ID BIG1_HUMAN Reviewed; 1849 AA. AC Q9Y6D6; Q9NV46; Q9UFV2; Q9UNL0; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 200. DE RecName: Full=Brefeldin A-inhibited guanine nucleotide-exchange protein 1; DE Short=Brefeldin A-inhibited GEP 1; DE AltName: Full=ADP-ribosylation factor guanine nucleotide-exchange factor 1; DE AltName: Full=p200 ARF guanine nucleotide exchange factor; DE AltName: Full=p200 ARF-GEP1; GN Name=ARFGEF1; Synonyms=ARFGEP1, BIG1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=10212200; DOI=10.1074/jbc.274.18.12308; RA Togawa A., Morinaga N., Ogasawara M., Moss J., Vaughan M.; RT "Purification and cloning of a brefeldin A-inhibited guanine nucleotide- RT exchange protein for ADP-ribosylation factors."; RL J. Biol. Chem. 274:12308-12315(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10393931; DOI=10.1073/pnas.96.14.7968; RA Mansour S.J., Skaug J., Zhao X.-H., Giordano J., Scherer S.W., Melancon P.; RT "p200 ARF-GEP1: a Golgi-localized guanine nucleotide exchange protein whose RT Sec7 domain is targeted by the drug brefeldin A."; RL Proc. Natl. Acad. Sci. U.S.A. 96:7968-7973(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1341-1849. RC TISSUE=Ovarian carcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP PROTEIN SEQUENCE OF 1569-1579, INTERACTION WITH TBC1D22A AND TBC1D22B, AND RP MASS SPECTROMETRY. RX PubMed=23572552; DOI=10.1128/mbio.00098-13; RA Greninger A.L., Knudsen G.M., Betegon M., Burlingame A.L., DeRisi J.L.; RT "ACBD3 interaction with TBC1 domain 22 protein is differentially affected RT by enteroviral and kobuviral 3A protein binding."; RL MBio 4:E00098-E00098(2013). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1637-1849. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP SUBCELLULAR LOCATION, AND INTERACTION WITH ARFGEF2. RX PubMed=10716990; DOI=10.1073/pnas.97.6.2567; RA Yamaji R., Adamik R., Takeda K., Togawa A., Pacheco-Rodriguez G., RA Ferrans V.J., Moss J., Vaughan M.; RT "Identification and localization of two brefeldin A-inhibited guanine RT nucleotide-exchange proteins for ADP-ribosylation factors in a RT macromolecular complex."; RL Proc. Natl. Acad. Sci. U.S.A. 97:2567-2572(2000). RN [7] RP FUNCTION, INTERACTION WITH PRKAR1A AND PRKAR2A, AND SUBCELLULAR LOCATION. RX PubMed=12571360; DOI=10.1073/pnas.0337678100; RA Li H., Adamik R., Pacheco-Rodriguez G., Moss J., Vaughan M.; RT "Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine RT nucleotide-exchange protein 2 (BIG2)."; RL Proc. Natl. Acad. Sci. U.S.A. 100:1627-1632(2003). RN [8] RP INTERACTION WITH FKBP2. RX PubMed=12606707; DOI=10.1073/pnas.2628047100; RA Padilla P.I., Chang M.J., Pacheco-Rodriguez G., Adamik R., Moss J., RA Vaughan M.; RT "Interaction of FK506-binding protein 13 with brefeldin A-inhibited guanine RT nucleotide-exchange protein 1 (BIG1): effects of FK506."; RL Proc. Natl. Acad. Sci. U.S.A. 100:2322-2327(2003). RN [9] RP SUBCELLULAR LOCATION, AND INTERACTION WITH NCL AND NUP62. RX PubMed=14973189; DOI=10.1073/pnas.0307345101; RA Padilla P.I., Pacheco-Rodriguez G., Moss J., Vaughan M.; RT "Nuclear localization and molecular partners of BIG1, a brefeldin A- RT inhibited guanine nucleotide-exchange protein for ADP-ribosylation RT factors."; RL Proc. Natl. Acad. Sci. U.S.A. 101:2752-2757(2004). RN [10] RP FUNCTION, AND INTERACTION WITH MYO9B. RX PubMed=15644318; DOI=10.1074/jbc.m413415200; RA Saeki N., Tokuo H., Ikebe M.; RT "BIG1 is a binding partner of myosin IXb and regulates its Rho-GTPase RT activating protein activity."; RL J. Biol. Chem. 280:10128-10134(2005). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 712-LYS--LYS-714 AND SER-883. RX PubMed=16467138; DOI=10.1073/pnas.0510571103; RA Citterio C., Jones H.D., Pacheco-Rodriguez G., Islam A., Moss J., RA Vaughan M.; RT "Effect of protein kinase A on accumulation of brefeldin A-inhibited RT guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei."; RL Proc. Natl. Acad. Sci. U.S.A. 103:2683-2688(2006). RN [13] RP HOMODIMERIZATION, AND MUTAGENESIS OF GLU-221. RX PubMed=17640864; DOI=10.1074/jbc.m705525200; RA Ramaen O., Joubert A., Simister P., Belgareh-Touze N., RA Olivares-Sanchez M.C., Zeeh J.C., Chantalat S., Golinelli-Cohen M.P., RA Jackson C.L., Biou V., Cherfils J.; RT "Interactions between conserved domains within homodimers in the BIG1, RT BIG2, and GBF1 Arf guanine nucleotide exchange factors."; RL J. Biol. Chem. 282:28834-28842(2007). RN [14] RP FUNCTION. RX PubMed=17227842; DOI=10.1073/pnas.0610535104; RA Shen X., Hong M.S., Moss J., Vaughan M.; RT "BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is RT required for correct glycosylation and function of integrin beta1."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1230-1235(2007). RN [15] RP PHOSPHORYLATION, AND INTERACTION WITH PPP1CC. RX PubMed=17360629; DOI=10.1073/pnas.0611696104; RA Kuroda F., Moss J., Vaughan M.; RT "Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 RT (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma."; RL Proc. Natl. Acad. Sci. U.S.A. 104:3201-3206(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [18] RP INTERACTION WITH NCL; FBL; NUP62 AND U3 SMALL NUCLEOLAR RNA, AND RP IDENTIFICATION IN SMALL NUCLEAR RIBONUCLEOPROTEIN COMPLEX. RX PubMed=18292223; DOI=10.1073/pnas.0712387105; RA Padilla P.I., Uhart M., Pacheco-Rodriguez G., Peculis B.A., Moss J., RA Vaughan M.; RT "Association of guanine nucleotide-exchange protein BIG1 in HepG2 cell RT nuclei with nucleolin, U3 snoRNA, and fibrillarin."; RL Proc. Natl. Acad. Sci. U.S.A. 105:3357-3361(2008). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [20] RP INTERACTION WITH DPY30. RX PubMed=19651892; DOI=10.1083/jcb.200902146; RA Xu Z., Gong Q., Xia B., Groves B., Zimmermann M., Mugler C., Mu D., RA Matsumoto B., Seaman M., Ma D.; RT "A role of histone H3 lysine 4 methyltransferase components in endosomal RT trafficking."; RL J. Cell Biol. 186:343-353(2009). RN [21] RP INTERACTION WITH PDE3A. RX PubMed=19332778; DOI=10.1073/pnas.0901558106; RA Puxeddu E., Uhart M., Li C.C., Ahmad F., Pacheco-Rodriguez G., RA Manganiello V.C., Moss J., Vaughan M.; RT "Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine RT nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity."; RL Proc. Natl. Acad. Sci. U.S.A. 106:6158-6163(2009). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KANK1. RX PubMed=22084092; DOI=10.1073/pnas.1117011108; RA Li C.C., Kuo J.C., Waterman C.M., Kiyama R., Moss J., Vaughan M.; RT "Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and RT KANK1 proteins on cell polarity and directed migration during wound RT healing."; RL Proc. Natl. Acad. Sci. U.S.A. 108:19228-19233(2011). RN [26] RP FUNCTION. RX PubMed=20360857; DOI=10.1371/journal.pone.0009898; RA Boal F., Stephens D.J.; RT "Specific functions of BIG1 and BIG2 in endomembrane organization."; RL PLoS ONE 5:E9898-E9898(2010). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1079 AND SER-1569, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-397; SER-410 AND RP SER-1569, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1569, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [30] RP INVOLVEMENT IN DEDISB, AND VARIANT DEDISB 1455-CYS--GLN-1849 DEL. RX PubMed=31678406; DOI=10.1016/j.nbd.2019.104632; RA Teoh J., Subramanian N., Pero M.E., Bartolini F., Amador A., Kanber A., RA Williams D., Petri S., Yang M., Allen A.S., Beal J., Haut S.R., RA Frankel W.N.; RT "Arfgef1 haploinsufficiency in mice alters neuronal endosome composition RT and decreases membrane surface postsynaptic GABAA receptors."; RL Neurobiol. Dis. 134:104632-104632(2020). RN [31] {ECO:0007744|PDB:5EE5} RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 1-229, INTERACTION WITH ARL1, AND RP SUBCELLULAR LOCATION. RX PubMed=27373159; DOI=10.1016/j.celrep.2016.06.022; RA Galindo A., Soler N., McLaughlin S.H., Yu M., Williams R.L., Munro S.; RT "Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to RT the trans-Golgi."; RL Cell Rep. 16:839-850(2016). RN [32] {ECO:0007744|PDB:5J5C} RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 1-224, INTERACTION WITH ARL1, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-105; TYR-109; LEU-156 AND RP GLN-200. RX PubMed=27436755; DOI=10.1093/jmcb/mjw033; RA Wang R., Wang Z., Wang K., Zhang T., Ding J.; RT "Structural basis for targeting BIG1 to Golgi apparatus through interaction RT of its DCB domain with Arl1."; RL J. Mol. Cell Biol. 8:459-461(2016). RN [33] RP VARIANT [LARGE SCALE ANALYSIS] GLU-316. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [34] RP VARIANTS DEDISB 648-GLN--GLN-1849 DEL; ASN-798; 842-GLN--GLN-1849 DEL AND RP 1774-ARG--GLN-1849 DEL, AND CHARACTERIZATION OF VARIANTS DEDISB RP 648-GLN--GLN-1849 DEL AND ASN-798. RX PubMed=34113008; DOI=10.1038/s41436-021-01218-6; RA Thomas Q., Gautier T., Marafi D., Besnard T., Willems M., Moutton S., RA Isidor B., Cogne B., Conrad S., Tenconi R., Iascone M., Sorlin A., RA Masurel A., Dabir T., Jackson A., Banka S., Delanne J., Lupski J.R., RA Saadi N.W., Alkuraya F.S., Zahrani F.A., Agrawal P.B., England E., RA Madden J.A., Posey J.E., Burglen L., Rodriguez D., Chevarin M., Nguyen S., RA Mau-Them F.T., Duffourd Y., Garret P., Bruel A.L., Callier P., Marle N., RA Denomme-Pichon A.S., Duplomb L., Philippe C., Thauvin-Robinet C., Govin J., RA Faivre L., Vitobello A.; RT "Haploinsufficiency of ARFGEF1 is associated with developmental delay, RT intellectual disability, and epilepsy with variable expressivity."; RL Genet. Med. 23:1901-1911(2021). CC -!- FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF3. CC Promotes the activation of ARF1/ARF3 through replacement of GDP with CC GTP. Involved in vesicular trafficking. Required for the maintenance of CC Golgi structure; the function may be independent of its GEF activity. CC Required for the maturaion of integrin beta-1 in the Golgi. Involved in CC the establishment and persistence of cell polarity during directed cell CC movement in wound healing. Proposed to act as A kinase-anchoring CC protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. CC Inhibits GAP activity of MYO9B probably through competitive RhoA CC binding. The function in the nucleus remains to be determined. CC {ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15644318, CC ECO:0000269|PubMed:17227842, ECO:0000269|PubMed:20360857, CC ECO:0000269|PubMed:22084092}. CC -!- ACTIVITY REGULATION: Inhibited by brefeldin A. CC -!- SUBUNIT: Homodimer (PubMed:17640864). Interacts with ARFGEF2/BIG2; both CC proteins are probably part of the same or very similar macromolecular CC complexes (PubMed:10716990). Interacts with FKBP2 (PubMed:12606707). CC Interacts with MYO9B (PubMed:15644318). Interacts with PRKAR1A and CC PRKAR2A (PubMed:12571360). Interacts with PPP1CC (PubMed:17360629). CC Interacts with NCL, FBL, NUP62 and U3 small nucleolar RNA CC (PubMed:14973189, PubMed:18292223). Interacts with DPY30 CC (PubMed:19651892). Interacts with PDE3A (PubMed:19332778). Interacts CC with KANK1 (PubMed:22084092). Interacts with TBC1D22A and TBC1D22B CC (PubMed:23572552). Interacts (via N-terminus) with ARL1 CC (PubMed:27373159, PubMed:27436755). {ECO:0000269|PubMed:10716990, CC ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:12606707, CC ECO:0000269|PubMed:14973189, ECO:0000269|PubMed:15644318, CC ECO:0000269|PubMed:17360629, ECO:0000269|PubMed:17640864, CC ECO:0000269|PubMed:18292223, ECO:0000269|PubMed:19332778, CC ECO:0000269|PubMed:19651892, ECO:0000269|PubMed:22084092, CC ECO:0000269|PubMed:23572552, ECO:0000269|PubMed:27373159, CC ECO:0000269|PubMed:27436755}. CC -!- INTERACTION: CC Q9Y6D6; Q9Y6D5: ARFGEF2; NbExp=12; IntAct=EBI-1044254, EBI-2837511; CC Q9Y6D6; Q14678: KANK1; NbExp=8; IntAct=EBI-1044254, EBI-2556221; CC Q9Y6D6; Q7Z4S6: KIF21A; NbExp=7; IntAct=EBI-1044254, EBI-2691397; CC Q9Y6D6; Q7Z4S6-2: KIF21A; NbExp=4; IntAct=EBI-1044254, EBI-6251716; CC Q9Y6D6; Q99417: MYCBP; NbExp=3; IntAct=EBI-1044254, EBI-716185; CC Q9Y6D6; Q13459-2: MYO9B; NbExp=2; IntAct=EBI-1044254, EBI-6251250; CC Q9Y6D6; P19338: NCL; NbExp=5; IntAct=EBI-1044254, EBI-346967; CC Q9Y6D6; Q14432: PDE3A; NbExp=6; IntAct=EBI-1044254, EBI-7192066; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region. Golgi CC apparatus {ECO:0000269|PubMed:12571360}. Golgi apparatus, trans-Golgi CC network membrane {ECO:0000269|PubMed:27373159, CC ECO:0000269|PubMed:27436755}. Nucleus {ECO:0000269|PubMed:14973189}. CC Nucleus, nucleolus {ECO:0000269|PubMed:14973189}. Nucleus matrix CC {ECO:0000269|PubMed:14973189}. Note=Translocates from cytoplasm to CC membranes and nucleus upon cAMP treatment. CC -!- TISSUE SPECIFICITY: Expressed in placenta, lung, heart, brain, kidney CC and pancreas. CC -!- PTM: Phosphorylated. In vitro phosphorylated by PKA reducing its GEF CC activity and dephosphorylated by phosphatase PP1. CC {ECO:0000269|PubMed:17360629}. CC -!- DISEASE: Developmental delay, impaired speech, and behavioral CC abnormalities, with or without seizures (DEDISB) [MIM:619964]: An CC autosomal dominant disorder characterized by mild to moderately CC impaired intellectual development, language delay, motor deficits, and CC behavioral abnormalities including aggression, hyperactivity, and CC autism spectrum disorder. About half of individuals develop various CC types of seizures. More variable features include dysmorphic facial CC features, mild ocular anomalies, and non-specific findings on brain CC imaging. {ECO:0000269|PubMed:31678406, ECO:0000269|PubMed:34113008}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. 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; AF084520; AAD38427.1; -; mRNA. DR EMBL; AF111162; AAD43651.1; -; mRNA. DR EMBL; AK001788; BAA91912.1; -; mRNA. DR EMBL; AL117446; CAB55931.1; -; mRNA. DR CCDS; CCDS6199.1; -. DR PIR; T17241; T17241. DR RefSeq; NP_006412.2; NM_006421.4. DR RefSeq; XP_005251191.1; XM_005251134.4. DR PDB; 3LTL; X-ray; 2.20 A; A/B=691-889. DR PDB; 5EE5; X-ray; 2.28 A; A=1-229. DR PDB; 5J5C; X-ray; 3.40 A; B=1-224. DR PDBsum; 3LTL; -. DR PDBsum; 5EE5; -. DR PDBsum; 5J5C; -. DR AlphaFoldDB; Q9Y6D6; -. DR SMR; Q9Y6D6; -. DR BioGRID; 115816; 168. DR DIP; DIP-29748N; -. DR IntAct; Q9Y6D6; 37. DR MINT; Q9Y6D6; -. DR STRING; 9606.ENSP00000262215; -. DR GlyGen; Q9Y6D6; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y6D6; -. DR PhosphoSitePlus; Q9Y6D6; -. DR BioMuta; ARFGEF1; -. DR DMDM; 116241267; -. DR EPD; Q9Y6D6; -. DR jPOST; Q9Y6D6; -. DR MassIVE; Q9Y6D6; -. DR MaxQB; Q9Y6D6; -. DR PaxDb; 9606-ENSP00000262215; -. DR PeptideAtlas; Q9Y6D6; -. DR ProteomicsDB; 86655; -. DR Pumba; Q9Y6D6; -. DR Antibodypedia; 12092; 99 antibodies from 15 providers. DR DNASU; 10565; -. DR Ensembl; ENST00000262215.8; ENSP00000262215.3; ENSG00000066777.9. DR GeneID; 10565; -. DR KEGG; hsa:10565; -. DR MANE-Select; ENST00000262215.8; ENSP00000262215.3; NM_006421.5; NP_006412.2. DR UCSC; uc003xxo.2; human. DR AGR; HGNC:15772; -. DR CTD; 10565; -. DR DisGeNET; 10565; -. DR GeneCards; ARFGEF1; -. DR HGNC; HGNC:15772; ARFGEF1. DR HPA; ENSG00000066777; Low tissue specificity. DR MalaCards; ARFGEF1; -. DR MIM; 604141; gene. DR MIM; 619964; phenotype. DR neXtProt; NX_Q9Y6D6; -. DR OpenTargets; ENSG00000066777; -. DR PharmGKB; PA134908197; -. DR VEuPathDB; HostDB:ENSG00000066777; -. DR eggNOG; KOG0929; Eukaryota. DR GeneTree; ENSGT00940000157108; -. DR InParanoid; Q9Y6D6; -. DR OMA; MENQVYE; -. DR OrthoDB; 204547at2759; -. DR PhylomeDB; Q9Y6D6; -. DR TreeFam; TF300714; -. DR PathwayCommons; Q9Y6D6; -. DR SignaLink; Q9Y6D6; -. DR SIGNOR; Q9Y6D6; -. DR BioGRID-ORCS; 10565; 25 hits in 1158 CRISPR screens. DR ChiTaRS; ARFGEF1; human. DR EvolutionaryTrace; Q9Y6D6; -. DR GeneWiki; ARFGEF1; -. DR GenomeRNAi; 10565; -. DR Pharos; Q9Y6D6; Tbio. DR PRO; PR:Q9Y6D6; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9Y6D6; Protein. DR Bgee; ENSG00000066777; Expressed in primordial germ cell in gonad and 204 other cell types or tissues. DR ExpressionAtlas; Q9Y6D6; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0030532; C:small nuclear ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0017022; F:myosin binding; IPI:UniProtKB. DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IDA:UniProtKB. DR GO; GO:0010256; P:endomembrane system organization; IMP:UniProtKB. DR GO; GO:0006887; P:exocytosis; TAS:ProtInc. DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB. DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:UniProtKB. DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB. DR GO; GO:0090303; P:positive regulation of wound healing; IMP:UniProtKB. DR GO; GO:0006486; P:protein glycosylation; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro. DR GO; GO:2000114; P:regulation of establishment of cell polarity; IMP:UniProtKB. DR CDD; cd00171; Sec7; 1. DR DisProt; DP02612; -. DR Gene3D; 1.10.220.20; -; 1. DR Gene3D; 1.10.1000.11; Arf Nucleotide-binding Site Opener,domain 2; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR032629; DCB_dom. DR InterPro; IPR015403; Mon2/Sec7/BIG1-like_HDS. DR InterPro; IPR032691; Mon2/Sec7/BIG1-like_HUS. DR InterPro; IPR046455; Sec7/BIG1-like_C. DR InterPro; IPR023394; Sec7_C_sf. DR InterPro; IPR000904; Sec7_dom. DR InterPro; IPR035999; Sec7_dom_sf. DR PANTHER; PTHR10663:SF137; BREFELDIN A-INHIBITED GUANINE NUCLEOTIDE-EXCHANGE PROTEIN 1; 1. DR PANTHER; PTHR10663; GUANYL-NUCLEOTIDE EXCHANGE FACTOR; 1. DR Pfam; PF20252; BIG2_C; 1. DR Pfam; PF16213; DCB; 1. DR Pfam; PF01369; Sec7; 1. DR Pfam; PF09324; Sec7-like_HDS; 1. DR Pfam; PF12783; Sec7-like_HUS; 1. DR SMART; SM00222; Sec7; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF48425; Sec7 domain; 1. DR PROSITE; PS50190; SEC7; 1. DR Genevisible; Q9Y6D6; HS. PE 1: Evidence at protein level; KW 3D-structure; Autism spectrum disorder; Cytoplasm; KW Direct protein sequencing; Disease variant; Epilepsy; Golgi apparatus; KW Guanine-nucleotide releasing factor; Intellectual disability; Membrane; KW Nucleus; Phosphoprotein; Protein transport; Reference proteome; Transport. FT CHAIN 1..1849 FT /note="Brefeldin A-inhibited guanine nucleotide-exchange FT protein 1" FT /id="PRO_0000120207" FT DOMAIN 709..840 FT /note="SEC7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189" FT REGION 2..224 FT /note="DCB; DCB:DCB domain and DCB:HUS domain interaction" FT REGION 46..65 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 216..248 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 264..302 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 378..413 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 557..577 FT /note="HUS; DCB:HUS domain interaction" FT REGION 1543..1562 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 711..715 FT /note="Nuclear localization signal (NLS)" FT COMPBIAS 216..236 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 264..281 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 282..302 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 390..413 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 52 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 286 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G3X9K3" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G3X9K3" FT MOD_RES 290 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D4A631" FT MOD_RES 397 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 410 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1079 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1566 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D4A631" FT MOD_RES 1569 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT VARIANT 273 FT /note="D -> Y (in dbSNP:rs4321984)" FT /id="VAR_028749" FT VARIANT 316 FT /note="G -> E (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036155" FT VARIANT 648..1849 FT /note="Missing (in DEDISB; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:34113008" FT /id="VAR_087629" FT VARIANT 798 FT /note="D -> N (in DEDISB; decreased protein abundance; FT dbSNP:rs1840520188)" FT /evidence="ECO:0000269|PubMed:34113008" FT /id="VAR_087630" FT VARIANT 842..1849 FT /note="Missing (in DEDISB)" FT /evidence="ECO:0000269|PubMed:34113008" FT /id="VAR_087631" FT VARIANT 1455..1849 FT /note="Missing (in DEDISB)" FT /evidence="ECO:0000269|PubMed:31678406" FT /id="VAR_087632" FT VARIANT 1774..1849 FT /note="Missing (in DEDISB)" FT /evidence="ECO:0000269|PubMed:34113008" FT /id="VAR_087633" FT MUTAGEN 105 FT /note="K->D: Loss of interaction with ARL1." FT /evidence="ECO:0000269|PubMed:27373159" FT MUTAGEN 109 FT /note="Y->K: LLoss of interaction with ARL1." FT /evidence="ECO:0000269|PubMed:27373159" FT MUTAGEN 156 FT /note="L->D: Loss of interaction with ARL1." FT /evidence="ECO:0000269|PubMed:27373159" FT MUTAGEN 200 FT /note="Q->E: Loss of interaction with ARL1." FT /evidence="ECO:0000269|PubMed:27373159" FT MUTAGEN 221 FT /note="E->K: No effect on self-association." FT /evidence="ECO:0000269|PubMed:17640864" FT MUTAGEN 712..714 FT /note="KPK->AAA: Inhibits nuclear localization." FT /evidence="ECO:0000269|PubMed:16467138" FT MUTAGEN 883 FT /note="S->A: Abolishes cAMP-induced nuclear localization." FT /evidence="ECO:0000269|PubMed:16467138" FT MUTAGEN 883 FT /note="S->D: No effect on cAMP-induced nuclear FT localization." FT /evidence="ECO:0000269|PubMed:16467138" FT CONFLICT 233 FT /note="Q -> P (in Ref. 1; AAD38427)" FT /evidence="ECO:0000305" FT CONFLICT 620 FT /note="L -> S (in Ref. 1; AAD38427)" FT /evidence="ECO:0000305" FT CONFLICT 1055 FT /note="E -> K (in Ref. 1; AAD38427)" FT /evidence="ECO:0000305" FT CONFLICT 1590 FT /note="V -> A (in Ref. 3; BAA91912)" FT /evidence="ECO:0000305" FT HELIX 7..21 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 23..25 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 28..30 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 31..48 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 77..80 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 81..88 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 93..108 FT /evidence="ECO:0007829|PDB:5EE5" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:5J5C" FT HELIX 126..135 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 145..160 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 168..184 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 188..194 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 197..224 FT /evidence="ECO:0007829|PDB:5EE5" FT HELIX 698..711 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 713..722 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 730..739 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 745..752 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 757..768 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 777..786 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 794..810 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 821..838 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 849..855 FT /evidence="ECO:0007829|PDB:3LTL" FT STRAND 861..864 FT /evidence="ECO:0007829|PDB:3LTL" FT HELIX 867..879 FT /evidence="ECO:0007829|PDB:3LTL" SQ SEQUENCE 1849 AA; 208767 MW; 1EB2547F28F63BCA CRC64; MYEGKKTKNM FLTRALEKIL ADKEVKKAHH SQLRKACEVA LEEIKAETEK QSPPHGEAKA GSSTLPPVKS KTNFIEADKY FLPFELACQS KCPRIVSTSL DCLQKLIAYG HLTGNAPDST TPGKKLIDRI IETICGCFQG PQTDEGVQLQ IIKALLTAVT SQHIEIHEGT VLQAVRTCYN IYLASKNLIN QTTAKATLTQ MLNVIFARME NQALQEAKQM EKERHRQHHH LLQSPVSHHE PESPQLRYLP PQTVDHISQE HEGDLDLHTN DVDKSLQDDT EPENGSDISS AENEQTEADQ ATAAETLSKN EVLYDGENHD CEEKPQDIVQ NIVEEMVNIV VGDMGEGTTI NASADGNIGT IEDGSDSENI QANGIPGTPI SVAYTPSLPD DRLSVSSNDT QESGNSSGPS PGAKFSHILQ KDAFLVFRSL CKLSMKPLSD GPPDPKSHEL RSKILSLQLL LSILQNAGPI FRTNEMFINA IKQYLCVALS KNGVSSVPEV FELSLSIFLT LLSNFKTHLK MQIEVFFKEI FLYILETSTS SFDHKWMVIQ TLTRICADAQ SVVDIYVNYD CDLNAANIFE RLVNDLSKIA QGRGSQELGM SNVQELSLRK KGLECLVSIL KCMVEWSKDQ YVNPNSQTTL GQEKPSEQEM SEIKHPETIN RYGSLNSLES TSSSGIGSYS TQMSGTDNPE QFEVLKQQKE IIEQGIDLFN KKPKRGIQYL QEQGMLGTTP EDIAQFLHQE ERLDSTQVGE FLGDNDKFNK EVMYAYVDQH DFSGKDFVSA LRMFLEGFRL PGEAQKIDRL MEKFAARYLE CNQGQTLFAS ADTAYVLAYS IIMLTTDLHS PQVKNKMTKE QYIKMNRGIN DSKDLPEEYL SAIYNEIAGK KISMKETKEL TIPTKSSKQN VASEKQRRLL YNLEMEQMAK TAKALMEAVS HVQAPFTSAT HLEHVRPMFK LAWTPFLAAF SVGLQDCDDT EVASLCLEGI RCAIRIACIF SIQLERDAYV QALARFTLLT VSSGITEMKQ KNIDTIKTLI TVAHTDGNYL GNSWHEILKC ISQLELAQLI GTGVKPRYIS GTVRGREGSL TGTKDQAPDE FVGLGLVGGN VDWKQIASIQ ESIGETSSQS VVVAVDRIFT GSTRLDGNAI VDFVRWLCAV SMDELLSTTH PRMFSLQKIV EISYYNMGRI RLQWSRIWEV IGDHFNKVGC NPNEDVAIFA VDSLRQLSMK FLEKGELANF RFQKDFLRPF EHIMKRNRSP TIRDMVVRCI AQMVNSQAAN IRSGWKNIFS VFHLAASDQD ESIVELAFQT TGHIVTLVFE KHFPATIDSF QDAVKCLSEF ACNAAFPDTS MEAIRLIRHC AKYVSDRPQA FKEYTSDDMN VAPEDRVWVR GWFPILFELS CIINRCKLDV RTRGLTVMFE IMKTYGHTYE KHWWQDLFRI VFRIFDNMKL PEQQTEKAEW MTTTCNHALY AICDVFTQYL EVLSDVLLDD IFAQLYWCVQ QDNEQLARSG TNCLENVVIL NGEKFTLEIW DKTCNCTLDI FKTTIPHALL TWRPNSGETA PPPPSPVSEK PLDTISQKSV DIHDSIQPRS VDNRPQAPLV SASAVNEEVS KIKSTAKFPE QKLFAALLIK CVVQLELIQT IDNIVFFPAT SKKEDAENLA AAQRDAVDFD VRVDTQDQGM YRFLTSQQLF KLLDCLLESH RFAKAFNSNN EQRTALWKAG FKGKSKPNLL KQETSSLACG LRILFRMYMD ESRVSAWEEV QQRLLNVCSE ALSYFLTLTS ESHREAWTNL LLLFLTKVLK ISDNRFKAHA SFYYPLLCEI MQFDLIPELR AVLRRFFLRI GVVFQISQPP EQELGINKQ //