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Q96M96 (FGD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FGD4
Synonyms:FRABP, ZFYVE6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length766 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4

Subunit structure

Homooligomer By similarity.

Subcellular location

Cytoplasmcytoskeleton By similarity. Cell projectionfilopodium 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. Ref.5

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.

Involvement in disease

Charcot-Marie-Tooth disease 4H (CMT4H) [MIM:609311]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 FYVE-type zinc finger.

Contains 2 PH domains.

Ontologies

Keywords
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
   DiseaseCharcot-Marie-Tooth disease
Disease mutation
Neurodegeneration
Neuropathy
   DomainRepeat
Zinc-finger
   LigandActin-binding
Metal-binding
Zinc
   Molecular functionGuanine-nucleotide releasing factor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

filopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium assembly

Inferred from electronic annotation. Source: Ensembl

microspike assembly

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

regulation of Cdc42 GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

actin cytoskeleton

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

filopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

small GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q96M96-1)

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.
Isoform 2 (identifier: Q96M96-2)

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.
Isoform 3 (identifier: Q96M96-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 766766FYVE, RhoGEF and PH domain-containing protein 4
PRO_0000080947

Regions

Domain206 – 393188DH
Domain422 – 521100PH 1
Domain643 – 74098PH 2
Zinc finger559 – 61961FYVE-type
Region1 – 150150Actin filament-binding By similarity

Natural variations

Alternative sequence1 – 248248Missing in isoform 2.
VSP_013078
Alternative sequence1 – 3030MEEIK…RFEGG → MFSCFLCILSF in isoform 3.
VSP_013079
Alternative sequence201 – 2077ETNEQKL → VEHETSS in isoform 3.
VSP_013080
Alternative sequence208 – 766559Missing in isoform 3.
VSP_013081
Alternative sequence515 – 766252ALQET…KKSEC → RRGFAMLPRLISNS in isoform 2.
VSP_013082
Natural variant2981M → R in fibroblasts from a CMT4H patient; absent from patient's peripheral nerve where splicing defects and aberrant transcripts are detected. Ref.5 Ref.6
VAR_034957
Natural variant2981M → T in CMT4H. Ref.5
VAR_044321

Experimental info

Sequence conflict791T → A in BAB71413. Ref.2
Sequence conflict3031V → A in AAQ72372. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: B919A7C1D164B05D

FASTA76686,626
        10         20         30         40         50         60 
MEEIKPASAS CVSKEKPSKV SDLISRFEGG SSLSNYSDLK KESAVNLNAP RTPGRHGLTT 

        70         80         90        100        110        120 
TPQQKLLSQH LPQRQGNDTD KTQGAQTCVA NGVMAAQNQM ECEEEKAATL SSDTSIQASE 

       130        140        150        160        170        180 
PLLDTHIVNG ERDETATAPA SPTTDSCDGN ASDSSYRTPG IGPVLPLEER GAETETKVQE 

       190        200        210        220        230        240 
RENGESPLEL EQLDQHHEMK ETNEQKLHKI ANELLLTERA YVNRLDLLDQ VFYCKLLEEA 

       250        260        270        280        290        300 
NRGSFPAEMV NKIFSNISSI NAFHSKFLLP ELEKRMQEWE TTPRIGDILQ KLAPFLKMYG 

       310        320        330        340        350        360 
EYVKGFDNAM ELVKNMTERI PQFKSVVEEI QKQKICGSLT LQHHMLEPVQ RIPRYEMLLK 

       370        380        390        400        410        420 
DYLRKLPPDS LDWNDAKKSL EIISTAASHS NSAIRKMENL KKLLEIYEML GEEEDIVNPS 

       430        440        450        460        470        480 
NELIKEGQIL KLAARNTSAQ ERYLFLFNNM LLYCVPKFSL VGSKFTVRTR VGIDGMKIVE 

       490        500        510        520        530        540 
TQNEEYPHTF QVSGKERTLE LQASSAQDKE EWIKALQETI DAFHQRHETF RNAIAKDNDI 

       550        560        570        580        590        600 
HSEVSTAELG KRAPRWIRDN EVTMCMKCKE PFNALTRRRH HCRACGYVVC WKCSDYKAQL 

       610        620        630        640        650        660 
EYDGGKLSKV CKDCYQIISG FTDSEEKKRK GILEIESAEV SGNSVVCSFL QYMEKSKPWQ 

       670        680        690        700        710        720 
KAWCVIPKQD PLVLYMYGAP QDVRAQATIP LLGYVVDEMP RSADLPHSFK LTQSKSVHSF 

       730        740        750        760 
AADSEELKQK WLKVILLAVT GETPGGPNEH PATLDDHPEP KKKSEC 

« Hide

Isoform 2 [UniParc].

Checksum: 1F353FCAB39FA086
Show »

FASTA28032,521
Isoform 3 [UniParc].

Checksum: EDFB9CE574C0495D
Show »

FASTA18820,388

References

« Hide 'large scale' references
[1]"Cloning a new transcript of actin-filament binding protein frabin in testis."
Lu L., Huang X.Y., Xu M., Yin L.L., Li J.M., Zhou Z.M., Sha J.H.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Testis.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Testis.
[4]"Phosphatidylinositol 3-kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of Cdc42."
Chen X.M., Splinter P.L., Tietz P.S., Huang B.Q., Billadeau D.D., LaRusso N.F.
J. Biol. Chem. 279:31671-31678(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H."
Delague V., Jacquier A., Hamadouche T., Poitelon Y., Baudot C., Boccaccio I., Chouery E., Chaouch M., Kassouri N., Jabbour R., Grid D., Megarbane A., Haase G., Levy N.
Am. J. Hum. Genet. 81:1-16(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT4H THR-298, VARIANT ARG-298, TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
[6]"Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4."
Stendel C., Roos A., Deconinck T., Pereira J., Castagner F., Niemann A., Kirschner J., Korinthenberg R., Ketelsen U.-P., Battaloglu E., Parman Y., Nicholson G., Ouvrier R., Seeger J., De Jonghe P., Weis J., Kruettgen A., Rudnik-Schoeneborn S. expand/collapse author list , Bergmann C., Suter U., Zerres K., Timmerman V., Relvas J.B., Senderek J.
Am. J. Hum. Genet. 81:158-164(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CMT4H, VARIANT ARG-298.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY367054 mRNA. Translation: AAQ72372.1.
AK057294 mRNA. Translation: BAB71413.1.
AL713762 mRNA. Translation: CAD28532.1.
RefSeqNP_640334.2. NM_139241.2.
UniGeneHs.117835.

3D structure databases

ProteinModelPortalQ96M96.
SMRQ96M96. Positions 210-522, 549-619, 645-738.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000394487.

PTM databases

PhosphoSiteQ96M96.

Polymorphism databases

DMDM116241363.

Proteomic databases

PaxDbQ96M96.
PRIDEQ96M96.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381025; ENSP00000370413; ENSG00000139132. [Q96M96-2]
ENST00000427716; ENSP00000394487; ENSG00000139132. [Q96M96-1]
GeneID121512.
KEGGhsa:121512.
UCSCuc001rkz.3. human. [Q96M96-1]

Organism-specific databases

CTD121512.
GeneCardsGC12P032546.
HGNCHGNC:19125. FGD4.
HPAHPA039235.
MIM609311. phenotype.
611104. gene.
neXtProtNX_Q96M96.
Orphanet99954. Charcot-Marie-Tooth disease type 4H.
PharmGKBPA134907925.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5422.
HOVERGENHBG007506.
InParanoidQ96M96.
KOK05723.
PhylomeDBQ96M96.
TreeFamTF316247.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ96M96.
BgeeQ96M96.
CleanExHS_FGD4.
GenevestigatorQ96M96.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProIPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
PROSITEPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFGD4. human.
GeneWikiFGD4.
GenomeRNAi121512.
NextBio80759.
PROQ96M96.
SOURCESearch...

Entry information

Entry nameFGD4_HUMAN
AccessionPrimary (citable) accession number: Q96M96
Secondary accession number(s): Q6ULS2, Q8TCP6
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM