Reviewed, UniProtKB/Swiss-Prot Q9Y6D5 (BIG2_HUMAN)

Names and origin

Protein names

Recommended name:
    Brefeldin A-inhibited guanine nucleotide-exchange protein 2
      Short name=Brefeldin A-inhibited GEP 2

Gene names

Name:	ARFGEF2
Synonyms:	ARFGEP2, BIG2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1785 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP.
Enzyme regulation	Inhibited by brefeldin A.
Tissue specificity	Expressed in placenta, lung, heart, brain, kidney and pancreas.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Involvement in disease	Defects in ARFGEF2 are the cause of autosomal recessive periventricular nodular heterotopia type 2 (PVNH2) [MIM:608097]; also known as periventricular heterotopia with microcephaly autosomal recessive. PVNH is 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. Ref.12
Sequence similarities	Contains 1 SEC7 domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	exocytosis Ref.1 Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from direct assay. Source: MGI regulation of ARF protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi membrane Inferred from direct assay. Source: MGI cytosol Inferred from direct assay. Source: MGI
Molecular function	ARF guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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
Amino acid modifications
	Modified residue	218	1	Phosphoserine Ref.4 Ref.7
	Modified residue	227	1	Phosphoserine Ref.4 Ref.7
	Modified residue	240	1	Phosphoserine
	Modified residue	244	1	Phosphothreonine Ref.7
	Modified residue	277	1	Phosphoserine Ref.6
	Modified residue	614	1	Phosphoserine Ref.7 Ref.8
	Modified residue	616	1	Phosphothreonine Ref.8
	Modified residue	621	1	Phosphothreonine Ref.7
	Modified residue	690	1	Phosphoserine Ref.3
	Modified residue	691	1	Phosphothreonine Ref.3
	Modified residue	1511	1	Phosphoserine Ref.4 Ref.7
	Modified residue	1513	1	Phosphoserine Ref.4 Ref.7
	Modified residue	1514	1	Phosphoserine Ref.4 Ref.7
	Modified residue	1525	1	Phosphoserine Ref.4 Ref.5 Ref.7
	Modified residue	1528	1	Phosphoserine Ref.4 Ref.5 Ref.7
	Modified residue	1782	1	Phosphoserine Ref.7
Natural variations
	Natural variant	209	1	E → K in PVNH2. dbSNP rs28937880. Ref.12		VAR_037438
	Natural variant	527	1	A → V: dbSNP rs6063343.		VAR_028750
	Natural variant	794	1	K → E in a breast cancer sample; somatic mutation. Ref.13		VAR_036156
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6D5-1 [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: 10212200] [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: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-690 AND THR-691, MASS SPECTROMETRY. Tissue: Epithelium.
[4]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-1511; SER-1513; SER-1514; SER-1525 AND SER-1528, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1525 AND SER-1528, MASS SPECTROMETRY.
[6]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, MASS SPECTROMETRY.
[7]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; THR-244; SER-614; THR-621; SER-1511; SER-1513; SER-1514; SER-1525; SER-1528 AND SER-1782, MASS SPECTROMETRY.
[8]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614 AND THR-616, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-240 AND THR-244, MASS SPECTROMETRY.
[11]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-227; SER-277; SER-1525 AND SER-1528, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"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: 14647276] [Abstract] Cited for: VARIANT PVNH2 LYS-209.
[13]	"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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-794.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.62578
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y6D5.
PTM databases
PhosphoSite	Q9Y6D5.
Proteomic databases
PRIDE	Q9Y6D5.
Genome annotation databases
Ensembl	ENST00000371917; ENSP00000360985; ENSG00000124198; Homo sapiens. [Genome view]
GeneID	10564.
KEGG	hsa:10564.
NMPDR	fig|9606.3.peg.20432.
UCSC	uc002xtx.2. human.
Organism-specific databases
CTD	10564.
GeneCards	GC20P046971.
H-InvDB	HIX0015895.
HGNC	HGNC:15853. ARFGEF2.
HPA	CAB026382. HPA026078.
MIM	605371. gene. 608097. phenotype.
Orphanet	2149. Nodular neuronal heterotopia. 98892. Periventricular nodular heterotopia.
PharmGKB	PA24945.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9Y6D5.
HOVERGEN	Q9Y6D5.
OMA	NIVELAF
OrthoDB	EOG9DBX0M
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
InterPro	IPR016024. ARM-type_fold. IPR015403. DUF1981_SEC7_assoc. IPR000904. Sec7. [Graphical view]
Pfam	PF09324. DUF1981. 1 hit. PF01369. Sec7. 1 hit. [Graphical view]
SMART	SM00222. Sec7. 1 hit. [Graphical view]
PROSITE	PS50190. SEC7. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 24, 2009
This is version 82 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.