AGAP2_MOUSE
ID AGAP2_MOUSE Reviewed; 1186 AA.
AC Q3UHD9; Q5DU45;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 151.
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=Phosphatidylinositol 3-kinase enhancer;
DE Short=PIKE;
GN Name=Agap2; Synonyms=Centg1, Kiaa0167;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 138-1186 (ISOFORM 2).
RC TISSUE=Fetal 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-128; SER-149;
RP SER-632; SER-744; SER-746; SER-802; SER-921 AND SER-979, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, 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: GTPase-activating protein (GAP) for ARF1 and ARF5, which also
CC shows strong GTPase activity. Participates in the prevention of
CC neuronal apoptosis by enhancing PI3 kinase activity. Aids the coupling
CC of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase
CC by interacting with Homer scaffolding proteins, and also seems to
CC mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase
CC (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UHD9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UHD9-2; Sequence=VSP_018542;
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: PH domain binds phospholipids and is required for nuclear
CC targeting.
CC -!- SIMILARITY: Belongs to the centaurin gamma-like family. {ECO:0000305}.
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DR EMBL; AK147446; BAE27918.1; -; mRNA.
DR EMBL; AK220325; BAD90236.1; -; mRNA.
DR CCDS; CCDS24228.1; -. [Q3UHD9-1]
DR CCDS; CCDS88097.1; -. [Q3UHD9-2]
DR RefSeq; NP_001028435.1; NM_001033263.5. [Q3UHD9-1]
DR RefSeq; NP_001287943.1; NM_001301014.1. [Q3UHD9-2]
DR AlphaFoldDB; Q3UHD9; -.
DR SMR; Q3UHD9; -.
DR BioGRID; 229744; 194.
DR IntAct; Q3UHD9; 199.
DR MINT; Q3UHD9; -.
DR STRING; 10090.ENSMUSP00000043466; -.
DR iPTMnet; Q3UHD9; -.
DR PhosphoSitePlus; Q3UHD9; -.
DR EPD; Q3UHD9; -.
DR jPOST; Q3UHD9; -.
DR MaxQB; Q3UHD9; -.
DR PaxDb; Q3UHD9; -.
DR PeptideAtlas; Q3UHD9; -.
DR PRIDE; Q3UHD9; -.
DR ProteomicsDB; 296078; -. [Q3UHD9-1]
DR ProteomicsDB; 296079; -. [Q3UHD9-2]
DR Antibodypedia; 16354; 303 antibodies from 34 providers.
DR DNASU; 216439; -.
DR Ensembl; ENSMUST00000039259; ENSMUSP00000043466; ENSMUSG00000025422. [Q3UHD9-1]
DR Ensembl; ENSMUST00000217941; ENSMUSP00000151946; ENSMUSG00000025422. [Q3UHD9-2]
DR GeneID; 216439; -.
DR KEGG; mmu:216439; -.
DR UCSC; uc007hhx.2; mouse. [Q3UHD9-1]
DR UCSC; uc007hhy.2; mouse. [Q3UHD9-2]
DR CTD; 116986; -.
DR MGI; MGI:3580016; Agap2.
DR VEuPathDB; HostDB:ENSMUSG00000025422; -.
DR eggNOG; KOG0705; Eukaryota.
DR GeneTree; ENSGT00940000158956; -.
DR HOGENOM; CLU_007326_3_0_1; -.
DR InParanoid; Q3UHD9; -.
DR OMA; EEPLGHQ; -.
DR OrthoDB; 751525at2759; -.
DR PhylomeDB; Q3UHD9; -.
DR TreeFam; TF317762; -.
DR BioGRID-ORCS; 216439; 5 hits in 77 CRISPR screens.
DR PRO; PR:Q3UHD9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3UHD9; protein.
DR Bgee; ENSMUSG00000025422; Expressed in striatum and 53 other tissues.
DR ExpressionAtlas; Q3UHD9; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0090543; C:Flemming body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISO:MGI.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0016197; P:endosomal transport; ISO:MGI.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IMP:MGI.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
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 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 SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF52540; SSF52540; 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; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; GTP-binding;
KW GTPase activation; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..1186
FT /note="Arf-GAP with GTPase, ANK repeat and PH domain-
FT containing protein 2"
FT /id="PRO_0000235913"
FT DOMAIN 670..904
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 925..1045
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 1084..1113
FT /note="ANK 1"
FT REPEAT 1117..1146
FT /note="ANK 2"
FT ZN_FING 940..963
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..380
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 262..384
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT REGION 399..566
FT /note="G domain"
FT REGION 576..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..667
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 759..784
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..844
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1145..1174
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 295..309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..611
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 644..661
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 407..414
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 451..455
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 509..512
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 802
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 979
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CGU4"
FT VAR_SEQ 847..866
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_018542"
FT CONFLICT 381
FT /note="T -> A (in Ref. 2; BAD90236)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1186 AA; 124511 MW; E9B4F3EDB66CBEC8 CRC64;
MSRGAGALQR RTTTYLISLT LVKLESVPPP PPSPSAAAAG APGARGSEPR DPGSPRGSEE
PGKKRHERLF HRQDALWIST SSAGTGGAEP PALSPAPASP ARPVSPAPGR RLSLWAAPPG
PPLSGGLSPD SKPGGAPSSS RRPLLSSPSW GGPEPEGRTG GGVPGSSSPH PGTGSRRLKV
APPPPAPKPF KTVTTSGAKA GGGKGAGSRL SWPESEGKPR VKGSKSTAGT GASAAAAGGG
GSAAVTTSGG VGAGAGTRGK LSPRKGKSKT LDNSDLHPGP SAGSPPLTVP AIPVPATSVT
ATSTQPLGPA PPITLEPPAP GLKRGREGGR ASTRDRKMLK FISGIFTKST GGPPGPGPLP
GPQGLSSSSG SRELLGAELR TSPKAVVNSQ EWTLSRSIPE LRLGVLGDVR SGKSSLIHRF
LTGSYQVLEK IESEQYKKEM LVDGQTHLVL IREEAGAPDA KFSGWADAVI FVFSLEDESS
FQAVSRLHGQ LSSLRGEGRG GLALALVGTQ DRISASSPRV VGDARARALC TDMKRCSYYE
TCATYGLNVD RVFQEVAQKV VTLRKQQQLL AACKSLPSSP SHSAASTPVA GQASNGGHTS
DYSSSLPSSP NVGHRELRAE AAAVAGLSTP GSLHRAAKRR TSLFANRRGS DAEKRSLDSR
GETTGSGRAI PIKQSFLLKR SGNSLNKEWK KKYVTLSSNG FLLYHPSIND YIHSTHGKEM
DLLRTTVKVP GKRPPRAISA FGPSASINGL VKDMSTVQMG EGPEASTPMP SPSPSPSSLQ
LPTDQTSKHL LKPDRNLARA LSTDCTPSGD LSPLSREPPP SPMVKKQRRK KLSTPSKTEG
SAVQAEAKRK MWKLKSFGSL RNIYKAEENF EFLIVSSTGQ TWHFEAASFE ERDAWVQAIE
SQILASLQCC ESSKVKLRTD SQSEAVAIQA IRNAKGNSTC VDCGAPNPTW ASLNLGALIC
IECSGIHRNL GTHLSRVRSL DLDDWPRELT LVLTAIGNDT ANRVWESDTR GRAKPTRDSS
REERESWIRA KYEQLLFLAP LGTTEEPLGR QLWAAVEAQD VAAVLLLLAH ARHGPLDTSV
EDPQLRSPLH LAAELAHVVI TQLLLWYGAD VAARDAQGRT ALFYARQAGS QLCADILLQH
GCPGEGGSTA TTPSAATTPS ITATPSPRRR SSAASLGRVD TTIALV
