A2A5R2 (BIG2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Arfgef2
Synonyms:	Arfgep2, Big2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1792 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Enzyme regulation	Inhibited by brefeldin A By similarity.
Subunit structure	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.
Subcellular location	Cytoplasm By similarity. Membrane By similarity. Golgi apparatus By similarity. Cytoplasm › perinuclear region By similarity. Golgi apparatus › trans-Golgi network By similarity. Endosome By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Cell projection › dendrite By similarity. Cytoplasmic vesicle By similarity. Cell junction › synapse By similarity. Cytoplasm › cytoskeleton By similarity. Note: Translocates from cytoplasm to membranes upon cAMP treatment. Localized in recycling endosomes By similarity.
Post-translational modification	In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1 By similarity.
Sequence similarities	Contains 1 SEC7 domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell junction Cell projection Cytoplasm Cytoplasmic vesicle Cytoskeleton Endosome Golgi apparatus Membrane Synapse
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Golgi to plasma membrane transport Inferred from sequence or structural similarity. Source: UniProtKB endomembrane system organization Inferred from sequence or structural similarity. Source: UniProtKB endosome organization Inferred from sequence or structural similarity. Source: UniProtKB exocytosis Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: Compara positive regulation of tumor necrosis factor production Inferred from sequence or structural similarity. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW receptor recycling Inferred from sequence or structural similarity. Source: UniProtKB regulation of ARF protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	Golgi membrane Inferred from sequence or structural similarity. Source: UniProtKB asymmetric synapse Inferred from sequence or structural similarity. Source: UniProtKB axonemal microtubule Inferred from sequence or structural similarity. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from electronic annotation. Source: Compara dendritic spine Inferred from sequence or structural similarity. Source: UniProtKB microtubule organizing center Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell recycling endosome Inferred from sequence or structural similarity. Source: UniProtKB symmetric synapse Inferred from sequence or structural similarity. Source: UniProtKB trans-Golgi network Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ARF guanyl-nucleotide exchange factor activity Inferred from sequence or structural similarity. Source: UniProtKB GABA receptor binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase A regulatory subunit binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1792	1792	Brefeldin A-inhibited guanine nucleotide-exchange protein 2		PRO_0000419332
Regions
	Domain	661 – 792	132	SEC7
	Region	2 – 224	223	DCB; DCB:DCB domain and DCB:HUS domain interaction By similarity
	Region	515 – 535	21	HUS; DCB:HUS domain interaction By similarity
Amino acid modifications
	Modified residue	214	1	Phosphoserine Ref.4
	Modified residue	218	1	Phosphoserine Ref.4
	Modified residue	227	1	Phosphoserine Ref.4
	Modified residue	621	1	Phosphoserine Ref.4
	Modified residue	623	1	Phosphothreonine Ref.4
	Modified residue	1532	1	Phosphoserine By similarity
	Modified residue	1535	1	Phosphoserine By similarity
	Modified residue	1789	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	A2A5R2 [UniParc]. Last modified February 20, 2007. Version 1. Checksum: 23DF06EA23A34A71	FASTA	1,792	202,240
	10 20 30 40 50 60 MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAELEKQ RLGAAAPPKA 70 80 90 100 110 120 NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI TGNAPDSGAP GKRLIDRIVE 130 140 150 160 170 180 TICNCFQGPQ TDEGVQLQII KALLTAVTSP HIEIHEGTIL QTVRTCYNIY LASKNLINQT 190 200 210 220 230 240 TAKATLTQML NVIFTRMENQ VLQEARELEK PMQSKPQSPV IQATAGSPKF SRLKQSQAQS 250 260 270 280 290 300 KPTTPEKAEL PNGDHAQSGL GKVSLENGEA PRERGSPVSG RAEPSRGTDS GAQEVVKDIL 310 320 330 340 350 360 EDVVTSAVKE AAEKHGLPEP DRALGALECQ ECAVPPGVDE NSQTNGIADD RQSLSSADNL 370 380 390 400 410 420 EPDVQGHQVA ARFSHILQKD AFLVFRSLCK LSMKPLGEGP PDPKSHELRS KVVSLQLLLS 430 440 450 460 470 480 VLQNAGPVFR SHEMFVTAIK QYLCVALSKN GVSSVPDVFE LSLAIFLTLL SNFKMHLKMQ 490 500 510 520 530 540 IEVFFKEIFL NILETSTSSF EHRWMVIQTL TRICADAQCV VDIYVNYDCD LNAANIFERL 550 560 570 580 590 600 VNDLSKIAQG RSGHELGMTP LQELSLRKKG LECLVSILKC MVEWSKDLYV NPNHQATLGQ 610 620 630 640 650 660 ERLPDQEMGD GKGLDMARRC SVTSVESTVS SGTQTAIQDD PEQFEVIKQQ KEIIEHGIEL 670 680 690 700 710 720 FNKKPKRGIQ FLQEQGMLGA AVEDIAQFLH QEERLDSTQV GEFLGDSTRF NKEVMYAYVD 730 740 750 760 770 780 QLDFCEKEFV SALRTFLEGF RLPGEAQKID RLMEKFAARY IECNQGQTLF ASADTAYVLA 790 800 810 820 830 840 YSIIMLTTDL HSPQVKNKMT KEQYIKMNRG INDSKDLPEE YLSSIYDEIE GKKIAMKETK 850 860 870 880 890 900 EHTIATKSTK QSVASEKQRR LLYNVEMEQM AKTAKALMEA VSHAKAPFTS ATHLDHVRPM 910 920 930 940 950 960 FKLVWTPLLA AYSIGLQNCD DTEVASLCLE GIRCAVRIAC IFGMQLERDA YVQALARFSL 970 980 990 1000 1010 1020 LTASSSITEM KQKNIDTIKT LITVAHTDGN YLGNSWHEIL KCISQLELAQ LIGTGVKTRY 1030 1040 1050 1060 1070 1080 LSGSGREREG SLKGHSLAGE EFMGLGLGNL VSGGVDKRQM ASFQESVGET SSQSVVVAVD 1090 1100 1110 1120 1130 1140 RIFTGSTRLD GNAIVDFVRW LCAVSMDELA SPHHPRMFSL QKIVEISYYN MNRIRLQWSR 1150 1160 1170 1180 1190 1200 IWHVIGDHFN KVGCNPNEDV AIFAVDSLRQ LSMKFLEKGE LANFRFQKDF LRPFEHIMKK 1210 1220 1230 1240 1250 1260 NRSPTIRDMV IRCIAQMVSS QAANIRSGWK NIFAVFHQAA SDHDGNIVEL AFQTTGHIVS 1270 1280 1290 1300 1310 1320 TIFQHHFPAA IDSFQDAVKC LSEFACNAAF PDTSMEAIRL IRFCGKYVSE RPRVLQEYTS 1330 1340 1350 1360 1370 1380 DDMNVAPGDR VWVRGWFPIL FELSCIINRC KLDVRTRGLT VMFEIMKSYG HTFAKHWWQD 1390 1400 1410 1420 1430 1440 LFRIVFRIFD NMKLPEQQSE KSEWMTTTCN HALYAICDVF TQFYEALHEV LLSDVFAQLQ 1450 1460 1470 1480 1490 1500 WCVKQDNEQL ARSGTNCLEN LVISNGEKFS PAVWDETCNC MLDIFKTTIP HVLLTWRPAG 1510 1520 1530 1540 1550 1560 MEEEVSDRHL DVDLDRQSLS SIDRNASERG QSQLSNPTDD SWKGAPYAHQ KLLASLLIKC 1570 1580 1590 1600 1610 1620 VVQLELIQTI DNIVFYPATS KKEDAEHMVA AQQDTLDAEI HIETENQGMY KFMSSQHLFK 1630 1640 1650 1660 1670 1680 LLDCLQESHS FSKAFNSNYE QRTVLWRAGF KGKSKPNLLK QETSSLACCL RILFRMYVDE 1690 1700 1710 1720 1730 1740 NRRDSWDEIQ QRLLRVCSEA LAYFITVNSE SHREAWTSLL LLLLTKTLKI SDEKFKAHAS 1750 1760 1770 1780 1790 MYYPYLCEIM QFDLIPELRA VLRKFFLRIG LVYKIWIPEE PSQVPAALSS TW

References

[1]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] 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]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214; SER-218; SER-227; SER-621 AND THR-623, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL591703, AL591911 Genomic DNA. Translation: CAM24646.1. AL591911 Genomic DNA. Translation: CAM17723.1. CH466551 Genomic DNA. Translation: EDL06489.1. BC158012 mRNA. Translation: AAI58013.1.
IPI	IPI00137087.
RefSeq	NP_001078964.1. NM_001085495.2.
UniGene	Mm.297192. Mm.488805.
3D structure databases
ProteinModelPortal	A2A5R2.
SMR	A2A5R2. Positions 644-835.
ModBase	Search...
Protein-protein interaction databases
IntAct	A2A5R2. 1 interaction.
STRING	10090.ENSMUSP00000096677.
PTM databases
PhosphoSite	A2A5R2.
Proteomic databases
PaxDb	A2A5R2.
PRIDE	A2A5R2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000099078; ENSMUSP00000096677; ENSMUSG00000074582.
GeneID	99371.
KEGG	mmu:99371.
UCSC	uc008nyr.2. mouse.
Organism-specific databases
CTD	10564.
MGI	MGI:2139354. Arfgef2.
Phylogenomic databases
eggNOG	COG5307.
GeneTree	ENSGT00660000095162.
HOGENOM	HOG000181045.
HOVERGEN	HBG004846.
InParanoid	A2A5R2.
OMA	GHQVAAR.
OrthoDB	EOG4V9TPR.
Enzyme and pathway databases
Reactome	REACT_93132. Metabolism of proteins.
Gene expression databases
ArrayExpress	A2A5R2.
Bgee	A2A5R2.
Genevestigator	A2A5R2.
Family and domain databases
Gene3D	1.10.1000.11. 1 hit. 1.25.10.10. 4 hits.
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR015403. DUF1981_SEC7_assoc. IPR000904. Sec7. IPR023394. SEC7_alpha_orthog. [Graphical view]
Pfam	PF09324. DUF1981. 1 hit. PF01369. Sec7. 1 hit. [Graphical view]
SMART	SM00222. Sec7. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF48425. Sec7. 1 hit.
PROSITE	PS50190. SEC7. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ARFGEF2. mouse.
NextBio	353893.
SOURCE	Search...

Entry information

Entry name

BIG2_MOUSE

Accession

Primary (citable) accession number: A2A5R2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2012
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program