Protein: Rho guanine nucleotide exchange factor 2 (Guanine nucleotide exchange factor H1) (GEF-H1) (Tight junction-associated guanine nucleotide exchange factor isoform A) (Q865S3)
Organism: Canis lupus familiaris (Dog) (Canis familiaris)
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. 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. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha 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. Involved in neuronal progenitor cell division and differentiation. Involved in the migration of precerebellar neurons (By similarity). Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability.
Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12604587}. Cytoplasm {ECO:0000269|PubMed:12604587}. Cell junction, tight junction {ECO:0000269|PubMed:12604587}. Golgi apparatus {ECO:0000250|UniProtKB:Q92974}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:12604587}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q92974}. Note=Colocalized with NOD2 and RIPK2 in vesicles and with the cytoskeleton (By similarity). Localizes to the mitotic spindle in mitotic cells, and to tight junctions in interphase cells (PubMed:12604587). {ECO:0000250|UniProtKB:Q92974, ECO:0000269|PubMed:12604587}.
Interaction partners:
- Transforming protein RhoA
- Cingulin
- Cingulin like 1.
- Protein tyrosine kinase 2
- Cdc42 guanine nucleotide exchange factor 9.
Sequence:
MSRIESLTRARTERSRELASKNREKEKMKEAKDARYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQKAALLKNSTALQSVSLRSKTTPRERPSSAIYPSDSFRQSLLGSRRGRSSLSLAKSVSTTNIAGHFSDESPLGLRRILSQSTDSLNMRNRALSVESLIDEGAEVIYSELMSDFETDERDFAADSWSLAVDSSFLQQQKKEVMKQQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELQLEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGSTRNFVIHRLADLLISQFSGPSAERMRKAYSEFCSRHTKALKLYKELYARDKRFQQFIRKVTRSAVLKRHGVQECILLVTQRITKYPVLINRILQHSHGTDEERQDLTTALGLVKELLSNVDQDVHELEKGARLQEIYHRMDPRAQAPVPSKGPFGREELLRRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPALDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMYEVHTASRDDRSTWVRVIQQSVRVCPSREDFPLIETEDEAYLRRIKMELQQKDKALVELLREKVGLFAEMTHFQVEEDSGGVALPALPRGLFRSESLECPRGERLLQDAIREVEGLKDLLVGPGVELLLTPRDPALLVDPDSGGSTSPGVTANGEARNFNGSIELCRTDSDSSQKDRNGNQLRAPQEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLARANSRDGEAGRVGPAPVAPDKQATELALLQRQHALLQEELRRCRRLGEERATEAGNLEARLRESEQARALLEREAEEARRQLAILGQSEPPPAEAPWARRPLDPRRRSLPAGDALYLSFTPPQPSRGHDRLDLSVTIRSVHRPFEDRERQELGSPEERLQDSSDPDTGSEEEGGGRLSPPHSPRDFTRMQDIPEETESRDGEPMVSES