BBS5_HUMAN
ID BBS5_HUMAN Reviewed; 341 AA.
AC Q8N3I7; D3DPC3; Q6PKN0;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Bardet-Biedl syndrome 5 protein;
GN Name=BBS5;
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 [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN BBS5, AND
RP VARIANTS SER-184 AND HIS-207.
RX PubMed=15137946; DOI=10.1016/s0092-8674(04)00450-7;
RA Li J.B., Gerdes J.M., Haycraft C.J., Fan Y., Teslovich T.M., May-Simera H.,
RA Li H., Blacque O.E., Li L., Leitch C.C., Lewis R.A., Green J.S.,
RA Parfrey P.S., Leroux M.R., Davidson W.S., Beales P.L., Guay-Woodford L.M.,
RA Yoder B.K., Stormo G.D., Katsanis N., Dutcher S.K.;
RT "Comparative genomics identifies a flagellar and basal body proteome that
RT includes the BBS5 human disease gene.";
RL Cell 117:541-552(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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=Testis;
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 INTERACTION WITH CCDC28B.
RX PubMed=16327777; DOI=10.1038/nature04370;
RA Badano J.L., Leitch C.C., Ansley S.J., May-Simera H., Lawson S.,
RA Lewis R.A., Beales P.L., Dietz H.C., Fisher S., Katsanis N.;
RT "Dissection of epistasis in oligogenic Bardet-Biedl syndrome.";
RL Nature 439:326-330(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, FUNCTION, SUBCELLULAR
RP LOCATION, AND BINDING TO PHOSPHOINOSITIDES.
RX PubMed=17574030; DOI=10.1016/j.cell.2007.03.053;
RA Nachury M.V., Loktev A.V., Zhang Q., Westlake C.J., Peraenen J., Merdes A.,
RA Slusarski D.C., Scheller R.H., Bazan J.F., Sheffield V.C., Jackson P.K.;
RT "A core complex of BBS proteins cooperates with the GTPase Rab8 to promote
RT ciliary membrane biogenesis.";
RL Cell 129:1201-1213(2007).
RN [8]
RP FUNCTION, FUNCTION OF THE BBSOME COMPLEX, IDENTIFICATION IN THE BBSOME
RP COMPLEX, INTERACTION WITH SMO, AND SUBCELLULAR LOCATION.
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 [9]
RP INTERACTION WITH PKD1.
RX PubMed=24939912; DOI=10.1093/hmg/ddu267;
RA Su X., Driscoll K., Yao G., Raed A., Wu M., Beales P.L., Zhou J.;
RT "Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of
RT polycystic kidney disease 1 protein.";
RL Hum. Mol. Genet. 23:5441-5451(2014).
RN [10]
RP INTERACTION WITH DLEC1.
RX PubMed=33144677; DOI=10.1038/s41598-020-75957-y;
RA Okitsu Y., Nagano M., Yamagata T., Ito C., Toshimori K., Dohra H.,
RA Fujii W., Yogo K.;
RT "Dlec1 is required for spermatogenesis and male fertility in mice.";
RL Sci. Rep. 10:18883-18883(2020).
RN [11]
RP VARIANTS BBS5 SER-72 AND ALA-183.
RX PubMed=18203199; DOI=10.1002/ajmg.a.32136;
RA Hjortshoj T.D., Gronskov K., Philp A.R., Nishimura D.Y., Adeyemo A.,
RA Rotimi C.N., Sheffield V.C., Rosenberg T., Brondum-Nielsen K.;
RT "Novel mutations in BBS5 highlight the importance of this gene in non-
RT Caucasian Bardet-Biedl syndrome patients.";
RL Am. J. Med. Genet. A 146A:517-520(2008).
RN [12]
RP VARIANT BBS5 SER-72, AND VARIANTS SER-184 AND ASP-251.
RX PubMed=21344540; DOI=10.1002/humu.21480;
RA Deveault C., Billingsley G., Duncan J.L., Bin J., Theal R., Vincent A.,
RA Fieggen K.J., Gerth C., Noordeh N., Traboulsi E.I., Fishman G.A.,
RA Chitayat D., Knueppel T., Millan J.M., Munier F.L., Kennedy D.,
RA Jacobson S.G., Innes A.M., Mitchell G.A., Boycott K., Heon E.;
RT "BBS genotype-phenotype assessment of a multiethnic patient cohort calls
RT for a revision of the disease definition.";
RL Hum. Mutat. 32:610-619(2011).
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 BBSome complex ciliary localization but not for the proper complex
CC assembly. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
CC -!- SUBUNIT: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5,
CC BBS7, BBS8/TTC8, BBS9 and BBIP10. Binds to phosphoinositides. Interacts
CC with CCDC28B. Interacts with SMO; the interaction is indicative for the
CC association of SMO with the BBsome complex to facilitate ciliary
CC localization of SMO. Interacts with PKD1 (PubMed:24939912). Interacts
CC with DLEC1 (PubMed:33144677). {ECO:0000269|PubMed:16327777,
CC ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986,
CC ECO:0000269|PubMed:24939912, ECO:0000269|PubMed:33144677}.
CC -!- INTERACTION:
CC Q8N3I7; Q3SYG4: BBS9; NbExp=6; IntAct=EBI-2892592, EBI-2826852;
CC Q8N3I7; P78560: CRADD; NbExp=3; IntAct=EBI-2892592, EBI-520375;
CC Q8N3I7; Q15051: IQCB1; NbExp=8; IntAct=EBI-2892592, EBI-2805823;
CC Q8N3I7; Q6P597: KLC3; NbExp=3; IntAct=EBI-2892592, EBI-1643885;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane. Cytoplasm.
CC Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome, centriolar
CC satellite. Note=Localizes to basal bodies. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N3I7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N3I7-2; Sequence=VSP_017240;
CC -!- DISEASE: Bardet-Biedl syndrome 5 (BBS5) [MIM:615983]: A syndrome
CC characterized by usually severe pigmentary retinopathy, early-onset
CC obesity, polydactyly, hypogenitalism, renal malformation and
CC intellectual disability. Secondary features include diabetes mellitus,
CC hypertension and congenital heart disease. Bardet-Biedl syndrome
CC inheritance is autosomal recessive, but three mutated alleles (two at
CC one locus, and a third at a second locus) may be required for clinical
CC manifestation of some forms of the disease.
CC {ECO:0000269|PubMed:15137946, ECO:0000269|PubMed:18203199,
CC ECO:0000269|PubMed:21344540}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: BBS5 may interact genetically with BBS1.
CC -!- SIMILARITY: Belongs to the BBS5 family. {ECO:0000305}.
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DR EMBL; AY604003; AAT08182.1; -; mRNA.
DR EMBL; AY604004; AAT08183.1; -; mRNA.
DR EMBL; AL834305; CAD38975.1; -; mRNA.
DR EMBL; AC093899; AAY24116.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11276.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11279.1; -; Genomic_DNA.
DR EMBL; BC044593; AAH44593.1; -; mRNA.
DR CCDS; CCDS2233.1; -. [Q8N3I7-1]
DR RefSeq; NP_689597.1; NM_152384.2. [Q8N3I7-1]
DR PDB; 6XTB; EM; 4.30 A; E=1-341.
DR PDBsum; 6XTB; -.
DR AlphaFoldDB; Q8N3I7; -.
DR SMR; Q8N3I7; -.
DR BioGRID; 126215; 16.
DR ComplexPortal; CPX-1908; BBSome complex.
DR CORUM; Q8N3I7; -.
DR DIP; DIP-60357N; -.
DR IntAct; Q8N3I7; 21.
DR STRING; 9606.ENSP00000295240; -.
DR iPTMnet; Q8N3I7; -.
DR PhosphoSitePlus; Q8N3I7; -.
DR BioMuta; BBS5; -.
DR DMDM; 74750959; -.
DR EPD; Q8N3I7; -.
DR MassIVE; Q8N3I7; -.
DR MaxQB; Q8N3I7; -.
DR PaxDb; Q8N3I7; -.
DR PeptideAtlas; Q8N3I7; -.
DR PRIDE; Q8N3I7; -.
DR ProteomicsDB; 71805; -. [Q8N3I7-1]
DR ProteomicsDB; 71806; -. [Q8N3I7-2]
DR ABCD; Q8N3I7; 1 sequenced antibody.
DR Antibodypedia; 35007; 141 antibodies from 27 providers.
DR DNASU; 129880; -.
DR Ensembl; ENST00000295240.8; ENSP00000295240.3; ENSG00000163093.12. [Q8N3I7-1]
DR Ensembl; ENST00000392663.6; ENSP00000376431.2; ENSG00000163093.12. [Q8N3I7-2]
DR GeneID; 129880; -.
DR KEGG; hsa:129880; -.
DR MANE-Select; ENST00000295240.8; ENSP00000295240.3; NM_152384.3; NP_689597.1.
DR UCSC; uc002uet.4; human. [Q8N3I7-1]
DR CTD; 129880; -.
DR DisGeNET; 129880; -.
DR GeneCards; BBS5; -.
DR GeneReviews; BBS5; -.
DR HGNC; HGNC:970; BBS5.
DR HPA; ENSG00000163093; Low tissue specificity.
DR MalaCards; BBS5; -.
DR MIM; 603650; gene.
DR MIM; 615983; phenotype.
DR neXtProt; NX_Q8N3I7; -.
DR OpenTargets; ENSG00000163093; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR PharmGKB; PA25279; -.
DR VEuPathDB; HostDB:ENSG00000163093; -.
DR eggNOG; ENOG502QR2Z; Eukaryota.
DR GeneTree; ENSGT00390000002753; -.
DR HOGENOM; CLU_052113_0_0_1; -.
DR InParanoid; Q8N3I7; -.
DR OMA; PNFGIQY; -.
DR PhylomeDB; Q8N3I7; -.
DR TreeFam; TF106129; -.
DR PathwayCommons; Q8N3I7; -.
DR Reactome; R-HSA-5620922; BBSome-mediated cargo-targeting to cilium.
DR SignaLink; Q8N3I7; -.
DR SIGNOR; Q8N3I7; -.
DR BioGRID-ORCS; 129880; 21 hits in 1039 CRISPR screens.
DR ChiTaRS; BBS5; human.
DR GeneWiki; BBS5; -.
DR GenomeRNAi; 129880; -.
DR Pharos; Q8N3I7; Tbio.
DR PRO; PR:Q8N3I7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8N3I7; protein.
DR Bgee; ENSG00000163093; Expressed in right uterine tube and 103 other tissues.
DR ExpressionAtlas; Q8N3I7; baseline and differential.
DR Genevisible; Q8N3I7; HS.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0034464; C:BBSome; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; ISS:BHF-UCL.
DR GO; GO:0060170; C:ciliary membrane; IDA:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:BHF-UCL.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0046907; P:intracellular transport; IBA:GO_Central.
DR GO; GO:0032402; P:melanosome transport; ISS:BHF-UCL.
DR GO; GO:0044458; P:motile cilium assembly; ISS:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR006606; BBL5.
DR InterPro; IPR030804; BBS5/fem-3.
DR InterPro; IPR014003; DM16_repeat.
DR InterPro; IPR011993; PH-like_dom_sf.
DR PANTHER; PTHR21351; PTHR21351; 1.
DR Pfam; PF07289; BBL5; 1.
DR PIRSF; PIRSF010072; DUF1448; 1.
DR SMART; SM00683; DM16; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Bardet-Biedl syndrome; Cell membrane;
KW Cell projection; Ciliopathy; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Disease variant; Intellectual disability;
KW Membrane; Obesity; Protein transport; Reference proteome;
KW Sensory transduction; Transport; Vision.
FT CHAIN 1..341
FT /note="Bardet-Biedl syndrome 5 protein"
FT /id="PRO_0000223254"
FT VAR_SEQ 207..227
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15137946"
FT /id="VSP_017240"
FT VARIANT 72
FT /note="G -> S (in BBS5; dbSNP:rs121908581)"
FT /evidence="ECO:0000269|PubMed:18203199,
FT ECO:0000269|PubMed:21344540"
FT /id="VAR_066290"
FT VARIANT 183
FT /note="T -> A (in BBS5; found in patient of Sri Lankan
FT origin; not detected in patients of Northern European
FT origin; dbSNP:rs121908582)"
FT /evidence="ECO:0000269|PubMed:18203199"
FT /id="VAR_072380"
FT VARIANT 184
FT /note="N -> S (found in patients with Bardet-Biedl syndrome
FT carrying homozygous mutations in other BBS genes; might
FT have a modifying effect on disease phenotype;
FT dbSNP:rs137853921)"
FT /evidence="ECO:0000269|PubMed:15137946,
FT ECO:0000269|PubMed:21344540"
FT /id="VAR_025316"
FT VARIANT 207
FT /note="R -> H (found as heterozygous variant in patients
FT with Bardet-Biedl syndrome; might have a modifying effect
FT on disease phenotype; dbSNP:rs35487251)"
FT /evidence="ECO:0000269|PubMed:15137946"
FT /id="VAR_025317"
FT VARIANT 251
FT /note="N -> D (in dbSNP:rs143113298)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066291"
SQ SEQUENCE 341 AA; 38755 MW; 63D67D877FDFD25B CRC64;
MSVLDALWED RDVRFDLSAQ QMKTRPGEVL IDCLDSIEDT KGNNGDRGRL LVTNLRILWH
SLALSRVNVS VGYNCILNIT TRTANSKLRG QTEALYILTK CNSTRFEFIF TNLVPGSPRL
FTSVMAVHRA YETSKMYRDF KLRSALIQNK QLRLLPQEHV YDKINGVWNL SSDQGNLGTF
FITNVRIVWH ANMNDSFNVS IPYLQIRSIK IRDSKFGLAL VIESSQQSGG YVLGFKIDPV
EKLQESVKEI NSLHKVYSAS PIFGVDYEME EKPQPLEALT VEQIQDDVEI DSDGHTDAFV
AYFADGNKQQ DREPVFSEEL GLAIEKLKDG FTLQGLWEVM S
