ID   FMNL3_DANRE             Reviewed;        1047 AA.
AC   Q6NXC0;
DT   22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 2.
DT   03-AUG-2022, entry version 122.
DE   RecName: Full=Formin-like protein 3;
DE   AltName: Full=Formin homology 2 domain-containing protein 3;
GN   Name=fmnl3; Synonyms=frl2; ORFNames=si:ch73-60e21.1;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 658-1047.
RC   TISSUE=Kidney;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=22275430; DOI=10.1242/jcs.091066;
RA   Hetheridge C., Scott A.N., Swain R.K., Copeland J.W., Higgs H.N.,
RA   Bicknell R., Mellor H.;
RT   "The formin FMNL3 is a cytoskeletal regulator of angiogenesis.";
RL   J. Cell Sci. 125:1420-1428(2012).
CC   -!- FUNCTION: Required for developmental angiogenesis, but not for
CC       vasculogenesis. {ECO:0000269|PubMed:22275430}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8IVF7}. Cell
CC       membrane {ECO:0000250|UniProtKB:Q8IVF7}; Lipid-anchor {ECO:0000255}.
CC   -!- DEVELOPMENTAL STAGE: At 24 hpf, expression almost entirely restricted
CC       to the endothelial cells of the developing vasculature, with high
CC       levels in the major head and trunk vessels and also in the intersomitic
CC       vessels. {ECO:0000269|PubMed:22275430}.
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC       profound defects in angiogenesis. Although sprouting of the
CC       intersomitic vessels occurs, the endothelial cells fail to extend fully
CC       across the intersomic region and there is no apparent formation of the
CC       dorsal longitudinal anastomosing vessel. No other obvious defect is
CC       observed in the developing morphant. {ECO:0000269|PubMed:22275430}.
CC   -!- SIMILARITY: Belongs to the formin homology family. {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; CR457457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CT573346; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC067154; AAH67154.1; -; mRNA.
DR   RefSeq; NP_001333083.1; NM_001346154.1.
DR   AlphaFoldDB; Q6NXC0; -.
DR   SMR; Q6NXC0; -.
DR   STRING; 7955.ENSDARP00000099869; -.
DR   PaxDb; Q6NXC0; -.
DR   Ensembl; ENSDART00000109023; ENSDARP00000099869; ENSDARG00000004372.
DR   GeneID; 407694; -.
DR   KEGG; dre:407694; -.
DR   CTD; 91010; -.
DR   ZFIN; ZDB-GENE-030131-1571; fmnl3.
DR   eggNOG; KOG1923; Eukaryota.
DR   GeneTree; ENSGT00940000159962; -.
DR   OrthoDB; 288325at2759; -.
DR   Reactome; R-DRE-5663220; RHO GTPases Activate Formins.
DR   Reactome; R-DRE-8980692; RHOA GTPase cycle.
DR   Reactome; R-DRE-9013106; RHOC GTPase cycle.
DR   Reactome; R-DRE-9013148; CDC42 GTPase cycle.
DR   Reactome; R-DRE-9013409; RHOJ GTPase cycle.
DR   PRO; PR:Q6NXC0; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 23.
DR   Bgee; ENSDARG00000004372; Expressed in swim bladder and 48 other tissues.
DR   ExpressionAtlas; Q6NXC0; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR   GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR   GO; GO:0030041; P:actin filament polymerization; IDA:ZFIN.
DR   GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
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:0046847; P:filopodium assembly; IMP:ZFIN.
DR   GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR   GO; GO:0002040; P:sprouting angiogenesis; IMP:ZFIN.
DR   Gene3D; 1.20.58.2220; -; 1.
DR   Gene3D; 1.25.10.10; -; 1.
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; IPR027655; Fmnl3.
DR   InterPro; IPR043592; FMNL_animal.
DR   InterPro; IPR014768; GBD/FH3_dom.
DR   InterPro; IPR010473; GTPase-bd.
DR   PANTHER; PTHR45857; PTHR45857; 1.
DR   PANTHER; PTHR45857:SF3; PTHR45857:SF3; 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   2: Evidence at transcript level;
KW   Actin-binding; Angiogenesis; Cell membrane; Cytoplasm;
KW   Developmental protein; Lipoprotein; Membrane; Myristate;
KW   Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000255"
FT   CHAIN           2..1047
FT                   /note="Formin-like protein 3"
FT                   /id="PRO_0000433514"
FT   DOMAIN          22..462
FT                   /note="GBD/FH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT   DOMAIN          580..970
FT                   /note="FH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT   DOMAIN          1000..1037
FT                   /note="DAD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT   REGION          520..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        524..561
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           2
FT                   /note="N-myristoyl glycine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1047 AA;  118946 MW;  4039846438B8718A CRC64;
     MGNIESVDGQ SEMKHHIMPL KVPMPDPTEL EERFAIVLNS MNLPPDKARL LRQYDNEKKW
     DLICDQERFQ VKNPPHTYIQ KLRGYLDPKV TRKKFRRRVQ ESTKVLRELE ISLRTNHIGW
     VREFLNDENR GLDILVEYLS FAQCAVMLDF EGLENGEDFS LDKAKSWSRS IEDLHQNGCN
     TLVRSARQSV LRYGSTSNSK TIKNSRLVSQ KDDVHVCIMC LRAIMNYQYG FNLVMSHAHA
     VNEIALSLNN KNPRTKALVL ELLAAVCLVR GGHEIILSAF DNFKEVCKEK HRFEKLMEYF
     RSEDGNIDFM VACMQFINIV VHSVEDMNFR VHLQYEFTKL GLDDFLEKSK HTESDKLSVQ
     IQAYLDNVFD VGGLLEDAET KNVALEKVEE LEEHLSHVTE KLLDVENETM TKVADLEKQL
     LHKDKELAVI KETYESASTQ VHTLRRMIQE KDAAFQRHNN IEKQLLELEQ QGTIRLRKQP
     DGDIAIETLG AGAVAGTPLT DLRSLTVGMS TIGGLGGTSA VPVEAVAPPP PPPPPPPPPP
     PAPPLPSEVE SIPIPPPPPP PLPGPSPSVI LSVGLSAIRI KKPIKTKFRL PVFNWTALKP
     NQINGTVFNE IDDDRVLEEL DLEKFEELFK TKAQGPVVDL SCSKSKVSQK VINKVQLLDA
     NRSKNLAITL RKANKTTEEI CKAIQTFDLK ALPVDFVECL MRFLPTEAES KLLRQYERER
     RPLDQLAEED RFMLLFSKIE RLTQRMSIIT FVGNFNDNVN MLTPQLNAII AASASVKSSP
     KLKKILEIIL ALGNYMNSSK RGSVYGFKLQ SLDLLLDTKS TDRKMTLLHY IALVVKEKYP
     ELANFYNELH FVDKAAAVSL ENVLLDVKEL GKGMDLVRRE CSLHDHAVLK GFAQTSDTQL
     DKLAKDAKTA EEAFNNVVLY FGESPKTTPP SVFFPVFVRF IRAYKEAVEE NEQRKKQEEA
     MREKLLAQEA KQHDPKVQAQ KKRHQQQELI AELRRRQAKD HRPVYEGKDG TIEDIITVLK
     SVPFTARTAK RGSRFFCDAN LFDESIC