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Growth arrest-specific protein 8 (GAS-8) (Growth arrest-specific protein 11) (GAS-11)

 DRC4_MOUSE              Reviewed;         478 AA.
Q60779; Q99L71;
19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
19-JUL-2003, sequence version 2.
23-MAY-2018, entry version 123.
RecName: Full=Dynein regulatory complex subunit 4 {ECO:0000303|PubMed:27472056};
AltName: Full=Growth arrest-specific protein 11;
Short=GAS-11;
AltName: Full=Growth arrest-specific protein 8;
Short=GAS-8;
Name=Gas8; Synonyms=Drc4 {ECO:0000303|PubMed:27472056}, Gas11;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
SPECIFICITY, AND DEVELOPMENTAL STAGE.
PubMed=11751847; DOI=10.1074/jbc.M106941200;
Yeh S.-D., Chen Y.-J., Chang A.C.Y., Ray R., She B.-R., Lee W.-S.,
Chiang H.-S., Cohen S.N., Lin-Chao S.;
"Isolation and properties of Gas8, a growth arrest-specific gene
regulated during male gametogenesis to produce a protein associated
with the sperm motility apparatus.";
J. Biol. Chem. 277:6311-6317(2002).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=FVB/N; TISSUE=Mammary gland;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
SUBCELLULAR LOCATION.
PubMed=16643277; DOI=10.1111/j.1600-0854.2006.00411.x;
Colantonio J.R., Bekker J.M., Kim S.J., Morrissey K.M., Crosbie R.H.,
Hill K.L.;
"Expanding the role of the dynein regulatory complex to non-axonemal
functions: association of GAS11 with the Golgi apparatus.";
Traffic 7:538-548(2006).
[4]
FUNCTION, INTERACTION WITH MICROTUBULES, AND SUBCELLULAR LOCATION.
PubMed=17366626; DOI=10.1002/cm.20196;
Bekker J.M., Colantonio J.R., Stephens A.D., Clarke W.T., King S.J.,
Hill K.L., Crosbie R.H.;
"Direct interaction of Gas11 with microtubules: implications for the
dynein regulatory complex.";
Cell Motil. Cytoskeleton 64:461-473(2007).
[5]
INTERACTION WITH RAB3B, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=18396146; DOI=10.1016/j.abb.2008.03.032;
Nishimura N., Araki K., Shinahara W., Nakano Y., Nishimura K.,
Higashio H., Sasaki T.;
"Interaction of Rab3B with microtubule-binding protein Gas8 in NIH 3T3
cells.";
Arch. Biochem. Biophys. 474:136-142(2008).
[6]
FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMO.
PubMed=21659505; DOI=10.1074/jbc.M111.234666;
Evron T., Philipp M., Lu J., Meloni A.R., Burkhalter M., Chen W.,
Caron M.G.;
"Growth arrest specific 8 (Gas8) and G protein-coupled receptor kinase
2 (GRK2) cooperate in the control of Smoothened signaling.";
J. Biol. Chem. 286:27676-27686(2011).
[7]
SUBCELLULAR LOCATION.
PubMed=26387594; DOI=10.1016/j.ajhg.2015.08.012;
Olbrich H., Cremers C., Loges N.T., Werner C., Nielsen K.G.,
Marthin J.K., Philipsen M., Wallmeier J., Pennekamp P., Menchen T.,
Edelbusch C., Dougherty G.W., Schwartz O., Thiele H., Altmueller J.,
Rommelmann F., Omran H.;
"Loss-of-function GAS8 mutations cause primary ciliary dyskinesia and
disrupt the nexin-dynein regulatory complex.";
Am. J. Hum. Genet. 97:546-554(2015).
[8]
FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS
OF ALA-391.
PubMed=27472056; DOI=10.1371/journal.pgen.1006220;
Lewis W.R., Malarkey E.B., Tritschler D., Bower R., Pasek R.C.,
Porath J.D., Birket S.E., Saunier S., Antignac C., Knowles M.R.,
Leigh M.W., Zariwala M.A., Challa A.K., Kesterson R.A., Rowe S.M.,
Drummond I.A., Parant J.M., Hildebrandt F., Porter M.E., Yoder B.K.,
Berbari N.F.;
"Mutation of growth arrest specific 8 reveals a role in motile cilia
function and human disease.";
PLoS Genet. 12:E1006220-E1006220(2016).
-!- FUNCTION: Component of the nexin-dynein regulatory complex (N-
DRC), a key regulator of ciliary/flagellar motility which
maintains the alignment and integrity of the distal axoneme and
regulates microtubule sliding in motile axonemes. Plays an
important role in the assembly of the N-DRC linker (By
similarity). Plays dual roles at both the primary (or non-motile)
cilia to regulate hedgehog signaling and in motile cilia to
coordinate cilia movement. Required for proper motile cilia
functioning. Positively regulates ciliary smoothened (SMO)-
dependent Hedgehog (Hh) signaling pathway by faciltating the
trafficking of SMO into the cilium and the stimulation of SMO
activity in a GRK2-dependent manner (PubMed:17366626,
PubMed:21659505, PubMed:27472056). May play a role in the
spermatozoa motility (PubMed:11751847).
{ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:11751847,
ECO:0000269|PubMed:17366626, ECO:0000269|PubMed:21659505,
ECO:0000269|PubMed:27472056}.
-!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC)
(By similarity). Interacts with microtubules (PubMed:17366626).
Interacts with SMO (PubMed:21659505). Interacts (via coiled-coil
domains) with RAB3B (in GTP-bound form) (PubMed:18396146).
{ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:17366626,
ECO:0000269|PubMed:18396146, ECO:0000269|PubMed:21659505}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11751847,
ECO:0000269|PubMed:21659505}. Cytoplasm, cytoskeleton
{ECO:0000269|PubMed:17366626}. Cell projection, cilium, flagellum
{ECO:0000269|PubMed:11751847}. Cytoplasm, cytoskeleton, cilium
axoneme {ECO:0000269|PubMed:11751847, ECO:0000269|PubMed:26387594,
ECO:0000269|PubMed:27472056}. Cytoplasm, cytoskeleton, cilium
basal body {ECO:0000269|PubMed:16643277,
ECO:0000269|PubMed:21659505}. Golgi apparatus
{ECO:0000269|PubMed:18396146}. Cell projection, cilium
{ECO:0000269|PubMed:27472056}. Cytoplasm, cytoskeleton, flagellum
axoneme {ECO:0000250|UniProtKB:Q7XJ96}. Note=Associates with
microtubules (PubMed:17366626). Localized to the cytoplasm of
round spermatids, the tails of elongating spermatids, and mature
spermatid tail bundles protruding into the lumen, and in the
flagellum of epididymal spermatozoa (PubMed:11751847).
{ECO:0000269|PubMed:11751847, ECO:0000269|PubMed:17366626}.
-!- TISSUE SPECIFICITY: Highly expressed in adult testes and lung.
Weakly or not expressed in other tested tissues.
{ECO:0000269|PubMed:11751847, ECO:0000269|PubMed:18396146}.
-!- DEVELOPMENTAL STAGE: Weakly or not expressed in neonates and young
adolescents. Then, it is strongly expressed postmeiotically.
Accumulates in gametocytes as they approach the lumen of
seminiferous tubules and thereafter.
{ECO:0000269|PubMed:11751847}.
-!- INDUCTION: Expressed during serum starvation or contact inhibition
of cells grown in murine fibroblasts.
-!- DISRUPTION PHENOTYPE: Mice show primary ciliary dyskinesia (PCD)
like symptoms including situs inversus and hydrocephalus.
Hydrocephalus starts at postnatal day 5 (P5) and becomes more
pronounced as the mice mature, eventually leading to mortality
between P14-P21. Development of hydrocephalus is associated with
severe impairment of cilia motility on ependymal cells lining the
ventricles of the brain. {ECO:0000269|PubMed:27472056}.
-!- SIMILARITY: Belongs to the DRC4 family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAA85258.1; Type=Frameshift; Positions=3, 471; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; U19859; AAA85258.1; ALT_FRAME; mRNA.
EMBL; BC003779; AAH03779.2; -; mRNA.
CCDS; CCDS40512.1; -.
RefSeq; NP_061343.2; NM_018855.2.
UniGene; Mm.117265; -.
ProteinModelPortal; Q60779; -.
SMR; Q60779; -.
STRING; 10090.ENSMUSP00000090730; -.
iPTMnet; Q60779; -.
PhosphoSitePlus; Q60779; -.
MaxQB; Q60779; -.
PaxDb; Q60779; -.
PRIDE; Q60779; -.
Ensembl; ENSMUST00000093043; ENSMUSP00000090730; ENSMUSG00000040220.
GeneID; 104346; -.
KEGG; mmu:104346; -.
UCSC; uc009nwk.1; mouse.
CTD; 2622; -.
MGI; MGI:1202386; Gas8.
eggNOG; ENOG410IE2T; Eukaryota.
eggNOG; ENOG410XPBD; LUCA.
GeneTree; ENSGT00390000009477; -.
HOGENOM; HOG000038763; -.
HOVERGEN; HBG039458; -.
InParanoid; Q60779; -.
KO; K19942; -.
OMA; AREEMSE; -.
OrthoDB; EOG091G0851; -.
PhylomeDB; Q60779; -.
TreeFam; TF323819; -.
Reactome; R-MMU-5635838; Activation of SMO.
PRO; PR:Q60779; -.
Proteomes; UP000000589; Chromosome 8.
Bgee; ENSMUSG00000040220; -.
CleanEx; MM_GAS8; -.
ExpressionAtlas; Q60779; baseline and differential.
Genevisible; Q60779; MM.
GO; GO:0097729; C:9+2 motile cilium; IDA:MGI.
GO; GO:0005930; C:axoneme; ISS:UniProtKB.
GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
GO; GO:0005929; C:cilium; ISO:MGI.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
GO; GO:0005874; C:microtubule; ISO:MGI.
GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
GO; GO:0031514; C:motile cilium; IDA:MGI.
GO; GO:0036126; C:sperm flagellum; IDA:UniProtKB.
GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
GO; GO:0017137; F:Rab GTPase binding; IDA:MGI.
GO; GO:0035082; P:axoneme assembly; IMP:MGI.
GO; GO:0007420; P:brain development; IMP:MGI.
GO; GO:0034613; P:cellular protein localization; IDA:MGI.
GO; GO:0060294; P:cilium movement involved in cell motility; ISO:MGI.
GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
GO; GO:0003351; P:epithelial cilium movement; IMP:MGI.
GO; GO:0030317; P:flagellated sperm motility; IEP:UniProtKB.
GO; GO:1903566; P:positive regulation of protein localization to cilium; IDA:UniProtKB.
GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
GO; GO:1904526; P:regulation of microtubule binding; IDA:UniProtKB.
InterPro; IPR025593; GAS8.
Pfam; PF13851; GAS; 1.
1: Evidence at protein level;
Cell projection; Cilium; Coiled coil; Complete proteome; Cytoplasm;
Cytoskeleton; Flagellum; Golgi apparatus; Microtubule;
Reference proteome.
CHAIN 1 478 Dynein regulatory complex subunit 4.
/FTId=PRO_0000220378.
REGION 1 114 Regulates microtubule-binding.
{ECO:0000269|PubMed:17366626}.
REGION 115 258 Microtubule-binding.
{ECO:0000269|PubMed:17366626}.
REGION 357 478 Interaction with SMO.
{ECO:0000269|PubMed:21659505}.
COILED 24 207 {ECO:0000255}.
COILED 242 426 {ECO:0000255}.
MUTAGEN 391 391 A->V: Moderate decrease in cilia
motility. {ECO:0000269|PubMed:27472056}.
CONFLICT 283 283 L -> Q (in Ref. 1; AAA85258).
{ECO:0000305}.
CONFLICT 339 339 Q -> L (in Ref. 1; AAA85258).
{ECO:0000305}.
CONFLICT 451 451 N -> D (in Ref. 1; AAA85258).
{ECO:0000305}.
CONFLICT 459 459 T -> I (in Ref. 1; AAA85258).
{ECO:0000305}.
CONFLICT 476 476 A -> S (in Ref. 1; AAA85258).
{ECO:0000305}.
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


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