Search Results

Overview

Uniprot ID	Q92974
Protein Name	Rho guanine nucleotide exchange factor 2
Gene Name	ARHGEF2
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
100	QQKAALLKNNTALQS
63	CNKSITAKEALICPT

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, innate immune response, 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. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (By similarity)

Protein Sequence

10 MSRIESLTRA 20 RIDRSRELAS 30 KTREKEKMKE 40 AKDARYTNGH 50 LFTTISVSGM 60 TMCYACNKSI 70 TAKEALICPT 80 CNVTIHNRCK 90 DTLANCTKVK 100 QKQQKAALLK 110 NNTALQSVSL 120 RSKTTIRERP 130 SSAIYPSDSF 140 RQSLLGSRRG 150 RSSLSLAKSV 160 STTNIAGHFN 170 DESPLGLRRI 180 LSQSTDSLNM 190 RNRTLSVESL 200 IDEAEVIYSE 210 LMSDFEMDEK 220 DFAADSWSLA 230 VDSSFLQQHK 240 KEVMKQQDVI 250 YELIQTELHH 260 VRTLKIMTRL 270 FRTGMLEELH 280 LEPGVVQGLF 290 PCVDELSDIH 300 TRFLSQLLER 310 RRQALCPGST 320 RNFVIHRLGD 330 LLISQFSGPS 340 AEQMCKTYSE 350 FCSRHSKALK 360 LYKELYARDK 370 RFQQFIRKVT 380 RPAVLKRHGV 390 QECILLVTQR 400 ITKYPLLISR 410 ILQHSHGIEE 420 ERQDLTTALG 430 LVKELLSNVD 440 EGIYQLEKGA 450 RLQEIYNRMD 460 PRAQTPVPGK 470 GPFGREELLR 480 RKLIHDGCLL 490 WKTATGRFKD 500 VLVLLMTDVL 510 VFLQEKDQKY 520 IFPTLDKPSV 530 VSLQNLIVRD 540 IANQEKGMFL 550 ISAAPPEMYE 560 VHTASRDDRS 570 TWIRVIQQSV 580 RTCPSREDFP 590 LIETEDEAYL 600 RRIKMELQQK 610 DRALVELLRE 620 KVGLFAEMTH 630 FQAEEDGGSG 640 MALPTLPRGL 650 FRSESLESPR 660 GERLLQDAIR 670 EVEGLKDLLV 680 GPGVELLLTP 690 REPALPLEPD 700 SGGNTSPGVT 710 ANGEARTFNG 720 SIELCRADSD 730 SSQRDRNGNQ 740 LRSPQEEALQ 750 RLVNLYGLLH 760 GLQAAVAQQD 770 TLMEARFPEG 780 PERREKLCRA 790 NSRDGEAGRA 800 GAAPVAPEKQ 810 ATELALLQRQ 820 HALLQEELRR 830 CRRLGEERAT 840 EAGSLEARLR 850 ESEQARALLE 860 REAEEARRQL 870 AALGQTEPLP 880 AEAPWARRPV 890 DPRRRSLPAG 900 DALYLSFNPP 910 QPSRGTDRLD 920 LPVTTRSVHR 930 NFEDRERQEL 940 GSPEERLQDS 950 SDPDTGSEEE 960 GSSRLSPPHS 970 PRDFTRMQDI 980 PEETESRDGE AVASES

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005923	bicellular tight junction
Biological Process	GO:0007015	actin filament organization
Biological Process	GO:0055059	asymmetric neuroblast division
Biological Process	GO:0000902	cell morphogenesis
Biological Process	GO:0071474	cellular hyperosmotic response
Biological Process	GO:0071225	cellular response to muramyl dipeptide
Biological Process	GO:0071356	cellular response to tumor necrosis factor
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0006886	intracellular protein transport
Biological Process	GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Biological Process	GO:1902219	negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress
Biological Process	GO:0007026	negative regulation of microtubule depolymerization
Biological Process	GO:0060546	negative regulation of necroptotic process
Biological Process	GO:0032755	positive regulation of interleukin-6 production
Biological Process	GO:0045666	positive regulation of neuron differentiation
Biological Process	GO:2001224	positive regulation of neuron migration
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0032760	positive regulation of tumor necrosis factor production
Biological Process	GO:0042127	regulation of cell population proliferation
Biological Process	GO:0035023	regulation of Rho protein signal transduction
Biological Process	GO:0051056	regulation of small GTPase mediated signal transduction
Biological Process	GO:0007264	small GTPase-mediated signal transduction
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0031410	cytoplasmic vesicle
Cellular Component	GO:0005856	cytoskeleton
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0005925	focal adhesion
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0005874	microtubule
Cellular Component	GO:0032991	protein-containing complex
Cellular Component	GO:0032587	ruffle membrane
Cellular Component	GO:0005819	spindle
Cellular Component	GO:0031982	vesicle
Molecular Function	GO:0005085	guanyl-nucleotide exchange factor activity
Molecular Function	GO:0008017	microtubule binding
Molecular Function	GO:0031267	small GTPase binding
Molecular Function	GO:0008270	zinc ion binding

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.