ID   TTC8_MOUSE              Reviewed;         515 AA.
AC   Q8VD72; Q9DCP7;
DT   19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   24-JAN-2024, entry version 168.
DE   RecName: Full=Tetratricopeptide repeat protein 8;
DE            Short=TPR repeat protein 8;
DE   AltName: Full=Bardet-Biedl syndrome 8 protein homolog;
GN   Name=Ttc8; Synonyms=Bbs8;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Head, and Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Retina;
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   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   [4]
RP   IDENTIFICATION IN THE BBSOME COMPLEX.
RX   PubMed=22072986; DOI=10.1371/journal.pgen.1002358;
RA   Seo S., Zhang Q., Bugge K., Breslow D.K., Searby C.C., Nachury M.V.,
RA   Sheffield V.C.;
RT   "A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and
RT   Smoothened.";
RL   PLoS Genet. 7:E1002358-E1002358(2011).
RN   [5]
RP   IDENTIFICATION OF ISOFORM 2, AND TISSUE SPECIFICITY.
RX   PubMed=20451172; DOI=10.1016/j.ajhg.2010.04.001;
RA   Riazuddin S.A., Iqbal M., Wang Y., Masuda T., Chen Y., Bowne S.,
RA   Sullivan L.S., Waseem N.H., Bhattacharya S., Daiger S.P., Zhang K.,
RA   Khan S.N., Riazuddin S., Hejtmancik J.F., Sieving P.A., Zack D.J.,
RA   Katsanis N.;
RT   "A splice-site mutation in a retina-specific exon of BBS8 causes
RT   nonsyndromic retinitis pigmentosa.";
RL   Am. J. Hum. Genet. 86:805-812(2010).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=25243405; DOI=10.1371/journal.pone.0108470;
RA   Broekhuis J.R., Verhey K.J., Jansen G.;
RT   "Regulation of cilium length and intraflagellar transport by the RCK-
RT   kinases ICK and MOK in renal epithelial cells.";
RL   PLoS ONE 9:E108470-E108470(2014).
CC   -!- FUNCTION: The BBSome complex is thought to function as a coat complex
CC       required for sorting of specific membrane proteins to the primary
CC       cilia. The BBSome complex is required for ciliogenesis but is
CC       dispensable for centriolar satellite function. This ciliogenic function
CC       is mediated in part by the Rab8 GDP/GTP exchange factor, which
CC       localizes to the basal body and contacts the BBSome. Rab8(GTP) enters
CC       the primary cilium and promotes extension of the ciliary membrane.
CC       Firstly the BBSome associates with the ciliary membrane and binds to
CC       RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the
CC       Rab8-GTP localizes to the cilium and promotes docking and fusion of
CC       carrier vesicles to the base of the ciliary membrane. The BBSome
CC       complex, together with the LTZL1, controls SMO ciliary trafficking and
CC       contributes to the sonic hedgehog (SHH) pathway regulation. Required
CC       for proper BBSome complex assembly and its ciliary localization (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5,
CC       BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1. Interacts with
CC       CCDC28B. Interacts with PKD1. {ECO:0000250|UniProtKB:Q8TAM2,
CC       ECO:0000269|PubMed:22072986}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC       center, centrosome, centriole {ECO:0000250|UniProtKB:Q8TAM2}. Cell
CC       projection, cilium membrane {ECO:0000250|UniProtKB:Q8TAM2}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q8TAM2}. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome, centriolar satellite
CC       {ECO:0000250|UniProtKB:Q8TAM2}. Cell projection, cilium
CC       {ECO:0000269|PubMed:25243405}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8VD72-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8VD72-2; Sequence=VSP_007825;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is retina-specific whereas isoform 2 is
CC       ubiquitously expressed. {ECO:0000269|PubMed:20451172}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at 12 dpc in ciliated structures,
CC       including maturing (stages X and XI) spermatids, the connecting cilium
CC       of the retina and bronchial epithelial cells. At 14 and 16 dpc,
CC       detected in the telencephalon, with prominent expression at the
CC       developing ependymal cell layer and the olfactory epithelium.
CC       {ECO:0000269|PubMed:14520415}.
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DR   EMBL; AK002597; BAB22218.1; -; mRNA.
DR   EMBL; AK081697; BAC38298.1; -; mRNA.
DR   EMBL; BC017523; AAH17523.1; -; mRNA.
DR   CCDS; CCDS26101.1; -. [Q8VD72-2]
DR   CCDS; CCDS26102.1; -. [Q8VD72-1]
DR   RefSeq; NP_083829.1; NM_029553.3. [Q8VD72-2]
DR   RefSeq; NP_938053.1; NM_198311.1. [Q8VD72-1]
DR   AlphaFoldDB; Q8VD72; -.
DR   SMR; Q8VD72; -.
DR   BioGRID; 218052; 1.
DR   ComplexPortal; CPX-1909; BBSome complex.
DR   DIP; DIP-60354N; -.
DR   IntAct; Q8VD72; 4.
DR   STRING; 10090.ENSMUSP00000078148; -.
DR   iPTMnet; Q8VD72; -.
DR   PhosphoSitePlus; Q8VD72; -.
DR   MaxQB; Q8VD72; -.
DR   PaxDb; 10090-ENSMUSP00000078148; -.
DR   ProteomicsDB; 300158; -. [Q8VD72-1]
DR   ProteomicsDB; 300159; -. [Q8VD72-2]
DR   Pumba; Q8VD72; -.
DR   Antibodypedia; 141; 248 antibodies from 30 providers.
DR   DNASU; 76260; -.
DR   Ensembl; ENSMUST00000079146.13; ENSMUSP00000078148.7; ENSMUSG00000021013.17. [Q8VD72-1]
DR   Ensembl; ENSMUST00000085109.10; ENSMUSP00000082190.4; ENSMUSG00000021013.17. [Q8VD72-2]
DR   GeneID; 76260; -.
DR   KEGG; mmu:76260; -.
DR   UCSC; uc007oro.2; mouse. [Q8VD72-1]
DR   UCSC; uc007orp.2; mouse. [Q8VD72-2]
DR   AGR; MGI:1923510; -.
DR   CTD; 123016; -.
DR   MGI; MGI:1923510; Ttc8.
DR   VEuPathDB; HostDB:ENSMUSG00000021013; -.
DR   eggNOG; KOG1129; Eukaryota.
DR   GeneTree; ENSGT00940000156816; -.
DR   HOGENOM; CLU_025029_0_0_1; -.
DR   InParanoid; Q8VD72; -.
DR   OMA; QMGVNSA; -.
DR   OrthoDB; 1328318at2759; -.
DR   PhylomeDB; Q8VD72; -.
DR   TreeFam; TF314892; -.
DR   Reactome; R-MMU-5620922; BBSome-mediated cargo-targeting to cilium.
DR   BioGRID-ORCS; 76260; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Ttc8; mouse.
DR   PRO; PR:Q8VD72; -.
DR   Proteomes; UP000000589; Chromosome 12.
DR   RNAct; Q8VD72; Protein.
DR   Bgee; ENSMUSG00000021013; Expressed in retinal neural layer and 242 other cell types or tissues.
DR   ExpressionAtlas; Q8VD72; baseline and differential.
DR   GO; GO:0034464; C:BBSome; IDA:UniProtKB.
DR   GO; GO:0034451; C:centriolar satellite; IEA:UniProtKB-SubCell.
DR   GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR   GO; GO:0005813; C:centrosome; ISO:MGI.
DR   GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR   GO; GO:0060170; C:ciliary membrane; ISO:MGI.
DR   GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0097730; C:non-motile cilium; IBA:GO_Central.
DR   GO; GO:0032391; C:photoreceptor connecting cilium; IDA:BHF-UCL.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0007411; P:axon guidance; IGI:MGI.
DR   GO; GO:0060219; P:camera-type eye photoreceptor cell differentiation; IMP:MGI.
DR   GO; GO:0060271; P:cilium assembly; IMP:FlyBase.
DR   GO; GO:0048560; P:establishment of anatomical structure orientation; ISO:MGI.
DR   GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:MGI.
DR   GO; GO:0001736; P:establishment of planar polarity; IMP:MGI.
DR   GO; GO:0045444; P:fat cell differentiation; IEP:BHF-UCL.
DR   GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IMP:MGI.
DR   GO; GO:1903251; P:multi-ciliated epithelial cell differentiation; IMP:MGI.
DR   GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR   GO; GO:1905515; P:non-motile cilium assembly; IBA:GO_Central.
DR   GO; GO:0021772; P:olfactory bulb development; IMP:MGI.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR   GO; GO:0051492; P:regulation of stress fiber assembly; IMP:MGI.
DR   GO; GO:0061326; P:renal tubule development; IMP:MGI.
DR   GO; GO:0007608; P:sensory perception of smell; IMP:MGI.
DR   CDD; cd21341; TTC8_N; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 2.
DR   InterPro; IPR028796; BBS8.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   InterPro; IPR019734; TPR_repeat.
DR   PANTHER; PTHR44177; TETRATRICOPEPTIDE REPEAT PROTEIN 8; 1.
DR   PANTHER; PTHR44177:SF1; TETRATRICOPEPTIDE REPEAT PROTEIN 8; 1.
DR   Pfam; PF13432; TPR_16; 1.
DR   Pfam; PF13181; TPR_8; 1.
DR   SMART; SM00028; TPR; 7.
DR   SUPFAM; SSF48452; TPR-like; 1.
DR   PROSITE; PS50005; TPR; 6.
DR   PROSITE; PS50293; TPR_REGION; 2.
DR   Genevisible; Q8VD72; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cell projection; Cilium;
KW   Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Membrane;
KW   Protein transport; Reference proteome; Repeat; TPR repeat; Transport.
FT   CHAIN           1..515
FT                   /note="Tetratricopeptide repeat protein 8"
FT                   /id="PRO_0000106389"
FT   REPEAT          4..37
FT                   /note="TPR 1"
FT   REPEAT          225..258
FT                   /note="TPR 2"
FT   REPEAT          259..291
FT                   /note="TPR 3"
FT   REPEAT          292..325
FT                   /note="TPR 4"
FT   REPEAT          326..359
FT                   /note="TPR 5"
FT   REPEAT          360..393
FT                   /note="TPR 6"
FT   REPEAT          397..430
FT                   /note="TPR 7"
FT   REPEAT          432..464
FT                   /note="TPR 8"
FT   REGION          89..109
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          118..137
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        93..109
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        120..135
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         38..47
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_007825"
SQ   SEQUENCE   515 AA;  58440 MW;  9A8ACDF59BB641C1 CRC64;
     MGSEMEPLLR AWSYFRRRKF QLCADLCTQM LEKSPYDQEP APDLPVSQAA WILKARALTE
     MVYIDEIDVD QEGIAEMILD ENAIAQVPRP GTSLKLPGTN QTGGPTQAVR PITQAGRPIT
     GFLRPSTQSG RPGTMEQAIR TPRTAYTARP ITSSSGRFVR LGTASMLTSP DGPFINLSRL
     NLTKYSQKPK LAKALFEYIL HHENDVKMAL DLASLSTEYS QYKDWWWKVQ IGKCYYRLGM
     YREAEKQFKS ALKQQEMVDT FLYLAKVYII LDQPVTALNL FKQGLDKFPG EVTLLCGIAR
     IYEEMNNSSS AAEYYKEVLK QDNTHVEAIA CIGSNHFYSD QPEVALRFYR RLLQMGVYNC
     QLFNNLGLCC FYAQQYDMTL TSFERALSLA ENEEEAADVW YNLGHIAVGI GDTNLAHQCF
     RLALVHNNHH AEAYNNLAVL EMRKGHVEQA RALLQTASSL APHMYEPHFN FATVSDKIGD
     LQRSYVAAQK SEVAFPEHVD TQHLIKQLKQ HFAML
//