BIG2_RAT
ID BIG2_RAT Reviewed; 1791 AA.
AC Q7TSU1;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH GABRB1; GABRB2 AND GABRB3.
RC STRAIN=Sprague-Dawley;
RX PubMed=15198677; DOI=10.1111/j.1471-4159.2004.02481.x;
RA Charych E.I., Yu W., Miralles C.P., Serwanski D.R., Li X., Rubio M.,
RA De Blas A.L.;
RT "The brefeldin A-inhibited GDP/GTP exchange factor 2, a protein involved in
RT vesicular trafficking, interacts with the beta subunits of the GABA
RT receptors.";
RL J. Neurochem. 90:173-189(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=11809827; DOI=10.1091/mbc.01-08-0420;
RA Zhao X., Lasell T.K., Melancon P.;
RT "Localization of large ADP-ribosylation factor-guanine nucleotide exchange
RT factors to different Golgi compartments: evidence for distinct functions in
RT protein traffic.";
RL Mol. Biol. Cell 13:119-133(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-355;
RP SER-356; SER-1518; SER-1520; SER-1521; SER-1532; SER-1535 AND SER-1541, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. {ECO:0000269|PubMed:15198677}.
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 (By similarity). Interacts with GABRB1,
CC GABRB2 and GABRB3. {ECO:0000250, ECO:0000269|PubMed:15198677}.
CC -!- INTERACTION:
CC Q7TSU1; P63079: Gabrb3; NbExp=3; IntAct=EBI-6257913, EBI-6257937;
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. Endosome
CC {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome {ECO:0000250}. Cell projection, dendrite. Cytoplasmic
CC vesicle. Synapse. Cytoplasm, cytoskeleton. Note=Translocates from
CC cytoplasm to membranes upon cAMP treatment. Localized in recycling
CC endosomes (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level).
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; AY255526; AAP04588.2; -; mRNA.
DR EMBL; AABR06027654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06027655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06027656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_851597.2; NM_181083.2.
DR AlphaFoldDB; Q7TSU1; -.
DR SMR; Q7TSU1; -.
DR IntAct; Q7TSU1; 9.
DR STRING; 10116.ENSRNOP00000010054; -.
DR iPTMnet; Q7TSU1; -.
DR PhosphoSitePlus; Q7TSU1; -.
DR jPOST; Q7TSU1; -.
DR PaxDb; Q7TSU1; -.
DR PRIDE; Q7TSU1; -.
DR Ensembl; ENSRNOT00000010054; ENSRNOP00000010054; ENSRNOG00000007485.
DR GeneID; 296380; -.
DR KEGG; rno:296380; -.
DR UCSC; RGD:631430; rat.
DR CTD; 10564; -.
DR RGD; 631430; Arfgef2.
DR eggNOG; KOG0929; Eukaryota.
DR GeneTree; ENSGT00940000158950; -.
DR HOGENOM; CLU_000691_1_1_1; -.
DR InParanoid; Q7TSU1; -.
DR OMA; DLYITFF; -.
DR OrthoDB; 815698at2759; -.
DR PhylomeDB; Q7TSU1; -.
DR TreeFam; TF300714; -.
DR PRO; PR:Q7TSU1; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000007485; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; Q7TSU1; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032279; C:asymmetric synapse; IDA:UniProtKB.
DR GO; GO:0005879; C:axonemal microtubule; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
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; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0050811; F:GABA receptor binding; IMP:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0017022; F:myosin binding; IPI:UniProtKB.
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; IMP:RGD.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
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 Disease variant; Endosome; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..1791
FT /note="Brefeldin A-inhibited guanine nucleotide-exchange
FT protein 2"
FT /id="PRO_0000419333"
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 208..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..350
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..247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..350
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:22673903"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 623
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2A5R2"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2A5R2"
FT MOD_RES 633
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2A5R2"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
FT MOD_RES 1518
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1520
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1532
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1541
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1788
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6D5"
SQ SEQUENCE 1791 AA; 201974 MW; 397CB889C2ABF569 CRC64;
MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAELEKQ RLGAAAPPKA
NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI TGNAPDSGAP GKRLIDRIVE
TVCNCFQGPQ TDEGVQLQII KALLTAVTSP HIEIHEGTIL QTVRTCYNIY LASKNLINQT
TAKATLTQML NVIFTRMENQ VLQEARELEK PIQSKPQSPV IQATAGSPKF SRLKQSQAQS
KPTTPEKTEL PNGDHARSSL GKVNSENGEA HRERGSSISG RAEPSGGSDN GAQEVVKDIL
EDVVTSAVKE AAEKQGLPEP DQAPGVPECQ ECTVPPAVDE NSQTNGIADD RQSLSSADNL
EPDAQGHPVA 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 SGTQTAIPDD PEQFEVIKQQ KEIIEHGIEL
FNKKPKRGIQ FLQEQGMLGA AVEDIAQFLH QEERLDSTQV GEFLGDSTRF NKEVMYAYVD
QLDFCEKEFV SALRTFLEGF RLPGEAQKID RLMEKFAARY IECNQGQTLF ASADTAYVLA
YSIIMLTTDL HSPQVKNKMT KEQYIKMNRG INDSKDLPEE YLSSIYEEIE GKKIAMKETK
EHTMATKSTK QNVASEKQRR 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 MLDIFRTTIP HVLLTWRPAG
MEEEVSDRHL DVDLDRQSLS SIDRNASERG QSQLSNPTDD SWKGAPYANQ KLLASLLIKC
VVQLELIQTI DNIVFYPATS KKEDAEHMVA AQQDTLDADI HIETENQGMY KFMSSQHLFK
LLDCLQESHS FSKAFNSNYE QRTVLWRAGF KGKSKPNLLK QETSSLACCL RILFRMYVDE
NRRDSWGEIQ QRLLTVCSEA LAYFITVNSE SHREAWTSLL LLLLTKTLKI NDEKFKAHAS
VYYPYLCEMM QFDLIPELRA VLRKFFLRIG LVYKIWVPEE PSQVPAASTA W
