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 27-MAR-2024, entry version 167. 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 INTERACTION WITH DRC1. RX PubMed=34169321; DOI=10.1093/hmg/ddab171; RA Zhang J., He X., Wu H., Zhang X., Yang S., Liu C., Liu S., Hua R., Zhou S., RA Zhao S., Hu F., Zhang J., Liu W., Cheng H., Gao Y., Zhang F., Cao Y., RA Liu M.; RT "Loss of DRC1 function leads to multiple morphological abnormalities of the RT sperm flagella and male infertility in human and mouse."; RL Hum. Mol. Genet. 30:1996-2011(2021). RN [11] 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 [12] 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 DRC1 (PubMed:34169321). CC Interacts with DRC7 (By similarity). {ECO:0000250|UniProtKB:Q60779, CC ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:21659505, CC ECO:0000269|PubMed:34169321}. 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; 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; Q6PI77: GPRASP3; NbExp=3; IntAct=EBI-1052570, EBI-11519926; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8J07; EM; 4.10 A; 0/4=1-478. DR PDBsum; 8J07; -. DR AlphaFoldDB; O95995; -. DR EMDB; EMD-35888; -. DR SMR; O95995; -. DR BioGRID; 108892; 121. DR ComplexPortal; CPX-8086; Nexin-dynein regulatory complex. 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; 9606-ENSP00000268699; -. DR PeptideAtlas; O95995; -. DR ProteomicsDB; 32370; -. DR ProteomicsDB; 51170; -. [O95995-1] DR Pumba; O95995; -. DR Antibodypedia; 30991; 204 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 AGR; HGNC:4166; -. 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; MKHLQYE; -. DR OrthoDB; 5481777at2759; -. 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 1157 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 178 other cell types or tissues. DR ExpressionAtlas; O95995; baseline and differential. 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; IEA:Ensembl. DR GO; GO:1904526; P:regulation of microtubule binding; ISS:UniProtKB. DR InterPro; IPR039308; GAS8. DR InterPro; IPR025593; GAS8_dom. DR PANTHER; PTHR31543; DYNEIN REGULATORY COMPLEX SUBUNIT 4; 1. DR PANTHER; PTHR31543:SF0; DYNEIN REGULATORY COMPLEX SUBUNIT 4; 1. DR Pfam; PF13851; GAS; 1. DR Genevisible; O95995; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell projection; Ciliopathy; Cilium; KW Coiled coil; Cytoplasm; Cytoskeleton; Flagellum; Golgi apparatus; KW Microtubule; 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 //