| IED ID | IndEnz0005000471 |
| Enzyme Type ID | lipase000471 |
| Protein Name |
Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 BFA-resistant GEF 1 |
| Gene Name | GBF1 KIAA0248 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MVDKNIYIIQGEINIVVGAIKRNARWSTHTPLDEERDPLLHSFGHLKEVLNSITELSEIEPNVFLRPFLEVIRSEDTTGPITGLALTSVNKFLSYALIDPTHEGTAEGMENMADAVTHARFVGTDPASDEVVLMKILQVLRTLLLTPVGAHLTNESVCEIMQSCFRICFEMRLSELLRKSAEHTLVDMVQLLFTRLPQFKEEPKNYVGTNMKKLKMRAGGMSDSSKWKKQKRSPRPPRHMTKVTPGSELPTPNGTTLSSNLTGGMPFIDVPTPISSASSEAASAVVSPSTDSGLEFSSQTTSKEDLTDLEQPGSPGYSTATEPGSSELGVPEQPDLQEGTHVEKSQSASVESIPEVLEECTSPADHSDSASVHDMDYVNPRGVRFTQSSQKEGTALVPYGLPCIRELFRFLISLTNPHDRHNSEVMIHMGLHLLTVALESAPVAQCQTLLGLIKDEMCRHLFQLLSIERLNLYAASLRVCFLLFESMREHLKFQMEMYIKKLMEIITVENPKMPYEMKEMALEAIVQLWRIPSFVTELYINYDCDYYCSNLFEELTKLLSKNAFPVSGQLYTTHLLSLDALLTVIDSTEAHCQAKVLNSLTQQEKKETARPSCEIVDGTREASNTERTASDGKAVGMASDIPGLHLPGGGRLPPEHGKSGCSDLEEAVDSGADKKFARKPPRFSCLLPDPRELIEIKNKKKLLITGTEQFNQKPKKGIQFLQEKGLLTIPMDNTEVAQWLRENPRLDKKMIGEFVSDRKNIDLLESFVSTFSFQGLRLDEALRLYLEAFRLPGEAPVIQRLLEAFTERWMNCNGSPFANSDACFSLAYAVIMLNTDQHNHNVRKQNAPMTLEEFRKNLKGVNGGKDFEQDILEDMYHAIKNEEIVMPEEQTGLVRENYVWNVLLHRGATPEGIFLRVPTASYDLDLFTMTWGPTIAALSYVFDKSLEETIIQKAISGFRKCAMISAHYGLSDVFDNLIISLCKFTALSSESIENLPSVFGSNPKAHIAAKTVFHLAHRHGDILREGWKNIMEAMLQLFRAQLLPKAMIEVEDFVDPNGKISLQREETPSNRGESTVLSFVSWLTLSGPEQSSVRGPSTENQEAKRVALECIKQCDPEKMITESKFLQLESLQELMKALVSVTPDEETYDEEDAAFCLEMLLRIVLENRDRVGCVWQTVRDHLYHLCVQAQDFCFLVERAVVGLLRLAIRLLRREEISAQVLLSLRILLLMKPSVLSRVSHQVAYGLHELLKTNAANIHSGDDWATLFTLLECIGSGVKPPAALQATARADAPDAGAQSDSELPSYHQNDVSLDRGYTSDSEVYTDHGRPGKIHRSATDADVVNSGWLVVGKDDVDNSKPGPSRPGPSPLINQYSLTVGLDLGPHDTKSLLKCVESLSFIVRDAAHITPDNFELCVKTLRIFVEASLNGGCKSQEKRGKSHKYDSKGNRFKKKSKEGSMLRRPRTSSQHASRGGQSDDDEDEGVPASYHTVSLQVSQDLLDLMHTLHTRAASIYSSWAEEQRHLETGGQKIEADSRTLWAHCWCPLLQGIACLCCDARRQVRMQALTYLQRALLVHDLQKLDALEWESCFNKVLFPLLTKLLENISPADVGGMEETRMRASTLLSKVFLQHLSPLLSLSTFAALWLTILDFMDKYMHAGSSDLLSEAIPESLKNMLLVMDTAEIFHSADARGGGPSALWEITWERIDCFLPHLRDELFKQTVIQDPMPMEPQGQKPLASAHLTSAAGDTRTPGHPPPPEIPSELGACDFEKPESPRAASSSSPGSPVASSPSRLSPTPDGPPPLAQPPLILQPLASPLQVGVPPMTLPIILNPALIEATSPVPLLATPRPTDPIPTSEVN |
| Enzyme Length | 1859 |
| Uniprot Accession Number | Q92538 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by brefeldin A (BFA) (PubMed:15616190). Inhibited by golgicide A (GCA) (By similarity). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:15616190}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:12047556, PubMed:12808027, PubMed:19039328, PubMed:24213530). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adapter protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609). Has GEF activity towards ARF1 (PubMed:15616190). Has in vitro GEF activity towards ARF5 (By similarity). Involved in the processing of PSAP (PubMed:17666033). Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980). The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352). May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782). In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891). Plays a role in maintaining mitochondrial morphology (PubMed:25190516). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:16926190, ECO:0000269|PubMed:17666033, ECO:0000269|PubMed:17956946, ECO:0000269|PubMed:18003980, ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:19461073, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:23386609, ECO:0000269|PubMed:23418352, ECO:0000269|PubMed:24213530, ECO:0000269|PubMed:25190516, ECO:0000305|PubMed:19039328, ECO:0000305|PubMed:22573891}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Chain (1); Compositional bias (6); Domain (1); Erroneous initiation (1); Modified residue (13); Mutagenesis (5); Natural variant (1); Region (11); Sequence conflict (4) |
| Keywords | Alternative splicing;Cytoplasm;Golgi apparatus;Guanine-nucleotide releasing factor;Host-virus interaction;Lipid droplet;Lipid-binding;Membrane;Phosphoprotein;Protein transport;Reference proteome;Transport |
| Interact With | Q9Y678; P53620; P09613; P03300; Q9C0D3 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network {ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269|PubMed:12808027}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:23386609}. Golgi apparatus {ECO:0000269|PubMed:31519766}. Cytoplasm {ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:31519766}. Lipid droplet {ECO:0000269|PubMed:21789191}. Membrane; Peripheral membrane protein {ECO:0000305}. Note=Cycles rapidly on and off early Golgi membranes (PubMed:15616190). Stabilized on membranes when complexed with ARF1-GDP and is released from both ARF1 and membranes after it catalyzes GDP displacement and ARF1 binds GTP. Continuous cycles of recruitment and dissociation of GBF1 to membranes are required for sustained ARF activation and COP I recruitment (PubMed:15813748). In neutrophils is translocated from the Golgi to the leading edge upon GPCR stimulation (PubMed:22573891). Localization to lipid droplets is questionable (PubMed:22185782). {ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000305|PubMed:15616190, ECO:0000305|PubMed:15813748}. |
| Modified Residue | MOD_RES 349; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 352; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 507; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18088087"; MOD_RES 662; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 1298; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"; MOD_RES 1316; /note="Phosphotyrosine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 1318; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 1320; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 1335; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 1337; /note="Phosphothreonine; by AMPK"; /evidence="ECO:0000269|PubMed:18063581"; MOD_RES 1475; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 1773; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 1784; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: AMPK-mediated phosphorylation at Thr-1337 is induced by 2-deoxyglucose (2-DG) and AICA ribonucleotide, and occurs during mitosis leading to membrane disassociation and inactivation of ARF1 during mitosis. {ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:23418352}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10052452; 10318838; 10761932; 10921873; 11172815; 11461920; 11689559; 11703931; 11726511; 11748249; 12646181; 14654841; 14743216; 15324660; 15632110; 16030262; 1631136; 16318580; 16385451; 16633337; 1680566; 16940185; 17079330; 17253781; 17329336; 17353931; 17360540; 17451557; 17760859; 17927562; 18182008; 18283113; 18287014; 18287528; 18524849; 18551169; 18799457; 18809720; 1898986; 19015319; 19023417; 19109418; 19296914; 1957170; 19631211; 19740986; 19773279; 19906930; 19913121; 20164217; 20175751; 20357002; 20427317; 20497182; 20530568; 20562859; 20628086; 20637885; 20711500; 20854417; 21219331; 21722633; 21844168; 21909260; 22013193; 22094269; 22304919; 22359663; 22360420; 22389062; 23416715; 23567335; 23840591; 24255178; 24855065; 25036637; 25410869; 25436559; 25609649; 25653442; 26496610; 26718629; 26814617; 29046456; 29112323; 29361542; 29507113; 29898406; 30459446; 30567983; 30943106; 31375590; 31570497; 31610914; 32484234; 32599855; 32652860; 32828303; 32937143; 33405949; 8001155; 8128252; 8132710; 8253837; 8505331; 8636227; 8810314; 8991093; 9114004; 9244307; 9288971; 9380700; 9405360; 9614177; 9671725; 9751720; 9990005; |
| Motif | |
| Gene Encoded By | |
| Mass | 206,446 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |