Reviewed,
UniProtKB/Swiss-Prot Q9Y6D5 (BIG2_HUMAN)
Last modified
November 24, 2009.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Brefeldin A-inhibited guanine nucleotide-exchange protein 2 Short name=Brefeldin A-inhibited GEP 2 | ||||
| Gene names |
| ||||
| 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 cascadeInferred from direct assay. Source: MGI regulation of ARF protein signal transductionInferred from electronic annotation. Source: InterPro |
| Cellular component | Golgi membrane Inferred from direct assay. Source: MGI cytosolInferred 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
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References
| « Hide '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. 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. 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 | |
|---|---|
| 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 |
| ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 20 Human chromosome 20: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


