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Q96M96

- FGD4_HUMAN

UniProt

Q96M96 - FGD4_HUMAN

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
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 2 (17 Oct 2006)
      Previous versions | rss
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    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

    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: UniProtKB-SubCell
    5. Golgi apparatus Source: UniProtKB
    6. lamellipodium Source: UniProtKB
    7. ruffle Source: UniProtKB

    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

    ArrayExpressiQ96M96.
    BgeeiQ96M96.
    CleanExiHS_FGD4.
    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.
    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

    MEEIKPASAS CVSKEKPSKV SDLISRFEGG SSLSNYSDLK KESAVNLNAP    50
    RTPGRHGLTT TPQQKLLSQH LPQRQGNDTD KTQGAQTCVA NGVMAAQNQM 100
    ECEEEKAATL SSDTSIQASE PLLDTHIVNG ERDETATAPA SPTTDSCDGN 150
    ASDSSYRTPG IGPVLPLEER GAETETKVQE RENGESPLEL EQLDQHHEMK 200
    ETNEQKLHKI ANELLLTERA YVNRLDLLDQ VFYCKLLEEA NRGSFPAEMV 250
    NKIFSNISSI NAFHSKFLLP ELEKRMQEWE TTPRIGDILQ KLAPFLKMYG 300
    EYVKGFDNAM ELVKNMTERI PQFKSVVEEI QKQKICGSLT LQHHMLEPVQ 350
    RIPRYEMLLK DYLRKLPPDS LDWNDAKKSL EIISTAASHS NSAIRKMENL 400
    KKLLEIYEML GEEEDIVNPS NELIKEGQIL KLAARNTSAQ ERYLFLFNNM 450
    LLYCVPKFSL VGSKFTVRTR VGIDGMKIVE TQNEEYPHTF QVSGKERTLE 500
    LQASSAQDKE EWIKALQETI DAFHQRHETF RNAIAKDNDI HSEVSTAELG 550
    KRAPRWIRDN EVTMCMKCKE PFNALTRRRH HCRACGYVVC WKCSDYKAQL 600
    EYDGGKLSKV CKDCYQIISG FTDSEEKKRK GILEIESAEV SGNSVVCSFL 650
    QYMEKSKPWQ KAWCVIPKQD PLVLYMYGAP QDVRAQATIP LLGYVVDEMP 700
    RSADLPHSFK LTQSKSVHSF AADSEELKQK WLKVILLAVT GETPGGPNEH 750
    PATLDDHPEP KKKSEC 766
    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.
    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

    ArrayExpressi Q96M96.
    Bgeei Q96M96.
    CleanExi HS_FGD4.
    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

    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 1, 2014
    This is version 119 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