TOCA2_CAEEL
ID TOCA2_CAEEL Reviewed; 610 AA.
AC Q9XUS7; Q9U3B8;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Transducer of Cdc42-dependent actin assembly protein 2 homolog {ECO:0000305};
GN Name=toca-2 {ECO:0000312|WormBase:K08E3.3b};
GN ORFNames=K08E3.3 {ECO:0000312|WormBase:K08E3.3b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, INTERACTION WITH WSP-1 AND ABI-1, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19798448; DOI=10.1371/journal.pgen.1000675;
RA Giuliani C., Troglio F., Bai Z., Patel F.B., Zucconi A., Malabarba M.G.,
RA Disanza A., Stradal T.B., Cassata G., Confalonieri S., Hardin J.D.,
RA Soto M.C., Grant B.D., Scita G.;
RT "Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin dynamics and
RT membrane trafficking during Caenorhabditis elegans oocyte growth and
RT embryonic epidermal morphogenesis.";
RL PLoS Genet. 5:E1000675-E1000675(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26578656; DOI=10.1093/jmcb/mjv062;
RA Ouellette M.H., Martin E., Lacoste-Caron G., Hamiche K., Jenna S.;
RT "Spatial control of active CDC-42 during collective migration of hypodermal
RT cells in Caenorhabditis elegans.";
RL J. Mol. Cell Biol. 8:313-327(2016).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CDC-42 AND WVE-1, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ILE-413 AND TRP-585.
RX PubMed=25775511; DOI=10.1073/pnas.1418651112;
RA Bai Z., Grant B.D.;
RT "A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic
RT recycling.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1443-E1452(2015).
CC -!- FUNCTION: Plays a role in protein trafficking, actin organization and
CC embryonic morphogenesis (PubMed:19798448). Potentially acts as cdc-42
CC effector (PubMed:25775511). May play a role in egg laying
CC (PubMed:19798448). Together with toca-1, is required for protein
CC trafficking regulating yolk protein clathrin-mediated endocytosis by
CC oocytes during oogenesis and retrograde recycling and the sorting of
CC recycling endosome cargo proteins such as mig-14 (PubMed:19798448,
CC PubMed:25775511). Also, together with toca-2, controls the distribution
CC of actin at cell junctions (PubMed:19798448, PubMed:26578656).
CC {ECO:0000269|PubMed:19798448, ECO:0000269|PubMed:25775511,
CC ECO:0000269|PubMed:26578656}.
CC -!- SUBUNIT: Interacts (via SH3 domain) with wsp-1 and abi-1
CC (PubMed:19798448). Interacts with cdc-42 and (via SH3 domain) with wve-
CC 1 (PubMed:25775511). {ECO:0000269|PubMed:19798448,
CC ECO:0000269|PubMed:25775511}.
CC -!- SUBCELLULAR LOCATION: Cell junction {ECO:0000269|PubMed:19798448}. Cell
CC membrane {ECO:0000269|PubMed:19798448}; Peripheral membrane protein
CC {ECO:0000269|PubMed:19798448}; Cytoplasmic side
CC {ECO:0000269|PubMed:19798448}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:19798448}. Cytoplasm {ECO:0000269|PubMed:19798448}.
CC Recycling endosome {ECO:0000269|PubMed:25775511}. Note=Diffuse
CC cytoplasmic localization (PubMed:19798448). Localizes to the rachis,
CC which is the central core of the cytoplasm connecting developing
CC oocytes in the syncytial gonad (PubMed:19798448). Co-localizes with
CC toca-1 on recycling endosomes (PubMed:25775511).
CC {ECO:0000269|PubMed:19798448, ECO:0000269|PubMed:25775511}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:K08E3.3b};
CC IsoId=Q9XUS7-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:K08E3.3a};
CC IsoId=Q9XUS7-2; Sequence=VSP_058523;
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in developing embryos.
CC {ECO:0000269|PubMed:19798448}.
CC -!- DISRUPTION PHENOTYPE: Double knockout with toca-1 results in nearly
CC 100% of mutants with defective endocytosis by oocytes characterized by
CC either reduced or non-detectable yolk protein in the oocytes and by an
CC accumulation of aggregated yolk protein in the pseudocoelomatic space.
CC Double knockout mutants with toca-1 also produce 20% fewer eggs
CC compared to wild-type animals and there is some embryonic lethality
CC whereby the dying embryos display defective morphogenesis including
CC failed epidermal enclosure with extruding gut cells and increased width
CC of the intestinal lumen (PubMed:19798448). This perhaps results from
CC failed intercalation and migration of hypodermal cells and irregular
CC protein trafficking as indicated by an accumulation of the cell
CC junction protein ajm-1 and diffuse localization of actin at cell
CC junctions (PubMed:19798448, PubMed:26578656). These double mutants also
CC demonstrate defective endosomal sorting of recycling cargo proteins
CC such as mig-14 (PubMed:25775511). {ECO:0000269|PubMed:19798448,
CC ECO:0000269|PubMed:25775511, ECO:0000269|PubMed:26578656}.
CC -!- SIMILARITY: Belongs to the FNBP1 family. {ECO:0000305}.
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DR EMBL; BX284603; CAB04595.2; -; Genomic_DNA.
DR EMBL; BX284603; CAB04591.2; -; Genomic_DNA.
DR PIR; T23452; T23452.
DR PIR; T23456; T23456.
DR RefSeq; NP_499838.2; NM_067437.3. [Q9XUS7-1]
DR RefSeq; NP_499839.2; NM_067438.3. [Q9XUS7-2]
DR AlphaFoldDB; Q9XUS7; -.
DR SMR; Q9XUS7; -.
DR IntAct; Q9XUS7; 4.
DR STRING; 6239.K08E3.3b; -.
DR PaxDb; Q9XUS7; -.
DR EnsemblMetazoa; K08E3.3a.1; K08E3.3a.1; WBGene00010663. [Q9XUS7-2]
DR EnsemblMetazoa; K08E3.3b.1; K08E3.3b.1; WBGene00010663. [Q9XUS7-1]
DR GeneID; 176812; -.
DR KEGG; cel:CELE_K08E3.3; -.
DR UCSC; K08E3.3a; c. elegans.
DR CTD; 176812; -.
DR WormBase; K08E3.3a; CE37123; WBGene00010663; toca-2. [Q9XUS7-2]
DR WormBase; K08E3.3b; CE37124; WBGene00010663; toca-2. [Q9XUS7-1]
DR eggNOG; KOG3565; Eukaryota.
DR GeneTree; ENSGT00950000183047; -.
DR HOGENOM; CLU_023320_2_0_1; -.
DR InParanoid; Q9XUS7; -.
DR OMA; FATRANP; -.
DR OrthoDB; 348563at2759; -.
DR PhylomeDB; Q9XUS7; -.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:Q9XUS7; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00010663; Expressed in germ line (C elegans) and 3 other tissues.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0097708; C:intracellular vesicle; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0048613; P:embryonic ectodermal digestive tract morphogenesis; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:1904703; P:negative regulation of protein localization to adherens junction; IGI:UniProtKB.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:1901046; P:positive regulation of oviposition; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IGI:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS51860; REM_1; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endocytosis; Endosome; Membrane; Reference proteome;
KW SH3 domain.
FT CHAIN 1..610
FT /note="Transducer of Cdc42-dependent actin assembly protein
FT 2 homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437444"
FT DOMAIN 1..267
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 352..429
FT /note="REM-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 547..610
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 283..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 436..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 499..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 355..385
FT /evidence="ECO:0000255"
FT COMPBIAS 300..315
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 499..516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 590..592
FT /note="NCR -> K (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058523"
FT MUTAGEN 413
FT /note="I->S: Abolishes binding to cdc-42 and rescues the
FT endosomal cargo sorting defect in the double toca-1 and
FT toca-2 mutant."
FT /evidence="ECO:0000269|PubMed:25775511"
FT MUTAGEN 585
FT /note="W->K: Abolishes binding to wve-1 and rescues the
FT endosomal cargo sorting defect in the double toca-1 and
FT toca-2 mutant."
FT /evidence="ECO:0000269|PubMed:25775511"
SQ SEQUENCE 610 AA; 68484 MW; 2DDBDDF416B30D5A CRC64;
MIPVSRFFTV QDPSNALLSY TQKGIDFFEK LGQFSKEKAA IEEEYSTKLR SLAKKYAKKS
EEDDEILKSV SYTSSFNSFL QQLDQIATRH QTSAEHIRGG VVSYVASKTC QMRSSRKNAI
NDLKTINDKL EDQINEMCKS GKCYLKSFKD AENSYQKFYK ADKNLEISRL ELEKARALAN
ARNEACELAK QDYSALVRKT NAEQKRYHVE LLPVIFARLK AVDKECIADM RQVLQKIVSF
DDSLADSTEE CRKIMQREVG KIDAEGDAQL VLKSVEATIE QPAPFEIEDL GDPKNCDSRT
NDSADGSGGK LLKSSPSKNR IIRNFLGILK EKEADEKPEA SNNDQLMYTD KSKPAHVRLS
CLRSKIRDME KQLEQAIQGR EGITRLQQAY YTNPQHGNPS ACTEPLISYA KKIEKLKMDI
HNLKEFYAML EMSVEEGQER SFGGRDTPDT TRSMSGSSTN QSSSKTIEDV LSGEAGNSSS
ADDSSKNILR QLFTTPKRLI SSPKTSKSST PTPLRRRAEI SSPKILRSSF SGAIRKSLST
PDSVKVETAV TVTALFEFAK SSAETMSIEQ GEILLVLEHD HGDGWTRTKN CRKHNEESGF
VPTSYLQFPQ
