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 25-MAY-2022, entry version 137. 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}. 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; 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 multi-cellular organism and 5 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 //