BIG2_MOUSE
ID BIG2_MOUSE Reviewed; 1792 AA.
AC A2A5R2;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Brefeldin A-inhibited guanine nucleotide-exchange protein 2;
DE Short=Brefeldin A-inhibited GEP 2;
DE AltName: Full=ADP-ribosylation factor guanine nucleotide-exchange factor 2;
GN Name=Arfgef2; Synonyms=Arfgep2, Big2;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-621 AND
RP THR-623, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-621;
RP THR-623; SER-624; THR-633 AND SER-1535, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
CC -!- FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to
CC a lower extent on ARF5 and ARF6. Promotes the activation of
CC ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the
CC regulation of Golgi vesicular transport. Required for the integrity of
CC the endosomal compartment. Involved in trafficking from the trans-Golgi
CC network (TGN) to endosomes and is required for membrane association of
CC the AP-1 complex and GGA1. Seems to be involved in recycling of the
CC transferrin receptor from recycling endosomes to the plasma membrane.
CC Probably is involved in the exit of GABA(A) receptors from the
CC endoplasmic reticulum. Involved in constitutive release of tumor
CC necrosis factor receptor 1 via exosome-like vesicles; the function
CC seems to involve PKA and specifically PRKAR2B. Proposed to act as A
CC kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf
CC and PKA pathways (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Inhibited by brefeldin A. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with ARFGEF1/BIG1; both proteins are
CC probably part of the same or very similar macromolecular complexes.
CC Interacts with PRKAR1A, PRKAR2A, PRKAR1B, PRKAR2B, PPP1CC, PDE3A,
CC TNFRSF1A, MYCBP and EXOC7. Interacts with GABRB1, GABRB2 and GABRB3 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250}.
CC Golgi apparatus {ECO:0000250}. Cytoplasm, perinuclear region
CC {ECO:0000250}. Golgi apparatus, trans-Golgi network {ECO:0000250}.
CC Endosome {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250}. Cell projection, dendrite
CC {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Synapse
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Translocates
CC from cytoplasm to membranes upon cAMP treatment. Localized in recycling
CC endosomes (By similarity). {ECO:0000250}.
CC -!- PTM: In vitro phosphorylated by PKA reducing its GEF activity and
CC dephosphorylated by phosphatase PP1. {ECO:0000250}.
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DR EMBL; AL591703; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06489.1; -; Genomic_DNA.
DR EMBL; BC158012; AAI58013.1; -; mRNA.
DR CCDS; CCDS38335.1; -.
DR RefSeq; NP_001078964.1; NM_001085495.2.
DR AlphaFoldDB; A2A5R2; -.
DR SMR; A2A5R2; -.
DR BioGRID; 221234; 6.
DR IntAct; A2A5R2; 2.
DR STRING; 10090.ENSMUSP00000096677; -.
DR iPTMnet; A2A5R2; -.
DR PhosphoSitePlus; A2A5R2; -.
DR SwissPalm; A2A5R2; -.
DR EPD; A2A5R2; -.
DR jPOST; A2A5R2; -.
DR MaxQB; A2A5R2; -.
DR PaxDb; A2A5R2; -.
DR PeptideAtlas; A2A5R2; -.
DR PRIDE; A2A5R2; -.
DR ProteomicsDB; 273489; -.
DR Antibodypedia; 13512; 157 antibodies from 24 providers.
DR Ensembl; ENSMUST00000099078; ENSMUSP00000096677; ENSMUSG00000074582.
DR GeneID; 99371; -.
DR KEGG; mmu:99371; -.
DR UCSC; uc008nyr.2; mouse.
DR CTD; 10564; -.
DR MGI; MGI:2139354; Arfgef2.
DR VEuPathDB; HostDB:ENSMUSG00000074582; -.
DR eggNOG; KOG0929; Eukaryota.
DR GeneTree; ENSGT00940000158950; -.
DR HOGENOM; CLU_000691_1_1_1; -.
DR InParanoid; A2A5R2; -.
DR OMA; DLYITFF; -.
DR OrthoDB; 815698at2759; -.
DR PhylomeDB; A2A5R2; -.
DR TreeFam; TF300714; -.
DR BioGRID-ORCS; 99371; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Arfgef2; mouse.
DR PRO; PR:A2A5R2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2A5R2; protein.
DR Bgee; ENSMUSG00000074582; Expressed in pigmented layer of retina and 224 other tissues.
DR ExpressionAtlas; A2A5R2; baseline and differential.
DR Genevisible; A2A5R2; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032279; C:asymmetric synapse; ISS:UniProtKB.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0032280; C:symmetric synapse; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0050811; F:GABA receptor binding; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0017022; F:myosin binding; ISO:MGI.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISS:UniProtKB.
DR GO; GO:0010256; P:endomembrane system organization; ISS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0006887; P:exocytosis; ISO:MGI.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0001881; P:receptor recycling; ISS:UniProtKB.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
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 Acetylation; Cell projection; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Endosome; Golgi apparatus; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..1792
FT /note="Brefeldin A-inhibited guanine nucleotide-exchange
FT protein 2"
FT /id="PRO_0000419332"
FT DOMAIN 661..792
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 /evidence="ECO:0000250"
FT REGION 207..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 515..535
FT /note="HUS; DCB:HUS domain interaction"
FT /evidence="ECO:0000250"
FT COMPBIAS 215..246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU1"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 623
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 633
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 1518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 1520
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU1"
FT MOD_RES 1521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU1"
FT MOD_RES 1532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 1535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1541
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU1"
FT MOD_RES 1789
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
SQ SEQUENCE 1792 AA; 202240 MW; 23DF06EA23A34A71 CRC64;
MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAELEKQ RLGAAAPPKA
NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI TGNAPDSGAP GKRLIDRIVE
TICNCFQGPQ TDEGVQLQII KALLTAVTSP HIEIHEGTIL QTVRTCYNIY LASKNLINQT
TAKATLTQML NVIFTRMENQ VLQEARELEK PMQSKPQSPV IQATAGSPKF SRLKQSQAQS
KPTTPEKAEL PNGDHAQSGL GKVSLENGEA PRERGSPVSG RAEPSRGTDS GAQEVVKDIL
EDVVTSAVKE AAEKHGLPEP DRALGALECQ ECAVPPGVDE NSQTNGIADD RQSLSSADNL
EPDVQGHQVA ARFSHILQKD AFLVFRSLCK LSMKPLGEGP PDPKSHELRS KVVSLQLLLS
VLQNAGPVFR SHEMFVTAIK QYLCVALSKN GVSSVPDVFE LSLAIFLTLL SNFKMHLKMQ
IEVFFKEIFL NILETSTSSF EHRWMVIQTL TRICADAQCV VDIYVNYDCD LNAANIFERL
VNDLSKIAQG RSGHELGMTP LQELSLRKKG LECLVSILKC MVEWSKDLYV NPNHQATLGQ
ERLPDQEMGD GKGLDMARRC SVTSVESTVS SGTQTAIQDD PEQFEVIKQQ KEIIEHGIEL
FNKKPKRGIQ FLQEQGMLGA AVEDIAQFLH QEERLDSTQV GEFLGDSTRF NKEVMYAYVD
QLDFCEKEFV SALRTFLEGF RLPGEAQKID RLMEKFAARY IECNQGQTLF ASADTAYVLA
YSIIMLTTDL HSPQVKNKMT KEQYIKMNRG INDSKDLPEE YLSSIYDEIE GKKIAMKETK
EHTIATKSTK QSVASEKQRR LLYNVEMEQM AKTAKALMEA VSHAKAPFTS ATHLDHVRPM
FKLVWTPLLA AYSIGLQNCD DTEVASLCLE GIRCAVRIAC IFGMQLERDA YVQALARFSL
LTASSSITEM KQKNIDTIKT LITVAHTDGN YLGNSWHEIL KCISQLELAQ LIGTGVKTRY
LSGSGREREG SLKGHSLAGE EFMGLGLGNL VSGGVDKRQM ASFQESVGET SSQSVVVAVD
RIFTGSTRLD GNAIVDFVRW LCAVSMDELA SPHHPRMFSL QKIVEISYYN MNRIRLQWSR
IWHVIGDHFN KVGCNPNEDV AIFAVDSLRQ LSMKFLEKGE LANFRFQKDF LRPFEHIMKK
NRSPTIRDMV IRCIAQMVSS QAANIRSGWK NIFAVFHQAA SDHDGNIVEL AFQTTGHIVS
TIFQHHFPAA IDSFQDAVKC LSEFACNAAF PDTSMEAIRL IRFCGKYVSE RPRVLQEYTS
DDMNVAPGDR VWVRGWFPIL FELSCIINRC KLDVRTRGLT VMFEIMKSYG HTFAKHWWQD
LFRIVFRIFD NMKLPEQQSE KSEWMTTTCN HALYAICDVF TQFYEALHEV LLSDVFAQLQ
WCVKQDNEQL ARSGTNCLEN LVISNGEKFS PAVWDETCNC MLDIFKTTIP HVLLTWRPAG
MEEEVSDRHL DVDLDRQSLS SIDRNASERG QSQLSNPTDD SWKGAPYAHQ KLLASLLIKC
VVQLELIQTI DNIVFYPATS KKEDAEHMVA AQQDTLDAEI HIETENQGMY KFMSSQHLFK
LLDCLQESHS FSKAFNSNYE QRTVLWRAGF KGKSKPNLLK QETSSLACCL RILFRMYVDE
NRRDSWDEIQ QRLLRVCSEA LAYFITVNSE SHREAWTSLL LLLLTKTLKI SDEKFKAHAS
MYYPYLCEIM QFDLIPELRA VLRKFFLRIG LVYKIWIPEE PSQVPAALSS TW
