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Protein

FYVE, RhoGEF and PH domain-containing protein 4

Gene

FGD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Actin-binding, Metal-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

HGNCiHGNC:19125. FGD4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 rs63749871dbSNPEnsembl.1
Natural variantiVAR_044321298M → T in CMT4H. 1 PublicationCorresponds to variant rs63749871dbSNPEnsembl.1

Keywords - Diseasei

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

Organism-specific databases

DisGeNETi121512.
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.

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.
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

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotation
Contains 2 PH domains.PROSITE-ProRule annotation

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.
GeneTreeiENSGT00750000117280.
HOVERGENiHBG007506.
InParanoidiQ96M96.
KOiK05723.
PhylomeDBiQ96M96.
TreeFamiTF316247.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

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 rs63749871dbSNPEnsembl.1
Natural variantiVAR_044321298M → T in CMT4H. 1 PublicationCorresponds to variant rs63749871dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ96M96.
SMRiQ96M96.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125734. 4 interactors.
STRINGi9606.ENSP00000394487.

PTM databases

iPTMnetiQ96M96.
PhosphoSitePlusiQ96M96.

Polymorphism and mutation databases

BioMutaiFGD4.
DMDMi116241363.

Proteomic databases

EPDiQ96M96.
MaxQBiQ96M96.
PaxDbiQ96M96.
PeptideAtlasiQ96M96.
PRIDEiQ96M96.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi121512.
DisGeNETi121512.
GeneCardsiFGD4.
GeneReviewsiFGD4.
HGNCiHGNC:19125. FGD4.
HPAiHPA039235.
MalaCardsiFGD4.
MIMi609311. phenotype.
611104. gene.
neXtProtiNX_Q96M96.
OpenTargetsiENSG00000139132.
Orphaneti99954. Charcot-Marie-Tooth disease type 4H.
PharmGKBiPA134907925.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4424. Eukaryota.
ENOG410XRXV. LUCA.
GeneTreeiENSGT00750000117280.
HOVERGENiHBG007506.
InParanoidiQ96M96.
KOiK05723.
PhylomeDBiQ96M96.
TreeFamiTF316247.

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.

Miscellaneous databases

ChiTaRSiFGD4. human.
GeneWikiiFGD4.
GenomeRNAii121512.
PROiQ96M96.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139132.
CleanExiHS_FGD4.
ExpressionAtlasiQ96M96. baseline and differential.
GenevisibleiQ96M96. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFGD4_HUMAN
AccessioniPrimary (citable) accession number: Q96M96
Secondary accession number(s): Q6ULS2, Q8TCP6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 139 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.