BIG1_HUMAN
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 03-AUG-2022, entry version 191.
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] {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 [31] {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 [32]
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).
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}.
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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; 120.
DR DIP; DIP-29748N; -.
DR IntAct; Q9Y6D6; 35.
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; Q9Y6D6; -.
DR PeptideAtlas; Q9Y6D6; -.
DR PRIDE; Q9Y6D6; -.
DR ProteomicsDB; 86655; -.
DR Antibodypedia; 12092; 78 antibodies from 14 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 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 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; LLWNMEM; -.
DR OrthoDB; 815698at2759; -.
DR PhylomeDB; Q9Y6D6; -.
DR TreeFam; TF300714; -.
DR PathwayCommons; Q9Y6D6; -.
DR SignaLink; Q9Y6D6; -.
DR BioGRID-ORCS; 10565; 25 hits in 1082 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 secondary oocyte and 203 other tissues.
DR ExpressionAtlas; Q9Y6D6; baseline and differential.
DR Genevisible; Q9Y6D6; HS.
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 Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032629; DCB_dom.
DR InterPro; IPR015403; Sec7_C.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR InterPro; IPR032691; Sec7_N.
DR Pfam; PF16213; DCB; 1.
DR Pfam; PF09324; DUF1981; 1.
DR Pfam; PF01369; Sec7; 1.
DR Pfam; PF12783; Sec7_N; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Membrane; Nucleus; Phosphoprotein;
KW 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 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
