DRC4_HUMAN
ID DRC4_HUMAN Reviewed; 478 AA.
AC O95995; B2RCT1; B7Z4U1; G3V1L5; Q2M234;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Dynein regulatory complex subunit 4 {ECO:0000303|PubMed:27120127};
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:27120127}, GAS11;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE
RP SPECIFICITY.
RX PubMed=9790751; DOI=10.1006/geno.1998.5457;
RA Whitmore S.A., Settasatian C., Crawford J., Lower K.M., McCallum B.,
RA Seshadri R., Cornelisse C.J., Moerland E.W., Cleton-Jansen A.-M.,
RA Tipping A.J., Mathew C.G., Savnio M., Savoia A., Verlander P.,
RA Auerbach A.D., Van Berkel C., Pronk J.C., Doggett N.A., Callen D.F.;
RT "Characterization and screening for mutations of the growth arrest-specific
RT 11 (GAS11) and C16orf3 genes at 16q24.3 in breast cancer.";
RL Genomics 52:325-331(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=10969087; DOI=10.1074/jbc.m006907200;
RA Hill K.L., Hutchings N.R., Grandgenett P.M., Donelson J.E.;
RT "T lymphocyte-triggering factor of African trypanosomes is associated with
RT the flagellar fraction of the cytoskeleton and represents a new family of
RT proteins that are present in several divergent eukaryotes.";
RL J. Biol. Chem. 275:39369-39378(2000).
RN [7]
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 [8]
RP 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 [9]
RP INVOLVEMENT IN CILD33, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
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 [10]
RP VARIANTS CILD33 183-ARG--THR-478 DEL AND 334-ARG--THR-478 DEL,
RP CHARACTERIZATION OF VARIANTS CILD33 183-ARG--THR-478 DEL AND
RP 334-ARG--THR-478 DEL, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=27120127; DOI=10.1002/humu.23005;
RA Jeanson L., Thomas L., Copin B., Coste A., Sermet-Gaudelus I.,
RA Dastot-Le Moal F., Duquesnoy P., Montantin G., Collot N., Tissier S.,
RA Papon J.F., Clement A., Louis B., Escudier E., Amselem S., Legendre M.;
RT "Mutations in GAS8, a gene encoding a nexin-dynein regulatory complex
RT subunit, cause primary ciliary dyskinesia with axonemal disorganization.";
RL Hum. Mutat. 37:776-785(2016).
RN [11]
RP VARIANT LYS-199, VARIANT CILD33 VAL-391, CHARACTERIZATION OF VARIANT CILD33
RP VAL-391, AND FUNCTION.
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).
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 (PubMed:26387594, PubMed:27120127, PubMed:27472056).
CC Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh)
CC signaling pathway by facilitating the trafficking of SMO into the
CC cilium and the stimulation of SMO activity in a GRK2-dependent manner
CC (By similarity). {ECO:0000250|UniProtKB:Q60779,
CC ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:26387594,
CC ECO:0000269|PubMed:27120127, ECO:0000269|PubMed:27472056}.
CC -!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC).
CC Interacts with microtubules (By similarity). Interacts with SMO
CC (PubMed:21659505). Interacts (via coiled-coil domains) with RAB3B (in
CC GTP-bound form) (By similarity). Interacts with DRC7 (By similarity).
CC {ECO:0000250|UniProtKB:Q60779, ECO:0000250|UniProtKB:Q7XJ96,
CC ECO:0000269|PubMed:21659505}.
CC -!- INTERACTION:
CC O95995; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-1052570, EBI-714543;
CC O95995; O75815: BCAR3; NbExp=3; IntAct=EBI-1052570, EBI-702336;
CC O95995; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-1052570, EBI-11519926;
CC O95995; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-1052570, EBI-10193358;
CC O95995; Q13895: BYSL; NbExp=3; IntAct=EBI-1052570, EBI-358049;
CC O95995; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-1052570, EBI-3866279;
CC O95995; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-1052570, EBI-11530605;
CC O95995; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-1052570, EBI-11977221;
CC O95995; Q8IYE0: CCDC146; NbExp=3; IntAct=EBI-1052570, EBI-10749669;
CC O95995; Q16204: CCDC6; NbExp=3; IntAct=EBI-1052570, EBI-1045350;
CC O95995; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-1052570, EBI-10175300;
CC O95995; P51959: CCNG1; NbExp=3; IntAct=EBI-1052570, EBI-3905829;
CC O95995; Q16543: CDC37; NbExp=3; IntAct=EBI-1052570, EBI-295634;
CC O95995; Q01850: CDR2; NbExp=3; IntAct=EBI-1052570, EBI-1181367;
CC O95995; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-1052570, EBI-739624;
CC O95995; Q96M91: CFAP53; NbExp=3; IntAct=EBI-1052570, EBI-742422;
CC O95995; Q9BW66: CINP; NbExp=3; IntAct=EBI-1052570, EBI-739784;
CC O95995; P61024: CKS1B; NbExp=3; IntAct=EBI-1052570, EBI-456371;
CC O95995; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-1052570, EBI-3866319;
CC O95995; Q8N684-3: CPSF7; NbExp=3; IntAct=EBI-1052570, EBI-11523759;
CC O95995; P53674: CRYBB1; NbExp=3; IntAct=EBI-1052570, EBI-7519424;
CC O95995; Q5HYN5: CT45A1; NbExp=3; IntAct=EBI-1052570, EBI-12051833;
CC O95995; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-1052570, EBI-5453285;
CC O95995; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1052570, EBI-3867333;
CC O95995; Q9UER7: DAXX; NbExp=5; IntAct=EBI-1052570, EBI-77321;
CC O95995; Q92841: DDX17; NbExp=3; IntAct=EBI-1052570, EBI-746012;
CC O95995; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-1052570, EBI-11988027;
CC O95995; Q9NPF5: DMAP1; NbExp=3; IntAct=EBI-1052570, EBI-399105;
CC O95995; Q96JC9: EAF1; NbExp=3; IntAct=EBI-1052570, EBI-769261;
CC O95995; Q08426: EHHADH; NbExp=3; IntAct=EBI-1052570, EBI-2339219;
CC O95995; Q8N9N8: EIF1AD; NbExp=3; IntAct=EBI-1052570, EBI-750700;
CC O95995; P07992-3: ERCC1; NbExp=3; IntAct=EBI-1052570, EBI-12699417;
CC O95995; Q96CN4: EVI5L; NbExp=3; IntAct=EBI-1052570, EBI-749523;
CC O95995; Q3B820: FAM161A; NbExp=3; IntAct=EBI-1052570, EBI-719941;
CC O95995; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-1052570, EBI-7225287;
CC O95995; Q14192: FHL2; NbExp=3; IntAct=EBI-1052570, EBI-701903;
CC O95995; Q8TAE8: GADD45GIP1; NbExp=3; IntAct=EBI-1052570, EBI-372506;
CC O95995; Q96CN9: GCC1; NbExp=3; IntAct=EBI-1052570, EBI-746252;
CC O95995; P55040: GEM; NbExp=3; IntAct=EBI-1052570, EBI-744104;
CC O95995; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1052570, EBI-618309;
CC O95995; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-1052570, EBI-717919;
CC O95995; O15217: GSTA4; NbExp=3; IntAct=EBI-1052570, EBI-752440;
CC O95995; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-1052570, EBI-5460660;
CC O95995; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-1052570, EBI-748420;
CC O95995; P49639: HOXA1; NbExp=3; IntAct=EBI-1052570, EBI-740785;
CC O95995; O75031: HSF2BP; NbExp=3; IntAct=EBI-1052570, EBI-7116203;
CC O95995; P24592: IGFBP6; NbExp=3; IntAct=EBI-1052570, EBI-947015;
CC O95995; O60341: KDM1A; NbExp=3; IntAct=EBI-1052570, EBI-710124;
CC O95995; P02533: KRT14; NbExp=3; IntAct=EBI-1052570, EBI-702178;
CC O95995; P19012: KRT15; NbExp=3; IntAct=EBI-1052570, EBI-739566;
CC O95995; P08779: KRT16; NbExp=3; IntAct=EBI-1052570, EBI-356410;
CC O95995; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-1052570, EBI-3044087;
CC O95995; Q969R5: L3MBTL2; NbExp=3; IntAct=EBI-1052570, EBI-739909;
CC O95995; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-1052570, EBI-11985629;
CC O95995; Q14847-2: LASP1; NbExp=3; IntAct=EBI-1052570, EBI-9088686;
CC O95995; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-1052570, EBI-12039345;
CC O95995; P25800: LMO1; NbExp=3; IntAct=EBI-1052570, EBI-8639312;
CC O95995; P25791-3: LMO2; NbExp=3; IntAct=EBI-1052570, EBI-11959475;
CC O95995; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-1052570, EBI-1216080;
CC O95995; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-1052570, EBI-742610;
CC O95995; P55081: MFAP1; NbExp=3; IntAct=EBI-1052570, EBI-1048159;
CC O95995; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-1052570, EBI-10172526;
CC O95995; Q9BU76: MMTAG2; NbExp=3; IntAct=EBI-1052570, EBI-742459;
CC O95995; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-1052570, EBI-748896;
CC O95995; Q9UHB4: NDOR1; NbExp=3; IntAct=EBI-1052570, EBI-10249760;
CC O95995; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-1052570, EBI-3920396;
CC O95995; O00444: PLK4; NbExp=3; IntAct=EBI-1052570, EBI-746202;
CC O95995; Q96T60: PNKP; NbExp=3; IntAct=EBI-1052570, EBI-1045072;
CC O95995; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-1052570, EBI-10171633;
CC O95995; O15160: POLR1C; NbExp=3; IntAct=EBI-1052570, EBI-1055079;
CC O95995; A0JP26: POTEB3; NbExp=3; IntAct=EBI-1052570, EBI-18165900;
CC O95995; Q13136: PPFIA1; NbExp=3; IntAct=EBI-1052570, EBI-745426;
CC O95995; Q9GZV8: PRDM14; NbExp=3; IntAct=EBI-1052570, EBI-3957793;
CC O95995; O14744: PRMT5; NbExp=3; IntAct=EBI-1052570, EBI-351098;
CC O95995; Q99633: PRPF18; NbExp=3; IntAct=EBI-1052570, EBI-2798416;
CC O95995; Q15311: RALBP1; NbExp=3; IntAct=EBI-1052570, EBI-749285;
CC O95995; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-1052570, EBI-1210429;
CC O95995; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-1052570, EBI-726876;
CC O95995; Q92622: RUBCN; NbExp=3; IntAct=EBI-1052570, EBI-2952709;
CC O95995; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-1052570, EBI-748391;
CC O95995; P12757: SKIL; NbExp=3; IntAct=EBI-1052570, EBI-2902468;
CC O95995; O60504: SORBS3; NbExp=3; IntAct=EBI-1052570, EBI-741237;
CC O95995; Q8TDD2: SP7; NbExp=3; IntAct=EBI-1052570, EBI-10713842;
CC O95995; Q8TC71: SPATA18; NbExp=3; IntAct=EBI-1052570, EBI-11334239;
CC O95995; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-1052570, EBI-742688;
CC O95995; Q96MF2: STAC3; NbExp=3; IntAct=EBI-1052570, EBI-745680;
CC O95995; Q15560: TCEA2; NbExp=3; IntAct=EBI-1052570, EBI-710310;
CC O95995; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-1052570, EBI-741515;
CC O95995; P21580: TNFAIP3; NbExp=3; IntAct=EBI-1052570, EBI-527670;
CC O95995; Q12933: TRAF2; NbExp=3; IntAct=EBI-1052570, EBI-355744;
CC O95995; O00463: TRAF5; NbExp=3; IntAct=EBI-1052570, EBI-523498;
CC O95995; Q8WV44: TRIM41; NbExp=3; IntAct=EBI-1052570, EBI-725997;
CC O95995; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-1052570, EBI-2130429;
CC O95995; P43897: TSFM; NbExp=3; IntAct=EBI-1052570, EBI-1049298;
CC O95995; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-1052570, EBI-10241197;
CC O95995; P40222: TXLNA; NbExp=3; IntAct=EBI-1052570, EBI-359793;
CC O95995; Q8N3L3: TXLNB; NbExp=3; IntAct=EBI-1052570, EBI-6116822;
CC O95995; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-1052570, EBI-739895;
CC O95995; P07947: YES1; NbExp=3; IntAct=EBI-1052570, EBI-515331;
CC O95995; Q9BW85: YJU2; NbExp=3; IntAct=EBI-1052570, EBI-10300345;
CC O95995; O15209: ZBTB22; NbExp=3; IntAct=EBI-1052570, EBI-723574;
CC O95995; Q9HCK0: ZBTB26; NbExp=5; IntAct=EBI-1052570, EBI-3918996;
CC O95995; O15060: ZBTB39; NbExp=3; IntAct=EBI-1052570, EBI-9995672;
CC O95995; Q9UDV6: ZNF212; NbExp=3; IntAct=EBI-1052570, EBI-1640204;
CC O95995; P15622-3: ZNF250; NbExp=3; IntAct=EBI-1052570, EBI-10177272;
CC O95995; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-1052570, EBI-10172590;
CC O95995; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-1052570, EBI-4395669;
CC O95995; Q9UEG4: ZNF629; NbExp=3; IntAct=EBI-1052570, EBI-9977294;
CC O95995; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-1052570, EBI-10240849;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60779}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10969087}. Cell projection,
CC cilium, flagellum {ECO:0000250|UniProtKB:Q60779}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:16643277,
CC ECO:0000269|PubMed:26387594}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:Q60779}. Golgi apparatus
CC {ECO:0000269|PubMed:16643277}. Cell projection, cilium
CC {ECO:0000269|PubMed:27120127}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:Q7XJ96}. Note=Associates with
CC microtubules (PubMed:10969087). 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 (By similarity). {ECO:0000250|UniProtKB:Q60779,
CC ECO:0000269|PubMed:10969087}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95995-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95995-2; Sequence=VSP_054805;
CC -!- TISSUE SPECIFICITY: Expressed in respiratory epithelial cells (at
CC protein level) (PubMed:26387594). Expressed in the heart, skeletal
CC muscle, pancreas, liver, brain, trachea and lung. Weakly or not
CC expressed in placenta and kidney (PubMed:9790751).
CC {ECO:0000269|PubMed:26387594, ECO:0000269|PubMed:27120127,
CC ECO:0000269|PubMed:9790751}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 33 (CILD33) [MIM:616726]: A form
CC of primary ciliary dyskinesia, a disorder characterized by
CC abnormalities of motile cilia. Respiratory infections leading to
CC chronic inflammation and bronchiectasis are recurrent, due to defects
CC in the respiratory cilia. CILD33 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:26387594, ECO:0000269|PubMed:27120127,
CC ECO:0000269|PubMed:27472056}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DRC4 family. {ECO:0000305}.
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DR EMBL; AF050079; AAC69519.1; -; mRNA.
DR EMBL; AF050078; AAC69518.1; -; Genomic_DNA.
DR EMBL; AF050068; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050069; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050070; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050071; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050072; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050073; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050074; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050075; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050076; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AF050077; AAC69518.1; JOINED; Genomic_DNA.
DR EMBL; AK315261; BAG37678.1; -; mRNA.
DR EMBL; AK297857; BAH12677.1; -; mRNA.
DR EMBL; AC133919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471184; EAW66661.1; -; Genomic_DNA.
DR EMBL; CH471184; EAW66659.1; -; Genomic_DNA.
DR EMBL; BC104785; AAI04786.1; -; mRNA.
DR EMBL; BC112121; AAI12122.1; -; mRNA.
DR CCDS; CCDS10992.1; -. [O95995-1]
DR CCDS; CCDS67101.1; -. [O95995-2]
DR RefSeq; NP_001273134.1; NM_001286205.1.
DR RefSeq; NP_001273137.1; NM_001286208.1.
DR RefSeq; NP_001273138.1; NM_001286209.1. [O95995-2]
DR RefSeq; NP_001472.1; NM_001481.2. [O95995-1]
DR RefSeq; XP_005256361.1; XM_005256304.4.
DR AlphaFoldDB; O95995; -.
DR SMR; O95995; -.
DR BioGRID; 108892; 120.
DR CORUM; O95995; -.
DR IntAct; O95995; 110.
DR STRING; 9606.ENSP00000268699; -.
DR iPTMnet; O95995; -.
DR PhosphoSitePlus; O95995; -.
DR BioMuta; GAS8; -.
DR EPD; O95995; -.
DR MassIVE; O95995; -.
DR MaxQB; O95995; -.
DR PaxDb; O95995; -.
DR PeptideAtlas; O95995; -.
DR PRIDE; O95995; -.
DR ProteomicsDB; 32370; -.
DR ProteomicsDB; 51170; -. [O95995-1]
DR Antibodypedia; 30991; 172 antibodies from 25 providers.
DR DNASU; 2622; -.
DR Ensembl; ENST00000268699.9; ENSP00000268699.4; ENSG00000141013.17. [O95995-1]
DR Ensembl; ENST00000536122.7; ENSP00000440977.1; ENSG00000141013.17. [O95995-2]
DR GeneID; 2622; -.
DR KEGG; hsa:2622; -.
DR MANE-Select; ENST00000268699.9; ENSP00000268699.4; NM_001481.3; NP_001472.1.
DR UCSC; uc002fqi.1; human. [O95995-1]
DR CTD; 2622; -.
DR DisGeNET; 2622; -.
DR GeneCards; GAS8; -.
DR HGNC; HGNC:4166; GAS8.
DR HPA; ENSG00000141013; Low tissue specificity.
DR MalaCards; GAS8; -.
DR MIM; 605178; gene.
DR MIM; 616726; phenotype.
DR neXtProt; NX_O95995; -.
DR OpenTargets; ENSG00000141013; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA28579; -.
DR VEuPathDB; HostDB:ENSG00000141013; -.
DR eggNOG; ENOG502QQDA; Eukaryota.
DR GeneTree; ENSGT00390000009477; -.
DR HOGENOM; CLU_045343_0_0_1; -.
DR InParanoid; O95995; -.
DR OMA; SWEHEVL; -.
DR OrthoDB; 1257437at2759; -.
DR PhylomeDB; O95995; -.
DR TreeFam; TF323819; -.
DR PathwayCommons; O95995; -.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR SignaLink; O95995; -.
DR BioGRID-ORCS; 2622; 17 hits in 1079 CRISPR screens.
DR ChiTaRS; GAS8; human.
DR GenomeRNAi; 2622; -.
DR Pharos; O95995; Tbio.
DR PRO; PR:O95995; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O95995; protein.
DR Bgee; ENSG00000141013; Expressed in right uterine tube and 176 other tissues.
DR ExpressionAtlas; O95995; baseline and differential.
DR Genevisible; O95995; HS.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0035082; P:axoneme assembly; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0060294; P:cilium movement involved in cell motility; IMP:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; IMP:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR GO; GO:1904526; P:regulation of microtubule binding; ISS: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 Alternative splicing; Cell projection; Ciliopathy; Cilium; Coiled coil;
KW Cytoplasm; Cytoskeleton; Flagellum; Golgi apparatus; Microtubule;
KW Primary ciliary dyskinesia; Reference proteome.
FT CHAIN 1..478
FT /note="Dynein regulatory complex subunit 4"
FT /id="PRO_0000220377"
FT REGION 1..114
FT /note="Regulates microtubule-binding"
FT /evidence="ECO:0000250|UniProtKB:Q60779"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..258
FT /note="Microtubule-binding"
FT /evidence="ECO:0000250|UniProtKB:Q60779"
FT REGION 357..478
FT /note="Interaction with SMO"
FT /evidence="ECO:0000269|PubMed:21659505"
FT COILED 242..427
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..25
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054805"
FT VARIANT 183..478
FT /note="Missing (in CILD33; loss of localization to cilia;
FT abnormal cilia with axonemal disorganization)"
FT /evidence="ECO:0000269|PubMed:27120127"
FT /id="VAR_080336"
FT VARIANT 199
FT /note="E -> K (in dbSNP:rs868044)"
FT /evidence="ECO:0000269|PubMed:27472056"
FT /id="VAR_016006"
FT VARIANT 259
FT /note="R -> Q (in dbSNP:rs17178299)"
FT /id="VAR_049230"
FT VARIANT 334..478
FT /note="Missing (in CILD33; loss of localization to cilia;
FT abnormal cilia with axonemal disorganization)"
FT /evidence="ECO:0000269|PubMed:27120127"
FT /id="VAR_080337"
FT VARIANT 391
FT /note="A -> V (in CILD33; the same mutation in the mouse
FT sequence shows a moderate decrease in cilia motility;
FT dbSNP:rs147993982)"
FT /evidence="ECO:0000269|PubMed:27472056"
FT /id="VAR_080338"
FT CONFLICT 33
FT /note="E -> G (in Ref. 2; BAH12677)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="A -> V (in Ref. 2; BAH12677)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 56356 MW; 2EDBC7981868EB12 CRC64;
MAPKKKGKKG KAKGTPIVDG LAPEDMSKEQ VEEHVSRIRE ELDREREERN YFQLERDKIH
TFWEITRRQL EEKKAELRNK DREMEEAEER HQVEIKVYKQ KVKHLLYEHQ NNLTEMKAEG
TVVMKLAQKE HRIQESVLRK DMRALKVELK EQELASEVVV KNLRLKHTEE ITRMRNDFER
QVREIEAKYD KKMKMLRDEL DLRRKTELHE VEERKNGQIH TLMQRHEEAF TDIKNYYNDI
TLNNLALINS LKEQMEDMRK KEDHLEREMA EVSGQNKRLA DPLQKAREEM SEMQKQLANY
ERDKQILLCT KARLKVREKE LKDLQWEHEV LEQRFTKVQQ ERDELYRKFT AAIQEVQQKT
GFKNLVLERK LQALSAAVEK KEVQFNEVLA ASNLDPAALT LVSRKLEDVL ESKNSTIKDL
QYELAQVCKA HNDLLRTYEA KLLAFGIPLD NVGFKPLETA VIGQTLGQGP AGLVGTPT
