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Identification
HMDB Protein ID HMDBP08310
Secondary Accession Numbers
  • 14022
Name Rho guanine nucleotide exchange factor 2
Synonyms
  1. GEF-H1
  2. Guanine nucleotide exchange factor H1
  3. Microtubule-regulated Rho-GEF
  4. Proliferating cell nucleolar antigen p40
Gene Name ARHGEF2
Protein Type Unknown
Biological Properties
General Function Involved in Rho guanyl-nucleotide exchange factor activity
Specific Function Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras- GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
small gtpase regulator activity
ras guanyl-nucleotide exchange factor activity
rho guanyl-nucleotide exchange factor activity
enzyme regulator activity
nucleoside-triphosphatase regulator activity
gtpase regulator activity
Process
regulation of ras protein signal transduction
regulation of rho protein signal transduction
biological regulation
regulation of biological process
regulation of cellular process
intracellular signaling pathway
signaling
signaling pathway
regulation of cell communication
regulation of signal transduction
regulation of small gtpase mediated signal transduction
Cellular Location
  1. Cytoplasm
  2. Cytoplasm
  3. Golgi apparatus
  4. cytoskeleton
  5. spindle
  6. Cell junction
  7. Cell projection
  8. tight junction
  9. ruffle membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 1q21-q22
SNPs ARHGEF2
Gene Sequence
>2961 bp
ATGTCTCGGATCGAATCCCTCACGCGGGCGCGGATCGACCGGAGCAGAGAGCTGGCGAGC
AAGACCCGGGAAAAGGAGAAGATGAAGGAAGCCAAGGATGCCCGCTATACCAATGGGCAC
CTCTTCACCACCATTTCAGTTTCAGGCATGACCATGTGCTATGCCTGTAACAAGAGCATC
ACAGCCAAGGAAGCCCTCATCTGCCCAACCTGCAATGTGACTATCCACAACCGCTGTAAA
GACACCCTCGCCAACTGTACCAAGGTCAAGCAGAAGCAACAGAAAGCGGCCCTGCTGAAG
AACAACACCGCCTTGCAGTCCGTTTCTCTTCGAAGTAAGACAACCATCCGGGAGCGGCCA
AGCTCGGCCATCTACCCCTCCGACAGCTTCCGGCAGTCCCTCCTGGGCTCCCGCCGTGGC
CGCTCCTCCTTGTCTTTAGCCAAGAGTGTTTCTACCACCAACATTGCTGGACATTTCAAT
GATGAGTCTCCCCTGGGGCTGCGCCGGATCCTCTCACAGTCCACAGACTCCCTCAACATG
CGGAACCGAACCCTATCCGTGGAATCCCTCATTGACGAAGCAGAGGTAATCTACAGTGAG
CTGATGAGTGACTTTGAGATGGATGAGAAGGACTTTGCAGCTGACTCTTGGAGTCTTGCT
GTGGACAGCAGCTTCCTGCAGCAGCATAAAAAGGAGGTGATGAAGCAGCAAGATGTCATC
TATGAGCTAATCCAGACAGAGCTGCACCATGTGAGGACACTGAAGATCATGACCCGCCTC
TTCCGCACGGGGATGCTGGAAGAGCTACACTTGGAGCCAGGAGTGGTCCAGGGCCTGTTC
CCCTGCGTGGACGAGCTCAGTGACATCCATACACGCTTCCTCAGCCAGCTATTAGAACGC
CGACGCCAGGCCCTGTGCCCTGGCAGCACCCGGAACTTTGTCATCCATCGCTTGGGTGAT
CTGCTCATCAGCCAGTTCTCAGGTCCTAGTGCGGAGCAGATGTGTAAGACCTACTCGGAG
TTCTGCAGCCGCCACAGCAAGGCCTTAAAGCTCTATAAGGAGCTGTACGCCCGAGACAAA
CGCTTCCAGCAATTCATCCGGAAAGTGACCCGCCCCGCCGTGCTCAAGCGGCACGGGGTA
CAGGAGTGCATCCTGCTGGTGACTCAGCGCATCACCAAGTACCCGTTACTCATCAGCCGC
ATCCTGCAGCATTCCCACGGGATCGAGGAGGAGCGCCAGGACCTGACCACAGCACTGGGG
CTAGTGAAGGAGCTGCTGTCCAATGTGGACGAGGGTATTTATCAGCTGGAGAAAGGGGCC
CGTCTGCAGGAGATCTACAACCGCATGGACCCTCGGGCCCAAACCCCAGTGCCTGGCAAG
GGCCCCTTTGGCCGAGAGGAACTTCTGAGGCGCAAACTCATCCACGATGGCTGCCTGCTC
TGGAAGACAGCGACGGGGCGCTTCAAAGATGTGCTAGTGCTGCTGATGACAGATGTACTG
GTGTTTCTCCAGGAAAAGGACCAGAAGTACATCTTTCCTACCCTGGACAAGCCTTCAGTG
GTATCGCTGCAGAATCTAATCGTACGAGACATTGCCAACCAGGAGAAAGGGATGTTTCTG
ATCAGCGCAGCCCCACCTGAGATGTACGAGGTGCACACAGCATCCCGGGATGACCGGAGC
ACCTGGATCCGGGTCATTCAGCAGAGCGTGCGCACATGCCCATCCAGGGAGGACTTCCCC
CTGATTGAGACAGAGGATGAGGCTTACCTGCGGCGAATTAAGATGGAGTTGCAGCAGAAG
GACCGGGCACTGGTGGAGCTGCTGCGAGAGAAGGTCGGGCTGTTTGCTGAGATGACCCAT
TTCCAGGCCGAAGAGGATGGTGGCAGTGGGATGGCCCTGCCCACCCTGCCCAGGGGCCTT
TTCCGCTCTGAGTCCCTTGAGTCCCCTCGTGGCGAGCGGCTGCTGCAGGATGCCATCCGT
GAGGTGGAGGGTCTGAAAGACCTGCTGGTGGGGCCAGGAGTGGAACTGCTCTTGACACCC
CGAGAGCCAGCCCTGCCCTTGGAACCAGACAGCGGTGGTAACACGAGTCCTGGGGTCACT
GCCAATGGTGAGGCCAGAACCTTCAATGGCTCCATTGAACTCTGCAGAGCTGACTCAGAC
TCTAGCCAGAGGGATCGAAATGGAAATCAGCTGAGATCACCGCAAGAGGAGGCGTTACAG
CGATTGGTCAATCTCTATGGACTTCTACATGGCCTACAGGCAGCTGTGGCCCAGCAGGAC
ACTCTGATGGAAGCCCGGTTCCCTGAGGGCCCTGAGCGGCGGGAGAAGCTGTGCCGAGCC
AACTCTCGGGATGGGGAGGCTGGCAGGGCTGGGGCTGCCCCTGTGGCCCCTGAAAAGCAG
GCCACGGAACTGGCATTACTGCAGCGGCAACATGCGCTGCTGCAGGAGGAGCTACGGCGC
TGCCGGCGGCTAGGTGAAGAACGGGCAACCGAAGCTGGCAGCCTGGAGGCCCGGCTCCGG
GAGAGTGAGCAGGCCCGGGCACTGCTGGAGCGTGAGGCCGAAGAGGCTCGAAGGCAGCTG
GCCGCCCTGGGCCAGACCGAGCCACTCCCAGCTGAGGCCCCCTGGGCCCGCAGACCTGTG
GATCCTCGGCGGCGCAGCCTCCCCGCAGGCGATGCCCTGTACTTGAGTTTCAACCCCCCA
CAGCCCAGCCGAGGCACTGACCGCCTGGATCTACCTGTCACTACTCGCTCTGTCCATCGA
AACTTTGAGGACCGAGAGAGGCAGGAACTGGGGAGCCCCGAAGAGCGGCTGCAAGACAGC
AGTGACCCTGACACTGGCAGCGAGGAGGAAGGTAGCAGCCGTCTGTCTCCGCCCCACAGT
CCACGAGACTTTACCAGAATGCAGGACATCCCGGAGGAGACGGAGAGCCGCGACGGGGAG
GCTGTAGCCTCCGAGAGCTAA
Protein Properties
Number of Residues 986
Molecular Weight 111541.3
Theoretical pI 7.27
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Rho guanine nucleotide exchange factor 2
MSRIESLTRARIDRSRELASKTREKEKMKEAKDARYTNGHLFTTISVSGMTMCYACNKSI
TAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQKAALLKNNTALQSVSLRSKTTIRERP
SSAIYPSDSFRQSLLGSRRGRSSLSLAKSVSTTNIAGHFNDESPLGLRRILSQSTDSLNM
RNRTLSVESLIDEAEVIYSELMSDFEMDEKDFAADSWSLAVDSSFLQQHKKEVMKQQDVI
YELIQTELHHVRTLKIMTRLFRTGMLEELHLEPGVVQGLFPCVDELSDIHTRFLSQLLER
RRQALCPGSTRNFVIHRLGDLLISQFSGPSAEQMCKTYSEFCSRHSKALKLYKELYARDK
RFQQFIRKVTRPAVLKRHGVQECILLVTQRITKYPLLISRILQHSHGIEEERQDLTTALG
LVKELLSNVDEGIYQLEKGARLQEIYNRMDPRAQTPVPGKGPFGREELLRRKLIHDGCLL
WKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLDKPSVVSLQNLIVRDIANQEKGMFL
ISAAPPEMYEVHTASRDDRSTWIRVIQQSVRTCPSREDFPLIETEDEAYLRRIKMELQQK
DRALVELLREKVGLFAEMTHFQAEEDGGSGMALPTLPRGLFRSESLESPRGERLLQDAIR
EVEGLKDLLVGPGVELLLTPREPALPLEPDSGGNTSPGVTANGEARTFNGSIELCRADSD
SSQRDRNGNQLRSPQEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLCRA
NSRDGEAGRAGAAPVAPEKQATELALLQRQHALLQEELRRCRRLGEERATEAGSLEARLR
ESEQARALLEREAEEARRQLAALGQTEPLPAEAPWARRPVDPRRRSLPAGDALYLSFNPP
QPSRGTDRLDLPVTTRSVHRNFEDRERQELGSPEERLQDSSDPDTGSEEEGSSRLSPPHS
PRDFTRMQDIPEETESRDGEAVASES
GenBank ID Protein 253735775
UniProtKB/Swiss-Prot ID Q92974
UniProtKB/Swiss-Prot Entry Name ARHG2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001162383.1
GeneCard ID ARHGEF2
GenAtlas ID ARHGEF2
HGNC ID HGNC:682
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  6. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  7. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087 ]
  8. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  9. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  10. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  11. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  12. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  13. Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R: Phosphoproteome analysis of the human mitotic spindle. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6. Epub 2006 Mar 24. [PubMed:16565220 ]
  14. Fujishiro SH, Tanimura S, Mure S, Kashimoto Y, Watanabe K, Kohno M: ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA. Biochem Biophys Res Commun. 2008 Mar 28;368(1):162-7. doi: 10.1016/j.bbrc.2008.01.066. Epub 2008 Jan 22. [PubMed:18211802 ]
  15. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Jun 30;5(3):169-76. [PubMed:9734811 ]
  16. Callow MG, Zozulya S, Gishizky ML, Jallal B, Smeal T: PAK4 mediates morphological changes through the regulation of GEF-H1. J Cell Sci. 2005 May 1;118(Pt 9):1861-72. Epub 2005 Apr 12. [PubMed:15827085 ]
  17. Birkenfeld J, Nalbant P, Bohl BP, Pertz O, Hahn KM, Bokoch GM: GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Dev Cell. 2007 May;12(5):699-712. [PubMed:17488622 ]
  18. Ren Y, Li R, Zheng Y, Busch H: Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J Biol Chem. 1998 Dec 25;273(52):34954-60. [PubMed:9857026 ]
  19. Zenke FT, Krendel M, DerMardirossian C, King CC, Bohl BP, Bokoch GM: p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor. J Biol Chem. 2004 Apr 30;279(18):18392-400. Epub 2004 Feb 17. [PubMed:14970201 ]
  20. Krendel M, Zenke FT, Bokoch GM: Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat Cell Biol. 2002 Apr;4(4):294-301. [PubMed:11912491 ]
  21. Reddy AB, Chatterjee A, Rothblum LI, Black A, Busch H: Isolation and characterization of complementary DNA to proliferating cell nucleolar antigen P40. Cancer Res. 1989 Apr 1;49(7):1763-7. [PubMed:2466560 ]
  22. Fukazawa A, Alonso C, Kurachi K, Gupta S, Lesser CF, McCormick BA, Reinecker HC: GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathog. 2008 Nov;4(11):e1000228. doi: 10.1371/journal.ppat.1000228. Epub 2008 Nov 28. [PubMed:19043560 ]
  23. Birkenfeld J, Nalbant P, Yoon SH, Bokoch GM: Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered GEF-H1 activity a crucial determinant of disease pathogenesis? Trends Cell Biol. 2008 May;18(5):210-9. doi: 10.1016/j.tcb.2008.02.006. Epub 2008 Apr 3. [PubMed:18394899 ]