DRC4_MOUSE
ID DRC4_MOUSE Reviewed; 478 AA.
AC Q60779; Q99L71;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Dynein regulatory complex subunit 4 {ECO:0000303|PubMed:27472056};
DE AltName: Full=Growth arrest-specific protein 11;
DE Short=GAS-11;
DE AltName: Full=Growth arrest-specific protein 8;
DE Short=GAS-8;
GN Name=Gas8; Synonyms=Drc4 {ECO:0000303|PubMed:27472056}, Gas11;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11751847; DOI=10.1074/jbc.m106941200;
RA Yeh S.-D., Chen Y.-J., Chang A.C.Y., Ray R., She B.-R., Lee W.-S.,
RA Chiang H.-S., Cohen S.N., Lin-Chao S.;
RT "Isolation and properties of Gas8, a growth arrest-specific gene regulated
RT during male gametogenesis to produce a protein associated with the sperm
RT motility apparatus.";
RL J. Biol. Chem. 277:6311-6317(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=16643277; DOI=10.1111/j.1600-0854.2006.00411.x;
RA Colantonio J.R., Bekker J.M., Kim S.J., Morrissey K.M., Crosbie R.H.,
RA Hill K.L.;
RT "Expanding the role of the dynein regulatory complex to non-axonemal
RT functions: association of GAS11 with the Golgi apparatus.";
RL Traffic 7:538-548(2006).
RN [4]
RP FUNCTION, INTERACTION WITH MICROTUBULES, AND SUBCELLULAR LOCATION.
RX PubMed=17366626; DOI=10.1002/cm.20196;
RA Bekker J.M., Colantonio J.R., Stephens A.D., Clarke W.T., King S.J.,
RA Hill K.L., Crosbie R.H.;
RT "Direct interaction of Gas11 with microtubules: implications for the dynein
RT regulatory complex.";
RL Cell Motil. Cytoskeleton 64:461-473(2007).
RN [5]
RP INTERACTION WITH RAB3B, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18396146; DOI=10.1016/j.abb.2008.03.032;
RA Nishimura N., Araki K., Shinahara W., Nakano Y., Nishimura K., Higashio H.,
RA Sasaki T.;
RT "Interaction of Rab3B with microtubule-binding protein Gas8 in NIH 3T3
RT cells.";
RL Arch. Biochem. Biophys. 474:136-142(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMO.
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).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=26387594; DOI=10.1016/j.ajhg.2015.08.012;
RA Olbrich H., Cremers C., Loges N.T., Werner C., Nielsen K.G., Marthin J.K.,
RA Philipsen M., Wallmeier J., Pennekamp P., Menchen T., Edelbusch C.,
RA Dougherty G.W., Schwartz O., Thiele H., Altmueller J., Rommelmann F.,
RA Omran H.;
RT "Loss-of-function GAS8 mutations cause primary ciliary dyskinesia and
RT disrupt the nexin-dynein regulatory complex.";
RL Am. J. Hum. Genet. 97:546-554(2015).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ALA-391.
RX PubMed=27472056; DOI=10.1371/journal.pgen.1006220;
RA Lewis W.R., Malarkey E.B., Tritschler D., Bower R., Pasek R.C.,
RA Porath J.D., Birket S.E., Saunier S., Antignac C., Knowles M.R.,
RA Leigh M.W., Zariwala M.A., Challa A.K., Kesterson R.A., Rowe S.M.,
RA Drummond I.A., Parant J.M., Hildebrandt F., Porter M.E., Yoder B.K.,
RA Berbari N.F.;
RT "Mutation of growth arrest specific 8 reveals a role in motile cilia
RT function and human disease.";
RL PLoS Genet. 12:E1006220-E1006220(2016).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH DRC7.
RX PubMed=31961863; DOI=10.1371/journal.pgen.1008585;
RA Morohoshi A., Miyata H., Shimada K., Nozawa K., Matsumura T., Yanase R.,
RA Shiba K., Inaba K., Ikawa M.;
RT "Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required
RT for sperm flagellum formation and male fertility in mice.";
RL PLoS Genet. 16:e1008585-e1008585(2020).
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 motile cilia
CC functioning. Positively regulates ciliary smoothened (SMO)-dependent
CC Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO
CC into the cilium and the stimulation of SMO activity in a GRK2-dependent
CC manner (PubMed:17366626, PubMed:21659505, PubMed:27472056). May play a
CC role in the spermatozoa motility (PubMed:11751847).
CC {ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:11751847,
CC ECO:0000269|PubMed:17366626, ECO:0000269|PubMed:21659505,
CC ECO:0000269|PubMed:27472056}.
CC -!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC) (By
CC similarity). Interacts with microtubules (PubMed:17366626). Interacts
CC with SMO (PubMed:21659505). Interacts (via coiled-coil domains) with
CC RAB3B (in GTP-bound form) (PubMed:18396146). Interacts with DRC7
CC (PubMed:31961863). {ECO:0000250|UniProtKB:Q7XJ96,
CC ECO:0000269|PubMed:17366626, ECO:0000269|PubMed:18396146,
CC ECO:0000269|PubMed:21659505, ECO:0000269|PubMed:31961863}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11751847,
CC ECO:0000269|PubMed:21659505}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:17366626}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:11751847, ECO:0000269|PubMed:31961863}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:11751847,
CC ECO:0000269|PubMed:26387594, ECO:0000269|PubMed:27472056}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:16643277,
CC ECO:0000269|PubMed:21659505}. Golgi apparatus
CC {ECO:0000269|PubMed:18396146}. Cell projection, cilium
CC {ECO:0000269|PubMed:27472056}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:Q7XJ96}. Note=Associates with
CC microtubules (PubMed:17366626). Localized to the cytoplasm of round
CC spermatids, the tails of elongating spermatids, and mature spermatid
CC tail bundles protruding into the lumen, and in the flagellum of
CC epididymal spermatozoa (PubMed:11751847). {ECO:0000269|PubMed:11751847,
CC ECO:0000269|PubMed:17366626}.
CC -!- TISSUE SPECIFICITY: Highly expressed in adult testes and lung. Weakly
CC or not expressed in other tested tissues. {ECO:0000269|PubMed:11751847,
CC ECO:0000269|PubMed:18396146}.
CC -!- DEVELOPMENTAL STAGE: Weakly or not expressed in neonates and young
CC adolescents. Then, it is strongly expressed postmeiotically.
CC Accumulates in gametocytes as they approach the lumen of seminiferous
CC tubules and thereafter. {ECO:0000269|PubMed:11751847}.
CC -!- INDUCTION: Expressed during serum starvation or contact inhibition of
CC cells grown in murine fibroblasts.
CC -!- DISRUPTION PHENOTYPE: Mice show primary ciliary dyskinesia (PCD) like
CC symptoms including situs inversus and hydrocephalus. Hydrocephalus
CC starts at postnatal day 5 (P5) and becomes more pronounced as the mice
CC mature, eventually leading to mortality between P14-P21. Development of
CC hydrocephalus is associated with severe impairment of cilia motility on
CC ependymal cells lining the ventricles of the brain.
CC {ECO:0000269|PubMed:27472056}.
CC -!- SIMILARITY: Belongs to the DRC4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA85258.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U19859; AAA85258.1; ALT_FRAME; mRNA.
DR EMBL; BC003779; AAH03779.2; -; mRNA.
DR CCDS; CCDS40512.1; -.
DR RefSeq; NP_061343.2; NM_018855.2.
DR AlphaFoldDB; Q60779; -.
DR SMR; Q60779; -.
DR BioGRID; 222565; 3.
DR STRING; 10090.ENSMUSP00000090730; -.
DR iPTMnet; Q60779; -.
DR PhosphoSitePlus; Q60779; -.
DR MaxQB; Q60779; -.
DR PaxDb; Q60779; -.
DR PRIDE; Q60779; -.
DR ProteomicsDB; 267564; -.
DR Antibodypedia; 30991; 172 antibodies from 25 providers.
DR DNASU; 104346; -.
DR Ensembl; ENSMUST00000093043; ENSMUSP00000090730; ENSMUSG00000040220.
DR GeneID; 104346; -.
DR KEGG; mmu:104346; -.
DR UCSC; uc009nwk.1; mouse.
DR CTD; 2622; -.
DR MGI; MGI:1202386; Gas8.
DR VEuPathDB; HostDB:ENSMUSG00000040220; -.
DR eggNOG; ENOG502QQDA; Eukaryota.
DR GeneTree; ENSGT00390000009477; -.
DR HOGENOM; CLU_045343_0_0_1; -.
DR InParanoid; Q60779; -.
DR OMA; SWEHEVL; -.
DR OrthoDB; 1257437at2759; -.
DR PhylomeDB; Q60779; -.
DR TreeFam; TF323819; -.
DR Reactome; R-MMU-5635838; Activation of SMO.
DR BioGRID-ORCS; 104346; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Gas8; mouse.
DR PRO; PR:Q60779; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q60779; protein.
DR Bgee; ENSMUSG00000040220; Expressed in ear vesicle and 225 other tissues.
DR ExpressionAtlas; Q60779; baseline and differential.
DR Genevisible; Q60779; MM.
DR GO; GO:0097729; C:9+2 motile cilium; IDA:MGI.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0036126; C:sperm flagellum; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:MGI.
DR GO; GO:0035082; P:axoneme assembly; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0060294; P:cilium movement involved in cell motility; ISO:MGI.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IEP:UniProtKB.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; IDA:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IDA:MGI.
DR GO; GO:1904526; P:regulation of microtubule binding; IDA:UniProtKB.
DR InterPro; IPR039308; GAS8.
DR InterPro; IPR025593; GAS8_dom.
DR PANTHER; PTHR31543; PTHR31543; 1.
DR Pfam; PF13851; GAS; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cilium; Coiled coil; Cytoplasm; Cytoskeleton; Flagellum;
KW Golgi apparatus; Microtubule; Reference proteome.
FT CHAIN 1..478
FT /note="Dynein regulatory complex subunit 4"
FT /id="PRO_0000220378"
FT REGION 1..114
FT /note="Regulates microtubule-binding"
FT /evidence="ECO:0000269|PubMed:17366626"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..258
FT /note="Microtubule-binding"
FT /evidence="ECO:0000269|PubMed:17366626"
FT REGION 357..478
FT /note="Interaction with SMO"
FT /evidence="ECO:0000269|PubMed:21659505"
FT COILED 24..207
FT /evidence="ECO:0000255"
FT COILED 242..426
FT /evidence="ECO:0000255"
FT MUTAGEN 391
FT /note="A->V: Moderate decrease in cilia motility."
FT /evidence="ECO:0000269|PubMed:27472056"
FT CONFLICT 283
FT /note="L -> Q (in Ref. 1; AAA85258)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="Q -> L (in Ref. 1; AAA85258)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="N -> D (in Ref. 1; AAA85258)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="T -> I (in Ref. 1; AAA85258)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="A -> S (in Ref. 1; AAA85258)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 56264 MW; A11AD16EFA2DE5E9 CRC64;
MAPKKKGKKG KAKGTAIVDG VAPEDMTKEQ VEEHVARIRE ELDREREERN YFQLERDKIH
TFWEITRRQL EEKKAELRNK DREMEEAEER HQVEIKVYKQ KVKHLLYEHQ NNLAEVKAEG
TVVMKLAQKE HRTQEGALRK DMRVLKVELK EQELANEVVI KNLCLKQAEE ITKMRNDFER
QVREIEAKYD KKMKMLRDEL DLRRKTEIHE VEERKNGQIS TLMQRHEEAF TDIKNYYNDI
TLNNLALINS LKEQMEDMRK KEEHMEREMA EVTLQNRRLA DPLQKAKDEM NEMQKRLGNH
ERDKQILVCT KARLKVAERE LKDLKWEHEV LEQRFIKVQQ EREELYRKFA DAIQEVQQKT
GFKNLLLERK LQALNAAVEK REVQFNEVLA ASNLDPTALT LVSRKLEDVL ESKNTTIKDL
QYELARVCKA HNDLLRTYEA KLLAFGIPLD NVGFKPLETA VIGQTLGQGP AGLVGAPT
