Reviewed, UniProtKB/Swiss-Prot Q96RK4 (BBS4_HUMAN)

Names and origin

Protein names

Recommended name:
    Bardet-Biedl syndrome 4 protein

Gene names

Name:

BBS4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May be required for the dynein-mediated transport of pericentriolar proteins to the centrosome. Required for microtubule anchoring at the centrosome but not for microtubule nucleation. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. Ref.5 Ref.7
Subunit structure	Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10. The BBSome complex binds to PCM1 and tubulin. Interacts with DCTN1. Ref.5 Ref.7
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton. Cell projection › cilium membrane. Cytoplasm. Note: Localizes to the pericentriolar region throughout the cell cycle. Centrosomal localization requires dynein. Localizes to nonmembranous centriolar satellites in the cytoplasm. Ref.5 Ref.7
Tissue specificity	Ubiquitously expressed. The highest level of expression is found in the kidney.
Involvement in disease	Defects in BBS4 are the cause of Bardet-Biedl syndrome type 4 (BBS4) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect. Ref.1 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the BBS4 family. Contains 10 TPR repeats.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Bardet-Biedl syndrome Disease mutation Obesity
Domain	Repeat TPR repeat
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	adult behavior Inferred from sequence or structural similarity. Source: UniProtKB brain morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB centrosome organization Ref.7 Inferred from mutant phenotype. Source: UniProtKB cerebral cortex development Inferred from sequence or structural similarity. Source: UniProtKB convergent extension involved in gastrulation Inferred from sequence or structural similarity. Source: UniProtKB cytokinesis during cell cycle Ref.7 Inferred from mutant phenotype. Source: UniProtKB dendrite development Inferred from sequence or structural similarity. Source: UniProtKB fat cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB heart looping Inferred from sequence or structural similarity. Source: UniProtKB hippocampus development Inferred from sequence or structural similarity. Source: UniProtKB intracellular transport Inferred from sequence or structural similarity. Source: UniProtKB maintenance of protein location in nucleus Ref.7 Inferred from genetic interaction. Source: UniProtKB melanosome transport Inferred from sequence or structural similarity. Source: UniProtKB microtubule anchoring at centrosome Ref.7 Inferred from mutant phenotype. Source: UniProtKB neural tube closure Inferred from sequence or structural similarity. Source: UniProtKB photoreceptor cell maintenance Inferred from sequence or structural similarity. Source: UniProtKB pigment granule aggregation in cell center Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of flagellum assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of cilium beat frequency involved in ciliary motility Inferred from sequence or structural similarity. Source: UniProtKB regulation of cytokinesis Ref.7 Inferred from mutant phenotype. Source: UniProtKB regulation of lipid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB retina homeostasis Inferred from sequence or structural similarity. Source: UniProtKB retinal rod cell development Inferred from sequence or structural similarity. Source: UniProtKB sensory cilium assembly Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of smell Inferred from sequence or structural similarity. Source: UniProtKB sensory processing Traceable author statement. Source: UniProtKB spermatid development Inferred from sequence or structural similarity. Source: UniProtKB striatum development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	BBSome Ref.5 Inferred from direct assay. Source: UniProtKB centriolar satellite Ref.7 Inferred from direct assay. Source: UniProtKB centriole Ref.7 Inferred from direct assay. Source: UniProtKB cilium membrane Ref.5 Inferred from direct assay. Source: UniProtKB microtubule basal body Ref.7 Inferred from direct assay. Source: UniProtKB motile secondary cilium Inferred from direct assay. Source: UniProtKB nonmotile primary cilium Ref.5 Inferred from direct assay. Source: UniProtKB pericentriolar material Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	alpha-tubulin binding Ref.5 Inferred from direct assay. Source: UniProtKB beta-tubulin binding Ref.5 Inferred from direct assay. Source: UniProtKB dynactin binding Ref.7 Inferred from direct assay. Source: UniProtKB microtubule motor activity Ref.7 Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ALDOB	P05062	3	EBI-1805814,EBI-1045507
DCTN1	Q14203	3	EBI-1805814,EBI-724352
EEF1A1	P68104	2	EBI-1805814,EBI-352162
EPAS1	Q99814	1	EBI-1805814,EBI-447470
PCM1	Q15154	6	EBI-1805814,EBI-741421

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96RK4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96RK4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MAEERVAT → MALTVVPSFSVSGVWK

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 519	519	Bardet-Biedl syndrome 4 protein		PRO_0000106263
Regions
	Repeat	67 – 100	34	TPR 1
	Repeat	101 – 134	34	TPR 2
	Repeat	135 – 168	34	TPR 3
	Repeat	169 – 201	33	TPR 4
	Repeat	203 – 235	33	TPR 5
	Repeat	237 – 269	33	TPR 6
	Repeat	270 – 303	34	TPR 7
	Repeat	304 – 337	34	TPR 8
	Repeat	339 – 371	33	TPR 9
	Repeat	373 – 408	36	TPR 10
	Region	1 – 66	66	Required for localization to centrosomes
	Region	101 – 337	237	Interaction with PCM1
	Region	338 – 519	182	Required for localization to centrosomes
Natural variations
	Alternative sequence	1 – 8	8	MAEERVAT → MALTVVPSFSVSGVWK in isoform 2.		VSP_024410
	Natural variant	46	1	K → R		VAR_038894
	Natural variant	165	1	N → H in BBS4. Ref.6		VAR_017049
	Natural variant	268	1	E → K: dbSNP rs11638283.		VAR_028722
	Natural variant	295	1	R → P in BBS4. Ref.1		VAR_013170
	Natural variant	327	1	L → P in BBS4. Ref.6		VAR_017050
	Natural variant	351	1	L → R in BBS4. Ref.11		VAR_038895
	Natural variant	354	1	I → T: dbSNP rs2277598. Ref.10 Ref.11 Ref.3		VAR_017054
	Natural variant	364	1	A → E in BBS4. Ref.6		VAR_017051
	Natural variant	368	1	D → G in BBS4. Ref.10		VAR_038896
	Natural variant	393	1	A → V: dbSNP rs17852452. Ref.4		VAR_028723
	Natural variant	457	1	S → I in BBS4. Ref.6		VAR_017052
	Natural variant	472	1	M → V in BBS4. dbSNP rs2277596. Ref.8 Ref.9		VAR_017053
	Natural variant	503	1	P → L in BBS4.		VAR_038897

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 23, 2007. Version 2. Checksum: 59BC9B29355C8E3C	FASTA	519	58,282
	10 20 30 40 50 60 MAEERVATRT QFPVSTESQK PRQKKAPEFP ILEKQNWLIH LHYIRKDYEA CKAVIKEQLQ 70 80 90 100 110 120 ETQGLCEYAI YVQALIFRLE GNIQESLELF QTCAVLSPQS ADNLKQVARS LFLLGKHKAA 130 140 150 160 170 180 IEVYNEAAKL NQKDWEISHN LGVCYIYLKQ FNKAQDQLHN ALNLNRHDLT YIMLGKIHLL 190 200 210 220 230 240 EGDLDKAIEV YKKAVEFSPE NTELLTTLGL LYLQLGIYQK AFEHLGNALT YDPTNYKAIL 250 260 270 280 290 300 AAGSMMQTHG DFDVALTKYR VVACAVPESP PLWNNIGMCF FGKKKYVAAI SCLKRANYLA 310 320 330 340 350 360 PFDWKILYNL GLVHLTMQQY ASAFHFLSAA INFQPKMGEL YMLLAVALTN LEDIENAKRA 370 380 390 400 410 420 YAEAVHLDKC NPLVNLNYAV LLYNQGEKKN ALAQYQEMEK KVSLLKDNSS LEFDSEMVEM 430 440 450 460 470 480 AQKLGAALQV GEALVWTKPV KDPKSKHQTT STSKPASFQQ PLGSNQALGQ AMSSAAAYRT 490 500 510 LPSGAGGTSQ FTKPPSLPLE PEPAVESSPT ETSEQIREK
	Isoform 2. Checksum: 09A45FF715582D14	FASTA	527	59,084
	10 20 30 40 50 60 MALTVVPSFS VSGVWKRTQF PVSTESQKPR QKKAPEFPIL EKQNWLIHLH YIRKDYEACK 70 80 90 100 110 120 AVIKEQLQET QGLCEYAIYV QALIFRLEGN IQESLELFQT CAVLSPQSAD NLKQVARSLF 130 140 150 160 170 180 LLGKHKAAIE VYNEAAKLNQ KDWEISHNLG VCYIYLKQFN KAQDQLHNAL NLNRHDLTYI 190 200 210 220 230 240 MLGKIHLLEG DLDKAIEVYK KAVEFSPENT ELLTTLGLLY LQLGIYQKAF EHLGNALTYD 250 260 270 280 290 300 PTNYKAILAA GSMMQTHGDF DVALTKYRVV ACAVPESPPL WNNIGMCFFG KKKYVAAISC 310 320 330 340 350 360 LKRANYLAPF DWKILYNLGL VHLTMQQYAS AFHFLSAAIN FQPKMGELYM LLAVALTNLE 370 380 390 400 410 420 DIENAKRAYA EAVHLDKCNP LVNLNYAVLL YNQGEKKNAL AQYQEMEKKV SLLKDNSSLE 430 440 450 460 470 480 FDSEMVEMAQ KLGAALQVGE ALVWTKPVKD PKSKHQTTST SKPASFQQPL GSNQALGQAM 490 500 510 520 SSAAAYRTLP SGAGGTSQFT KPPSLPLEPE PAVESSPTET SEQIREK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the gene that, when mutated, causes the human obesity syndrome BBS4." Mykytyn K., Braun T., Carmi R., Haider N.B., Searby C.C., Shastri M., Beck G., Wright A.F., Iannaccone A., Elbedour K., Riise R., Baldi A., Raas-Rothschild A., Gorman S.W., Duhl D.M., Jacobson S.G., Casavant T., Stone E.M., Sheffield V.C. Nat. Genet. 28:188-191(2001) [PubMed: 11381270] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT BBS4 PRO-295.
[2]	"Cloning and characterization of a splice variant of human Bardet-Biedl syndrome 4 gene (BBS4)." Ye X., Dai J., Fang W., Jin W., Guo Y., Song J., Ji C., Gu S., Xie Y., Mao Y. DNA Seq. 15:213-218(2004) [PubMed: 15497446] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-354.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-393. Tissue: Testis and Uterus.
[5]	"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis." Nachury M.V., Loktev A.V., Zhang Q., Westlake C.J., Peraenen J., Merdes A., Slusarski D.C., Scheller R.H., Bazan J.F., Sheffield V.C., Jackson P.K. Cell 129:1201-1213(2007) [PubMed: 17574030] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, FUNCTION, SUBCELLULAR LOCATION.
[6]	"BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance." Katsanis N., Eichers E.R., Ansley S.J., Lewis R.A., Kayserili H., Hoskins B.E., Scambler P.J., Beales P.L., Lupski J.R. Am. J. Hum. Genet. 71:22-29(2002) [PubMed: 12016587] [Abstract] Cited for: VARIANTS BBS4 HIS-165; PRO-327; GLU-364 AND ILE-457.
[7]	"The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression." Kim J.C., Badano J.L., Sibold S., Esmail M.A., Hill J., Hoskins B.E., Leitch C.C., Venner K., Ansley S.J., Ross A.J., Leroux M.R., Katsanis N., Beales P.L. Nat. Genet. 36:462-470(2004) [PubMed: 15107855] [Abstract] Cited for: FUNCTION, INTERACTION WITH DCTN1 AND PCM1, SUBCELLULAR LOCATION.
[8]	"Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome." Beales P.L., Badano J.L., Ross A.J., Ansley S.J., Hoskins B.E., Kirsten B., Mein C.A., Froguel P., Scambler P.J., Lewis R.A., Lupski J.R., Katsanis N. Am. J. Hum. Genet. 72:1187-1199(2003) [PubMed: 12677556] [Abstract] Cited for: VARIANT BBS4 VAL-472.
[9]	"Evaluation of multiplex capillary heteroduplex analysis: a rapid and sensitive mutation screening technique." Hoskins B.E., Thorn A., Scambler P.J., Beales P.L. Hum. Mutat. 22:151-157(2003) [PubMed: 12872256] [Abstract] Cited for: VARIANT BBS4 VAL-472.
[10]	"Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome." Karmous-Benailly H., Martinovic J., Gubler M.-C., Sirot Y., Clech L., Ozilou C., Auge J., Brahimi N., Etchevers H., Detrait E., Esculpavit C., Audollent S., Goudefroye G., Gonzales M., Tantau J., Loget P., Joubert M., Gaillard D. , Jeanne-Pasquier C., Delezoide A.-L., Peter M.-O., Plessis G., Simon-Bouy B., Dollfus H., Le Merrer M., Munnich A., Encha-Razavi F., Vekemans M., Attie-Bitach T. Am. J. Hum. Genet. 76:493-504(2005) [PubMed: 15666242] [Abstract] Cited for: VARIANT BBS4 GLY-368, VARIANTS ARG-46 AND THR-354.
[11]	"Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome family cohort." Hichri H., Stoetzel C., Laurier V., Caron S., Sigaudy S., Sarda P., Hamel C., Martin-Coignard D., Gilles M., Leheup B., Holder M., Kaplan J., Bitoun P., Lacombe D., Verloes A., Bonneau D., Perrin-Schmitt F., Brandt C. , Besancon A.-F., Mandel J.-L., Cossee M., Dollfus H. Eur. J. Hum. Genet. 13:607-616(2005) [PubMed: 15770229] [Abstract] Cited for: VARIANT BBS4 ARG-351, VARIANT THR-354.
+	Additional computationally mapped references.

Web resources

Mutations of the BBS4 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF359281 mRNA. Translation: AAK58868.1. AY457143 mRNA. Translation: AAS13441.1. AK075321 mRNA. Translation: BAC11547.1. BC008923 mRNA. Translation: AAH08923.2. BC027624 mRNA. Translation: AAH27624.1.
IPI	IPI00290189. IPI00798373.
RefSeq	NP_149017.2.
UniGene	Hs.208681
3D structure databases
SMR	Q96RK4. Positions 36-386.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96RK4. 17 interactions.
STRING	Q96RK4.
Genome annotation databases
Ensembl	ENST00000268057; ENSP00000268057; ENSG00000140463; Homo sapiens. [Genome view]
GeneID	585.
KEGG	hsa:585.
UCSC	uc002avb.1. human. uc002avd.1. human.
Organism-specific databases
CTD	585.
GeneCards	GC15P070765.
H-InvDB	HIX0012411.
HGNC	HGNC:969. BBS4.
MIM	209900. phenotype. 600374. gene.
Orphanet	110. Bardet-Biedl syndrome.
PharmGKB	PA25278.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06583.
HOGENOM	HBG525471.
HOVERGEN	Q96RK4.
InParanoid	Q96RK4.
OMA	RLDKCNP.
OrthoDB	EOG9WM7F7.
PhylomeDB	Q96RK4.
Gene expression databases
ArrayExpress	Q96RK4.
Bgee	Q96RK4.
CleanEx	HS_BBS4.
Genevestigator	Q96RK4.
GermOnline	ENSG00000140463. Homo sapiens.
Family and domain databases
InterPro	IPR013026. TPR-contain. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
Gene3D	G3DSA:1.25.40.10. TPR-like_helical. 2 hits.
SMART	SM00028. TPR. 8 hits. [Graphical view]
PROSITE	PS50005. TPR. 8 hits. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	2391.
SOURCE	Search...

Entry information

Entry name

BBS4_HUMAN

Accession

Primary (citable) accession number: Q96RK4
Secondary accession number(s): Q53DZ5, Q8NHU9, Q96H45

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	October 23, 2007
Last modified:	February 9, 2010
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.