CYFIP_DROME
ID CYFIP_DROME Reviewed; 1291 AA.
AC Q9VF87; Q6NP16; Q8MR06;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Cytoplasmic FMR1-interacting protein;
DE AltName: Full=Specifically Rac1-associated protein 1;
DE Short=DSra-1;
GN Name=Sra-1 {ECO:0000312|EMBL:AAF55173.1, ECO:0000312|FlyBase:FBgn0038320};
GN Synonyms=Cyfip {ECO:0000303|PubMed:11438699}; ORFNames=CG4931;
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] {ECO:0000312|EMBL:AAG61254.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11438699; DOI=10.1073/pnas.151231598;
RA Schenck A., Bardoni B., Moro A., Bagni C., Mandel J.-L.;
RT "A highly conserved protein family interacting with the fragile X mental
RT retardation protein (FMRP) and displaying selective interactions with FMRP-
RT related proteins FXR1P and FXR2P.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8844-8849(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAK31584.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Langmann C., Harden N.;
RT "DSra-1 is an effector for DRac1 during Drosophila embryogenesis.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAF55173.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAF55173.1};
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 [4] {ECO:0000312|EMBL:AAF55173.1}
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 [5] {ECO:0000305, ECO:0000312|EMBL:AAK31584.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1152.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAR82782.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAR82782.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAM52715.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-1291.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM52715.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM52715.1};
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 [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14588242; DOI=10.1016/j.cub.2003.10.005;
RA Kunda P., Craig G., Dominguez V., Baum B.;
RT "Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE
RT to regulate the formation of actin-based protrusions.";
RL Curr. Biol. 13:1867-1875(2003).
RN [8] {ECO:0000305}
RP FUNCTION, INTERACTION WITH FMR1 AND RAC1, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=12818175; DOI=10.1016/s0896-6273(03)00354-4;
RA Schenck A., Bardoni B., Langmann C., Harden N., Mandel J.-L.,
RA Giangrande A.;
RT "CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the
RT Rac1 GTPase pathway to the fragile X protein.";
RL Neuron 38:887-898(2003).
RN [9] {ECO:0000305}
RP FUNCTION, AND COMPONENT OF WAVE COMPLEX.
RX PubMed=15385157; DOI=10.1016/j.ydbio.2004.07.009;
RA Schenck A., Qurashi A., Carrera P., Bardoni B., Diebold C., Schejter E.,
RA Mandel J.-L., Giangrande A.;
RT "WAVE/SCAR, a multifunctional complex coordinating different aspects of
RT neuronal connectivity.";
RL Dev. Biol. 274:260-270(2004).
RN [10] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HEM, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15269173; DOI=10.1242/dev.01274;
RA Bogdan S., Grewe O., Strunk M., Mertens A., Klaembt C.;
RT "Sra-1 interacts with Kette and Wasp and is required for neuronal and
RT bristle development in Drosophila.";
RL Development 131:3981-3989(2004).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32200800; DOI=10.1016/j.cell.2020.02.044;
RA Kanellopoulos A.K., Mariano V., Spinazzi M., Woo Y.J., McLean C., Pech U.,
RA Li K.W., Armstrong J.D., Giangrande A., Callaerts P., Smit A.B.,
RA Abrahams B.S., Fiala A., Achsel T., Bagni C.;
RT "Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social
RT Behavior Deficits.";
RL Cell 180:1178-1197.e20(2020).
CC -!- FUNCTION: Plays a role in guidance and morphology of central and
CC peripheral axons and in synaptic morphology. Also required for
CC formation of cell membrane protrusions and for bristle development
CC (PubMed:12818175, PubMed:14588242, PubMed:15269173, PubMed:15385157).
CC Plays a role in regulating mitochondrial activity, energy metabolism
CC and membrane potential which maintains normal gamma-aminobutyric acid
CC (GABA) signaling and ensures normal social behavior (PubMed:32200800).
CC {ECO:0000269|PubMed:12818175, ECO:0000269|PubMed:14588242,
CC ECO:0000269|PubMed:15269173, ECO:0000269|PubMed:15385157,
CC ECO:0000269|PubMed:32200800}.
CC -!- SUBUNIT: Interacts with Fmr1 and Rac1. Component of the WAVE complex
CC composed of Hem/Kette, Scar/Wave and Sra-1/Cyfip where it binds through
CC its C-terminus directly to Hem. {ECO:0000269|PubMed:12818175,
CC ECO:0000269|PubMed:15269173, ECO:0000269|PubMed:15385157}.
CC -!- INTERACTION:
CC Q9VF87; Q24150: Nap1; NbExp=2; IntAct=EBI-116862, EBI-603430;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12818175}.
CC Note=Accumulates in central axons and motor neuron terminals.
CC {ECO:0000269|PubMed:12818175}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed mainly in the gut and in
CC the developing central nervous system where high levels of expression
CC are found in the CNS neuropile. Expression in the gut diminishes as
CC development proceeds (at protein level). In the adult, expressed
CC specifically in the nervous system. {ECO:0000269|PubMed:12818175,
CC ECO:0000269|PubMed:15269173}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout the life cycle with no major
CC peaks of expression. In the embryo, uniquitously and highly expressed
CC at precellular and cellular blastoderm stages.
CC {ECO:0000269|PubMed:12818175}.
CC -!- DISRUPTION PHENOTYPE: Flies display pupal lethality with defects in
CC axon growth, branching and pathfinding, synaptic length and
CC organization of the neuromuscular junction. They also display defects
CC in cell morphology with cells exhibiting a starfish-like shape with
CC multiple slender cell extensions and loss of actin filaments at the
CC cell periphery (PubMed:12818175, PubMed:14588242, PubMed:15269173).
CC RNAi-mediated knockdown in gamma-aminobutyric acid (GABA)ergic neurons,
CC or specifically in the anterior paired lateral (APL) neurons or in the
CC antennal lobe local interneurons (LNs), results in feeding-dependent
CC socialization defects (PubMed:32200800). {ECO:0000269|PubMed:12818175,
CC ECO:0000269|PubMed:14588242, ECO:0000269|PubMed:15269173,
CC ECO:0000269|PubMed:32200800}.
CC -!- SIMILARITY: Belongs to the CYFIP family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM52715.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY017343; AAG61254.1; -; mRNA.
DR EMBL; AY029211; AAK31584.1; -; mRNA.
DR EMBL; AE014297; AAF55173.1; -; Genomic_DNA.
DR EMBL; BT011115; AAR82782.1; -; mRNA.
DR EMBL; AY122203; AAM52715.1; ALT_INIT; mRNA.
DR RefSeq; NP_650447.1; NM_142190.3.
DR AlphaFoldDB; Q9VF87; -.
DR SMR; Q9VF87; -.
DR BioGRID; 66924; 11.
DR ComplexPortal; CPX-2972; WAVE regulatory complex.
DR DIP; DIP-33370N; -.
DR IntAct; Q9VF87; 6.
DR MINT; Q9VF87; -.
DR STRING; 7227.FBpp0082541; -.
DR PaxDb; Q9VF87; -.
DR PRIDE; Q9VF87; -.
DR EnsemblMetazoa; FBtr0083085; FBpp0082541; FBgn0038320.
DR GeneID; 41861; -.
DR KEGG; dme:Dmel_CG4931; -.
DR CTD; 41861; -.
DR FlyBase; FBgn0038320; Sra-1.
DR VEuPathDB; VectorBase:FBgn0038320; -.
DR eggNOG; KOG3534; Eukaryota.
DR HOGENOM; CLU_002688_2_1_1; -.
DR InParanoid; Q9VF87; -.
DR OMA; MPKVCKL; -.
DR OrthoDB; 108507at2759; -.
DR PhylomeDB; Q9VF87; -.
DR Reactome; R-DME-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-DME-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-DME-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR SignaLink; Q9VF87; -.
DR BioGRID-ORCS; 41861; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41861; -.
DR PRO; PR:Q9VF87; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038320; Expressed in embryonic/larval hemocyte (Drosophila) and 25 other tissues.
DR ExpressionAtlas; Q9VF87; baseline and differential.
DR Genevisible; Q9VF87; DM.
DR GO; GO:0045177; C:apical part of cell; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0031209; C:SCAR complex; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:FlyBase.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IMP:FlyBase.
DR GO; GO:0000902; P:cell morphogenesis; IMP:FlyBase.
DR GO; GO:0030031; P:cell projection assembly; IMP:FlyBase.
DR GO; GO:0060269; P:centripetally migrating follicle cell migration; IMP:FlyBase.
DR GO; GO:0022416; P:chaeta development; IMP:UniProtKB.
DR GO; GO:0001745; P:compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:FlyBase.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:FlyBase.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IEA:InterPro.
DR GO; GO:0008360; P:regulation of cell shape; IMP:FlyBase.
DR GO; GO:0050807; P:regulation of synapse organization; IMP:FlyBase.
DR GO; GO:0006417; P:regulation of translation; IBA:GO_Central.
DR InterPro; IPR009828; CYRIA/CYRIB_Rac1-bd.
DR InterPro; IPR008081; Cytoplasmic_FMR1-int.
DR PANTHER; PTHR12195; PTHR12195; 1.
DR Pfam; PF07159; DUF1394; 1.
DR Pfam; PF05994; FragX_IP; 1.
DR PIRSF; PIRSF008153; FMR1_interacting; 1.
DR PRINTS; PR01698; CYTOFMRPINTP.
PE 1: Evidence at protein level;
KW Cell shape; Cytoplasm; Developmental protein; Differentiation;
KW Neurogenesis; Reference proteome.
FT CHAIN 1..1291
FT /note="Cytoplasmic FMR1-interacting protein"
FT /id="PRO_0000279714"
FT REGION 1270..1291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1291 AA; 149261 MW; F3E4254BAD41015B CRC64;
MTEKITLADA LSNVEVLDEL SLPDEQPCIE AQPCSIIYKA NFDTNFEDRN GFVTGIAKYI
EEATTHANLN VLLDEGQKHA VMLYTWRCCS RAIPQPKSNE QPNRVEIYEK TVEVLAPEVN
KLLNFMYFQR KAIEAFSGEV KRLCHAEKRK DFVSEAYLLT LGKFINMFAV LDELKNMKSS
VKNDYSTYRR AAQFLKVMSD SHTLQESQNL SMFLATQNKI RDTVKDTLEK IVGYEDLLSD
VVNICVHMFE TKMYLTPEEK HMLVKVMGFG LFLMDSDACN INKLDQKKKI RLDRIDRIFK
NLEVVPLFGD MQIAPFNYIK RSKHFDSSKW PLSSSNAISP QADLMVHLPQ IREDHVKYIS
ELARYTNEVT TTVKENPSDA ENRITADLAL RGLQLLSEWT SVVTELYSWK LLHPTDHHQN
KECPVEAEEY ERATRYNYTS EEKFALIEVI AMIKGLQVLM ARIETVLCEA IRRNIYSELQ
DFVQLSLREP LRKAVKNKKD LIRSIIMSVR ETSADWQKGY EPTDDPVAKG KKDPDGGFRI
QVPRLNVGPS STQLYMVRTM LESLIADKSG GKRTLRKDID GNCLLQIDTF HKTSFYWSYL
LNFSDTLQKC CDLSQLWYRE FYLEMTMGRK VNKCLVRHQH NEECKDLITM EKRIQFPIEM
SMPWILTDHI LQTKEPSMME FVLYPLDLYN DSAYYALTVF RKQFLYDEVE AEVNLCFDQF
VYKLSEQIFA HYKQLAGSIF LDKRFRLECE VLGFNFQSYP RNNRYETLLK QRHVQLLGRS
IDLNKLITQR INANMHKSIE LAISRFEGND ITGIVELEGL LEANRICHKL LSKYLALDNF
DGMVKEANHN VLAPYGRITL HVFVELNYDF LVNYCYNAAT NRFIRTKVNL SSSQAIQREK
PPQMSHYYLW GSKQLNAAYS TQYGQYTGFV GSPHFHAMCR LLGYQGIAVV MDIILKDIVK
PLIQGSLLQF TKTLMIAMPK SCKLPRCEYG SPGVLSYYQA HLTDIVQYPD AKTELFQSFR
EFGNSIIFCL LIEQALSQEE VCDLLHAALF QNIFPRPFCK ENEKPEAKQK RLEAQFANLQ
IVSNVEKIGT AKQAMIAREG DLLTRERLCC GLSIFEVILN RVKSYLDDPV WCGPPPANGI
IHVDECSEFH RLWSALQFVY CIPVRGTEYT IEELFGEGLN WAGCVMIVLL GQQRRFEALD
FCYHILRVQR VDGKDEDVKG IQLKRMVDRI RRFQVLNSQI FSILNKYLKG GDGEGSNVEH
VRCFPPPQHP SVISSSSHYQ DPQKLRQSIN N
