_018533;
CC -!- TISSUE SPECIFICITY: Isoform 1 is brain-specific. Isoform 2 is
CC ubiquitously expressed, with highest levels in brain and heart.
CC {ECO:0000269|PubMed:12640130, ECO:0000269|PubMed:14761976,
CC ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16079295,
CC ECO:0000269|PubMed:16150119}.
CC -!- DOMAIN: G domain binds GTP and has GTPase activity.
CC -!- DOMAIN: Arf-GAP domain interacts with G domain and may regulate its
CC GTPase activity.
CC -!- DOMAIN: Although both PH domains of isoforms 1 and 2 bind
CC phospholipids, they differently regulate subcellular location. PH
CC domain of isoform 1 directs the protein to the nucleus, but PH domain
CC of isoform 2 directs it to the cytosol. PH domain of isoform 2 is
CC required for binding to AP-1.
CC -!- PTM: Isoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN,
CC preventing its apoptotic cleavage. {ECO:0000269|PubMed:16841086}.
CC -!- SIMILARITY: Belongs to the centaurin gamma-like family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11484.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/44037/CENTG1";
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DR EMBL; U81031; AAC39522.2; -; Genomic_DNA.
DR EMBL; AF384128; AAO39848.1; -; mRNA.
DR EMBL; AY128689; AAM97540.1; -; mRNA.
DR EMBL; D79989; BAA11484.2; ALT_INIT; mRNA.
DR EMBL; AF413077; AAL04171.1; -; mRNA.
DR EMBL; AK292672; BAF85361.1; -; mRNA.
DR EMBL; CH471054; EAW97049.1; -; Genomic_DNA.
DR EMBL; BC028020; AAH28020.1; -; mRNA.
DR CCDS; CCDS44932.1; -. [Q99490-1]
DR CCDS; CCDS8951.1; -. [Q99490-2]
DR RefSeq; NP_001116244.1; NM_001122772.2.
DR RefSeq; NP_055585.1; NM_014770.3. [Q99490-2]
DR PDB; 2BMJ; X-ray; 2.10 A; A=402-577.
DR PDB; 2IWR; X-ray; 1.50 A; A=402-577.
DR PDB; 2RLO; NMR; -; A=674-914.
DR PDBsum; 2BMJ; -.
DR PDBsum; 2IWR; -.
DR PDBsum; 2RLO; -.
DR AlphaFoldDB; Q99490; -.
DR SMR; Q99490; -.
DR BioGRID; 125549; 22.
DR IntAct; Q99490; 10.
DR MINT; Q99490; -.
DR STRING; 9606.ENSP00000449241; -.
DR GlyGen; Q99490; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99490; -.
DR PhosphoSitePlus; Q99490; -.
DR BioMuta; AGAP2; -.
DR DMDM; 97535883; -.
DR EPD; Q99490; -.
DR jPOST; Q99490; -.
DR MassIVE; Q99490; -.
DR MaxQB; Q99490; -.
DR PaxDb; 9606-ENSP00000449241; -.
DR PeptideAtlas; Q99490; -.
DR ProteomicsDB; 78295; -. [Q99490-1]
DR ProteomicsDB; 78296; -. [Q99490-2]
DR Pumba; Q99490; -.
DR Antibodypedia; 16354; 322 antibodies from 34 providers.
DR DNASU; 116986; -.
DR Ensembl; ENST00000257897.7; ENSP00000257897.3; ENSG00000135439.12. [Q99490-2]
DR GeneID; 116986; -.
DR KEGG; hsa:116986; -.
DR UCSC; uc001spr.4; human. [Q99490-1]
DR AGR; HGNC:16921; -.
DR CTD; 116986; -.
DR DisGeNET; 116986; -.
DR GeneCards; AGAP2; -.
DR HGNC; HGNC:16921; AGAP2.
DR HPA; ENSG00000135439; Tissue enriched (brain).
DR MIM; 605476; gene.
DR neXtProt; NX_Q99490; -.
DR OpenTargets; ENSG00000135439; -.
DR PharmGKB; PA26411; -.
DR VEuPathDB; HostDB:ENSG00000135439; -.
DR eggNOG; KOG0705; Eukaryota.
DR GeneTree; ENSGT00940000158956; -.
DR HOGENOM; CLU_007326_1_0_1; -.
DR InParanoid; Q99490; -.
DR OrthoDB; 1449795at2759; -.
DR PhylomeDB; Q99490; -.
DR PathwayCommons; Q99490; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR SignaLink; Q99490; -.
DR SIGNOR; Q99490; -.
DR BioGRID-ORCS; 116986; 56 hits in 1149 CRISPR screens.
DR ChiTaRS; AGAP2; human.
DR EvolutionaryTrace; Q99490; -.
DR GeneWiki; CENTG1; -.
DR GenomeRNAi; 116986; -.
DR Pharos; Q99490; Tbio.
DR PRO; PR:Q99490; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q99490; Protein.
DR Bgee; ENSG00000135439; Expressed in right hemisphere of cerebellum and 159 other cell types or tissues.
DR ExpressionAtlas; Q99490; baseline and differential.
DR Genevisible; Q99490; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0090543; C:Flemming body; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0005525; F:GTP binding; IDA:MGI.
DR GO; GO:0005096; F:GTPase activator activity; IDA:MGI.
DR GO; GO:0003924; F:GTPase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0141038; F:phosphatidylinositol 3-kinase activator activity; TAS:ARUK-UCL.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; IDA:MGI.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IDA:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI.
DR GO; GO:0016197; P:endosomal transport; IDA:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR CDD; cd08836; ArfGap_AGAP; 1.
DR CDD; cd04103; Centaurin_gamma; 1.
DR CDD; cd01250; PH_AGAP; 1.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR Gene3D; 1.10.220.150; Arf GTPase activating protein; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2.
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; IPR027417; P-loop_NTPase.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001806; Small_GTPase.
DR PANTHER; PTHR45819:SF3; ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 2; 1.
DR PANTHER; PTHR45819; CENTAURIN-GAMMA-1A; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00175; RAB; 1.
DR SMART; SM00173; RAS; 1.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR SUPFAM; SSF57863; ArfGap/RecO-like zinc finger; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF50729; PH domain-like; 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; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Cytoplasm; GTP-binding;
KW GTPase activation; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport;
KW Tumor suppressor; Zinc; Zinc-finger.
FT CHAIN 1..1192
FT /note="Arf-GAP with GTPase, ANK repeat and PH domain-
FT containing protein 2"
FT /id="PRO_0000074217"
FT DOMAIN 676..910
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 931..1051
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 1090..1119
FT /note="ANK 1"
FT REPEAT 1123..1152
FT /note="ANK 2"
FT ZN_FING 946..969
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REGION 1..23
FT /note="Interaction with EPB41L1"
FT /evidence="ECO:0000250"
FT REGION 24..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..225
FT /note="Interactions with HOMER1 and NF2"
FT /evidence="ECO:0000250"
FT REGION 267..390
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT REGION 405..572
FT /note="G domain"
FT REGION 582..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 634..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 769..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1153..1192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..73
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..299
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..667
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1156..1177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 413..420
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 457..461
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 515..518
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 750
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 927
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHD9"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CGU4"
FT VAR_SEQ 1..336
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12640130,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8724849, ECO:0000303|Ref.5"
FT /id="VSP_018531"
FT VAR_SEQ 337..390
FT /note="ASTRDRKMLKFISGIFTKSTGGPPGSGPLPGPPSLSSGSGSRELLGAELRAS
FT PK -> MHAQRQFVVAAVRAEVRRHEVAKQALNRLRKLAERVDDPELQDSIQASLDSIR
FT E (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12640130,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8724849, ECO:0000303|Ref.5"
FT /id="VSP_018532"
FT VAR_SEQ 853..872
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12640130,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8724849, ECO:0000303|Ref.5"
FT /id="VSP_018533"
FT VARIANT 339
FT /note="T -> A (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036183"
FT VARIANT 455
FT /note="V -> A (in a glioblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026438"
FT VARIANT 507
FT /note="G -> S (in dbSNP:rs2301553)"
FT /id="VAR_022046"
FT VARIANT 518
FT /note="R -> G (in a sarcoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026439"
FT VARIANT 568
FT /note="T -> I (in a neuroblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026440"
FT VARIANT 651
FT /note="A -> V (in a glioblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026441"
FT VARIANT 767
FT /note="E -> V (in a glioblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026442"
FT VARIANT 816
FT /note="D -> Y (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036184"
FT VARIANT 939
FT /note="N -> D (in a glioblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026443"
FT VARIANT 947
FT /note="V -> M (in a sarcoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026444"
FT VARIANT 1022
FT /note="S -> P (in a glioblastoma cell line)"
FT /evidence="ECO:0000269|PubMed:16263930"
FT /id="VAR_026445"
FT VARIANT 1124
FT /note="G -> V (in dbSNP:rs238521)"
FT /evidence="ECO:0000269|PubMed:9192850"
FT /id="VAR_055532"
FT CONFLICT 1137
FT /note="Q -> H (in Ref. 1; AAC39522)"
FT /evidence="ECO:0000305"
FT CONFLICT 1147
FT /note="G -> A (in Ref. 1; AAC39522)"
FT /evidence="ECO:0000305"
FT STRAND 406..412
FT /evidence="ECO:0007829|PDB:2IWR"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:2IWR"
FT HELIX 419..428
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 438..448
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 451..459
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:2IWR"
FT HELIX 466..471
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 473..480
FT /evidence="ECO:0007829|PDB:2IWR"
FT HELIX 484..501
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 509..515
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:2BMJ"
FT HELIX 529..539
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 540..548
FT /evidence="ECO:0007829|PDB:2IWR"
FT TURN 549..552
FT /evidence="ECO:0007829|PDB:2IWR"
FT HELIX 555..574
FT /evidence="ECO:0007829|PDB:2IWR"
FT STRAND 677..686
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 695..703
FT /evidence="ECO:0007829|PDB:2RLO"
FT TURN 704..706
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 707..713
FT /evidence="ECO:0007829|PDB:2RLO"
FT HELIX 714..719
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 724..730
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 732..734
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 878..881
FT /evidence="ECO:0007829|PDB:2RLO"
FT STRAND 887..894
FT /evidence="ECO:0007829|PDB:2RLO"
FT HELIX 895..913
FT /evidence="ECO:0007829|PDB:2RLO"
FT MOD_RES Q99490-2:682
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16841086"
FT MOD_RES Q99490-2:774
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16841086"
SQ SEQUENCE 1192 AA; 124674 MW; 8DA53707C0127984 CRC64;
MSRGAGALQR RTTTYLISLT LVKLESVPPP PPSPSAAAVG APGARGSEPR DPGSPRGAEE
PGKKRHERLF HRQDALWIST SSAGAGGAEP PALSPAPASP ARPVSPAPGR RLSLWAAPPG
PPLSGGLSPD SKPGGAPSSS RRPLLSSPSW GGPEPEGRTG GGVPGSSSPH PGTGSRRLKV
APPPPAPKPC KTVTTSGAKA GGGKGAGSRL SWPESEGKPR VKGSKSSAGT GASVSAAATA
AAAGGGGSTA STSGGVGAGA GARGKLSPRK GKSKTLDNSD LHPGPPAGSP PPLTLPPTPS
PATAVTAASA QPPGPAPPIT LEPPAPGLKR GREGGRASTR DRKMLKFISG IFTKSTGGPP
GSGPLPGPPS LSSGSGSREL LGAELRASPK AVINSQEWTL SRSIPELRLG VLGDARSGKS
SLIHRFLTGS YQVLEKTESE QYKKEMLVDG QTHLVLIREE AGAPDAKFSG WADAVIFVFS
LEDENSFQAV SRLHGQLSSL RGEGRGGLAL ALVGTQDRIS ASSPRVVGDA RARALCADMK
RCSYYETCAT YGLNVDRVFQ EVAQKVVTLR KQQQLLAACK SLPSSPSHSA ASTPVAGQAS
NGGHTSDYSS SLPSSPNVGH RELRAEAAAV AGLSTPGSLH RAAKRRTSLF ANRRGSDSEK
RSLDSRGETT GSGRAIPIKQ SFLLKRSGNS LNKEWKKKYV TLSSNGFLLY HPSINDYIHS
THGKEMDLLR TTVKVPGKRP PRAISAFGPS ASINGLVKDM STVQMGEGLE ATTPMPSPSP
SPSSLQPPPD QTSKHLLKPD RNLARALSTD CTPSGDLSPL SREPPPSPMV KKQRRKKLTT
PSKTEGSAGQ AEAKRKMWKL KSFGSLRNIY KAEENFEFLI VSSTGQTWHF EAASFEERDA
WVQAIESQIL ASLQCCESSK VKLRTDSQSE AVAIQAIRNA KGNSICVDCG APNPTWASLN
LGALICIECS GIHRNLGTHL SRVRSLDLDD WPRELTLVLT AIGNDTANRV WESDTRGRAK
PSRDSSREER ESWIRAKYEQ LLFLAPLSTS EEPLGRQLWA AVQAQDVATV LLLLAHARHG
PLDTSVEDPQ LRSPLHLAAE LAHVVITQLL LWYGADVAAR DAQGRTALFY ARQAGSQLCA
DILLQHGCPG EGGSAATTPS AATTPSITAT PSPRRRSSAA SVGRADAPVA LV
//
