Q9NR80 · ARHG4_HUMAN
- ProteinRho guanine nucleotide exchange factor 4
- GeneARHGEF4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids690 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.
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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Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | ruffle membrane | |
Molecular Function | guanyl-nucleotide exchange factor activity | |
Molecular Function | protein domain specific binding | |
Biological Process | filopodium assembly | |
Biological Process | intracellular signal transduction | |
Biological Process | lamellipodium assembly | |
Biological Process | regulation of small GTPase mediated signal transduction |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRho guanine nucleotide exchange factor 4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NR80
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 3
Cell projection, ruffle membrane ; Peripheral membrane protein
Note: Associated with membrane ruffles.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_057187 | 33 | in dbSNP:rs10188052 | |||
Sequence: D → H | ||||||
Natural variant | VAR_035970 | 100 | in a breast cancer sample; somatic mutation | |||
Sequence: K → R | ||||||
Natural variant | VAR_035971 | 441 | in a breast cancer sample; somatic mutation | |||
Sequence: T → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 789 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000080914 | 1-690 | UniProt | Rho guanine nucleotide exchange factor 4 | |||
Sequence: MPWEEPAGEKPSCSHSQKAFHMEPAQKPCFTTDMVTWALLCISAETVRGEAPSQPRGIPHRSPVSVDDLWLEKTQRKKLQKQAHVERRLHIGAVHKDGVKCWRKTIITSPESLNLPRRSHPLSQSAPTGLNHMGWPEHTPGTAMPDGALDTAVCADEVGSEEDLYDDLHSSSHHYSHPGGGGEQLAINELISDGSVVCAEALWDHVTMDDQELGFKAGDVIEVMDATNREWWWGRVADGEGWFPASFVRLRVNQDEPADDDAPLAGNSGAEDGGAEAQSSKDQMRTNVINEILSTERDYIKHLRDICEGYVRQCRKRADMFSEEQLRTIFGNIEDIYRCQKAFVKALEQRFNRERPHLSELGACFLEHQADFQIYSEYCNNHPNACVELSRLTKLSKYVYFFEACRLLQKMIDISLDGFLLTPVQKICKYPLQLAELLKYTHPQHRDFKDVEAALHAMKNVAQLINERKRRLENIDKIAQWQSSIEDWEGEDLLVRSSELIYSGELTRVTQPQAKSQQRMFFLFDHQLIYCKKDLLRRDVLYYKGRLDMDGLEVVDLEDGKDRDLHVSIKNAFRLHRGATGDSHLLCTRKPEQKQRWLKAFAREREQVQLDQETGFSITELQRKQAMLNASKQQVTGKPKAVGRPCYLTRQKHPALPSNRPQQQVLVLAEPRRKPSTFWHSISRLAPFRK | |||||||
Modified residue (large scale data) | 62 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 65 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 109 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 112 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at high levels in the brain, skeletal muscle and testis and at low levels in the kidney, lung, small intestine, ovary and prostate. Expression is aberrantly enhanced in most colorectal tumors.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Isoform 3 interacts with RHOA and RAC1, and (via ABR domain) with APC. Found in a complex consisting of ARHGEF4, APC and CTNNB1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NR80 | HSF2BP O75031 | 3 | EBI-3389984, EBI-7116203 | |
BINARY | Q9NR80-3 | APC P25054 | 5 | EBI-13639160, EBI-727707 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 73-126 | ABR (APC-binding region) domain | ||||
Sequence: KTQRKKLQKQAHVERRLHIGAVHKDGVKCWRKTIITSPESLNLPRRSHPLSQSA | ||||||
Compositional bias | 113-130 | Polar residues | ||||
Sequence: LNLPRRSHPLSQSAPTGL | ||||||
Region | 113-145 | Disordered | ||||
Sequence: LNLPRRSHPLSQSAPTGLNHMGWPEHTPGTAMP | ||||||
Domain | 194-253 | SH3 | ||||
Sequence: GSVVCAEALWDHVTMDDQELGFKAGDVIEVMDATNREWWWGRVADGEGWFPASFVRLRVN | ||||||
Region | 257-282 | Disordered | ||||
Sequence: PADDDAPLAGNSGAEDGGAEAQSSKD | ||||||
Domain | 284-468 | DH | ||||
Sequence: MRTNVINEILSTERDYIKHLRDICEGYVRQCRKRADMFSEEQLRTIFGNIEDIYRCQKAFVKALEQRFNRERPHLSELGACFLEHQADFQIYSEYCNNHPNACVELSRLTKLSKYVYFFEACRLLQKMIDISLDGFLLTPVQKICKYPLQLAELLKYTHPQHRDFKDVEAALHAMKNVAQLINER | ||||||
Domain | 499-606 | PH | ||||
Sequence: ELIYSGELTRVTQPQAKSQQRMFFLFDHQLIYCKKDLLRRDVLYYKGRLDMDGLEVVDLEDGKDRDLHVSIKNAFRLHRGATGDSHLLCTRKPEQKQRWLKAFARERE |
Domain
In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q9NR80-1
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
- Length690
- Mass (Da)79,067
- Last updated2009-05-05 v3
- Checksum47E5B61C91950CD2
Q9NR80-3
- Name3
Q9NR80-4
- Name4
- Differences from canonical
- 641-690: AVGRPCYLTRQKHPALPSNRPQQQVLVLAEPRRKPSTFWHSISRLAPFRK → GRRTAAPPPRLPGPYPADIIPFSEPQSQAS
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E7EV07 | E7EV07_HUMAN | ARHGEF4 | 1876 | ||
H0YCT6 | H0YCT6_HUMAN | ARHGEF4 | 287 | ||
A0A1B0GW00 | A0A1B0GW00_HUMAN | ARHGEF4 | 142 | ||
H0Y451 | H0Y451_HUMAN | ARHGEF4 | 372 | ||
E9PEM0 | E9PEM0_HUMAN | ARHGEF4 | 517 | ||
A0A087X0P1 | A0A087X0P1_HUMAN | ARHGEF4 | 630 | ||
A4QPB6 | A4QPB6_HUMAN | ARHGEF4 | 192 | ||
A0A0C4DFY6 | A0A0C4DFY6_HUMAN | ARHGEF4 | 695 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_011617 | 1-71 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_011618 | 72-142 | in isoform 3 | |||
Sequence: EKTQRKKLQKQAHVERRLHIGAVHKDGVKCWRKTIITSPESLNLPRRSHPLSQSAPTGLNHMGWPEHTPGT → MRPDGQQALDAVVRSFDCHSEAALRQRNDVIYCSLPRTAQGIVQREDQLEVLVSLREVWGRRRGRDGTCTG | ||||||
Compositional bias | 113-130 | Polar residues | ||||
Sequence: LNLPRRSHPLSQSAPTGL | ||||||
Alternative sequence | VSP_037119 | 641-690 | in isoform 4 | |||
Sequence: AVGRPCYLTRQKHPALPSNRPQQQVLVLAEPRRKPSTFWHSISRLAPFRK → GRRTAAPPPRLPGPYPADIIPFSEPQSQAS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF249745 EMBL· GenBank· DDBJ | AAF79955.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AB042199 EMBL· GenBank· DDBJ | BAB11941.1 EMBL· GenBank· DDBJ | mRNA | ||
AB029035 EMBL· GenBank· DDBJ | BAA83064.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |