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A2A5R2

- BIG2_MOUSE

UniProt

A2A5R2 - BIG2_MOUSE

Protein

Brefeldin A-inhibited guanine nucleotide-exchange protein 2

Gene

Arfgef2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 66 (01 Oct 2014)
      Sequence version 1 (20 Feb 2007)
      Previous versions | rss
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    Functioni

    Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extend on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways By similarity.By similarity

    Enzyme regulationi

    Inhibited by brefeldin A.By similarity

    GO - Molecular functioni

    1. ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
    2. GABA receptor binding Source: UniProtKB
    3. protein kinase A regulatory subunit binding Source: UniProtKB

    GO - Biological processi

    1. endomembrane system organization Source: UniProtKB
    2. endosome organization Source: UniProtKB
    3. exocytosis Source: Ensembl
    4. Golgi to plasma membrane transport Source: UniProtKB
    5. intracellular signal transduction Source: Ensembl
    6. positive regulation of GTPase activity Source: GOC
    7. positive regulation of tumor necrosis factor production Source: UniProtKB
    8. protein transport Source: UniProtKB-KW
    9. receptor recycling Source: UniProtKB
    10. regulation of ARF protein signal transduction Source: InterPro
    11. vesicle-mediated transport Source: RefGenome

    Keywords - Molecular functioni

    Guanine-nucleotide releasing factor

    Keywords - Biological processi

    Protein transport, Transport

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Brefeldin A-inhibited guanine nucleotide-exchange protein 2
    Short name:
    Brefeldin A-inhibited GEP 2
    Alternative name(s):
    ADP-ribosylation factor guanine nucleotide-exchange factor 2
    Gene namesi
    Name:Arfgef2
    Synonyms:Arfgep2, Big2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:2139354. Arfgef2.

    Subcellular locationi

    Cytoplasm By similarity. Membrane By similarity. Golgi apparatus By similarity. Cytoplasmperinuclear region By similarity. Golgi apparatustrans-Golgi network By similarity. Endosome By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cell projectiondendrite By similarity. Cytoplasmic vesicle By similarity. Cell junctionsynapse By similarity. Cytoplasmcytoskeleton By similarity
    Note: Translocates from cytoplasm to membranes upon cAMP treatment. Localized in recycling endosomes By similarity.By similarity

    GO - Cellular componenti

    1. asymmetric synapse Source: UniProtKB
    2. axonemal microtubule Source: UniProtKB
    3. cell junction Source: UniProtKB-KW
    4. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
    5. cytoplasmic vesicle Source: UniProtKB
    6. cytosol Source: Ensembl
    7. dendritic spine Source: UniProtKB
    8. Golgi membrane Source: UniProtKB
    9. microtubule organizing center Source: UniProtKB
    10. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    11. recycling endosome Source: UniProtKB
    12. symmetric synapse Source: UniProtKB
    13. trans-Golgi network Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Golgi apparatus, Membrane, Synapse

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 17921792Brefeldin A-inhibited guanine nucleotide-exchange protein 2PRO_0000419332Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei218 – 2181Phosphoserine1 Publication
    Modified residuei227 – 2271Phosphoserine1 Publication
    Modified residuei621 – 6211Phosphoserine1 Publication
    Modified residuei623 – 6231Phosphothreonine1 Publication
    Modified residuei1532 – 15321PhosphoserineBy similarity
    Modified residuei1535 – 15351PhosphoserineBy similarity
    Modified residuei1789 – 17891PhosphoserineBy similarity

    Post-translational modificationi

    In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiA2A5R2.
    PaxDbiA2A5R2.
    PRIDEiA2A5R2.

    PTM databases

    PhosphoSiteiA2A5R2.

    Expressioni

    Gene expression databases

    ArrayExpressiA2A5R2.
    BgeeiA2A5R2.
    GenevestigatoriA2A5R2.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with BIG1; both proteins are probably part of the same or very similar macromolecular complexes. Interacts with PRKAR1A, PRKAR2A, PRKAR1B, PRKAR2B, PPP1CC, PDE3A, TNFRSF1A, MYCBP and EXOC7. Interacts with GABRB1, GABRB2 and GABRB3 By similarity.By similarity

    Protein-protein interaction databases

    IntActiA2A5R2. 1 interaction.
    STRINGi10090.ENSMUSP00000096677.

    Structurei

    3D structure databases

    ProteinModelPortaliA2A5R2.
    SMRiA2A5R2. Positions 644-835.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini661 – 792132SEC7PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 224223DCB; DCB:DCB domain and DCB:HUS domain interactionBy similarityAdd
    BLAST
    Regioni515 – 53521HUS; DCB:HUS domain interactionBy similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 SEC7 domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5307.
    GeneTreeiENSGT00660000095162.
    HOGENOMiHOG000181045.
    HOVERGENiHBG004846.
    InParanoidiA2A5R2.
    OMAiEQGMLGA.
    OrthoDBiEOG7QVM1S.
    PhylomeDBiA2A5R2.
    TreeFamiTF300714.

    Family and domain databases

    Gene3Di1.10.1000.11. 1 hit.
    1.25.10.10. 4 hits.
    InterProiIPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR015403. DUF1981_Sec7_assoc.
    IPR023394. Sec7_alpha_orthog.
    IPR000904. Sec7_dom.
    [Graphical view]
    PfamiPF09324. DUF1981. 1 hit.
    PF01369. Sec7. 1 hit.
    [Graphical view]
    SMARTiSM00222. Sec7. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 3 hits.
    SSF48425. SSF48425. 1 hit.
    PROSITEiPS50190. SEC7. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    A2A5R2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAELEKQ     50
    RLGAAAPPKA NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI 100
    TGNAPDSGAP GKRLIDRIVE TICNCFQGPQ TDEGVQLQII KALLTAVTSP 150
    HIEIHEGTIL QTVRTCYNIY LASKNLINQT TAKATLTQML NVIFTRMENQ 200
    VLQEARELEK PMQSKPQSPV IQATAGSPKF SRLKQSQAQS KPTTPEKAEL 250
    PNGDHAQSGL GKVSLENGEA PRERGSPVSG RAEPSRGTDS GAQEVVKDIL 300
    EDVVTSAVKE AAEKHGLPEP DRALGALECQ ECAVPPGVDE NSQTNGIADD 350
    RQSLSSADNL EPDVQGHQVA ARFSHILQKD AFLVFRSLCK LSMKPLGEGP 400
    PDPKSHELRS KVVSLQLLLS VLQNAGPVFR SHEMFVTAIK QYLCVALSKN 450
    GVSSVPDVFE LSLAIFLTLL SNFKMHLKMQ IEVFFKEIFL NILETSTSSF 500
    EHRWMVIQTL TRICADAQCV VDIYVNYDCD LNAANIFERL VNDLSKIAQG 550
    RSGHELGMTP LQELSLRKKG LECLVSILKC MVEWSKDLYV NPNHQATLGQ 600
    ERLPDQEMGD GKGLDMARRC SVTSVESTVS SGTQTAIQDD PEQFEVIKQQ 650
    KEIIEHGIEL FNKKPKRGIQ FLQEQGMLGA AVEDIAQFLH QEERLDSTQV 700
    GEFLGDSTRF NKEVMYAYVD QLDFCEKEFV SALRTFLEGF RLPGEAQKID 750
    RLMEKFAARY IECNQGQTLF ASADTAYVLA YSIIMLTTDL HSPQVKNKMT 800
    KEQYIKMNRG INDSKDLPEE YLSSIYDEIE GKKIAMKETK EHTIATKSTK 850
    QSVASEKQRR LLYNVEMEQM AKTAKALMEA VSHAKAPFTS ATHLDHVRPM 900
    FKLVWTPLLA AYSIGLQNCD DTEVASLCLE GIRCAVRIAC IFGMQLERDA 950
    YVQALARFSL LTASSSITEM KQKNIDTIKT LITVAHTDGN YLGNSWHEIL 1000
    KCISQLELAQ LIGTGVKTRY LSGSGREREG SLKGHSLAGE EFMGLGLGNL 1050
    VSGGVDKRQM ASFQESVGET SSQSVVVAVD RIFTGSTRLD GNAIVDFVRW 1100
    LCAVSMDELA SPHHPRMFSL QKIVEISYYN MNRIRLQWSR IWHVIGDHFN 1150
    KVGCNPNEDV AIFAVDSLRQ LSMKFLEKGE LANFRFQKDF LRPFEHIMKK 1200
    NRSPTIRDMV IRCIAQMVSS QAANIRSGWK NIFAVFHQAA SDHDGNIVEL 1250
    AFQTTGHIVS TIFQHHFPAA IDSFQDAVKC LSEFACNAAF PDTSMEAIRL 1300
    IRFCGKYVSE RPRVLQEYTS DDMNVAPGDR VWVRGWFPIL FELSCIINRC 1350
    KLDVRTRGLT VMFEIMKSYG HTFAKHWWQD LFRIVFRIFD NMKLPEQQSE 1400
    KSEWMTTTCN HALYAICDVF TQFYEALHEV LLSDVFAQLQ WCVKQDNEQL 1450
    ARSGTNCLEN LVISNGEKFS PAVWDETCNC MLDIFKTTIP HVLLTWRPAG 1500
    MEEEVSDRHL DVDLDRQSLS SIDRNASERG QSQLSNPTDD SWKGAPYAHQ 1550
    KLLASLLIKC VVQLELIQTI DNIVFYPATS KKEDAEHMVA AQQDTLDAEI 1600
    HIETENQGMY KFMSSQHLFK LLDCLQESHS FSKAFNSNYE QRTVLWRAGF 1650
    KGKSKPNLLK QETSSLACCL RILFRMYVDE NRRDSWDEIQ QRLLRVCSEA 1700
    LAYFITVNSE SHREAWTSLL LLLLTKTLKI SDEKFKAHAS MYYPYLCEIM 1750
    QFDLIPELRA VLRKFFLRIG LVYKIWIPEE PSQVPAALSS TW 1792
    Length:1,792
    Mass (Da):202,240
    Last modified:February 20, 2007 - v1
    Checksum:i23DF06EA23A34A71
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL591703, AL591911 Genomic DNA. Translation: CAM24646.1.
    AL591911 Genomic DNA. Translation: CAM17723.1.
    CH466551 Genomic DNA. Translation: EDL06489.1.
    BC158012 mRNA. Translation: AAI58013.1.
    CCDSiCCDS38335.1.
    RefSeqiNP_001078964.1. NM_001085495.2.
    UniGeneiMm.297192.
    Mm.488805.

    Genome annotation databases

    EnsembliENSMUST00000099078; ENSMUSP00000096677; ENSMUSG00000074582.
    GeneIDi99371.
    KEGGimmu:99371.
    UCSCiuc008nyr.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL591703 , AL591911 Genomic DNA. Translation: CAM24646.1 .
    AL591911 Genomic DNA. Translation: CAM17723.1 .
    CH466551 Genomic DNA. Translation: EDL06489.1 .
    BC158012 mRNA. Translation: AAI58013.1 .
    CCDSi CCDS38335.1.
    RefSeqi NP_001078964.1. NM_001085495.2.
    UniGenei Mm.297192.
    Mm.488805.

    3D structure databases

    ProteinModelPortali A2A5R2.
    SMRi A2A5R2. Positions 644-835.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi A2A5R2. 1 interaction.
    STRINGi 10090.ENSMUSP00000096677.

    PTM databases

    PhosphoSitei A2A5R2.

    Proteomic databases

    MaxQBi A2A5R2.
    PaxDbi A2A5R2.
    PRIDEi A2A5R2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000099078 ; ENSMUSP00000096677 ; ENSMUSG00000074582 .
    GeneIDi 99371.
    KEGGi mmu:99371.
    UCSCi uc008nyr.2. mouse.

    Organism-specific databases

    CTDi 10564.
    MGIi MGI:2139354. Arfgef2.

    Phylogenomic databases

    eggNOGi COG5307.
    GeneTreei ENSGT00660000095162.
    HOGENOMi HOG000181045.
    HOVERGENi HBG004846.
    InParanoidi A2A5R2.
    OMAi EQGMLGA.
    OrthoDBi EOG7QVM1S.
    PhylomeDBi A2A5R2.
    TreeFami TF300714.

    Miscellaneous databases

    ChiTaRSi ARFGEF2. mouse.
    NextBioi 353893.
    PROi A2A5R2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi A2A5R2.
    Bgeei A2A5R2.
    Genevestigatori A2A5R2.

    Family and domain databases

    Gene3Di 1.10.1000.11. 1 hit.
    1.25.10.10. 4 hits.
    InterProi IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR015403. DUF1981_Sec7_assoc.
    IPR023394. Sec7_alpha_orthog.
    IPR000904. Sec7_dom.
    [Graphical view ]
    Pfami PF09324. DUF1981. 1 hit.
    PF01369. Sec7. 1 hit.
    [Graphical view ]
    SMARTi SM00222. Sec7. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 3 hits.
    SSF48425. SSF48425. 1 hit.
    PROSITEi PS50190. SEC7. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-621 AND THR-623, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    5. "Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
      Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
      J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    6. "Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
      Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
      Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiBIG2_MOUSE
    AccessioniPrimary (citable) accession number: A2A5R2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2012
    Last sequence update: February 20, 2007
    Last modified: October 1, 2014
    This is version 66 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3