BIG3_MOUSE
ID BIG3_MOUSE Reviewed; 2170 AA.
AC Q3UGY8; Q80TH0;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Brefeldin A-inhibited guanine nucleotide-exchange protein 3 {ECO:0000305};
DE AltName: Full=ARFGEF family member 3 {ECO:0000312|MGI:MGI:106387};
GN Name=Arfgef3 {ECO:0000312|MGI:MGI:106387};
GN Synonyms=Big3, D10Bwg1379e, Kiaa1244;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 503-2170.
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471; SER-628; SER-632;
RP SER-1045; SER-1881; SER-1975; SER-2072; SER-2074; SER-2088; SER-2094 AND
RP SER-2096, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24711543; DOI=10.1002/embr.201338181;
RA Li H., Wei S., Cheng K., Gounko N.V., Ericksen R.E., Xu A., Hong W.,
RA Han W.;
RT "BIG3 inhibits insulin granule biogenesis and insulin secretion.";
RL EMBO Rep. 15:714-722(2014).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25737957; DOI=10.1016/j.molmet.2015.01.001;
RA Li H., Liu T., Lim J., Gounko N.V., Hong W., Han W.;
RT "Increased biogenesis of glucagon-containing secretory granules and
RT glucagon secretion in BIG3-knockout mice.";
RL Mol. Metab. 4:246-252(2015).
CC -!- FUNCTION: Participates in the regulation of systemic glucose
CC homeostasis, where it negatively regulates insulin granule biogenesis
CC in pancreatic islet beta cells (PubMed:24711543). Also regulates
CC glucagon granule production in pancreatic alpha cells
CC (PubMed:25737957). Inhibits nuclear translocation of the
CC transcriptional coregulator PHB2 and may enhance estrogen receptor
CC alpha (ESR1) transcriptional activity in breast cancer cells (By
CC similarity). {ECO:0000250|UniProtKB:Q5TH69,
CC ECO:0000269|PubMed:24711543, ECO:0000269|PubMed:25737957}.
CC -!- SUBUNIT: Interacts with PHB2 (By similarity).
CC {ECO:0000250|UniProtKB:Q5TH69}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:24711543}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000305|PubMed:24711543}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic islet (insulin granules of
CC islet alpha and beta cells) and brain (at protein level).
CC {ECO:0000269|PubMed:24711543, ECO:0000269|PubMed:25737957}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile with normal body weight gain.
CC Mice exhibit postprandial hyperinsulinemia and hyperglycemia, and
CC impaired glucose tolerance. Three month old animals show severe insulin
CC resistance in liver and muscle tissue, probably due to chronic insulin
CC exposure. {ECO:0000269|PubMed:24711543}.
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DR EMBL; AK147679; BAE28069.1; -; mRNA.
DR EMBL; AK122475; BAC65757.1; -; mRNA.
DR CCDS; CCDS23712.1; -.
DR RefSeq; NP_001028430.1; NM_001033258.4.
DR AlphaFoldDB; Q3UGY8; -.
DR SMR; Q3UGY8; -.
DR BioGRID; 229664; 2.
DR IntAct; Q3UGY8; 1.
DR STRING; 10090.ENSMUSP00000019999; -.
DR iPTMnet; Q3UGY8; -.
DR PhosphoSitePlus; Q3UGY8; -.
DR SwissPalm; Q3UGY8; -.
DR MaxQB; Q3UGY8; -.
DR PaxDb; Q3UGY8; -.
DR PeptideAtlas; Q3UGY8; -.
DR PRIDE; Q3UGY8; -.
DR ProteomicsDB; 273690; -.
DR Antibodypedia; 52580; 8 antibodies from 6 providers.
DR Ensembl; ENSMUST00000215836; ENSMUSP00000149210; ENSMUSG00000019852.
DR GeneID; 215821; -.
DR KEGG; mmu:215821; -.
DR UCSC; uc007emn.1; mouse.
DR CTD; 57221; -.
DR MGI; MGI:106387; Arfgef3.
DR VEuPathDB; HostDB:ENSMUSG00000019852; -.
DR eggNOG; KOG1846; Eukaryota.
DR GeneTree; ENSGT00530000064150; -.
DR HOGENOM; CLU_000867_1_0_1; -.
DR InParanoid; Q3UGY8; -.
DR OMA; AGYYEQV; -.
DR OrthoDB; 40522at2759; -.
DR PhylomeDB; Q3UGY8; -.
DR TreeFam; TF300714; -.
DR BioGRID-ORCS; 215821; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Arfgef3; mouse.
DR PRO; PR:Q3UGY8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3UGY8; protein.
DR Bgee; ENSMUSG00000019852; Expressed in superior cervical ganglion and 182 other tissues.
DR ExpressionAtlas; Q3UGY8; baseline and differential.
DR Genevisible; Q3UGY8; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032629; DCB_dom.
DR InterPro; IPR015403; Sec7_C.
DR InterPro; IPR000904; Sec7_dom.
DR Pfam; PF16213; DCB; 1.
DR Pfam; PF09324; DUF1981; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..2170
FT /note="Brefeldin A-inhibited guanine nucleotide-exchange
FT protein 3"
FT /id="PRO_0000286672"
FT TRANSMEM 1488..1508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 579..792
FT /note="SEC7"
FT REGION 489..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..634
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1843..1872
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1938..1997
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2024..2058
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2078..2097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..521
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1938..1954
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2024..2048
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 628
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1045
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1881
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1975
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1984
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5TH69"
FT MOD_RES 2072
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2074
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2088
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2094
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2096
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 2170 AA; 240091 MW; D759EA53B747F56C CRC64;
MEEILRKLQR DASGSKYKAI KESCTWALET LGGLDTVVKI PPHLLREKCL LPLQLALESK
NVKLAQHALA GMQKLLSEER FVSMETDSDE KQLLNQILNA VKVTPSLNED LQVEVMKVLL
CITYTPTFDM NGSAVLKIAE VCIETYTCSC HQRSINTAVR ATLSQMLGDL TLQLRQRQEN
TIIENPDAPQ EFRSQGLTVE ALCDDVISVL AVLCEKLQAS INDSQQLQLL YLECILSVLS
SSSSSMHLHR GFTDLIWKSL CPALVVILGN PIHDKTITSA HSTSTSTSME SDSASLGVSD
HGRGSGCSCT APTLSGPVAR TIYYLAAELV RLVGSVDSMK PVLQSLYHRV LLYPPPQHRV
EAIKIMKEIL GSPQRLYDLA GPSSIESEPR KRSISKRKSH LDLLKLIMDG MTEACIKGGI
EACYAAVSCV CTLLGALDEL SQGKGLNDTQ VQQLLLRLEE LRDGAESSRD SMEINEADFR
WQRRVLSSEH TPWESGNERS PDISISVTTD TGQTTLEGEL GQTTPEDHKN GLKSPAIQEG
KGTMGKVSEP EAIDQPDVVQ RSHTVPYPDI TNFLSVDCRT RSYGSRYSES NFSVDDQDLS
RTEFDSCDQY SMAAEKDSGR SDVSDIGSDN CSLADEEQTP RDYIGHRSLR TAALSLKLLK
NQEADQHSAR LFIQSLEGLL PRLLALSSVE EVDSALQNFA STFCSGMMHS PGFDGGSSLS
FQMLMNADSL YTAAHCALLL NLKLSHGDYY RKRPTVAPGM MKEFMKQVQT SGVLMVFSQA
WLEELYHQVL DRNMLGEAGY WGSPEDNSLP LITMLTDIDG LESSAIGGQL MASASVESPF
TQSRRLDDST VAGVAFARYI LVGCWKNLID TLSTPLTGRM AGSSKGLAFI LGAEGIKEQN
QKERDAICMS LDGLRKAARL SCALGVAANC ASALAQMAAA SCVQEEKEER QSQEPSDALA
QVKLKVEQKL EQMGKVQGVW LHTAHVLCMD AILSVGLEMG SHNPDCWPHV FRVCEYVGTL
EHTHFSDGIS QPPLTIHQPQ KTSGSSGLLG EIEFKSSSQE QSLEQGPSLN TAPVVQPHSI
QELVRECSRG RTSDFRGGSL SGNSAAKVVL SLSTQADRLF DDATDKLNLT ALGGFLYQLK
KASQSQLFHS VTDTVDYSLT MPGEVKSTQD QKSALHLFRL GDAMLRIVRS KARPLLHVMR
CWSLVAPHLV EAACHKERHV SQKAVSFIHD ILTEVLTDWS EPPHFHFNEA LFRPFERIMQ
LELCDEDVQD QVVTSIGELV EVCSAQIQSG WRPLFSALET VRSGNKSEVK EYLVGDYSMG
KGQAPVFDVF EAFLNTDNIQ VFANAATSYI MCLMKFVKGL GEVDCKEIGD CVPGAGATST
DLCLPALDYL RRCSQLLAKI YKMPLKPIFL SGRLASLPRR LQEQSASSED GIESVLSDFD
DDTGLIEVWI ILLEQLTAAV SNCPRQHQPP TLDLLFELLR DVTKTPGPGF GIYAVVHLLL
PVMSLWLLRS HKDHSYWDVA SANFKHAIGL SCELVVEHIQ SFLHSDIRYE SMINTMLKDL
FELLVVCVAK PTETISRVGC SCIRYVLVTA GPVFTEEMWR LACCALQDAF SATLKPVKDL
LGCFHGGTEG FSGEGCQVRV AAPSSSPSAE AEYWRIRAMA QQVFMLDTQC SPKTPNNFDH
AQSCQLIIEL PHDEKPNGHA KKSVSFREIV VSLLSHQVLL QNLYDILLEE FVKGPSPGEE
KTVQVPDTKL AGFLRYISMQ NLAVIFDLLL DSYRTAREFD TSPGLKCLLK KVSGIGGAAN
LYRQSAMSFN IYFHALVCAV LTNQETITAE QVKKVLFEEE ERSSDSSQQC SSEDEDIFEE
TAQVSPPRGK EKRQWRARLP SLSVQPVSNA DWVWLVKRLH KLCMELCNHY IQMHLDLESS
LEEPLTFKSD PFFILPSFQS ESSTPSTGGF SGKNTPSEDD RREHLSEPQS LRVGSGDMLM
LPPSPKTEKK DPGRKKEWWE SAGNKICTMA ADKTISKLMT EYKKRRQPHN LPPFPKEVKV
DKKGEPLGPR GPDSPLLQRP QHLIDQGQMR HSFSAGPELL RQEKRPRSGS TGSSLSVSVR
DAEAQIQAWT NMVLTVLNQI QILPDQTFTA LQPAVFPCIS QLTCHVTDIR VRQAVREWLG
RVGRVYDIIT
