CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-018888
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Rho guanine nucleotide exchange factor 2 
Protein Synonyms/Alias
 Guanine nucleotide exchange factor H1; GEF-H1; Microtubule-regulated Rho-GEF; Proliferating cell nucleolar antigen p40 
Gene Name
 ARHGEF2 
Gene Synonyms/Alias
 KIAA0651; LFP40 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
336PSAEQMCKTYSEFCSubiquitination[1]
353SKALKLYKELYARDKacetylation[2]
594EAYLRRIKMELQQKDubiquitination[1]
666IREVEGLKDLLVGPGubiquitination[1]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 235 432 DH.
 DOMAIN 472 571 PH.
 ZN_FING 39 86 Phorbol-ester/DAG-type.
 MOD_RES 143 143 Phosphoserine; by PAK4.
 MOD_RES 163 163 Phosphoserine.
 MOD_RES 172 172 Phosphoserine.
 MOD_RES 353 353 N6-acetyllysine.
 MOD_RES 645 645 Phosphoserine.
 MOD_RES 648 648 Phosphoserine.
 MOD_RES 679 679 Phosphothreonine; by MAPK1 or MAPK3.
 MOD_RES 691 691 Phosphoserine.
 MOD_RES 696 696 Phosphoserine.
 MOD_RES 782 782 Phosphoserine (By similarity).
 MOD_RES 886 886 Phosphoserine; by PAK1 and AURKA.
 MOD_RES 894 894 Phosphotyrosine.
 MOD_RES 896 896 Phosphoserine; by PAK4.
 MOD_RES 932 932 Phosphoserine.
 MOD_RES 940 940 Phosphoserine.
 MOD_RES 941 941 Phosphoserine.
 MOD_RES 945 945 Phosphothreonine.
 MOD_RES 947 947 Phosphoserine.
 MOD_RES 953 953 Phosphoserine.
 MOD_RES 956 956 Phosphoserine.
 MOD_RES 960 960 Phosphoserine.  
Keyword
 Acetylation; Alternative splicing; Cell cycle; Cell division; Cell junction; Cell membrane; Cell projection; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton; Golgi apparatus; Guanine-nucleotide releasing factor; Membrane; Metal-binding; Microtubule; Mitosis; Phosphoprotein; Reference proteome; Tight junction; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 986 AA 
Protein Sequence
MSRIESLTRA RIDRSRELAS KTREKEKMKE AKDARYTNGH LFTTISVSGM TMCYACNKSI 60
TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLK NNTALQSVSL RSKTTIRERP 120
SSAIYPSDSF RQSLLGSRRG RSSLSLAKSV STTNIAGHFN DESPLGLRRI LSQSTDSLNM 180
RNRTLSVESL IDEAEVIYSE LMSDFEMDEK DFAADSWSLA VDSSFLQQHK KEVMKQQDVI 240
YELIQTELHH VRTLKIMTRL FRTGMLEELH LEPGVVQGLF PCVDELSDIH TRFLSQLLER 300
RRQALCPGST RNFVIHRLGD LLISQFSGPS AEQMCKTYSE FCSRHSKALK LYKELYARDK 360
RFQQFIRKVT RPAVLKRHGV QECILLVTQR ITKYPLLISR ILQHSHGIEE ERQDLTTALG 420
LVKELLSNVD EGIYQLEKGA RLQEIYNRMD PRAQTPVPGK GPFGREELLR RKLIHDGCLL 480
WKTATGRFKD VLVLLMTDVL VFLQEKDQKY IFPTLDKPSV VSLQNLIVRD IANQEKGMFL 540
ISAAPPEMYE VHTASRDDRS TWIRVIQQSV RTCPSREDFP LIETEDEAYL RRIKMELQQK 600
DRALVELLRE KVGLFAEMTH FQAEEDGGSG MALPTLPRGL FRSESLESPR GERLLQDAIR 660
EVEGLKDLLV GPGVELLLTP REPALPLEPD SGGNTSPGVT ANGEARTFNG SIELCRADSD 720
SSQRDRNGNQ LRSPQEEALQ RLVNLYGLLH GLQAAVAQQD TLMEARFPEG PERREKLCRA 780
NSRDGEAGRA GAAPVAPEKQ ATELALLQRQ HALLQEELRR CRRLGEERAT EAGSLEARLR 840
ESEQARALLE REAEEARRQL AALGQTEPLP AEAPWARRPV DPRRRSLPAG DALYLSFNPP 900
QPSRGTDRLD LPVTTRSVHR NFEDRERQEL GSPEERLQDS SDPDTGSEEE GSSRLSPPHS 960
PRDFTRMQDI PEETESRDGE AVASES 986 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0043198; C:dendritic shaft; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0005874; C:microtubule; IDA:UniProtKB.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0032587; C:ruffle membrane; IDA:UniProtKB.
 GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
 GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
 GO:0008017; F:microtubule binding; IDA:UniProtKB.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0048365; F:Rac GTPase binding; IDA:UniProtKB.
 GO:0030676; F:Rac guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
 GO:0008134; F:transcription factor binding; ISS:BHF-UCL.
 GO:0008270; F:zinc ion binding; NAS:UniProtKB.
 GO:0007015; P:actin filament organization; IMP:UniProtKB.
 GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0000902; P:cell morphogenesis; IMP:UniProtKB.
 GO:0071474; P:cellular hyperosmotic response; ISS:BHF-UCL.
 GO:0071356; P:cellular response to tumor necrosis factor; ISS:BHF-UCL.
 GO:0000132; P:establishment of mitotic spindle orientation; IEA:Compara.
 GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
 GO:0007067; P:mitosis; IEA:UniProtKB-KW.
 GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
 GO:0007026; P:negative regulation of microtubule depolymerization; IMP:UniProtKB.
 GO:0060547; P:negative regulation of necrotic cell death; ISS:BHF-UCL.
 GO:0050768; P:negative regulation of neurogenesis; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
 GO:0035023; P:regulation of Rho protein signal transduction; NAS:UniProtKB.
 GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. 
Interpro
 IPR000219; DH-domain.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR015721; RhoGEF-like. 
Pfam
 PF00169; PH
 PF00621; RhoGEF 
SMART
 SM00109; C1
 SM00233; PH
 SM00325; RhoGEF 
PROSITE
 PS00741; DH_1
 PS50010; DH_2
 PS50003; PH_DOMAIN
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS