Q9Y6D5 (BIG2_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1785 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. Ref.4 Ref.5 Ref.6 Ref.10 Ref.11 Ref.14 Ref.20
Enzyme regulation	Inhibited by brefeldin A.
Subunit structure	Homodimer Probable. 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. Ref.3 Ref.5 Ref.7 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18
Subcellular location	Cytoplasm. Membrane. Golgi apparatus. Cytoplasm › perinuclear region. Golgi apparatus › trans-Golgi network By similarity. Endosome By similarity. Cytoplasm › cytoskeleton › centrosome. 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. Ref.3 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10
Tissue specificity	Expressed in placenta, lung, heart, brain, kidney and pancreas.
Post-translational modification	In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1. Ref.13
Involvement in disease	Periventricular nodular heterotopia 2 (PVNH2) [MIM:608097]: A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH2 is an autosomal recessive form characterized by microcephaly (small brain), severe developmental delay and recurrent infections. No anomalies extrinsic to the central nervous system, such as dysmorphic features or grossly abnormal endocrine or other conditions, are associated with PVNH2. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24
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
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Golgi to plasma membrane transport Inferred from mutant phenotype Ref.11. Source: UniProtKB endomembrane system organization Inferred from mutant phenotype Ref.20. Source: UniProtKB endosome organization Inferred from mutant phenotype Ref.20. Source: UniProtKB exocytosis Traceable author statement Ref.1. Source: ProtInc intracellular signal transduction Inferred from direct assay Ref.5. Source: MGI positive regulation of tumor necrosis factor production Inferred from mutant phenotype Ref.11. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW receptor recycling Inferred from direct assay Ref.10. Source: UniProtKB regulation of ARF protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	Golgi membrane Inferred from direct assay Ref.3. 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 direct assay Ref.5. Source: MGI dendritic spine Inferred from sequence or structural similarity. Source: UniProtKB microtubule organizing center Inferred from direct assay Ref.7. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell recycling endosome Inferred from direct assay Ref.6. 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 direct assay Ref.6. Source: UniProtKB GABA receptor binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase A regulatory subunit binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARFGEF1	Q9Y6D6	3	EBI-2837511,EBI-1044254
EXOC7	Q9UPT5-1	4	EBI-2837511,EBI-6251402
MYCBP	Q99417	5	EBI-2837511,EBI-716185

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1785

1785

Brefeldin A-inhibited guanine nucleotide-exchange protein 2

PRO_0000120208

Regions

Domain

654 – 785

132

SEC7

Region

2 – 224

223

DCB; DCB:DCB domain and DCB:HUS domain interaction

Region

508 – 528

21

HUS; DCB:HUS domain interaction

Amino acid modifications

Modified residue

214

1

Phosphoserine By similarity

Modified residue

218

1

Phosphoserine Ref.8 Ref.15 Ref.21 Ref.23

Modified residue

227

1

Phosphoserine Ref.8 Ref.15 Ref.19 Ref.21 Ref.23

Modified residue

277

1

Phosphoserine Ref.19

Modified residue

614

1

Phosphoserine Ref.16

Modified residue

616

1

Phosphothreonine By similarity

Modified residue

1525

1

Phosphoserine Ref.8 Ref.19

Modified residue

1528

1

Phosphoserine Ref.8 Ref.15 Ref.17 Ref.19 Ref.21

Modified residue

1782

1

Phosphoserine Ref.15

Natural variations

Natural variant

209

1

E → K in PVNH2. Ref.24
Corresponds to variant rs28937880 [ dbSNP | Ensembl ].

VAR_037438

Natural variant

527

1

A → V.
Corresponds to variant rs6063343 [ dbSNP | Ensembl ].

VAR_028750

Natural variant

794

1

K → E in a breast cancer sample; somatic mutation. Ref.25

VAR_036156

Experimental info

Mutagenesis

289

1

V → W: Abolishes interaction with PRKAR2B and impairs TNFRSF1A release. Ref.14

Mutagenesis

534

1

V → W: Abolishes interaction with PRKAR2B and impairs TNFRSF1A release. Ref.14

Mutagenesis

738

1

E → K: Disturbs membrane organization at the TGN, impairs association of the AP-1 complex and GGA1 with the TGN membranes. Ref.4 Ref.6

Sequence conflict

207

1

E → R in AAD38428. Ref.1

Sequence conflict

962

1

E → K in AAD38428. Ref.1

Sequence conflict

1049

1

D → N in AAD38428. Ref.1

Sequence conflict

1763

1

G → S in AAD38428. Ref.1

Secondary structure

1

.

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1785

Helix Strand Turn

Details...

Helix

641 – 643

3

Turn

644 – 648

5

Helix

649 – 654

6

Helix

658 – 667

10

Turn

674 – 678

5

Helix

679 – 682

4

Helix

690 – 694

5

Turn

695 – 698

4

Turn

702 – 705

4

Helix

706 – 712

7

Helix

723 – 729

7

Helix

739 – 753

15

Helix

766 – 777

12

Turn

778 – 782

5

Turn

796 – 798

3

Beta strand

799 – 801

3

Beta strand

804 – 808

5

Helix

812 – 822

11

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6D5 [UniParc]. Last modified March 6, 2007. Version 3. Checksum: D419106E5BAF19C2	FASTA	1,785	202,038
	10 20 30 40 50 60 MQESQTKSMF VSRALEKILA DKEVKRPQHS QLRRACQVAL DEIKAEIEKQ RLGTAAPPKA 70 80 90 100 110 120 NFIEADKYFL PFELACQSKS PRVVSTSLDC LQKLIAYGHI TGNAPDSGAP GKRLIDRIVE 130 140 150 160 170 180 TICSCFQGPQ TDEGVQLQII KALLTAVTSP HIEIHEGTIL QTVRTCYNIY LASKNLINQT 190 200 210 220 230 240 TAKATLTQML NVIFTRMENQ VLQEARELEK PIQSKPQSPV IQAAAVSPKF VRLKHSQAQS 250 260 270 280 290 300 KPTTPEKTDL TNGEHARSDS GKVSTENGDA PRERGSSLSG TDDGAQEVVK DILEDVVTSA 310 320 330 340 350 360 IKEAAEKHGL TEPERVLGEL ECQECAIPPG VDENSQTNGI ADDRQSLSSA DNLESDAQGH 370 380 390 400 410 420 QVAARFSHVL QKDAFLVFRS LCKLSMKPLG EGPPDPKSHE LRSKVVSLQL LLSVLQNAGP 430 440 450 460 470 480 VFRTHEMFIN AIKQYLCVAL SKNGVSSVPD VFELSLAIFL TLLSNFKMHL KMQIEVFFKE 490 500 510 520 530 540 IFLNILETST SSFEHRWMVI QTLTRICADA QCVVDIYVNY DCDLNAANIF ERLVNDLSKI 550 560 570 580 590 600 AQGRSGHELG MTPLQELSLR KKGLECLVSI LKCMVEWSKD LYVNPNHQTS LGQERLTDQE 610 620 630 640 650 660 IGDGKGLDMA RRCSVTSMES TVSSGTQTTV QDDPEQFEVI KQQKEIIEHG IELFNKKPKR 670 680 690 700 710 720 GIQFLQEQGM LGTSVEDIAQ FLHQEERLDS TQVGDFLGDS ARFNKEVMYA YVDQLDFCEK 730 740 750 760 770 780 EFVSALRTFL EGFRLPGEAQ KIDRLMEKFA ARYIECNQGQ TLFASADTAY VLAYSIIMLT 790 800 810 820 830 840 TDLHSPQVKN KMTKEQYIKM NRGINDSKDL PEEYLSSIYE EIEGKKIAMK ETKELTIATK 850 860 870 880 890 900 STKQNVASEK QRRLLYNLEM EQMAKTAKAL MEAVSHAKAP FTSATHLDHV RPMFKLVWTP 910 920 930 940 950 960 LLAAYSIGLQ NCDDTEVASL CLEGIRCAIR IACIFGMQLE RDAYVQALAR FSLLTASSSI 970 980 990 1000 1010 1020 TEMKQKNIDT IKTLITVAHT DGNYLGNSWH EILKCISQLE LAQLIGTGVK TRYLSGSGRE 1030 1040 1050 1060 1070 1080 REGSLKGHTL AGEEFMGLGL GNLVSGGVDK RQMASFQESV GETSSQSVVV AVDRIFTGST 1090 1100 1110 1120 1130 1140 RLDGNAIVDF VRWLCAVSMD ELASPHHPRM FSLQKIVEIS YYNMNRIRLQ WSRIWHVIGD 1150 1160 1170 1180 1190 1200 HFNKVGCNPN EDVAIFAVDS LRQLSMKFLE KGELANFRFQ KDFLRPFEHI MKKNRSPTIR 1210 1220 1230 1240 1250 1260 DMAIRCIAQM VNSQAANIRS GWKNIFAVFH QAASDHDGNI VELAFQTTCH IVTTIFQHHF 1270 1280 1290 1300 1310 1320 PAAIDSFQDA VKCLSEFACN AAFPDTSMEA IRLIRFCGKY VSERPRVLQE YTSDDMNVAP 1330 1340 1350 1360 1370 1380 GDRVWVRGWF PILFELSCII NRCKLDVRTR GLTVMFEIMK SYGHTFEKHW WQDLFRIVFR 1390 1400 1410 1420 1430 1440 IFDNMKLPEQ LSEKSEWMTT TCNHALYAIC DVFTQFYEAL NEVLLSDVFA QLQWCVKQDN 1450 1460 1470 1480 1490 1500 EQLARSGTNC LENLVISNGE KFSPEVWDET CNCMLDIFKT TIPHVLLTWR PVGMEEDSSE 1510 1520 1530 1540 1550 1560 KHLDVDLDRQ SLSSIDKNPS ERGQSQLSNP TDDSWKGRPY ANQKLFASLL IKCVVQLELI 1570 1580 1590 1600 1610 1620 QTIDNIVFYP ATSKKEDAEH MVAAQQDTLD ADIHIETEDQ GMYKYMSSQH LFKLLDCLQE 1630 1640 1650 1660 1670 1680 SHSFSKAFNS NYEQRTVLWR AGFKGKSKPN LLKQETSSLA CCLRILFRMY VDENRRDSWE 1690 1700 1710 1720 1730 1740 EIQQRLLTVC SEALAYFITV NSESHREAWT SLLLLLLTKT LKINDEKFKA HASMYYPYLC 1750 1760 1770 1780 EIMQFDLIPE LRAVLRKFFL RIGVVYKIWI PEEPSQVPAA LSPVW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors." Togawa A., Morinaga N., Ogasawara M., Moss J., Vaughan M. J. Biol. Chem. 274:12308-12315(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Identification and localization of two brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors in a macromolecular complex." Yamaji R., Adamik R., Takeda K., Togawa A., Pacheco-Rodriguez G., Ferrans V.J., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 97:2567-2572(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH BIG1.
[4]	"Dominant-negative mutant of BIG2, an ARF-guanine nucleotide exchange factor, specifically affects membrane trafficking from the trans-Golgi network through inhibiting membrane association of AP-1 and GGA coat proteins." Shinotsuka C., Waguri S., Wakasugi M., Uchiyama Y., Nakayama K. Biochem. Biophys. Res. Commun. 294:254-260(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-738.
[5]	"Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2)." Li H., Adamik R., Pacheco-Rodriguez G., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 100:1627-1632(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRKAR1A; PRKAR2A; PRKAR1B AND PRKAR2B, SUBCELLULAR LOCATION.
[6]	"BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity." Shin H.W., Morinaga N., Noda M., Nakayama K. Mol. Biol. Cell 15:5283-5294(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-738.
[7]	"Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70." Xu K.F., Shen X., Li H., Pacheco-Rodriguez G., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 102:2784-2789(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EXOC7, SUBCELLULAR LOCATION.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-1525 AND SER-1528, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors." Ishizaki R., Shin H.W., Iguchi-Ariga S.M., Ariga H., Nakayama K. Genes Cells 11:949-959(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MYCBP.
[10]	"Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake." Shen X., Xu K.F., Fan Q., Pacheco-Rodriguez G., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 103:2635-2640(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"The brefeldin A-inhibited guanine nucleotide-exchange protein, BIG2, regulates the constitutive release of TNFR1 exosome-like vesicles." Islam A., Shen X., Hiroi T., Moss J., Vaughan M., Levine S.J. J. Biol. Chem. 282:9591-9599(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TNFRSF1A.
[12]	"Interactions between conserved domains within homodimers in the BIG1, BIG2, and GBF1 Arf guanine nucleotide exchange factors." Ramaen O., Joubert A., Simister P., Belgareh-Touze N., Olivares-Sanchez M.C., Zeeh J.C., Chantalat S., Golinelli-Cohen M.P., Jackson C.L., Biou V., Cherfils J. J. Biol. Chem. 282:28834-28842(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[13]	"Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma." Kuroda F., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 104:3201-3206(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PPP1CC.
[14]	"cAMP-dependent protein kinase A (PKA) signaling induces TNFR1 exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to BIG2." Islam A., Jones H., Hiroi T., Lam J., Zhang J., Moss J., Vaughan M., Levine S.J. J. Biol. Chem. 283:25364-25371(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRKAR2B, MUTAGENESIS OF VAL-289 AND VAL-534.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-1528 AND SER-1782, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1528, MASS SPECTROMETRY.
[18]	"Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity." Puxeddu E., Uhart M., Li C.C., Ahmad F., Pacheco-Rodriguez G., Manganiello V.C., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 106:6158-6163(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDE3A.
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; SER-277; SER-1525 AND SER-1528, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"Specific functions of BIG1 and BIG2 in endomembrane organization." Boal F., Stephens D.J. PLoS ONE 5:E9898-E9898(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227 AND SER-1528, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218 AND SER-227, MASS SPECTROMETRY.
[24]	"Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex." Sheen V.L., Ganesh V.S., Topcu M., Sebire G., Bodell A., Hill R.S., Grant P.E., Shugart Y.Y., Imitola J., Khoury S.J., Guerrini R., Walsh C.A. Nat. Genet. 36:69-76(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PVNH2 LYS-209.
[25]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-794.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF084521 mRNA. Translation: AAD38428.1.
AL049537, AL121903 Genomic DNA. Translation: CAI19320.1.
AL121903, AL049537 Genomic DNA. Translation: CAI19614.1.

IPI

IPI00002186.

RefSeq

NP_006411.2. NM_006420.2.

UniGene

Hs.62578.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3L8N	X-ray	2.86	A	635-836	[»]
3SWV	X-ray	3.00	A	635-836	[»]

ProteinModelPortal

Q9Y6D5.

ModBase

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Protein-protein interaction databases

DIP

DIP-48794N.

IntAct

Q9Y6D5. 10 interactions.

MINT

MINT-1200143.

STRING

9606.ENSP00000360985.

PTM databases

PhosphoSite

Q9Y6D5.

Polymorphism databases

DMDM

146329988.

Proteomic databases

PaxDb

Q9Y6D5.

PRIDE

Q9Y6D5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371917; ENSP00000360985; ENSG00000124198.

GeneID

10564.

KEGG

hsa:10564.

UCSC

uc002xtx.4. human.

Organism-specific databases

CTD

10564.

GeneCards

GC20P047538.

H-InvDB

HIX0015895.

HGNC

HGNC:15853. ARFGEF2.

HPA

CAB026382.
HPA026078.

MIM

605371. gene.
608097. phenotype.

neXtProt

NX_Q9Y6D5.

Orphanet

98892. Periventricular nodular heterotopia.

PharmGKB

PA24945.

GenAtlas

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Phylogenomic databases

eggNOG

COG5307.

HOGENOM

HOG000181045.

HOVERGEN

HBG004846.

InParanoid

Q9Y6D5.

OMA

GHQVAAR.

OrthoDB

EOG4V9TPR.

PhylomeDB

Q9Y6D5.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpress

Q9Y6D5.

Bgee

Q9Y6D5.

CleanEx

HS_ARFGEF2.

Genevestigator

Q9Y6D5.

GermOnline

ENSG00000124198. Homo sapiens.

Family and domain databases

Gene3D

1.10.1000.11. 1 hit.

InterPro

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. human.

GenomeRNAi

10564.

NextBio

40093.

SOURCE

Search...

Entry information

Entry name

BIG2_HUMAN

Accession

Primary (citable) accession number: Q9Y6D5
Secondary accession number(s): Q5TFT9, Q9NTS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	March 6, 2007
Last modified:	May 1, 2013
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.