Human Gene FGD4 (ENST00000427716.7) from GENCODE V44
Description: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8 (By similarity). (from UniProt Q96M96) RefSeq Summary (NM_139241): This gene encodes a protein that is involved in the regulation of the actin cytoskeleton and cell shape. This protein contains an actin filament-binding domain, which together with its Dbl homology domain and one of its pleckstrin homology domains, can form microspikes. This protein can activate MAPK8 independently of the actin filament-binding domain, and it is also involved in the activation of CDC42 via the exchange of bound GDP for free GTP. The activation of CDC42 also enables this protein to play a role in mediating the cellular invasion of Cryptosporidium parvum, an intracellular parasite that infects the gastrointestinal tract. Mutations in this gene can cause Charcot-Marie-Tooth disease type 4H (CMT4H), a disorder of the peripheral nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000427716.7 Gencode Gene: ENSG00000139132.16 Transcript (Including UTRs) Position: hg38 chr12:32,502,157-32,644,877 Size: 142,721 Total Exon Count: 18 Strand: + Coding Region Position: hg38 chr12:32,576,358-32,640,533 Size: 64,176 Coding Exon Count: 15
ID:FGD4_HUMAN DESCRIPTION: RecName: Full=FYVE, RhoGEF and PH domain-containing protein 4; AltName: Full=Actin filament-binding protein frabin; AltName: Full=FGD1-related F-actin-binding protein; AltName: Full=Zinc finger FYVE domain-containing protein 6; FUNCTION: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8 (By similarity). SUBUNIT: Homooligomer (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity). Cell projection, filopodium (By similarity). Note=Concentrated in filopodia and poorly detected at lamellipodia. Binds along the sides of actin fibers (By similarity). TISSUE SPECIFICITY: Expressed in different tissues, including brain, cerebellum, peripheral nerve, skeletal muscle, heart, uterus, placenta and testis. DOMAIN: The part of the protein spanning the actin filament- binding domain together with the DH domain and the first PH domain is necessary and sufficient for microspike formation. Activation of MAPK8 requires the presence of all domains with the exception of the actin filament-binding domain (By similarity). DISEASE: Defects in FGD4 are the cause of Charcot-Marie-Tooth disease type 4H (CMT4H) [MIM:609311]; also known as Charcot-Marie- Tooth disease neuropathy type 4H. CMT4H is a recessive demyelinating form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy and primary peripheral axonal neuropathy. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention, autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. SIMILARITY: Contains 1 DH (DBL-homology) domain. SIMILARITY: Contains 1 FYVE-type zinc finger. SIMILARITY: Contains 2 PH domains. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FGD4";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96M96
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003779 actin binding GO:0005085 guanyl-nucleotide exchange factor activity GO:0005089 Rho guanyl-nucleotide exchange factor activity GO:0031267 small GTPase binding GO:0046872 metal ion binding
Biological Process: GO:0007010 cytoskeleton organization GO:0007186 G-protein coupled receptor signaling pathway GO:0008360 regulation of cell shape GO:0030036 actin cytoskeleton organization GO:0035023 regulation of Rho protein signal transduction GO:0043065 positive regulation of apoptotic process GO:0043087 regulation of GTPase activity GO:0046847 filopodium assembly GO:0051056 regulation of small GTPase mediated signal transduction
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