FGD1 FYVE, RhoGEF and PH domain containing 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: FGD1provided by HGNC
Official Full Name: FYVE, RhoGEF and PH domain containing 1provided by HGNC
Primary source: HGNC:3663
Locus tag: RP1-112K5.1
See related: Ensembl:ENSG00000102302; HPRD:02373; MIM:300546; Vega:OTTHUMG00000021627
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AAS; FGDY; MRXS16; ZFYVE3
Summary: This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of faciogenital dysplasia and X-linked mental retardation, syndromatic 16.[provided by RefSeq, Mar 2011]

Genomic context

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Location :: Xp11.21

Sequence :: Chromosome: X; NC_000023.10 (54471887..54522599, complement)

See FGD1 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Authors discuss the hypothesis that FGD1 might be an important regulator of events controlling extracellular matrix remodelling and possibly cell invasion in physiological and pathological settings.
Title: FGD1 as a central regulator of extracellular matrix remodelling--lessons from faciogenital dysplasia.
The faciogenital dysplasia 1 (FGD1)gene encodes for a protein involved in skeletal and neuronal development.
Title: X-linked Aarskog syndrome: report on a novel FGD1 gene mutation. Executive dysfunction as part of the behavioural phenotype.
This is the first report of inheritance by germline mosaicism for the FGD1 gene
Title: Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism.
These results demonstrate an important role for FGD1/Cdc42 signaling in human mesenchymal stem cells osteogenesis.
Title: The Cdc42 guanine nucleotide exchange factor FGD1 regulates osteogenesis in human mesenchymal stem cells.
This study showed that the proline-rich doman of FGD1 is critical for persistent cell migration; FGD1 also augments EGF-stimulated c-Jun NH(2)-terminal kinase (JNK) activation.
Title: Role of FGD1, a Cdc42 guanine nucleotide exchange factor, in epidermal growth factor-stimulated c-Jun NH2-terminal kinase activation and cell migration.
Mutations in the FGD1 gene is not associated with Aarskog syndrome.
Title: Familial syndrome resembling Aarskog syndrome.
analysis of nine novel mutations of the FGD1 gene in Aarskog-Scott syndrome
Title: Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene.
First case of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome.
Title: First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome.
FGD1 is preferentially associated with the trans-Golgi network (TGN), suggesting its involvement in export of proteins from the Golgi.
Title: Faciogenital dysplasia protein (FGD1) regulates export of cargo proteins from the golgi complex via Cdc42 activation.
Findings suggest a central role for Fgd1 in the focal degradation of the ECM in vitro and, for the first time, show a connection between Fgd1 and cancer progression, proposing that it might function during tumorigenesis.
Title: Faciogenital dysplasia protein Fgd1 regulates invadopodia biogenesis and extracellular matrix degradation and is up-regulated in prostate and breast cancer.

Submit: New GeneRIF Correction See all (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P98174	P19801	ABP1	HPRD	PubMed
P98174	P60953	CDC42	HPRD	PubMed
P98174	Q14247	CTTN	HPRD	PubMed
P98174	Q92556	ELMO1	HPRD	PubMed
BioGRID:108536	BioGRID:114457	BTRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108536	BioGRID:107433	CDC42	BioGRID	PubMed	Reconstituted Complex
BioGRID:108536	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:108536	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
G alpha (12/13) signalling events, organism-specific biosystem (from REACTOME)
G alpha (12/13) signalling events, organism-specific biosystemThe G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay te...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
NRAGE signals death through JNK, organism-specific biosystem (from REACTOME)
NRAGE signals death through JNK, organism-specific biosystemOnce bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pr...
Regulation of Actin Cytoskeleton, organism-specific biosystem (from WikiPathways)
Regulation of Actin Cytoskeleton, organism-specific biosystemhttp://www.genome.jp/kegg/pathway/hsa/hsa04810.html
Regulation of CDC42 activity, organism-specific biosystem (from Pathway Interaction Database)
Regulation of CDC42 activity, organism-specific biosystem
Regulation of CDC42 activity
Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
Regulation of actin cytoskeleton, organism-specific biosystem
Regulation of actin cytoskeleton
Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
Regulation of actin cytoskeleton, conserved biosystem
Regulation of actin cytoskeleton
Rho GTPase cycle, organism-specific biosystem (from REACTOME)
Rho GTPase cycle, organism-specific biosystemThe cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
Signalling by NGF, organism-specific biosystem (from REACTOME)
Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...

General gene information

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Markers

SGC30464 (e-PCR)
- UniSTS:7

DXS1044 (e-PCR)
- UniSTS:8207

RH75708 (e-PCR)
- UniSTS:87311

FGD1 (e-PCR)
- UniSTS:99395

G35013 (e-PCR)
- UniSTS:68686

RH98842 (e-PCR)
- UniSTS:84567

DXS7573E (e-PCR)
- UniSTS:154056

FGD1 (e-PCR)
- UniSTS:506596

FGD1_8347 (e-PCR)
- UniSTS:467689

SHGC-24021 (e-PCR)
- UniSTS:74988

Genotypes

See FGD1 SNP Geneview Report
See FGD1 SNP Genotype Report
See FGD1 SNP Variation Viewer Report

Homology

Homologs of the FGD1 gene: The FGD1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
Rho guanyl-nucleotide exchange factor activity	IEA Inferred from Electronic Annotation more info
guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
phospholipid binding	IEA Inferred from Electronic Annotation more info
small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
apoptotic process	TAS Traceable Author Statement more info
apoptotic signaling pathway	TAS Traceable Author Statement more info
cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
filopodium assembly	IDA Inferred from Direct Assay more info	PubMed
multicellular organismal development	TAS Traceable Author Statement more info	PubMed
neurotrophin TRK receptor signaling pathway	TAS Traceable Author Statement more info
organ morphogenesis	TAS Traceable Author Statement more info	PubMed
regulation of Cdc42 GTPase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of cell shape	ISS Inferred from Sequence or Structural Similarity more info
regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
signal transduction	TAS Traceable Author Statement more info	PubMed
small GTPase mediated signal transduction	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	IDA Inferred from Direct Assay more info
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
cytoskeleton	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
lamellipodium	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info
ruffle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: FYVE, RhoGEF and PH domain-containing protein 1

Names: FYVE, RhoGEF and PH domain-containing protein 1; rho/Rac GEF; faciogenital dysplasia 1 protein; zinc finger FYVE domain-containing protein 3; rho/Rac guanine nucleotide exchange factor FGD1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008054.1 RefSeqGene

Range

5001..55713

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004463.2 → NP_004454.2 FYVE, RhoGEF and PH domain-containing protein 1

Status: REVIEWED

Source sequence(s)

BC034530, U11690

Consensus CDS

CCDS14359.1

UniProtKB/Swiss-Prot

P98174

Related

ENSP00000364277, OTTHUMP00000023372, ENST00000375135, OTTHUMT00000056801

Conserved Domains (5) summary

cd00065
Location:732 – 788
Blast Score: 184

FYVE; FYVE domain; Zinc-binding domain; targets proteins to membrane lipids via interaction with phosphatidylinositol-3-phosphate, PI3P; present in Fab1, YOTB, Vac1, and EEA1;

cd00160
Location:376 – 559
Blast Score: 409

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00821
Location:824 – 919
Blast Score: 127

PH; Pleckstrin homology (PH) domain

cd01219
Location:590 – 690
Blast Score: 458

PH_FGD; FGD (faciogenital dysplasia protein) pleckstrin homology (PH) domain

smart00064
Location:724 – 791
Blast Score: 230

FYVE; Protein present in Fab1, YOTB, Vac1, and EEA1

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

54471887..54522599, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

51522464..51572796, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

54486173..54536885, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01069620.1	None
genomic	ABBA01069621.1	None
genomic	ABBA01069622.1	None
genomic	ABBA01069623.1	None
genomic	ABBA01069624.1	None
genomic	ABBA01069625.1	None
genomic	ABBA01069626.1	None
genomic	ABBA01069627.1	None
genomic	ABBA01069628.1	None
genomic	ABBA01069629.1	None
genomic	ABBA01069630.1	None
genomic	AMYH01022430.1 (323422..374134)	None
genomic	CH471154.1	EAW93179.1
		EAW93180.1
		EAW93181.1
genomic	Z85987.13 (11370..62082)	None
mRNA	AK226117.1	None
mRNA	AK299635.1	BAG61561.1
mRNA	BC034530.1	AAH34530.1
mRNA	U11690.1	AAA57004.1