Q865S3 · ARHG2_CANLF
- ProteinRho guanine nucleotide exchange factor 2
- GeneARHGEF2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids986 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:12604587).
Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (PubMed:12604587).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameRho guanine nucleotide exchange factor 2
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionQ865S3
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
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).
Localizes to the mitotic spindle in mitotic cells, and to tight junctions in interphase cells (PubMed:12604587).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 138 | Decreases interaction with DYNLT1; when associated with A-139. | ||||
Sequence: R → A | ||||||
Mutagenesis | 139 | Decreases interaction with DYNLT1; when associated with A-138. | ||||
Sequence: R → A | ||||||
Mutagenesis | 140 | Decreases interaction with DYNLT1. | ||||
Sequence: G → A | ||||||
Mutagenesis | 150 | Disrupts interaction with DYNLT1; when associated with A-151. | ||||
Sequence: V → A | ||||||
Mutagenesis | 151 | Disrupts interaction with DYNLT1; when associated with A-150. | ||||
Sequence: S → A |
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000345622 | 1-986 | Rho guanine nucleotide exchange factor 2 | |||
Sequence: MSRIESLTRARTERSRELASKNREKEKMKEAKDARYTNGHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQKAALLKNSTALQSVSLRSKTTPRERPSSAIYPSDSFRQSLLGSRRGRSSLSLAKSVSTTNIAGHFSDESPLGLRRILSQSTDSLNMRNRALSVESLIDEGAEVIYSELMSDFETDERDFAADSWSLAVDSSFLQQQKKEVMKQQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELQLEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGSTRNFVIHRLADLLISQFSGPSAERMRKAYSEFCSRHTKALKLYKELYARDKRFQQFIRKVTRSAVLKRHGVQECILLVTQRITKYPVLINRILQHSHGTDEERQDLTTALGLVKELLSNVDQDVHELEKGARLQEIYHRMDPRAQAPVPSKGPFGREELLRRKLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPALDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMYEVHTASRDDRSTWVRVIQQSVRVCPSREDFPLIETEDEAYLRRIKMELQQKDKALVELLREKVGLFAEMTHFQVEEDSGGVALPALPRGLFRSESLECPRGERLLQDAIREVEGLKDLLVGPGVELLLTPRDPALLVDPDSGGSTSPGVTANGEARNFNGSIELCRTDSDSSQKDRNGNQLRAPQEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLARANSRDGEAGRVGPAPVAPDKQATELALLQRQHALLQEELRRCRRLGEERATEAGNLEARLRESEQARALLEREAEEARRQLAILGQSEPPPAEAPWARRPLDPRRRSLPAGDALYLSFTPPQPSRGHDRLDLSVTIRSVHRPFEDRERQELGSPEERLQDSSDPDTGSEEEGGGRLSPPHSPRDFTRMQDIPEETESRDGEPMVSES | ||||||
Modified residue | 109 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 122 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 129 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 133 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 137 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 143 | Phosphoserine; by PAK4 | ||||
Sequence: S | ||||||
Modified residue | 151 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 163 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 172 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 174 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 177 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 354 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 645 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 679 | Phosphothreonine; by MAPK1 or MAPK3 | ||||
Sequence: T | ||||||
Modified residue | 691 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 696 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 711 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 782 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 886 | Phosphoserine; by PAK1 and AURKA | ||||
Sequence: S | ||||||
Modified residue | 894 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 896 | Phosphoserine; by PAK4 | ||||
Sequence: S | ||||||
Modified residue | 932 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 940 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 941 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 945 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 947 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 956 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 960 | Phosphoserine; by CDK1 | ||||
Sequence: S |
Post-translational modification
Phosphorylation of Ser-886 by PAK1 induces binding to protein YWHAZ, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by AURKA and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules. Phosphorylated on serine, threonine and tyrosine residues in a RIPK2-dependent manner (By similarity).
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-886. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1. Interacts (via the N- terminal zinc finger) with CAPN6 (via domain II). Found in a complex composed at least of ARHGEF2, NOD2 and RIPK2. Interacts with RIPK2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and RIPK3 (By similarity).
Interacts with DYNLT1
Interacts with DYNLT1
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q865S3 | ZONAB Q9N1Q2 | 5 | EBI-7207989, EBI-7207962 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, zinc finger, domain, coiled coil, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-30 | Disordered | ||||
Sequence: MSRIESLTRARTERSRELASKNREKEKMKE | ||||||
Zinc finger | 39-86 | Phorbol-ester/DAG-type | ||||
Sequence: GHLFTTISVSGMTMCYACNKSITAKEALICPTCNVTIHNRCKDTLANC | ||||||
Region | 131-161 | Interaction with DYNLT1 | ||||
Sequence: RQSLLGSRRGRSSLSLAKSVSTTNIAGHFSD | ||||||
Domain | 236-433 | DH | ||||
Sequence: KQQDVIYELIQTELHHVRTLKIMTRLFRTGMLEELQLEPGVVQGLFPCVDELSDIHTRFLSQLLERRRQALCPGSTRNFVIHRLADLLISQFSGPSAERMRKAYSEFCSRHTKALKLYKELYARDKRFQQFIRKVTRSAVLKRHGVQECILLVTQRITKYPVLINRILQHSHGTDEERQDLTTALGLVKELLSNVDQD | ||||||
Domain | 473-572 | PH | ||||
Sequence: KLIHDGCLLWKTATGRFKDVLMLLMTDVLVFLQEKDQKYIFPALDKPSVVSLQNLIVRDIANQEKGMFLISAAPPEMYEVHTASRDDRSTWVRVIQQSVR | ||||||
Coiled coil | 591-612 | |||||
Sequence: LRRIKMELQQKDKALVELLREK | ||||||
Region | 687-707 | Disordered | ||||
Sequence: VDPDSGGSTSPGVTANGEARN | ||||||
Compositional bias | 693-707 | Polar residues | ||||
Sequence: GSTSPGVTANGEARN | ||||||
Coiled coil | 798-867 | |||||
Sequence: DKQATELALLQRQHALLQEELRRCRRLGEERATEAGNLEARLRESEQARALLEREAEEARRQLAILGQSE | ||||||
Region | 862-887 | Disordered | ||||
Sequence: ILGQSEPPPAEAPWARRPLDPRRRSL | ||||||
Region | 893-912 | Disordered | ||||
Sequence: LYLSFTPPQPSRGHDRLDLS | ||||||
Compositional bias | 920-949 | Basic and acidic residues | ||||
Sequence: RPFEDRERQELGSPEERLQDSSDPDTGSEE | ||||||
Region | 920-986 | Disordered | ||||
Sequence: RPFEDRERQELGSPEERLQDSSDPDTGSEEEGGGRLSPPHSPRDFTRMQDIPEETESRDGEPMVSES | ||||||
Compositional bias | 965-986 | Basic and acidic residues | ||||
Sequence: TRMQDIPEETESRDGEPMVSES |
Domain
The DH (DBL-homology) domain promotes tyrosine phosphorylation of RIPK2 (By similarity).
The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA
The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA
The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes.
The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q865S3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length986
- Mass (Da)111,516
- Last updated2003-06-01 v1
- Checksum2D72FFB44F108290
Q865S3-2
- Name2
- Differences from canonical
- 902-923: Missing
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 693-707 | Polar residues | ||||
Sequence: GSTSPGVTANGEARN | ||||||
Alternative sequence | VSP_034959 | 902-923 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 920-949 | Basic and acidic residues | ||||
Sequence: RPFEDRERQELGSPEERLQDSSDPDTGSEE | ||||||
Compositional bias | 965-986 | Basic and acidic residues | ||||
Sequence: TRMQDIPEETESRDGEPMVSES | ||||||
Sequence conflict | 978 | in Ref. 1; AAO91668 | ||||
Sequence: D → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF494096 EMBL· GenBank· DDBJ | AAO91667.1 EMBL· GenBank· DDBJ | mRNA | ||
AF494097 EMBL· GenBank· DDBJ | AAO91668.1 EMBL· GenBank· DDBJ | mRNA |