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Q96M96

- FGD4_HUMAN

UniProt

Q96M96 - FGD4_HUMAN

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Protein

FYVE, RhoGEF and PH domain-containing protein 4

Gene

FGD4

Organism
Homo sapiens (Human)
Status
Reviewed - 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 similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri559 – 61961FYVE-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. guanyl-nucleotide exchange factor activity Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW
  3. Rho guanyl-nucleotide exchange factor activity Source: InterPro
  4. small GTPase binding Source: UniProtKB

GO - Biological processi

  1. actin cytoskeleton organization Source: UniProtKB
  2. apoptotic signaling pathway Source: Reactome
  3. cytoskeleton organization Source: UniProtKB
  4. filopodium assembly Source: UniProtKB
  5. lamellipodium assembly Source: Ensembl
  6. microspike assembly Source: Ensembl
  7. neurotrophin TRK receptor signaling pathway Source: Reactome
  8. positive regulation of apoptotic process Source: Reactome
  9. positive regulation of GTPase activity Source: GOC
  10. regulation of Cdc42 GTPase activity Source: UniProtKB
  11. regulation of cell shape Source: UniProtKB
  12. regulation of small GTPase mediated signal transduction Source: Reactome
  13. small GTPase mediated signal transduction Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Actin-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. 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
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:19125. FGD4.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. actin cytoskeleton Source: HPA
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: Reactome
  4. filopodium Source: Ensembl
  5. Golgi apparatus Source: UniProtKB
  6. lamellipodium Source: UniProtKB
  7. ruffle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

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 CMT4.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti298 – 2981M → R in fibroblasts from a CMT4H patient; absent from patient's peripheral nerve where splicing defects and aberrant transcripts are detected. 2 Publications
VAR_034957
Natural varianti298 – 2981M → T in CMT4H. 1 Publication
VAR_044321

Keywords - Diseasei

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

Organism-specific databases

MIMi609311. phenotype.
Orphaneti99954. Charcot-Marie-Tooth disease type 4H.
PharmGKBiPA134907925.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 766766FYVE, RhoGEF and PH domain-containing protein 4PRO_0000080947Add
BLAST

Proteomic databases

MaxQBiQ96M96.
PaxDbiQ96M96.
PRIDEiQ96M96.

PTM databases

PhosphoSiteiQ96M96.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ96M96.
CleanExiHS_FGD4.
ExpressionAtlasiQ96M96. baseline and differential.
GenevestigatoriQ96M96.

Organism-specific databases

HPAiHPA039235.

Interactioni

Subunit structurei

Homooligomer.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000394487.

Structurei

3D structure databases

ProteinModelPortaliQ96M96.
SMRiQ96M96. Positions 210-522, 549-619, 645-738.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini206 – 393188DHPROSITE-ProRule annotationAdd
BLAST
Domaini422 – 521100PH 1PROSITE-ProRule annotationAdd
BLAST
Domaini643 – 74098PH 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 150150Actin filament-bindingBy similarityAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri559 – 61961FYVE-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5422.
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.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
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.
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti79 – 791T → A in BAB71413. (PubMed:14702039)Curated
Sequence conflicti303 – 3031V → A in AAQ72372. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti298 – 2981M → R in fibroblasts from a CMT4H patient; absent from patient's peripheral nerve where splicing defects and aberrant transcripts are detected. 2 Publications
VAR_034957
Natural varianti298 – 2981M → T in CMT4H. 1 Publication
VAR_044321

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 248248Missing in isoform 2. 1 PublicationVSP_013078Add
BLAST
Alternative sequencei1 – 3030MEEIK…RFEGG → MFSCFLCILSF in isoform 3. 1 PublicationVSP_013079Add
BLAST
Alternative sequencei201 – 2077ETNEQKL → VEHETSS in isoform 3. 1 PublicationVSP_013080
Alternative sequencei208 – 766559Missing in isoform 3. 1 PublicationVSP_013081Add
BLAST
Alternative sequencei515 – 766252ALQET…KKSEC → RRGFAMLPRLISNS in isoform 2. 1 PublicationVSP_013082Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY367054 mRNA. Translation: AAQ72372.1.
AK057294 mRNA. Translation: BAB71413.1.
AL713762 mRNA. Translation: CAD28532.1.
CCDSiCCDS8727.1. [Q96M96-1]
RefSeqiNP_640334.2. NM_139241.2. [Q96M96-1]
UniGeneiHs.117835.

Genome annotation databases

EnsembliENST00000427716; ENSP00000394487; ENSG00000139132. [Q96M96-1]
GeneIDi121512.
KEGGihsa:121512.
UCSCiuc001rkz.3. human. [Q96M96-1]

Polymorphism databases

DMDMi116241363.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY367054 mRNA. Translation: AAQ72372.1 .
AK057294 mRNA. Translation: BAB71413.1 .
AL713762 mRNA. Translation: CAD28532.1 .
CCDSi CCDS8727.1. [Q96M96-1 ]
RefSeqi NP_640334.2. NM_139241.2. [Q96M96-1 ]
UniGenei Hs.117835.

3D structure databases

ProteinModelPortali Q96M96.
SMRi Q96M96. Positions 210-522, 549-619, 645-738.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000394487.

PTM databases

PhosphoSitei Q96M96.

Polymorphism databases

DMDMi 116241363.

Proteomic databases

MaxQBi Q96M96.
PaxDbi Q96M96.
PRIDEi Q96M96.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000427716 ; ENSP00000394487 ; ENSG00000139132 . [Q96M96-1 ]
GeneIDi 121512.
KEGGi hsa:121512.
UCSCi uc001rkz.3. human. [Q96M96-1 ]

Organism-specific databases

CTDi 121512.
GeneCardsi GC12P032546.
GeneReviewsi FGD4.
HGNCi HGNC:19125. FGD4.
HPAi HPA039235.
MIMi 609311. phenotype.
611104. gene.
neXtProti NX_Q96M96.
Orphaneti 99954. Charcot-Marie-Tooth disease type 4H.
PharmGKBi PA134907925.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5422.
GeneTreei ENSGT00750000117280.
HOVERGENi HBG007506.
InParanoidi Q96M96.
KOi K05723.
PhylomeDBi Q96M96.
TreeFami TF316247.

Enzyme and pathway databases

Reactomei REACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSi FGD4. human.
GeneWikii FGD4.
GenomeRNAii 121512.
NextBioi 80759.
PROi Q96M96.
SOURCEi Search...

Gene expression databases

Bgeei Q96M96.
CleanExi HS_FGD4.
ExpressionAtlasi Q96M96. baseline and differential.
Genevestigatori Q96M96.

Family and domain databases

Gene3Di 1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProi IPR000219. DH-domain.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view ]
Pfami PF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view ]
SMARTi SM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view ]
SUPFAMi SSF48065. SSF48065. 1 hit.
PROSITEi PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: INVOLVEMENT IN CMT4H, VARIANT ARG-298.

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: October 29, 2014
This is version 120 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

External Data

Dasty 3