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
