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Protein

FYVE, RhoGEF and PH domain-containing protein 4

Gene

FGD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri559 – 619FYVE-typePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Guanine-nucleotide releasing factor
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
FYVE, RhoGEF and PH domain-containing protein 4
Alternative name(s):
Actin filament-binding protein frabin
FGD1-related F-actin-binding protein
Zinc finger FYVE domain-containing protein 6
Gene namesi
Name:FGD4
Synonyms:FRABP, ZFYVE6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000139132.14
HGNCiHGNC:19125 FGD4
MIMi611104 gene
neXtProtiNX_Q96M96

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 4H (CMT4H)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating 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.
See also OMIM:609311
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034957298M → R in CMT4H; found in patient's fibroblasts but absent from peripheral nerve where splicing defects and aberrant transcripts are detected. 2 PublicationsCorresponds to variant dbSNP:rs63749871EnsemblClinVar.1
Natural variantiVAR_044321298M → T in CMT4H. 1 PublicationCorresponds to variant dbSNP:rs63749871EnsemblClinVar.1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi121512
GeneReviewsiFGD4
MalaCardsiFGD4
MIMi609311 phenotype
OpenTargetsiENSG00000139132
Orphaneti99954 Charcot-Marie-Tooth disease type 4H
PharmGKBiPA134907925

Polymorphism and mutation databases

BioMutaiFGD4
DMDMi116241363

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809471 – 766FYVE, RhoGEF and PH domain-containing protein 4Add BLAST766

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei702PhosphoserineCombined sources1
Modified residuei716PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96M96
MaxQBiQ96M96
PaxDbiQ96M96
PeptideAtlasiQ96M96
PRIDEiQ96M96
ProteomicsDBi77320
77321 [Q96M96-2]
77322 [Q96M96-3]

PTM databases

iPTMnetiQ96M96
PhosphoSitePlusiQ96M96

Expressioni

Tissue specificityi

Expressed in different tissues, including brain, cerebellum, peripheral nerve, skeletal muscle, heart, uterus, placenta and testis.1 Publication

Gene expression databases

BgeeiENSG00000139132
CleanExiHS_FGD4
ExpressionAtlasiQ96M96 baseline and differential
GenevisibleiQ96M96 HS

Organism-specific databases

HPAiHPA039235

Interactioni

Subunit structurei

Homooligomer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi125734, 4 interactors
IntActiQ96M96, 1 interactor
STRINGi9606.ENSP00000394487

Structurei

3D structure databases

ProteinModelPortaliQ96M96
SMRiQ96M96
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini206 – 393DHPROSITE-ProRule annotationAdd BLAST188
Domaini422 – 521PH 1PROSITE-ProRule annotationAdd BLAST100
Domaini643 – 740PH 2PROSITE-ProRule annotationAdd BLAST98

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 150Actin filament-bindingBy similarityAdd BLAST150

Domaini

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).By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri559 – 619FYVE-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4424 Eukaryota
ENOG410XRXV LUCA
GeneTreeiENSGT00920000148981
HOVERGENiHBG007506
InParanoidiQ96M96
KOiK05723
PhylomeDBiQ96M96
TreeFamiTF316247

Family and domain databases

CDDicd15791 PH1_FDG4, 1 hit
cd13236 PH2_FGD1-4, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 2 hits
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR037742 FDG4_N_PH
IPR035941 FGD1-4_PH2
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000306 Znf_FYVE
IPR017455 Znf_FYVE-rel
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF01363 FYVE, 1 hit
PF00169 PH, 2 hits
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00064 FYVE, 1 hit
SM00233 PH, 2 hits
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
PROSITEiView protein in PROSITE
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 2 hits
PS50178 ZF_FYVE, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q96M96-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEEIKPASAS CVSKEKPSKV SDLISRFEGG SSLSNYSDLK KESAVNLNAP
60 70 80 90 100
RTPGRHGLTT TPQQKLLSQH LPQRQGNDTD KTQGAQTCVA NGVMAAQNQM
110 120 130 140 150
ECEEEKAATL SSDTSIQASE PLLDTHIVNG ERDETATAPA SPTTDSCDGN
160 170 180 190 200
ASDSSYRTPG IGPVLPLEER GAETETKVQE RENGESPLEL EQLDQHHEMK
210 220 230 240 250
ETNEQKLHKI ANELLLTERA YVNRLDLLDQ VFYCKLLEEA NRGSFPAEMV
260 270 280 290 300
NKIFSNISSI NAFHSKFLLP ELEKRMQEWE TTPRIGDILQ KLAPFLKMYG
310 320 330 340 350
EYVKGFDNAM ELVKNMTERI PQFKSVVEEI QKQKICGSLT LQHHMLEPVQ
360 370 380 390 400
RIPRYEMLLK DYLRKLPPDS LDWNDAKKSL EIISTAASHS NSAIRKMENL
410 420 430 440 450
KKLLEIYEML GEEEDIVNPS NELIKEGQIL KLAARNTSAQ ERYLFLFNNM
460 470 480 490 500
LLYCVPKFSL VGSKFTVRTR VGIDGMKIVE TQNEEYPHTF QVSGKERTLE
510 520 530 540 550
LQASSAQDKE EWIKALQETI DAFHQRHETF RNAIAKDNDI HSEVSTAELG
560 570 580 590 600
KRAPRWIRDN EVTMCMKCKE PFNALTRRRH HCRACGYVVC WKCSDYKAQL
610 620 630 640 650
EYDGGKLSKV CKDCYQIISG FTDSEEKKRK GILEIESAEV SGNSVVCSFL
660 670 680 690 700
QYMEKSKPWQ KAWCVIPKQD PLVLYMYGAP QDVRAQATIP LLGYVVDEMP
710 720 730 740 750
RSADLPHSFK LTQSKSVHSF AADSEELKQK WLKVILLAVT GETPGGPNEH
760
PATLDDHPEP KKKSEC
Length:766
Mass (Da):86,626
Last modified:October 17, 2006 - v2
Checksum:iB919A7C1D164B05D
GO
Isoform 2 (identifier: Q96M96-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-248: Missing.
     515-766: ALQETIDAFH...HPEPKKKSEC → RRGFAMLPRLISNS

Note: No experimental confirmation available.
Show »
Length:280
Mass (Da):32,521
Checksum:i1F353FCAB39FA086
GO
Isoform 3 (identifier: Q96M96-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MEEIKPASASCVSKEKPSKVSDLISRFEGG → MFSCFLCILSF
     201-207: ETNEQKL → VEHETSS
     208-766: Missing.

Note: No experimental confirmation available.
Show »
Length:188
Mass (Da):20,388
Checksum:iEDFB9CE574C0495D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79T → A in BAB71413 (PubMed:14702039).Curated1
Sequence conflicti303V → A in AAQ72372 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034957298M → R in CMT4H; found in patient's fibroblasts but absent from peripheral nerve where splicing defects and aberrant transcripts are detected. 2 PublicationsCorresponds to variant dbSNP:rs63749871EnsemblClinVar.1
Natural variantiVAR_044321298M → T in CMT4H. 1 PublicationCorresponds to variant dbSNP:rs63749871EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0130781 – 248Missing in isoform 2. 1 PublicationAdd BLAST248
Alternative sequenceiVSP_0130791 – 30MEEIK…RFEGG → MFSCFLCILSF in isoform 3. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_013080201 – 207ETNEQKL → VEHETSS in isoform 3. 1 Publication7
Alternative sequenceiVSP_013081208 – 766Missing in isoform 3. 1 PublicationAdd BLAST559
Alternative sequenceiVSP_013082515 – 766ALQET…KKSEC → RRGFAMLPRLISNS in isoform 2. 1 PublicationAdd BLAST252

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY367054 mRNA Translation: AAQ72372.1
AK057294 mRNA Translation: BAB71413.1
AL713762 mRNA Translation: CAD28532.1
CCDSiCCDS8727.1 [Q96M96-1]
RefSeqiNP_001291409.1, NM_001304480.1
NP_001317302.1, NM_001330373.1
NP_001317303.1, NM_001330374.1
NP_640334.2, NM_139241.3 [Q96M96-1]
XP_011518857.1, XM_011520555.1 [Q96M96-1]
XP_011518858.1, XM_011520556.1 [Q96M96-1]
UniGeneiHs.117835

Genome annotation databases

EnsembliENST00000427716; ENSP00000394487; ENSG00000139132 [Q96M96-1]
GeneIDi121512
KEGGihsa:121512
UCSCiuc001rkz.5 human [Q96M96-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFGD4_HUMAN
AccessioniPrimary (citable) accession number: Q96M96
Secondary accession number(s): Q6ULS2, Q8TCP6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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