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DRC4_DANRE
ID   DRC4_DANRE              Reviewed;         475 AA.
AC   F1QNW4; Q6PFL7;
DT   25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT   03-MAY-2011, sequence version 1.
DT   03-AUG-2022, entry version 73.
DE   RecName: Full=Dynein regulatory complex subunit 4 {ECO:0000250|UniProtKB:Q60779};
DE   AltName: Full=Growth arrest-specific protein 8;
DE            Short=GAS-8;
GN   Name=gas8; Synonyms=drc4 {ECO:0000250|UniProtKB:Q60779};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19043402; DOI=10.1038/nature07520;
RA   Colantonio J.R., Vermot J., Wu D., Langenbacher A.D., Fraser S., Chen J.N.,
RA   Hill K.L.;
RT   "The dynein regulatory complex is required for ciliary motility and otolith
RT   biogenesis in the inner ear.";
RL   Nature 457:205-209(2009).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21659505; DOI=10.1074/jbc.m111.234666;
RA   Evron T., Philipp M., Lu J., Meloni A.R., Burkhalter M., Chen W.,
RA   Caron M.G.;
RT   "Growth arrest specific 8 (Gas8) and G protein-coupled receptor kinase 2
RT   (GRK2) cooperate in the control of Smoothened signaling.";
RL   J. Biol. Chem. 286:27676-27686(2011).
CC   -!- FUNCTION: Component of the nexin-dynein regulatory complex (N-DRC), a
CC       key regulator of ciliary/flagellar motility which maintains the
CC       alignment and integrity of the distal axoneme and regulates microtubule
CC       sliding in motile axonemes. Plays an important role in the assembly of
CC       the N-DRC linker (By similarity). Plays dual roles at both the primary
CC       (or non-motile) cilia to regulate hedgehog signaling and in motile
CC       cilia to coordinate cilia movement. Required for proper slow muscle
CC       development and positively regulates ciliary smoothened (SMO)-dependent
CC       Hedgehog (Hh) signaling pathway (PubMed:21659505). Required for tether
CC       cilia motility which is essential for normal otolith formation and
CC       localization in the developing inner ear (PubMed:19043402).
CC       {ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:19043402,
CC       ECO:0000269|PubMed:21659505}.
CC   -!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC).
CC       Interacts with microtubules. {ECO:0000250|UniProtKB:Q7XJ96}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60779}.
CC       Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:O95995}. Cell
CC       projection, cilium, flagellum {ECO:0000250|UniProtKB:Q60779}.
CC       Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:O95995}.
CC       Cytoplasm, cytoskeleton, cilium basal body
CC       {ECO:0000250|UniProtKB:Q60779}. Golgi apparatus
CC       {ECO:0000250|UniProtKB:O95995}. Cell projection, cilium
CC       {ECO:0000250|UniProtKB:O95995}. Cytoplasm, cytoskeleton, flagellum
CC       axoneme {ECO:0000250|UniProtKB:Q7XJ96}.
CC   -!- DEVELOPMENTAL STAGE: Maternal transcripts are ubiquitous throughout the
CC       embryo during early development. By the 12-somite stage, expression
CC       becomes concentrated in the developing ears and this persists through
CC       the 18- to 20-somite stage. Transcripts are also present in the brain,
CC       neural tube and pronephric ducts. {ECO:0000269|PubMed:19043402}.
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in attenuated
CC       Hedgehog (Hh) transcriptional responses and impaired early muscle
CC       development (PubMed:21659505). Morphants exhibit developmental
CC       abnormalities, abnormal ear development and defective cilia motility
CC       (PubMed:19043402). {ECO:0000269|PubMed:19043402,
CC       ECO:0000269|PubMed:21659505}.
CC   -!- SIMILARITY: Belongs to the DRC4 family. {ECO:0000305}.
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DR   EMBL; CU570687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CU656039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC057501; AAH57501.1; -; mRNA.
DR   RefSeq; NP_955928.1; NM_199634.1.
DR   AlphaFoldDB; F1QNW4; -.
DR   SMR; F1QNW4; -.
DR   STRING; 7955.ENSDARP00000059906; -.
DR   PaxDb; F1QNW4; -.
DR   Ensembl; ENSDART00000170982; ENSDARP00000135402; ENSDARG00000101431.
DR   GeneID; 323260; -.
DR   KEGG; dre:323260; -.
DR   CTD; 2622; -.
DR   ZFIN; ZDB-GENE-030131-1980; gas8.
DR   eggNOG; ENOG502QQDA; Eukaryota.
DR   GeneTree; ENSGT00390000009477; -.
DR   HOGENOM; CLU_045343_0_0_1; -.
DR   InParanoid; F1QNW4; -.
DR   OMA; HEETDIK; -.
DR   OrthoDB; 1257437at2759; -.
DR   PhylomeDB; F1QNW4; -.
DR   TreeFam; TF323819; -.
DR   Reactome; R-DRE-5635838; Activation of SMO.
DR   PRO; PR:F1QNW4; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 18.
DR   Bgee; ENSDARG00000101431; Expressed in testis and 29 other tissues.
DR   GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IEA:GOC.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR   GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR   GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR   GO; GO:0008017; F:microtubule binding; IEA:InterPro.
DR   GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR   GO; GO:0035082; P:axoneme assembly; ISS:UniProtKB.
DR   GO; GO:0003355; P:cilium movement involved in otolith formation; IMP:UniProtKB.
DR   GO; GO:0030317; P:flagellated sperm motility; IBA:GO_Central.
DR   GO; GO:0055001; P:muscle cell development; IMP:ZFIN.
DR   GO; GO:0035889; P:otolith tethering; IMP:UniProtKB.
DR   GO; GO:1903566; P:positive regulation of protein localization to cilium; ISS:UniProtKB.
DR   GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:ZFIN.
DR   GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR   InterPro; IPR039308; GAS8.
DR   InterPro; IPR025593; GAS8_dom.
DR   PANTHER; PTHR31543; PTHR31543; 1.
DR   Pfam; PF13851; GAS; 1.
PE   2: Evidence at transcript level;
KW   Cell projection; Cilium; Coiled coil; Cytoplasm; Cytoskeleton; Flagellum;
KW   Golgi apparatus; Microtubule; Reference proteome.
FT   CHAIN           1..475
FT                   /note="Dynein regulatory complex subunit 4"
FT                   /id="PRO_0000444014"
FT   REGION          1..113
FT                   /note="Regulates microtubule-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q60779"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          114..257
FT                   /note="Microtubule-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q60779"
FT   COILED          20..104
FT                   /evidence="ECO:0000255"
FT   COILED          142..200
FT                   /evidence="ECO:0000255"
FT   COILED          242..426
FT                   /evidence="ECO:0000255"
FT   CONFLICT        229
FT                   /note="F -> Y (in Ref. 2; AAH57501)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   475 AA;  56662 MW;  D3BAAE8E2EB34915 CRC64;
     MPPKRKSSPK GKTPTVVDGL STEEMSKEQL EEHIMRLREE LDREREERNY FQLERDKIHT
     FWEITRRHLE ENKCELRNRE RELEEVEERH QVEIKVYKQK VKHLLYEQQN MLSELKAESI
     ISTKLLQDEH ADLEKEQWKD MRSLKLELKQ QELSSENVLK RIHLKHDEET TDLRNDFARQ
     VQEIGSKYEK RMQKLRQEEE LRRKTEIHEI EERKNTHINM LMKNHEKAFR DIRNYFSDIV
     YKNLDLITSL KEELKEMKKN EEKRNKEMAE VLEQNKELKE SSQKAKEQVA ELQKQLANYE
     KDKSILTRSR ARLKMSDREM KELKWELEVL EQRFSKVQLE RDELYMKFTK AILEVQQKSG
     FKNLLLECKL NTLNDTLEKK EAQLSEVLSA SNLDPTTLSV VTHKLEEVLE SKNHTIKDLQ
     YEVARVCKAH NDLLKTSEAK LRAFGIPVEE LCFEPLKSNG QSVGQGPAMF VSSSN
 
 
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