BBS4_MOUSE
ID BBS4_MOUSE Reviewed; 520 AA.
AC Q8C1Z7; Q3UYF0; Q562E1; Q5EBJ7; Q8CA57;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Bardet-Biedl syndrome 4 protein homolog;
GN Name=Bbs4;
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 [MRNA].
RX PubMed=12016587; DOI=10.1086/341031;
RA Katsanis N., Eichers E.R., Ansley S.J., Lewis R.A., Kayserili H.,
RA Hoskins B.E., Scambler P.J., Beales P.L., Lupski J.R.;
RT "BBS4 is a minor contributor to Bardet-Biedl syndrome and may also
RT participate in triallelic inheritance.";
RL Am. J. Hum. Genet. 71:22-29(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Pituitary;
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 [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15107855; DOI=10.1038/ng1352;
RA Kim J.C., Badano J.L., Sibold S., Esmail M.A., Hill J., Hoskins B.E.,
RA Leitch C.C., Venner K., Ansley S.J., Ross A.J., Leroux M.R., Katsanis N.,
RA Beales P.L.;
RT "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region
RT and is required for microtubule anchoring and cell cycle progression.";
RL Nat. Genet. 36:462-470(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=18317593; DOI=10.1172/jci32357;
RA Rahmouni K., Fath M.A., Seo S., Thedens D.R., Berry C.J., Weiss R.,
RA Nishimura D.Y., Sheffield V.C.;
RT "Leptin resistance contributes to obesity and hypertension in mouse models
RT of Bardet-Biedl syndrome.";
RL J. Clin. Invest. 118:1458-1467(2008).
RN [6]
RP IDENTIFICATION IN THE BBSOME COMPLEX, DISRUPTION PHENOTYPE, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [7]
RP SUBCELLULAR LOCATION.
RX PubMed=23943788; DOI=10.1093/hmg/ddt394;
RA Zhang Y., Seo S., Bhattarai S., Bugge K., Searby C.C., Zhang Q.,
RA Drack A.V., Stone E.M., Sheffield V.C.;
RT "BBS mutations modify phenotypic expression of CEP290-related
RT ciliopathies.";
RL Hum. Mol. Genet. 23:40-51(2014).
RN [8]
RP INTERACTION WITH C2CD3.
RX PubMed=24469809; DOI=10.1073/pnas.1318737111;
RA Ye X., Zeng H., Ning G., Reiter J.F., Liu A.;
RT "C2cd3 is critical for centriolar distal appendage assembly and ciliary
RT vesicle docking in mammals.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2164-2169(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.
CC Required for microtubule anchoring at the centrosome but not for
CC microtubule nucleation. May be required for the dynein-mediated
CC transport of pericentriolar proteins to the centrosome (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5,
CC BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1 and DCTN1.
CC Interacts with DC28B. Interacts with ALDOB and C2CD3. Interacts with
CC PKD1 (By similarity). Interacts with CEP290 (By similarity). Interacts
CC with DLEC1 (By similarity). {ECO:0000250|UniProtKB:Q96RK4,
CC ECO:0000269|PubMed:22072986, ECO:0000269|PubMed:24469809}.
CC -!- INTERACTION:
CC Q8C1Z7; Q3V3N7: Bbs1; NbExp=5; IntAct=EBI-2892887, EBI-2892836;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250}. Cell projection, cilium membrane
CC {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriolar satellite
CC {ECO:0000250}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:15107855, ECO:0000269|PubMed:22072986}. Cell
CC projection, cilium {ECO:0000269|PubMed:23943788}. Note=Localizes to the
CC pericentriolar material. Centrosomal localization requires dynein (By
CC similarity). Localizes to the connecting cilium of photoreceptor cells
CC (PubMed:23943788).
CC -!- TISSUE SPECIFICITY: Expressed in the hippocampus and dentate gyrus, the
CC columnar epithelial cells of bronchioles, the olfactory epithelium and
CC the inner segment and outer nuclear layer of the retina. Expressed in
CC testis. {ECO:0000269|PubMed:15107855, ECO:0000269|PubMed:22072986}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the pericardium of the developing
CC embryo and in the epidermal layer surrounding the digits.
CC {ECO:0000269|PubMed:15107855}.
CC -!- DISRUPTION PHENOTYPE: Males are sterile due to a loss of sperm
CC flagella. In mice obesity is associated with hyperleptinemia and
CC resistance to the anorectic and weight-reducing effects of leptin.
CC Although mice are resistant to the metabolic actions of leptin, animals
CC remain responsive to the effects of leptin on renal sympathetic nerve
CC activity and arterial pressure and developed hypertension. BBS mice
CC have decreased hypothalamic expression of proopiomelanocortin (POMC).
CC BBS genes play an important role in maintaining leptin sensitivity in
CC POMC neurons. {ECO:0000269|PubMed:18317593,
CC ECO:0000269|PubMed:22072986}.
CC -!- SIMILARITY: Belongs to the BBS4 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; AK039560; BAC30384.1; -; mRNA.
DR EMBL; AK089970; BAC41021.1; -; mRNA.
DR EMBL; AK134734; BAE22262.1; -; mRNA.
DR EMBL; BC055797; AAH55797.1; -; mRNA.
DR EMBL; BC089507; AAH89507.1; ALT_TERM; mRNA.
DR EMBL; BC092531; AAH92531.1; ALT_TERM; mRNA.
DR CCDS; CCDS40658.1; -.
DR RefSeq; NP_780534.1; NM_175325.3.
DR AlphaFoldDB; Q8C1Z7; -.
DR SMR; Q8C1Z7; -.
DR BioGRID; 221946; 3.
DR ComplexPortal; CPX-1909; BBSome complex.
DR DIP; DIP-60352N; -.
DR IntAct; Q8C1Z7; 5.
DR STRING; 10090.ENSMUSP00000026265; -.
DR iPTMnet; Q8C1Z7; -.
DR PhosphoSitePlus; Q8C1Z7; -.
DR MaxQB; Q8C1Z7; -.
DR PaxDb; Q8C1Z7; -.
DR PRIDE; Q8C1Z7; -.
DR ProteomicsDB; 273547; -.
DR Antibodypedia; 26730; 290 antibodies from 32 providers.
DR Ensembl; ENSMUST00000026265; ENSMUSP00000026265; ENSMUSG00000025235.
DR GeneID; 102774; -.
DR KEGG; mmu:102774; -.
DR UCSC; uc009pxr.2; mouse.
DR CTD; 585; -.
DR MGI; MGI:2143311; Bbs4.
DR VEuPathDB; HostDB:ENSMUSG00000025235; -.
DR eggNOG; KOG1124; Eukaryota.
DR GeneTree; ENSGT00940000158166; -.
DR HOGENOM; CLU_033477_1_0_1; -.
DR InParanoid; Q8C1Z7; -.
DR OMA; WNNIGAC; -.
DR OrthoDB; 609083at2759; -.
DR PhylomeDB; Q8C1Z7; -.
DR TreeFam; TF324966; -.
DR Reactome; R-MMU-5620922; BBSome-mediated cargo-targeting to cilium.
DR BioGRID-ORCS; 102774; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Bbs4; mouse.
DR PRO; PR:Q8C1Z7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8C1Z7; protein.
DR Bgee; ENSMUSG00000025235; Expressed in primary oocyte and 228 other tissues.
DR ExpressionAtlas; Q8C1Z7; baseline and differential.
DR Genevisible; Q8C1Z7; MM.
DR GO; GO:0034464; C:BBSome; IDA:MGI.
DR GO; GO:0034451; C:centriolar satellite; IDA:MGI.
DR GO; GO:0005814; C:centriole; ISO:MGI.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0060170; C:ciliary membrane; ISO:MGI.
DR GO; GO:0035869; C:ciliary transition zone; ISO:MGI.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0031514; C:motile cilium; IMP:BHF-UCL.
DR GO; GO:0097730; C:non-motile cilium; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:GOC.
DR GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:MGI.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:MGI.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:MGI.
DR GO; GO:0043014; F:alpha-tubulin binding; ISO:MGI.
DR GO; GO:0048487; F:beta-tubulin binding; ISO:MGI.
DR GO; GO:0034452; F:dynactin binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0030534; P:adult behavior; IMP:MGI.
DR GO; GO:0048854; P:brain morphogenesis; IMP:MGI.
DR GO; GO:0007098; P:centrosome cycle; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:BHF-UCL.
DR GO; GO:0016358; P:dendrite development; IMP:MGI.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IEP:BHF-UCL.
DR GO; GO:0060613; P:fat pad development; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; IMP:MGI.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; ISO:MGI.
DR GO; GO:0034454; P:microtubule anchoring at centrosome; ISO:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:MGI.
DR GO; GO:0000281; P:mitotic cytokinesis; ISO:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:MGI.
DR GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:MGI.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:MGI.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IMP:MGI.
DR GO; GO:0045724; P:positive regulation of cilium assembly; IMP:MGI.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0071539; P:protein localization to centrosome; ISO:MGI.
DR GO; GO:0061512; P:protein localization to cilium; ISO:MGI.
DR GO; GO:0033365; P:protein localization to organelle; IDA:BHF-UCL.
DR GO; GO:1903546; P:protein localization to photoreceptor outer segment; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; IMP:BHF-UCL.
DR GO; GO:0032465; P:regulation of cytokinesis; ISO:MGI.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:MGI.
DR GO; GO:1902855; P:regulation of non-motile cilium assembly; IMP:MGI.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IMP:MGI.
DR GO; GO:0044321; P:response to leptin; IMP:MGI.
DR GO; GO:0001895; P:retina homeostasis; IMP:MGI.
DR GO; GO:0046548; P:retinal rod cell development; IMP:MGI.
DR GO; GO:0007608; P:sensory perception of smell; IMP:MGI.
DR GO; GO:0035176; P:social behavior; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR GO; GO:0021756; P:striatum development; IMP:MGI.
DR GO; GO:0021591; P:ventricular system development; IMP:MGI.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR028786; BBS4.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR44186; PTHR44186; 1.
DR Pfam; PF13181; TPR_8; 2.
DR SMART; SM00028; TPR; 8.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50005; TPR; 8.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Flagellum; Membrane; Protein transport;
KW Reference proteome; Repeat; TPR repeat; Transport.
FT CHAIN 1..520
FT /note="Bardet-Biedl syndrome 4 protein homolog"
FT /id="PRO_0000106264"
FT REPEAT 67..100
FT /note="TPR 1"
FT REPEAT 102..134
FT /note="TPR 2"
FT REPEAT 135..167
FT /note="TPR 3"
FT REPEAT 168..201
FT /note="TPR 4"
FT REPEAT 203..235
FT /note="TPR 5"
FT REPEAT 237..269
FT /note="TPR 6"
FT REPEAT 270..303
FT /note="TPR 7"
FT REPEAT 304..337
FT /note="TPR 8"
FT REPEAT 339..371
FT /note="TPR 9"
FT REPEAT 373..408
FT /note="TPR 10"
FT REGION 1..66
FT /note="Required for localization to centrosomes"
FT /evidence="ECO:0000250"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..337
FT /note="Interaction with PCM1"
FT /evidence="ECO:0000250"
FT REGION 338..520
FT /note="Required for localization to centrosomes"
FT /evidence="ECO:0000250"
FT REGION 488..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 515
FT /note="E -> V (in Ref. 3; AAH92531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 58255 MW; 70640E41509F2479 CRC64;
MAEVKLGMKT QVPASVESQK PRSKKAPDFP IVEKQNWLIH LHYIRKDYEA CKAVIKEQLQ
ETQGLCEYAI YVQALIFRLE GNIQESLELF QTCAVLSPQC ADNLKQVARS LFLLGKHKAA
TEVYNEAAKL NQKDWEICHN LGVCYTYLKQ FNKAQDQLHS ALQLNKHDLT YIMLGKIHLL
QGDLDKAIEI YKKAVEFSPE NTELLTTLGL LYLQLGVYQK AFEHLGNALT YDPANYKAIL
AAGSMMQTHG DFDVALTKYR VVACAIPESP PLWNNIGMCF FGKKKYVAAI SCLKRANYLA
PFDWKILYNL GLVHLTMQQY ASAFHFLSAA INFQPKMGEL YMLLAVALTN LEDIENARRA
YVEAVRLDKC NPLVNLNYAV LLYNQGEKKS ALAQYQEMEK KVNFLKDNSP LEFDSEMVEM
AQKLGAALQV GEALVWTKPV KDPKTKHRTN SGSKSATLQQ PLGSIQALGQ AMSSAAAYRK
ILSGAVGAQL PKPPSLPLEP EPEPTVEASP TEASEQKKEK
