TTC8_CAEEL
ID TTC8_CAEEL Reviewed; 506 AA.
AC Q23049;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Tetratricopeptide repeat protein 8 {ECO:0000250|UniProtKB:Q8TAM2};
DE AltName: Full=Bardet-Biedl syndrome 8 protein homolog {ECO:0000312|WormBase:T25F10.5};
GN Name=bbs-8 {ECO:0000312|WormBase:T25F10.5};
GN ORFNames=T25F10.5 {ECO:0000312|WormBase:T25F10.5};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14520415; DOI=10.1038/nature02030;
RA Ansley S.J., Badano J.L., Blacque O.E., Hill J., Hoskins B.E., Leitch C.C.,
RA Kim J.C., Ross A.J., Eichers E.R., Teslovich T.M., Mah A.K., Johnsen R.C.,
RA Cavender J.C., Lewis R.A., Leroux M.R., Beales P.L., Katsanis N.;
RT "Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl
RT syndrome.";
RL Nature 425:628-633(2003).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15231740; DOI=10.1101/gad.1194004;
RA Blacque O.E., Reardon M.J., Li C., McCarthy J., Mahjoub M.R., Ansley S.J.,
RA Badano J.L., Mah A.K., Beales P.L., Davidson W.S., Johnsen R.C., Audeh M.,
RA Plasterk R.H., Baillie D.L., Katsanis N., Quarmby L.M., Wicks S.R.,
RA Leroux M.R.;
RT "Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia
RT defects and compromised intraflagellar transport.";
RL Genes Dev. 18:1630-1642(2004).
RN [4]
RP FUNCTION.
RX PubMed=17000880; DOI=10.1083/jcb.200606003;
RA Pan X., Ou G., Civelekoglu-Scholey G., Blacque O.E., Endres N.F., Tao L.,
RA Mogilner A., Leroux M.R., Vale R.D., Scholey J.M.;
RT "Mechanism of transport of IFT particles in C. elegans cilia by the
RT concerted action of kinesin-II and OSM-3 motors.";
RL J. Cell Biol. 174:1035-1045(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22022287; DOI=10.1371/journal.pgen.1002335;
RA Mok C.A., Healey M.P., Shekhar T., Leroux M.R., Heon E., Zhen M.;
RT "Mutations in a guanylate cyclase GCY-35/GCY-36 modify Bardet-Biedl
RT syndrome-associated phenotypes in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1002335-E1002335(2011).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22922713; DOI=10.1038/ncb2560;
RA Wei Q., Zhang Y., Li Y., Zhang Q., Ling K., Hu J.;
RT "The BBSome controls IFT assembly and turnaround in cilia.";
RL Nat. Cell Biol. 14:950-957(2012).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=25335890; DOI=10.1242/jcs.157610;
RA Nguyen P.A., Liou W., Hall D.H., Leroux M.R.;
RT "Ciliopathy proteins establish a bipartite signaling compartment in a C.
RT elegans thermosensory neuron.";
RL J. Cell Sci. 127:5317-5330(2014).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27930654; DOI=10.1371/journal.pgen.1006469;
RA Jensen V.L., Carter S., Sanders A.A., Li C., Kennedy J., Timbers T.A.,
RA Cai J., Scheidel N., Kennedy B.N., Morin R.D., Leroux M.R., Blacque O.E.;
RT "Whole-organism developmental expression profiling identifies rab-28 as a
RT novel ciliary GTPase associated with the BBSome and intraflagellar
RT transport.";
RL PLoS Genet. 12:E1006469-E1006469(2016).
CC -!- FUNCTION: Component of the BBSome complex (By similarity). The BBSome
CC complex is thought to function as a coat complex required for sorting
CC of specific membrane proteins to the primary cilia (By similarity). The
CC BBSome complex is required for ciliogenesis but is dispensable for
CC centriolar satellite function (By similarity). Required for proper
CC BBSome complex assembly and its ciliary localization (PubMed:22922713).
CC Required for cilia biogenesis and both the assembly and movement of
CC intraflagellar transport proteins along the ciliary axoneme
CC (PubMed:15231740, PubMed:17000880, PubMed:22022287, PubMed:22922713,
CC PubMed:27930654). Plays a role in guanylyl cyclase localization in the
CC ring-like structures at the base of the finger compartment in AFD
CC sensory neurons (PubMed:25335890). {ECO:0000250|UniProtKB:Q8TAM2,
CC ECO:0000269|PubMed:15231740, ECO:0000269|PubMed:17000880,
CC ECO:0000269|PubMed:22022287, ECO:0000269|PubMed:22922713,
CC ECO:0000269|PubMed:25335890, ECO:0000269|PubMed:27930654}.
CC -!- SUBUNIT: Part of BBSome complex, that contains at least bbs-1, bbs-2,
CC bbs-4, bbs-5, osm-12, bbs-8/ttc-8 and bbs-9.
CC {ECO:0000250|UniProtKB:Q8TAM2}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:15231740, ECO:0000269|PubMed:25335890}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:15231740}.
CC Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269|PubMed:15231740}.
CC Note=Localized at the ciliary base and also in ring-like structures
CC between the base of the AFD sensory neuron finger compartment and the
CC dendritic membrane. {ECO:0000269|PubMed:25335890}.
CC -!- TISSUE SPECIFICITY: Expressed in head and tail neurons
CC (PubMed:15231740). Expressed in ciliated male tail-neurons
CC (PubMed:14520415). Expressed in thermosensory and CO(2) sensory AFD
CC neurons (PubMed:25335890). {ECO:0000269|PubMed:14520415,
CC ECO:0000269|PubMed:15231740, ECO:0000269|PubMed:25335890}.
CC -!- DEVELOPMENTAL STAGE: Expressed from the embryonic stage to adulthood.
CC Expressed in embryos from the 1.5-fold stage, with expression
CC increasing to the 3-fold stage. Expressed in ciliated cells including
CC amphid and both inner and outer labial neurons of the head at larval
CC stages L1 and L2. Expressed in both phasmid neurons PHA and PHB in the
CC tail and in the PDE sensory neuron in the mid-body at larval stage L3
CC and L4. {ECO:0000269|PubMed:14520415}.
CC -!- DISRUPTION PHENOTYPE: Mutants have normal body morphology, but with
CC reduced body length and width, delayed larval development and decreased
CC roaming movements (PubMed:22022287). May exhibit defective chemotaxis
CC tendencies (PubMed:15231740). Defective sensory cilia structure and
CC function (PubMed:15231740, PubMed:22022287). This is characterized by
CC increased accumulation and mislocalization of intraflagellar transport
CC proteins and impaired movement of intraflagellar transport proteins
CC such as rab-28 along the ciliary axoneme (PubMed:15231740,
CC PubMed:27930654). Disrupted assembly of the BBSome complex at the base
CC of the cilia (PubMed:22922713). Impaired localization of the guanylyl
CC cyclase proteins, gcy-8, gcy-18 and gcy-23, within AFD sensory neurons,
CC with accumulation along the dendrite as well as in the finger
CC compartment of AFD neurons (PubMed:25335890). Thermotaxis defects and
CC impaired tendencies to migrate to a food source (PubMed:25335890).
CC {ECO:0000269|PubMed:15231740, ECO:0000269|PubMed:22022287,
CC ECO:0000269|PubMed:22922713, ECO:0000269|PubMed:25335890,
CC ECO:0000269|PubMed:27930654}.
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DR EMBL; BX284605; CCD74239.1; -; Genomic_DNA.
DR PIR; T29520; T29520.
DR RefSeq; NP_504711.2; NM_072310.4.
DR AlphaFoldDB; Q23049; -.
DR SMR; Q23049; -.
DR ComplexPortal; CPX-428; BBSome complex.
DR DIP; DIP-26481N; -.
DR STRING; 6239.T25F10.5; -.
DR EPD; Q23049; -.
DR PaxDb; Q23049; -.
DR EnsemblMetazoa; T25F10.5.1; T25F10.5.1; WBGene00000244.
DR GeneID; 188904; -.
DR KEGG; cel:CELE_T25F10.5; -.
DR UCSC; T25F10.5; c. elegans.
DR CTD; 188904; -.
DR WormBase; T25F10.5; CE31071; WBGene00000244; bbs-8.
DR eggNOG; KOG1129; Eukaryota.
DR GeneTree; ENSGT00940000156816; -.
DR HOGENOM; CLU_025029_0_0_1; -.
DR InParanoid; Q23049; -.
DR OMA; QMGVNSA; -.
DR OrthoDB; 637646at2759; -.
DR PhylomeDB; Q23049; -.
DR Reactome; R-CEL-5620922; BBSome-mediated cargo-targeting to cilium.
DR PRO; PR:Q23049; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000244; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0034464; C:BBSome; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0097546; C:ciliary base; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0044292; C:dendrite terminus; IDA:WormBase.
DR GO; GO:0043005; C:neuron projection; IDA:BHF-UCL.
DR GO; GO:0097730; C:non-motile cilium; IDA:WormBase.
DR GO; GO:0006935; P:chemotaxis; IMP:WormBase.
DR GO; GO:0060271; P:cilium assembly; IMP:WormBase.
DR GO; GO:0042073; P:intraciliary transport; IMP:WormBase.
DR GO; GO:1905515; P:non-motile cilium assembly; IEP:BHF-UCL.
DR GO; GO:0008355; P:olfactory learning; IMP:WormBase.
DR GO; GO:1905798; P:positive regulation of intraciliary anterograde transport; IMP:UniProtKB.
DR GO; GO:1905801; P:positive regulation of intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:1903569; P:positive regulation of protein localization to ciliary membrane; IMP:UniProtKB.
DR GO; GO:1904107; P:protein localization to microvillus membrane; IMP:WormBase.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR028796; BBS8.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR44177; PTHR44177; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 7.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 7.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 2: Evidence at transcript level;
KW Cell projection; Cilium; Cilium biogenesis/degradation; Cytoplasm;
KW Cytoskeleton; Protein transport; Reference proteome; Repeat; TPR repeat;
KW Transport.
FT CHAIN 1..506
FT /note="Tetratricopeptide repeat protein 8"
FT /evidence="ECO:0000305"
FT /id="PRO_0000435001"
FT REPEAT 217..250
FT /note="TPR 1"
FT /evidence="ECO:0000255"
FT REPEAT 251..283
FT /note="TPR 2"
FT /evidence="ECO:0000255"
FT REPEAT 284..317
FT /note="TPR 3"
FT /evidence="ECO:0000255"
FT REPEAT 319..351
FT /note="TPR 4"
FT /evidence="ECO:0000255"
FT REPEAT 353..385
FT /note="TPR 5"
FT /evidence="ECO:0000255"
FT REPEAT 388..421
FT /note="TPR 6"
FT /evidence="ECO:0000255"
FT REPEAT 423..455
FT /note="TPR 7"
FT /evidence="ECO:0000255"
FT REPEAT 456..489
FT /note="TPR 8"
FT /evidence="ECO:0000255"
FT REGION 83..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 506 AA; 56304 MW; E72170400424F53B CRC64;
MSGESVIEFT GFIKACRLFR ENRLAEAEAV CTNLLRKNPL DQATWALKMQ CLSDSTYVDE
LENEDMGLAE TFLDQNVIAP NARPGTSFAR PKTSAKGVNP ILRPTTNAGR PLSGVVRPQS
SFKSGSMDQA VRTARTAKTA RAVSSTSARN MRLGTASMAA GADGEFVNLA RLNIDKYAAD
PQVNRQLFEY VFYYLNDIRV AHQIAGTASK AAGFEDYYWK NQLAKCYLRL GMLQDATKQL
QSSLEQKKLI ETFALLSKAY NRVDQPMAAL KTYSAGLEVF PENVTMLTGM ARVQEALGEY
DESVKLYKRV LDAESNNIEA IACVATTYYY GGKPELAMRY YRRILQMGVS SPELFLNIGL
CCMAAQQFDF ALSSILRAQS TMTDDVAADV WYNIGQILVD IGDLVSAARS FRIALSHDPD
HSESLVNLGI LKHREGKIDE ARSLYSSATS KNPYMFEGNY NLGLVSFTQG KYHECRELIE
KALAAFPEHE HCKKILNHLK PLYESI
