FRL_DROME
ID FRL_DROME Reviewed; 1183 AA.
AC Q9VUC6; B7Z050; M9PCF8; Q86NT2; Q9VUC5;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Formin-like protein {ECO:0000305};
DE AltName: Full=Formin related in leukocytes {ECO:0000303|PubMed:26801180};
GN Name=Frl {ECO:0000303|PubMed:26801180, ECO:0000312|FlyBase:FBgn0267795};
GN ORFNames=CG32138 {ECO:0000312|FlyBase:FBgn0267795};
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] (ISOFORM C).
RC STRAIN=Berkeley; TISSUE=Testis;
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 (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [5]
RP FUNCTION, SELF-ASSOCIATION, INTERACTION WITH CDC42, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 373-ARG--CYS-1183 AND 683-GLY--LYS-1131.
RX PubMed=26801180; DOI=10.1534/genetics.115.181438;
RA Dollar G., Gombos R., Barnett A.A., Sanchez Hernandez D., Maung S.M.,
RA Mihaly J., Jenny A.;
RT "Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial
RT Rotation and Neuronal Development in Drosophila.";
RL Genetics 202:1135-1151(2016).
CC -!- FUNCTION: Together with Cdc42, involved in establishment of planar cell
CC polarity in the developing compound eye by contributing to ommatidial
CC rotation. Together with DAAM and Cdc42, has a role in neuronal
CC development of mushroom bodies. {ECO:0000269|PubMed:26801180}.
CC -!- SUBUNIT: Self-associates. Interacts (via GBD/FH3 domain) with Cdc42;
CC the interaction is stronger with the GTP bound form of Cdc42.
CC {ECO:0000269|PubMed:26801180}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=Q9VUC6-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VUC6-2; Sequence=VSP_037173, VSP_037175;
CC Name=C;
CC IsoId=Q9VUC6-3; Sequence=VSP_037173;
CC Name=D {ECO:0000312|FlyBase:FBgn0267795};
CC IsoId=Q9VUC6-4; Sequence=VSP_037173, VSP_059691, VSP_059692;
CC -!- DOMAIN: The DAD domain regulates activation via by an autoinhibitory
CC interaction with the GBD/FH3 domain. This autoinhibition is released
CC upon competitive binding of an activated GTPase. The release of DAD
CC allows the FH2 domain to then nucleate and elongate nonbranched actin
CC filaments. {ECO:0000305|PubMed:26801180}.
CC -!- DISRUPTION PHENOTYPE: Lethal; shows planar cell polarity defects with
CC abnormal ommatidial orientation. RNAi-mediated knockdown in the eye
CC results in planar cell polarity defects with ommatidia showing
CC defective rotation. {ECO:0000269|PubMed:26801180}.
CC -!- SIMILARITY: Belongs to the formin homology family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO39658.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE014296; AAF49761.3; -; Genomic_DNA.
DR EMBL; AE014296; AAF49762.3; -; Genomic_DNA.
DR EMBL; AE014296; ACL83303.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94517.1; -; Genomic_DNA.
DR EMBL; BT003654; AAO39658.1; ALT_INIT; mRNA.
DR RefSeq; NP_001137948.1; NM_001144476.3. [Q9VUC6-3]
DR RefSeq; NP_001261824.1; NM_001274895.2. [Q9VUC6-4]
DR RefSeq; NP_729954.2; NM_168575.4. [Q9VUC6-1]
DR RefSeq; NP_729955.2; NM_168576.4. [Q9VUC6-2]
DR AlphaFoldDB; Q9VUC6; -.
DR SMR; Q9VUC6; -.
DR BioGRID; 64899; 30.
DR IntAct; Q9VUC6; 5.
DR STRING; 7227.FBpp0075517; -.
DR iPTMnet; Q9VUC6; -.
DR PaxDb; Q9VUC6; -.
DR PRIDE; Q9VUC6; -.
DR EnsemblMetazoa; FBtr0075775; FBpp0075517; FBgn0267795. [Q9VUC6-1]
DR EnsemblMetazoa; FBtr0075776; FBpp0075518; FBgn0267795. [Q9VUC6-2]
DR EnsemblMetazoa; FBtr0114573; FBpp0113065; FBgn0267795. [Q9VUC6-3]
DR EnsemblMetazoa; FBtr0334053; FBpp0306179; FBgn0267795. [Q9VUC6-4]
DR GeneID; 39561; -.
DR KEGG; dme:Dmel_CG32138; -.
DR UCSC; CG32138-RA; d. melanogaster. [Q9VUC6-1]
DR UCSC; CG32138-RB; d. melanogaster.
DR UCSC; CG32138-RC; d. melanogaster.
DR CTD; 103936; -.
DR FlyBase; FBgn0267795; Frl.
DR VEuPathDB; VectorBase:FBgn0267795; -.
DR eggNOG; KOG1923; Eukaryota.
DR GeneTree; ENSGT00940000169082; -.
DR InParanoid; Q9VUC6; -.
DR OMA; MMPGFSP; -.
DR PhylomeDB; Q9VUC6; -.
DR Reactome; R-DME-5663220; RHO GTPases Activate Formins.
DR Reactome; R-DME-8980692; RHOA GTPase cycle.
DR Reactome; R-DME-9013106; RHOC GTPase cycle.
DR SignaLink; Q9VUC6; -.
DR BioGRID-ORCS; 39561; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 39561; -.
DR PRO; PR:Q9VUC6; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0267795; Expressed in seminal fluid secreting gland and 27 other tissues.
DR ExpressionAtlas; Q9VUC6; baseline and differential.
DR Genevisible; Q9VUC6; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0048675; P:axon extension; IGI:FlyBase.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0016319; P:mushroom body development; IMP:FlyBase.
DR GO; GO:0016318; P:ommatidial rotation; IMP:FlyBase.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014767; DAD_dom.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR010472; FH3_dom.
DR InterPro; IPR043592; FMNL_animal.
DR InterPro; IPR014768; GBD/FH3_dom.
DR InterPro; IPR010473; GTPase-bd.
DR PANTHER; PTHR45857; PTHR45857; 1.
DR Pfam; PF06367; Drf_FH3; 1.
DR Pfam; PF06371; Drf_GBD; 2.
DR Pfam; PF02181; FH2; 1.
DR SMART; SM01139; Drf_FH3; 1.
DR SMART; SM01140; Drf_GBD; 1.
DR SMART; SM00498; FH2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51231; DAD; 1.
DR PROSITE; PS51444; FH2; 1.
DR PROSITE; PS51232; GBD_FH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome.
FT CHAIN 1..1183
FT /note="Formin-like protein"
FT /id="PRO_0000372648"
FT DOMAIN 76..559
FT /note="GBD/FH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT DOMAIN 687..1088
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT DOMAIN 1136..1169
FT /note="DAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 572..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 572..602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 603..643
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..678
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT VAR_SEQ 150..158
FT /note="Missing (in isoform B, isoform C and isoform D)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_037173"
FT VAR_SEQ 1104..1122
FT /note="LPSNGALSLQEAVINELKS -> QIHCLLDFANQQQKQLAQS (in
FT isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_059691"
FT VAR_SEQ 1104..1113
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_037175"
FT VAR_SEQ 1123..1183
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_059692"
FT MUTAGEN 373..1183
FT /note="Missing: Loss of autoinhibition mediated by self-
FT association results in severe eye defects including loss of
FT R-cells."
FT /evidence="ECO:0000269|PubMed:26801180"
FT MUTAGEN 683..1131
FT /note="Missing: Loss of autoinhibition mediated by self-
FT association results in rotation defects in the adult eye."
FT /evidence="ECO:0000269|PubMed:26801180"
FT CONFLICT 25
FT /note="S -> P (in Ref. 3; AAO39658)"
FT /evidence="ECO:0000305"
FT CONFLICT 246..248
FT /note="SSV -> TSF (in Ref. 3; AAO39658)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1183 AA; 133159 MW; 52347E7178704576 CRC64;
MGAVKSRTIT SADVDADEQL QHPHSHAHHH SMRNGHQHNG SISSGTLQKQ DLRYDIGCSS
QYQHVRQPSL RSRSQQPMPT TDELDRRFAK VLASMDLPPD KAKLLRNYDD EKKWDMICDQ
EMVQAKDPPS HYLSKLRTYL DPKASRSHRL YLFYFLCQKR KMVGESTSTQ VLRDLEISLR
TNHIEWVKEF LDDTNQGLDA LVDYLSFRLQ MMRHEQRLQG VLCASEERLN LTNGGDGGEI
VMGNSSSVSP GGGGGLLSHG NSTGHGLANG TLDSRQQHTM SYGFLRPTIA DALDSPSLKR
RSRHIAKLNM GAATDDIHVS IMCLRAIMNN KYGFNMVIQH REAINCIALS LIHKSLRTKA
LVLELLAAIC LVKGGHEIIL GSFDNFKDVC QEKRRFQTLM EYFMNFEAFN IDFMVACMQF
MNIVVHSVED MNYRVHLQYE FTALGLDKYL ERIRLTESEE LKVQISAYLD NVFDVAALME
DSETKTSALE RVQELEDQLE REIDRNSEFL YKYAELESES LTLKTEREQL AMIRQKLEEE
LTVMQRMLQH NEQELKKRDT LLHTKNMELQ TLSRSLPRSA SSGDGSLANG GLMAGSTSGA
ASLTLPPPPP PMPASPTASS AAPPPPPPPA PPAPPPPPGF SPLGSPSGSL ASTAPSPPHA
PPMLSSFQPP PPPVAGFMPA PDGAMTIKRK VPTKYKLPTL NWIALKPNQV RGTIFNELDD
EKIFKQIDFN EFEERFKIGI GGALRNGSNG TEVDGSLQSS KRFKRPDNVS LLEHTRLRNI
AISRRKLGMP IDDVIAAIHS LDLKKLSLEN VELLQKMVPT DAEVKSYKEY IIERKDQQLL
TEEDKFMLQL SRVERISSKL AIMNYMGNFV DSVHLISPQV QSIAGASTSL KQSRKFKAVL
EIVLAFGNYL NSNKRGPAYG FKLQSLDTLI DTKSTDKRSS LLHYIVATIR AKFPELLNFE
SELYGTDKAA SVALENVVAD VQELEKGMDL VRKEAELRVK GAQTHILRDF LNNSEDKLKK
IKSDLRHAQE AFKECVEYFG DSSRNADAAA FFALIVRFTR AFKQHDQENE QRLRLEKAAA
LAASKKENDQ VLMRNKVNQK KQQLPSNGAL SLQEAVINEL KSKAHSVREK KLLQQDEVYN
GALEDILLGL KSEPYRRADA VRRSQRRRID NNRLSRTLEE MDC
