BBS4_HUMAN
ID BBS4_HUMAN Reviewed; 519 AA.
AC Q96RK4; B4E178; Q53DZ5; Q8NHU9; Q96H45;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Bardet-Biedl syndrome 4 protein;
GN Name=BBS4;
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] (ISOFORM 1), AND VARIANT BBS4 PRO-295.
RX PubMed=11381270; DOI=10.1038/88925;
RA Mykytyn K., Braun T., Carmi R., Haider N.B., Searby C.C., Shastri M.,
RA Beck G., Wright A.F., Iannaccone A., Elbedour K., Riise R., Baldi A.,
RA Raas-Rothschild A., Gorman S.W., Duhl D.M., Jacobson S.G., Casavant T.,
RA Stone E.M., Sheffield V.C.;
RT "Identification of the gene that, when mutated, causes the human obesity
RT syndrome BBS4.";
RL Nat. Genet. 28:188-191(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=15497446; DOI=10.1080/10425170410001679165;
RA Ye X., Dai J., Fang W., Jin W., Guo Y., Song J., Ji C., Gu S., Xie Y.,
RA Mao Y.;
RT "Cloning and characterization of a splice variant of human Bardet-Biedl
RT syndrome 4 gene (BBS4).";
RL DNA Seq. 15:213-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP THR-354.
RC TISSUE=Kidney;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-393.
RC TISSUE=Testis, and Uterus;
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, AND SUBCELLULAR
RP LOCATION.
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 INTERACTION WITH ALDOB.
RX PubMed=18000879; DOI=10.1002/cm.20250;
RA Oeffner F., Moch C., Neundorf A., Hofmann J., Koch M., Grzeschik K.H.;
RT "Novel interaction partners of Bardet-Biedl syndrome proteins.";
RL Cell Motil. Cytoskeleton 65:143-155(2008).
RN [9]
RP INTERACTION WITH CEP290.
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 [10]
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 [11]
RP FUNCTION, INTERACTION WITH DCTN1 AND PCM1, AND SUBCELLULAR LOCATION.
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 [12]
RP FUNCTION, FUNCTION OF THE BBSOME COMPLEX, IDENTIFICATION IN THE BBSOME
RP COMPLEX, AND INTERACTION WITH LZTL1.
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 [13]
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 [14]
RP VARIANTS BBS4 HIS-165; PRO-327; GLU-364 AND ILE-457.
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 [15]
RP VARIANT BBS4 VAL-472.
RX PubMed=12677556; DOI=10.1086/375178;
RA Beales P.L., Badano J.L., Ross A.J., Ansley S.J., Hoskins B.E., Kirsten B.,
RA Mein C.A., Froguel P., Scambler P.J., Lewis R.A., Lupski J.R., Katsanis N.;
RT "Genetic interaction of BBS1 mutations with alleles at other BBS loci can
RT result in non-Mendelian Bardet-Biedl syndrome.";
RL Am. J. Hum. Genet. 72:1187-1199(2003).
RN [16]
RP VARIANT BBS4 VAL-472.
RX PubMed=12872256; DOI=10.1002/humu.10241;
RA Hoskins B.E., Thorn A., Scambler P.J., Beales P.L.;
RT "Evaluation of multiplex capillary heteroduplex analysis: a rapid and
RT sensitive mutation screening technique.";
RL Hum. Mutat. 22:151-157(2003).
RN [17]
RP VARIANT BBS4 GLY-368, AND VARIANTS ARG-46 AND THR-354.
RX PubMed=15666242; DOI=10.1086/428679;
RA Karmous-Benailly H., Martinovic J., Gubler M.-C., Sirot Y., Clech L.,
RA Ozilou C., Auge J., Brahimi N., Etchevers H., Detrait E., Esculpavit C.,
RA Audollent S., Goudefroye G., Gonzales M., Tantau J., Loget P., Joubert M.,
RA Gaillard D., Jeanne-Pasquier C., Delezoide A.-L., Peter M.-O., Plessis G.,
RA Simon-Bouy B., Dollfus H., Le Merrer M., Munnich A., Encha-Razavi F.,
RA Vekemans M., Attie-Bitach T.;
RT "Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel
RT syndrome.";
RL Am. J. Hum. Genet. 76:493-504(2005).
RN [18]
RP VARIANT BBS4 ARG-351, AND VARIANT THR-354.
RX PubMed=15770229; DOI=10.1038/sj.ejhg.5201372;
RA Hichri H., Stoetzel C., Laurier V., Caron S., Sigaudy S., Sarda P.,
RA Hamel C., Martin-Coignard D., Gilles M., Leheup B., Holder M., Kaplan J.,
RA Bitoun P., Lacombe D., Verloes A., Bonneau D., Perrin-Schmitt F.,
RA Brandt C., Besancon A.-F., Mandel J.-L., Cossee M., Dollfus H.;
RT "Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl
RT syndrome family cohort.";
RL Eur. J. Hum. Genet. 13:607-616(2005).
RN [19]
RP VARIANTS ARG-46; LYS-61; ASP-412 AND LYS-488.
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 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.
CC {ECO:0000269|PubMed:15107855, ECO:0000269|PubMed:17574030,
CC ECO:0000269|PubMed:22072986}.
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 (PubMed:24939912). Interacts with CEP290 (PubMed:23943788).
CC Interacts with DLEC1 (PubMed:33144677). {ECO:0000269|PubMed:15107855,
CC ECO:0000269|PubMed:16327777, ECO:0000269|PubMed:17574030,
CC ECO:0000269|PubMed:18000879, ECO:0000269|PubMed:22072986,
CC ECO:0000269|PubMed:23943788, ECO:0000269|PubMed:24939912,
CC ECO:0000269|PubMed:33144677}.
CC -!- INTERACTION:
CC Q96RK4; P05062: ALDOB; NbExp=4; IntAct=EBI-1805814, EBI-1045507;
CC Q96RK4; A8MTZ0: BBIP1; NbExp=14; IntAct=EBI-1805814, EBI-2892417;
CC Q96RK4; Q8NFJ9: BBS1; NbExp=8; IntAct=EBI-1805814, EBI-1805484;
CC Q96RK4; Q3SYG4: BBS9; NbExp=6; IntAct=EBI-1805814, EBI-2826852;
CC Q96RK4; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-1805814, EBI-739879;
CC Q96RK4; Q9BUN5: CCDC28B; NbExp=3; IntAct=EBI-1805814, EBI-10299032;
CC Q96RK4; Q14203: DCTN1; NbExp=3; IntAct=EBI-1805814, EBI-724352;
CC Q96RK4; Q99814: EPAS1; NbExp=2; IntAct=EBI-1805814, EBI-447470;
CC Q96RK4; Q15051: IQCB1; NbExp=5; IntAct=EBI-1805814, EBI-2805823;
CC Q96RK4; P15173: MYOG; NbExp=3; IntAct=EBI-1805814, EBI-3906629;
CC Q96RK4; P00973-2: OAS1; NbExp=5; IntAct=EBI-1805814, EBI-12081862;
CC Q96RK4; P07237: P4HB; NbExp=3; IntAct=EBI-1805814, EBI-395883;
CC Q96RK4; Q15154: PCM1; NbExp=17; IntAct=EBI-1805814, EBI-741421;
CC Q96RK4; P60201-2: PLP1; NbExp=3; IntAct=EBI-1805814, EBI-12188331;
CC Q96RK4; P10276: RARA; NbExp=3; IntAct=EBI-1805814, EBI-413374;
CC Q96RK4; P13631: RARG; NbExp=5; IntAct=EBI-1805814, EBI-2568901;
CC Q96RK4; Q04864-2: REL; NbExp=3; IntAct=EBI-1805814, EBI-10829018;
CC Q96RK4; Q08AE8: SPIRE1; NbExp=3; IntAct=EBI-1805814, EBI-1055655;
CC Q96RK4; Q15915: ZIC1; NbExp=3; IntAct=EBI-1805814, EBI-11963196;
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:0000250|UniProtKB:Q8C1Z7}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8C1Z7}. Note=Localizes to the pericentriolar
CC material. Centrosomal localization requires dynein (By similarity).
CC Localizes to the connecting cilium of photoreceptor cells (By
CC similarity). {ECO:0000250|UniProtKB:Q8C1Z7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96RK4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RK4-2; Sequence=VSP_024410;
CC Name=3;
CC IsoId=Q96RK4-3; Sequence=VSP_047507;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. The highest level of
CC expression is found in the kidney.
CC -!- DISEASE: Bardet-Biedl syndrome 4 (BBS4) [MIM:615982]: 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:11381270, ECO:0000269|PubMed:12016587,
CC ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:12872256,
CC ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15770229}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the BBS4 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the BBS4 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/bbs4mut.htm";
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DR EMBL; AF359281; AAK58868.1; -; mRNA.
DR EMBL; AY457143; AAS13441.1; -; mRNA.
DR EMBL; AK075321; BAC11547.1; -; mRNA.
DR EMBL; AK303706; BAG64690.1; -; mRNA.
DR EMBL; AC009712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008923; AAH08923.2; -; mRNA.
DR EMBL; BC027624; AAH27624.1; -; mRNA.
DR CCDS; CCDS10246.1; -. [Q96RK4-1]
DR CCDS; CCDS58377.1; -. [Q96RK4-3]
DR RefSeq; NP_001239607.1; NM_001252678.1. [Q96RK4-3]
DR RefSeq; NP_001307594.1; NM_001320665.1.
DR RefSeq; NP_149017.2; NM_033028.4. [Q96RK4-1]
DR RefSeq; XP_011520150.1; XM_011521848.1. [Q96RK4-3]
DR RefSeq; XP_011520151.1; XM_011521849.1. [Q96RK4-3]
DR RefSeq; XP_016877940.1; XM_017022451.1.
DR RefSeq; XP_016877941.1; XM_017022452.1. [Q96RK4-3]
DR RefSeq; XP_016877942.1; XM_017022453.1. [Q96RK4-3]
DR RefSeq; XP_016877943.1; XM_017022454.1. [Q96RK4-3]
DR PDB; 6XT9; EM; 3.80 A; D=1-519.
DR PDBsum; 6XT9; -.
DR AlphaFoldDB; Q96RK4; -.
DR SMR; Q96RK4; -.
DR BioGRID; 107060; 46.
DR ComplexPortal; CPX-1908; BBSome complex.
DR CORUM; Q96RK4; -.
DR DIP; DIP-46540N; -.
DR IntAct; Q96RK4; 65.
DR STRING; 9606.ENSP00000268057; -.
DR iPTMnet; Q96RK4; -.
DR PhosphoSitePlus; Q96RK4; -.
DR BioMuta; BBS4; -.
DR DMDM; 160359000; -.
DR EPD; Q96RK4; -.
DR MassIVE; Q96RK4; -.
DR MaxQB; Q96RK4; -.
DR PaxDb; Q96RK4; -.
DR PeptideAtlas; Q96RK4; -.
DR PRIDE; Q96RK4; -.
DR ProteomicsDB; 5732; -.
DR ProteomicsDB; 77975; -. [Q96RK4-1]
DR ProteomicsDB; 77976; -. [Q96RK4-2]
DR Antibodypedia; 26730; 290 antibodies from 32 providers.
DR DNASU; 585; -.
DR Ensembl; ENST00000268057.9; ENSP00000268057.4; ENSG00000140463.14. [Q96RK4-1]
DR Ensembl; ENST00000395205.6; ENSP00000378631.3; ENSG00000140463.14. [Q96RK4-3]
DR GeneID; 585; -.
DR KEGG; hsa:585; -.
DR MANE-Select; ENST00000268057.9; ENSP00000268057.4; NM_033028.5; NP_149017.2.
DR UCSC; uc002avb.4; human. [Q96RK4-1]
DR CTD; 585; -.
DR DisGeNET; 585; -.
DR GeneCards; BBS4; -.
DR GeneReviews; BBS4; -.
DR HGNC; HGNC:969; BBS4.
DR HPA; ENSG00000140463; Low tissue specificity.
DR MalaCards; BBS4; -.
DR MIM; 600374; gene.
DR MIM; 615982; phenotype.
DR neXtProt; NX_Q96RK4; -.
DR OpenTargets; ENSG00000140463; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR PharmGKB; PA25278; -.
DR VEuPathDB; HostDB:ENSG00000140463; -.
DR eggNOG; KOG1124; Eukaryota.
DR GeneTree; ENSGT00940000158166; -.
DR HOGENOM; CLU_033477_1_0_1; -.
DR InParanoid; Q96RK4; -.
DR OMA; WNNIGAC; -.
DR PhylomeDB; Q96RK4; -.
DR TreeFam; TF324966; -.
DR PathwayCommons; Q96RK4; -.
DR Reactome; R-HSA-5620922; BBSome-mediated cargo-targeting to cilium.
DR SignaLink; Q96RK4; -.
DR SIGNOR; Q96RK4; -.
DR BioGRID-ORCS; 585; 5 hits in 1069 CRISPR screens.
DR ChiTaRS; BBS4; human.
DR GeneWiki; BBS4; -.
DR GenomeRNAi; 585; -.
DR Pharos; Q96RK4; Tbio.
DR PRO; PR:Q96RK4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96RK4; protein.
DR Bgee; ENSG00000140463; Expressed in right uterine tube and 188 other tissues.
DR ExpressionAtlas; Q96RK4; baseline and differential.
DR Genevisible; Q96RK4; HS.
DR GO; GO:0034464; C:BBSome; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; IDA:UniProtKB.
DR GO; GO:0005814; C:centriole; IDA:BHF-UCL.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:BHF-UCL.
DR GO; GO:0060170; C:ciliary membrane; IDA:BHF-UCL.
DR GO; GO:0035869; C:ciliary transition zone; IDA:GO_Central.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031514; C:motile cilium; IDA:BHF-UCL.
DR GO; GO:0097730; C:non-motile cilium; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:GOC.
DR GO; GO:0000242; C:pericentriolar material; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IEA:Ensembl.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:Ensembl.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:BHF-UCL.
DR GO; GO:0034452; F:dynactin binding; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:MGI.
DR GO; GO:0030534; P:adult behavior; ISS:BHF-UCL.
DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; ISS:BHF-UCL.
DR GO; GO:0060271; P:cilium assembly; ISS:BHF-UCL.
DR GO; GO:0016358; P:dendrite development; ISS:BHF-UCL.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0060613; P:fat pad development; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0021766; P:hippocampus development; ISS:BHF-UCL.
DR GO; GO:0046907; P:intracellular transport; ISS:BHF-UCL.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; IGI:BHF-UCL.
DR GO; GO:0032402; P:melanosome transport; ISS:BHF-UCL.
DR GO; GO:0034454; P:microtubule anchoring at centrosome; IMP:BHF-UCL.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:BHF-UCL.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:BHF-UCL.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0038108; P:negative regulation of appetite by leptin-mediated signaling pathway; ISS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; ISS:BHF-UCL.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISS:BHF-UCL.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IEA:Ensembl.
DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0071539; P:protein localization to centrosome; IMP:BHF-UCL.
DR GO; GO:0061512; P:protein localization to cilium; IMP:GO_Central.
DR GO; GO:0033365; P:protein localization to organelle; ISS:BHF-UCL.
DR GO; GO:1903546; P:protein localization to photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; ISS:BHF-UCL.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:BHF-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:BHF-UCL.
DR GO; GO:1902855; P:regulation of non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0001895; P:retina homeostasis; ISS:BHF-UCL.
DR GO; GO:0046548; P:retinal rod cell development; ISS:BHF-UCL.
DR GO; GO:0007608; P:sensory perception of smell; ISS:BHF-UCL.
DR GO; GO:0050893; P:sensory processing; TAS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; ISS:BHF-UCL.
DR GO; GO:0021756; P:striatum development; ISS:BHF-UCL.
DR GO; GO:0021591; P:ventricular system development; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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 3D-structure; Alternative splicing; Bardet-Biedl syndrome; Cell membrane;
KW Cell projection; Ciliopathy; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Disease variant; Flagellum;
KW Intellectual disability; Membrane; Obesity; Protein transport;
KW Reference proteome; Repeat; Sensory transduction; TPR repeat; Transport;
KW Vision.
FT CHAIN 1..519
FT /note="Bardet-Biedl syndrome 4 protein"
FT /id="PRO_0000106263"
FT REPEAT 67..100
FT /note="TPR 1"
FT REPEAT 101..134
FT /note="TPR 2"
FT REPEAT 135..168
FT /note="TPR 3"
FT REPEAT 169..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 REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..337
FT /note="Interaction with PCM1"
FT /evidence="ECO:0000269|PubMed:15107855"
FT REGION 338..519
FT /note="Required for localization to centrosomes"
FT REGION 440..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..495
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..172
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047507"
FT VAR_SEQ 1..8
FT /note="MAEERVAT -> MALTVVPSFSVSGVWK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15497446"
FT /id="VSP_024410"
FT VARIANT 46
FT /note="K -> R (in dbSNP:rs75295839)"
FT /evidence="ECO:0000269|PubMed:15666242,
FT ECO:0000269|PubMed:21344540"
FT /id="VAR_038894"
FT VARIANT 61
FT /note="E -> K (found in patients with Bardet-Biedl syndrome
FT carrying mutations in other BBS genes; uncertain
FT pathological role; dbSNP:rs1251827333)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066287"
FT VARIANT 165
FT /note="N -> H (in BBS4)"
FT /evidence="ECO:0000269|PubMed:12016587"
FT /id="VAR_017049"
FT VARIANT 268
FT /note="E -> K (in dbSNP:rs11638283)"
FT /id="VAR_028722"
FT VARIANT 295
FT /note="R -> P (in BBS4; dbSNP:rs121434632)"
FT /evidence="ECO:0000269|PubMed:11381270"
FT /id="VAR_013170"
FT VARIANT 327
FT /note="L -> P (in BBS4)"
FT /evidence="ECO:0000269|PubMed:12016587"
FT /id="VAR_017050"
FT VARIANT 351
FT /note="L -> R (in BBS4)"
FT /evidence="ECO:0000269|PubMed:15770229"
FT /id="VAR_038895"
FT VARIANT 354
FT /note="I -> T (in dbSNP:rs2277598)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15770229"
FT /id="VAR_017054"
FT VARIANT 364
FT /note="A -> E (in BBS4; dbSNP:rs28938468)"
FT /evidence="ECO:0000269|PubMed:12016587"
FT /id="VAR_017051"
FT VARIANT 368
FT /note="D -> G (in BBS4; dbSNP:rs772548770)"
FT /evidence="ECO:0000269|PubMed:15666242"
FT /id="VAR_038896"
FT VARIANT 393
FT /note="A -> V (in dbSNP:rs17852452)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028723"
FT VARIANT 412
FT /note="E -> D (in a patient with Bardet-Biedl syndrome
FT compound heterozygote for mutations in BBS1; uncertain
FT pathological role; dbSNP:rs147202164)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066288"
FT VARIANT 457
FT /note="S -> I (in BBS4)"
FT /evidence="ECO:0000269|PubMed:12016587"
FT /id="VAR_017052"
FT VARIANT 472
FT /note="M -> V (in BBS4; dbSNP:rs2277596)"
FT /evidence="ECO:0000269|PubMed:12677556,
FT ECO:0000269|PubMed:12872256"
FT /id="VAR_017053"
FT VARIANT 488
FT /note="T -> K (in a patient with Bardet-Biedl syndrome
FT homozygous for a mutation in BBS12; uncertain pathological
FT role; dbSNP:rs561284402)"
FT /evidence="ECO:0000269|PubMed:21344540"
FT /id="VAR_066289"
FT VARIANT 503
FT /note="P -> L (in BBS4; dbSNP:rs756419611)"
FT /id="VAR_038897"
SQ SEQUENCE 519 AA; 58282 MW; 59BC9B29355C8E3C CRC64;
MAEERVATRT QFPVSTESQK PRQKKAPEFP ILEKQNWLIH LHYIRKDYEA CKAVIKEQLQ
ETQGLCEYAI YVQALIFRLE GNIQESLELF QTCAVLSPQS ADNLKQVARS LFLLGKHKAA
IEVYNEAAKL NQKDWEISHN LGVCYIYLKQ FNKAQDQLHN ALNLNRHDLT YIMLGKIHLL
EGDLDKAIEV YKKAVEFSPE NTELLTTLGL LYLQLGIYQK AFEHLGNALT YDPTNYKAIL
AAGSMMQTHG DFDVALTKYR VVACAVPESP PLWNNIGMCF FGKKKYVAAI SCLKRANYLA
PFDWKILYNL GLVHLTMQQY ASAFHFLSAA INFQPKMGEL YMLLAVALTN LEDIENAKRA
YAEAVHLDKC NPLVNLNYAV LLYNQGEKKN ALAQYQEMEK KVSLLKDNSS LEFDSEMVEM
AQKLGAALQV GEALVWTKPV KDPKSKHQTT STSKPASFQQ PLGSNQALGQ AMSSAAAYRT
LPSGAGGTSQ FTKPPSLPLE PEPAVESSPT ETSEQIREK
