TFG_CAEEL
ID TFG_CAEEL Reviewed; 486 AA.
AC Q9U1W1;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Protein tfg-1 {ECO:0000305};
GN Name=tfg-1 {ECO:0000312|WormBase:Y63D3A.5};
GN ORFNames=Y63D3A.5 {ECO:0000312|WormBase:Y63D3A.5};
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, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18635357; DOI=10.1016/j.cub.2008.06.065;
RA Chen L., McCloskey T., Joshi P.M., Rothman J.H.;
RT "ced-4 and proto-oncogene tfg-1 antagonistically regulate cell size and
RT apoptosis in C. elegans.";
RL Curr. Biol. 18:1025-1033(2008).
RN [3] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBUNIT, INTERACTION WITH
RP SEC-16A.1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21478858; DOI=10.1038/ncb2225;
RA Witte K., Schuh A.L., Hegermann J., Sarkeshik A., Mayers J.R., Schwarze K.,
RA Yates J.R. III, Eimer S., Audhya A.;
RT "TFG-1 function in protein secretion and oncogenesis.";
RL Nat. Cell Biol. 13:550-558(2011).
CC -!- FUNCTION: In its hexameric form, promotes the accumulation of sec-16A.1
CC and the COPII subunit npp-20 at endoplasmic reticulum exit sites
CC (ERES), also known as transitional endoplasmic reticulum (tER), to
CC positively regulate secretory cargo trafficking from the endoplasmic
CC reticulum to the endoplasmic reticulum-Golgi intermediate compartment
CC (ERGIC) and Golgi apparatus (PubMed:21478858). Required for the
CC assembly of proteins, such as the GTPase rab-6, at the Golgi apparatus
CC (PubMed:21478858). Plays a role in negatively regulating cell death and
CC promoting cell and body growth (PubMed:18635357).
CC {ECO:0000269|PubMed:18635357, ECO:0000269|PubMed:21478858}.
CC -!- SUBUNIT: Hexamer (PubMed:21478858). The N-terminus assembles into an
CC octamer and the C-terminus forms a dimer thus the N-terminus mediates
CC its oligomerization, whereas the C-terminus restricts the full-length
CC protein to form hexamers in solution in vitro (PubMed:21478858).
CC Interacts (via N-terminus) with sec-16A.1; the interaction is direct
CC and is required for both the localization of tfg-1 and to maintain the
CC distribution of sec-16A.1 at endoplasmic reticulum exit sites (ERES)
CC (PubMed:21478858). {ECO:0000269|PubMed:21478858}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:21478858}. Endoplasmic reticulum-Golgi intermediate
CC compartment {ECO:0000269|PubMed:21478858}. Mitochondrion
CC {ECO:0000269|PubMed:18635357}. Note=In oocytes, co-localizes with sec-
CC 16A.1 at endoplasmic reticulum exit sites (ERES) (PubMed:21478858). In
CC proximal oocytes, localizes to a cloud-like region at endoplasmic
CC reticulum exit sites that spreads to the endoplasmic reticulum-Golgi
CC intermediate compartment (ERGIC) (PubMed:21478858).
CC {ECO:0000269|PubMed:21478858}.
CC -!- TISSUE SPECIFICITY: Expressed in intestinal, hypodermal and muscle
CC tissues (PubMed:21478858). Highly expressed in the reproductive system
CC (PubMed:21478858). {ECO:0000269|PubMed:21478858}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis (at protein
CC level) (PubMed:18635357). First expressed at the two-cell stage of
CC embryogenesis (at protein level) (PubMed:18635357).
CC {ECO:0000269|PubMed:18635357}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in embryos results in
CC lethality prior to hatching and an increased number of apoptotic cell
CC corpses at the comma stage of embryogenesis (PubMed:18635357). RNAi-
CC mediated knockdown in developing larvae results in smaller adults which
CC have reduced locomotory muscle and epidermal cell sizes, and reduced
CC total body protein content (PubMed:18635357). Cell size defects are
CC suppressed in a ced-4 n1162 or ced-4 RNAi mutant background
CC (PubMed:18635357). RNAi-mediated knockdown results in smaller and
CC poorly stacked endoplasmic reticulum-Golgi intermediate compartment
CC (ERGIC) and Golgi membranes, fragmentation of the endoplasmic reticulum
CC and few Golgi networks (PubMed:21478858). RNAi-mediated knockdown
CC reduces the accumulation of sec-16A.1 and the COPII subunit npp-20 at
CC endoplasmic reticulum exit sites (ERES) within the germline
CC (PubMed:21478858). Does not reduce the expression of sec-16A.1 and does
CC not affect the localization of npp-20 to the nuclear envelope
CC (PubMed:21478858). RNAi-mediated knockdown causes the disassembly of
CC the npp-20-containing heterotetrameric complex, resulting in monomeric
CC npp-20 (PubMed:21478858). RNAi-mediated knockdown results in defective
CC secretory cargo trafficking from the endoplasmic reticulum to the ERGIC
CC and Golgi apparatus, and the subsequence accumulation of secreted
CC integral membrane proteins including snb-1, cav-1 and sqv-8 in the
CC endoplasmic reticulum (PubMed:21478858). RNAi-mediated knockdown
CC results in disrupted retrograde trafficking of the GTPase rab-6 from
CC the Golgi apparatus to the endoplasmic reticulum and causes the
CC accumulation of rab-6 at enlarged early endosomes (PubMed:21478858).
CC {ECO:0000269|PubMed:18635357, ECO:0000269|PubMed:21478858}.
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DR EMBL; BX284601; CAB63398.1; -; Genomic_DNA.
DR RefSeq; NP_493462.1; NM_061061.5.
DR AlphaFoldDB; Q9U1W1; -.
DR SMR; Q9U1W1; -.
DR DIP; DIP-26017N; -.
DR IntAct; Q9U1W1; 12.
DR STRING; 6239.Y63D3A.5.2; -.
DR EPD; Q9U1W1; -.
DR PaxDb; Q9U1W1; -.
DR PeptideAtlas; Q9U1W1; -.
DR EnsemblMetazoa; Y63D3A.5.1; Y63D3A.5.1; WBGene00006565.
DR EnsemblMetazoa; Y63D3A.5.2; Y63D3A.5.2; WBGene00006565.
DR GeneID; 173277; -.
DR KEGG; cel:CELE_Y63D3A.5; -.
DR UCSC; Y63D3A.5.1; c. elegans.
DR CTD; 173277; -.
DR WormBase; Y63D3A.5; CE20336; WBGene00006565; tfg-1.
DR eggNOG; ENOG502QR6R; Eukaryota.
DR GeneTree; ENSGT00510000047809; -.
DR HOGENOM; CLU_525000_0_0_1; -.
DR InParanoid; Q9U1W1; -.
DR OMA; FNHRPAH; -.
DR OrthoDB; 1428791at2759; -.
DR Reactome; R-CEL-204005; COPII-mediated vesicle transport.
DR SignaLink; Q9U1W1; -.
DR PRO; PR:Q9U1W1; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00006565; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:WormBase.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:WormBase.
DR GO; GO:0042802; F:identical protein binding; IEA:InterPro.
DR GO; GO:0048208; P:COPII vesicle coating; IEA:InterPro.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:WormBase.
DR GO; GO:0072595; P:maintenance of protein localization in organelle; IMP:WormBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:WormBase.
DR GO; GO:0009306; P:protein secretion; IMP:WormBase.
DR GO; GO:0001558; P:regulation of cell growth; IMP:WormBase.
DR GO; GO:0008361; P:regulation of cell size; IMP:WormBase.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:WormBase.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR033512; TFG.
DR PANTHER; PTHR15335; PTHR15335; 1.
DR Pfam; PF00564; PB1; 1.
DR SMART; SM00666; PB1; 1.
DR PROSITE; PS51745; PB1; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; ER-Golgi transport; Mitochondrion;
KW Reference proteome; Transport.
FT CHAIN 1..486
FT /note="Protein tfg-1"
FT /id="PRO_0000450676"
FT DOMAIN 10..91
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT REGION 1..195
FT /note="Required for interaction with sec-16A.1"
FT /evidence="ECO:0000269|PubMed:21478858"
FT REGION 197..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..237
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..264
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..290
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..305
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..464
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 486 AA; 49739 MW; A1788AC56E08B98C CRC64;
MVHSNGAITS TILKARHADV VRKTSLHHAN DLTLIDLVLN VQRLLALPSD ANFVLKYKDE
EGDLVTLAED SDLLLALHTS GATLDVTVVV DSRAREAVHD VQKQVEQIKL DVGKLLGALS
ALDVAQIAEQ SNTSVANLSA PKQSHHDNIV FQKSFEAAPP SPVPSEKAEL PATIQPSVHE
QFNHRPAHVE EEIPLENHYA PPPHQQIPDD LNTSFSSQPP PPIEQFGAIP PPNATIPSFP
TSNAASPPVQ EFAPPPPQQQ QQQFQAPPPP MASHSSISST PVQQQGFAPP QQFGGPPPSG
PPSEYGGYAP PQQQQQQFGA PPPQGAPQQG FGAPPQGPPQ GGPPQGSFGA PPPQQFHAPS
PQSFGGPPPP VSSAPGNFAP PPQSGPPGAF APPPSAFGAP QGPGGPGGYG PPPPGGPGAP
GSYGPPQGGP GGFGPPPPGG PGAYGPPPTG FPPVGAPPPG AAGAPGGNPF ARGPSATGYR
QSPYQQ
