GIT_DROME
ID GIT_DROME Reviewed; 731 AA.
AC Q95RG8; Q9V5N5;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=ARF GTPase-activating protein Git;
DE Short=ARF GAP GIT;
DE Short=dGIT protein {ECO:0000303|PubMed:18996366};
DE AltName: Full=G protein-coupled receptor kinase interacting ArfGAP;
GN Name=Git; Synonyms=arfgap2;
GN ORFNames=CG16728 {ECO:0000312|FlyBase:FBgn0033539};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, INTERACTION WITH PIX AND PAK, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18996366; DOI=10.1016/j.ydbio.2008.09.001;
RA Bahri S.M., Choy J.M., Manser E., Lim L., Yang X.;
RT "The Drosophila homologue of Arf-GAP GIT1, dGIT, is required for proper
RT muscle morphogenesis and guidance during embryogenesis.";
RL Dev. Biol. 325:15-23(2009).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25792865; DOI=10.5607/en.2015.24.1.8;
RA Hong S.T., Mah W.;
RT "A critical role of GIT1 in vertebrate and invertebrate brain
RT development.";
RL Exp. Neurobiol. 24:8-16(2015).
CC -!- FUNCTION: GTPase-activating protein for ADP ribosylation factor family
CC members, including ARF1. Multidomain scaffold protein that interacts
CC with numerous proteins and therefore participates in many cellular
CC functions, including receptor internalization, focal adhesion
CC remodeling, and signaling by both G protein-coupled receptors and
CC tyrosine kinase receptors (By similarity). Through Pak activation, may
CC positively regulate microtubule nucleation during interphase. May play
CC a role in the regulation of cytokinesis (By similarity). During
CC embryogenesis, promotes proper muscle morphogenesis and proper guidance
CC and targeting of subsets of myotubes (PubMed:18996366). Required for
CC the recruitment of Pak to muscle attachments in the embryo, probably
CC indirectly through pix/dPIX (PubMed:18996366). May be important for
CC brain development (PubMed:25792865). {ECO:0000250|UniProtKB:Q9Y2X7,
CC ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:18996366,
CC ECO:0000269|PubMed:25792865}.
CC -!- SUBUNIT: May form homodimers (via coiled coil) (By similarity). Forms a
CC complex with pix and Pak; the interaction with Pak may be indirect and
CC mediated by pix/dPIX (PubMed:18996366). {ECO:0000250|UniProtKB:Q9Z272,
CC ECO:0000269|PubMed:18996366}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18996366}. Synapse
CC {ECO:0000250|UniProtKB:Q9Y2X7}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:Q9Y2X7}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q9Y2X7}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q9Y2X7}.
CC Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q9Y2X7}.
CC Note=Localizes to the leading edge of growing myotubes.
CC {ECO:0000269|PubMed:18996366}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic muscle syncytia (at protein
CC level). {ECO:0000269|PubMed:18996366}.
CC -!- DEVELOPMENTAL STAGE: Detected muscle syncytia in embryonic stage 14 and
CC early stage 15. At mid stage 15, localizes at the leading edge of
CC growing myotubes. In the ventral ends of VO5 and VO6 muscles enriched
CC at the base of membrane protrusions at the leading edge of growing
CC myotubes, while it is less expressed in filopodia. In the late stage
CC embryo, concentrated at all muscle attachment sites, although subtle
CC variation in expression and/or localization may be observed in
CC different muscles subsets. Remains enriched in myotubes until the end
CC of embryogenesis (at protein level). {ECO:0000269|PubMed:18996366}.
CC -!- DOMAIN: The coiled coil region may mediate dimerization.
CC {ECO:0000250|UniProtKB:Q9Z272}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout flies show a semi-lethal
CC phenotype and exhibit defective wing morphology at 100% penetrance
CC (PubMed:18996366). Mutant embryos show striking guidance phenotypes in
CC ventral oblique muscle 5 (VO5) and ventral oblique muscle 6 (VO6),
CC characterized by bypass and mistargeting of the mutant muscles toward
CC the ventral midline. Defects in targeting of the growing ventral tips
CC of mutant muscles toward the ventral midline are already detectable at
CC late stage 14/early stage 15 embryos. Defects in other ventral muscles
CC are less obvious, although ventral acute muscle 3 (VA3) occasionally
CC show mistargeting toward the ventral midline (PubMed:18996366). Defects
CC in number and shape of subsets of muscles are also observed, but at low
CC frequency (PubMed:18996366). Adult knockout flies show decreased
CC central brain size and abnormal morphology of the mushroom body, the
CC most common pattern being early termination of one alpha-lobe. The
CC penetrance of the impaired mushroom body development is incomplete
CC (PubMed:25792865). {ECO:0000269|PubMed:18996366,
CC ECO:0000269|PubMed:25792865}.
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DR EMBL; AE013599; AAF58766.2; -; Genomic_DNA.
DR EMBL; AY061380; AAL28928.1; -; mRNA.
DR RefSeq; NP_610599.3; NM_136755.4.
DR AlphaFoldDB; Q95RG8; -.
DR SMR; Q95RG8; -.
DR IntAct; Q95RG8; 10.
DR STRING; 7227.FBpp0087353; -.
DR PaxDb; Q95RG8; -.
DR PRIDE; Q95RG8; -.
DR DNASU; 36122; -.
DR EnsemblMetazoa; FBtr0088258; FBpp0087353; FBgn0033539.
DR GeneID; 36122; -.
DR KEGG; dme:Dmel_CG16728; -.
DR UCSC; CG16728-RA; d. melanogaster.
DR CTD; 36122; -.
DR FlyBase; FBgn0033539; Git.
DR VEuPathDB; VectorBase:FBgn0033539; -.
DR eggNOG; KOG0818; Eukaryota.
DR GeneTree; ENSGT00940000169561; -.
DR HOGENOM; CLU_009739_0_0_1; -.
DR InParanoid; Q95RG8; -.
DR OMA; NSVWEHH; -.
DR OrthoDB; 349344at2759; -.
DR PhylomeDB; Q95RG8; -.
DR Reactome; R-DME-3928664; Ephrin signaling.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR Reactome; R-DME-9013420; RHOU GTPase cycle.
DR Reactome; R-DME-9013424; RHOV GTPase cycle.
DR SignaLink; Q95RG8; -.
DR BioGRID-ORCS; 36122; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 36122; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033539; Expressed in embryonic/larval hemocyte (Drosophila) and 31 other tissues.
DR GO; GO:0031252; C:cell leading edge; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0048786; C:presynaptic active zone; IDA:FlyBase.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; ISM:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0016319; P:mushroom body development; IMP:FlyBase.
DR GO; GO:0046621; P:negative regulation of organ growth; IGI:FlyBase.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IGI:FlyBase.
DR GO; GO:1905383; P:protein localization to presynapse; IMP:FlyBase.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IBA:GO_Central.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043087; P:regulation of GTPase activity; ISM:FlyBase.
DR GO; GO:0007525; P:somatic muscle development; IMP:FlyBase.
DR GO; GO:0099504; P:synaptic vesicle cycle; IMP:FlyBase.
DR GO; GO:0036465; P:synaptic vesicle recycling; IMP:FlyBase.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.25.40.20; -; 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; IPR022018; GIT1_C.
DR InterPro; IPR013724; GIT_SHD.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF12205; GIT1_C; 1.
DR Pfam; PF08518; GIT_SHD; 2.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00555; GIT; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS50115; ARFGAP; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Cell junction; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; GTPase activation; Metal-binding; Reference proteome; Repeat;
KW Synapse; Zinc; Zinc-finger.
FT CHAIN 1..731
FT /note="ARF GTPase-activating protein Git"
FT /id="PRO_0000452578"
FT DOMAIN 32..168
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 216..245
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 249..278
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT ZN_FING 49..72
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REGION 124..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 477..518
FT /evidence="ECO:0000255"
FT COMPBIAS 555..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 731 AA; 80773 MW; 6E7680AE32155B3A CRC64;
MCFASSIIEA HRKLFIAPPD LDHSDPATPT ISTRSKMPRG KSRLQTEVCG DCGAGDPSWA
SINRGILLCA DCCSVHRSLG RHISIVKSLR QGNWEPSVLN FVNSLNAHGA NSVWEHHLLD
GSTNSTGGKH VPRWRKPTPK DALHPTKSDF IKAKHVNLTF VLKPSLQDDD DGNGSAGCLE
QELSRQLHAS VRTSNLETSL RFLVQGADPN YYHEDKLSTP LHMAAKFGQA SQIEMLLIYG
ADVNALDGNG MTPLELARAN NHNTIAERLL DAMYDVTDRI ITFLGGKKPD HASGRHMIIP
DANGADISEQ LKIARGKLQL VPNKMFEELV MDLYDEVDRR ECEAIWSTST LNADHATVPF
LPANPFLSAT RNQGRQKLAR FNRAEFTGLL TDVLVDAMRR QNMANLRPMD APVAGHQSLQ
SLPYANNSML LGSFEQGGHD PNLSDDEPIY DPVASDDDYA PVPPMAQQAI VHTPPRSANS
HNEMETLRKQ LNDYKSEINQ LKNVVQMLSS ENTQLKSKFS SASNNSVYDE PLRIDLSLSS
PDTEHEPLSL PEGGTANGES GSSNDSSNQS TIKRPASMYE RRLVPNVAKG NTDIRNTTSM
YQMAGDGKPF GEEVKVRSDL VTRRLKELIR AMQPVPEDQK QSIAPHGELI RSAVTDLIAL
YANLPPNASD PSRETLKLLT RQNILIQHEC ENLQKAIEAD DKQAIQKNTL EVRDCAFHIA
SAIKTLVLQF Y
