Q9BXC9 (BBS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bardet-Biedl syndrome 2 protein

Gene names

Name:

BBS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	721 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 RAB3IP/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
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 (via C-terminus) with BBS7. Interacts (via coiled coil domain) with MKKS. Interacts with CCDC28B. Ref.4 Ref.5 Ref.6
Subcellular location	Cell projection › cilium membrane. Cytoplasm. Note: Localizes to nonmembranous centriolar satellites in the cytoplasm. Ref.5
Tissue specificity	Widely expressed.
Involvement in disease	Bardet-Biedl syndrome 2 (BBS2) [MIM:209900]: A syndrome 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. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Bardet-Biedl syndrome Ciliopathy Disease mutation Mental retardation Obesity
Domain	Coiled coil
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Golgi to plasma membrane protein transport Inferred from mutant phenotype PubMed 19150989. Source: MGI adult behavior Inferred from sequence or structural similarity. Source: BHF-UCL brain morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cerebral cortex development Inferred from sequence or structural similarity. Source: BHF-UCL cilium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL fat cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL hippocampus development Inferred from sequence or structural similarity. Source: BHF-UCL melanosome transport Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of appetite by leptin-mediated signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of multicellular organism growth Inferred from sequence or structural similarity. Source: BHF-UCL photoreceptor cell maintenance Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara protein localization to organelle Inferred from sequence or structural similarity. Source: BHF-UCL regulation of cilium beat frequency involved in ciliary motility Inferred from sequence or structural similarity. Source: BHF-UCL sperm axoneme assembly Inferred from sequence or structural similarity. Source: BHF-UCL striatum development Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	BBSome Inferred from direct assay Ref.5. Source: BHF-UCL cilium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule basal body Inferred from direct assay PubMed 18299575. Source: BHF-UCL motile cilium Inferred from direct assay PubMed 18299575. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ALDOB	P05062	4	EBI-748297,EBI-1045507
BBS1	Q8NFJ9	6	EBI-748297,EBI-1805484
BBS7	Q8IWZ6	11	EBI-748297,EBI-1806001
BBS9	Q3SYG4	9	EBI-748297,EBI-2826852
MKKS	Q9NPJ1	4	EBI-748297,EBI-721319

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 721	721	Bardet-Biedl syndrome 2 protein		PRO_0000064843
Regions
	Coiled coil	325 – 369	45	Potential
Natural variations
	Natural variant	23	1	R → P in BBS2. Ref.11		VAR_038889
	Natural variant	70	1	N → S in BBS2. Ref.7 Corresponds to variant rs4784677 [ dbSNP | Ensembl ].		VAR_013162
	Natural variant	75	1	V → G in BBS2; in linkage disequilibrium with V-123 in a Bedouin kindred. Ref.1		VAR_013163
	Natural variant	81	1	G → C in BBS2. Ref.14		VAR_066280
	Natural variant	104	1	D → A in BBS2. Ref.7 Ref.14		VAR_013164
	Natural variant	122	1	A → V. Ref.3 Corresponds to variant rs17856449 [ dbSNP | Ensembl ].		VAR_029747
	Natural variant	123	1	I → V Polymorphism in linkage disequilibrium with G-75 in a Bedouin kindred. Ref.1 Ref.11 Ref.12 Corresponds to variant rs11373 [ dbSNP | Ensembl ].		VAR_013165
	Natural variant	125	1	L → R in BBS2. Ref.14		VAR_066281
	Natural variant	136	1	A → P in BBS2. Ref.14		VAR_066282
	Natural variant	174	1	D → E in BBS2. Ref.9		VAR_038890
	Natural variant	307	1	C → W in BBS2. Ref.14		VAR_066283
	Natural variant	315	1	R → Q in BBS2. Ref.7 Ref.8		VAR_013166
	Natural variant	315	1	R → W in BBS2. Ref.7		VAR_013167
	Natural variant	317	1	Y → C in BBS2. Ref.14		VAR_066284
	Natural variant	349	1	L → W in BBS2; has a modifier effect on BBS. Ref.8		VAR_038891
	Natural variant	504	1	A → V. Corresponds to variant rs16957538 [ dbSNP | Ensembl ].		VAR_029748
	Natural variant	558	1	T → I in BBS2. Ref.7		VAR_013168
	Natural variant	629	1	E → K in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS10; uncertain pathological role. Ref.13		VAR_066285
	Natural variant	632	1	R → P in BBS2. Ref.7 Ref.14		VAR_013169
	Natural variant	643	1	R → H in BBS2. Ref.10		VAR_038892
Experimental info
	Sequence conflict	63	1	E → G in BAB55252. Ref.2
	Sequence conflict	169	1	C → R in BAB55252. Ref.2
	Sequence conflict	457	1	L → S in BAB55252. Ref.2
	Sequence conflict	648	1	Y → H in BAB55252. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9BXC9 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 8FA1CDAED725BEAF	FASTA	721	79,871
	10 20 30 40 50 60 MLLPVFTLKL RHKISPRMVA IGRYDGTHPC LAAATQTGKV FIHNPHTRNQ HVSASRVFQS 70 80 90 100 110 120 PLESDVSLLN INQAVSCLTA GVLNPELGYD ALLVGTQTNL LAYDVYNNSD LFYREVADGA 130 140 150 160 170 180 NAIVLGTLGD ISSPLAIIGG NCALQGFNHE GSDLFWTVTG DNVNSLALCD FDGDGKKELL 190 200 210 220 230 240 VGSEDFDIRV FKEDEIVAEM TETEIVTSLC PMYGSRFGYA LSNGTVGVYD KTSRYWRIKS 250 260 270 280 290 300 KNHAMSIHAF DLNSDGVNEL ITGWSNGKVD ARSDRTGEVI FKDNFSSAIA GVVEGDYRMD 310 320 330 340 350 360 GHIQLICCSV DGEIRGYLPG TAEMRGNLMD TSAEQDLIRE LSQKKQNLLL ELRNYEENAK 370 380 390 400 410 420 AELASPLNEA DGHRGIIPAN TRLHTTLSVS LGNETQTAHT ELRISTSNDT IIRAVLIFAE 430 440 450 460 470 480 GIFTGESHVV HPSIHNLSSS ICIPIVPPKD VPVDLHLKAF VGYRSSTQFH VFESTRQLPR 490 500 510 520 530 540 FSMYALTSLD PASEPISYVN FTIAERAQRV VVWLGQNFLL PEDTHIQNAP FQVCFTSLRN 550 560 570 580 590 600 GGHLHIKIKL SGEITINTDD IDLAGDIIQS MASFFAIEDL QVEADFPVYF EELRKVLVKV 610 620 630 640 650 660 DEYHSVHQKL SADMADHSNL IRSLLVGAED ARLMRDMKTM KSRYMELYDL NRDLLNGYKI 670 680 690 700 710 720 RCNNHTELLG NLKAVNQAIQ RAGRLRVGKP KNQVITACRD AIRSNNINTL FKIMRVGTAS S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2)." Nishimura D.Y., Searby C.C., Carmi R., Elbedour K., Van Maldergem L., Fulton A.B., Lam B.L., Powell B.R., Swiderski R.E., Bugge K.E., Haider N.B., Kwitek-Black A.E., Ying L., Duhl D.M., Gorman S.M., Heon E., Iannaccone A., Bonneau D. , Biesecker L.G., Jacobson S.G., Stone E.M., Sheffield V.C. Hum. Mol. Genet. 10:865-874(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT BBS2 GLY-75, VARIANT VAL-123.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-122. Tissue: Placenta.
[4]	"Dissection of epistasis in oligogenic Bardet-Biedl syndrome." Badano J.L., Leitch C.C., Ansley S.J., May-Simera H., Lawson S., Lewis R.A., Beales P.L., Dietz H.C., Fisher S., Katsanis N. Nature 439:326-330(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CCDC28B.
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, FUNCTION, SUBCELLULAR LOCATION.
[6]	"BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly." Seo S., Baye L.M., Schulz N.P., Beck J.S., Zhang Q., Slusarski D.C., Sheffield V.C. Proc. Natl. Acad. Sci. U.S.A. 107:1488-1493(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BBS7 AND MKKS.
[7]	"Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder." Katsanis N., Ansley S.J., Badano J.L., Eichers E.R., Lewis R.A., Hoskins B.E., Scambler P.J., Davidson W.S., Beales P.L., Lupski J.R. Science 293:2256-2259(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BBS2 SER-70; ALA-104; GLN-315; TRP-315; ILE-558 AND PRO-632.
[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] [Europe PMC] [Abstract] Cited for: VARIANTS BBS2 GLN-315 AND TRP-349.
[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] [Europe PMC] [Abstract] Cited for: VARIANT BBS2 GLU-174.
[10]	"Further support for digenic inheritance in Bardet-Biedl syndrome." Fauser S., Munz M., Besch D. J. Med. Genet. 40:E104-E104(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BBS2 HIS-643.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BBS2 PRO-23, VARIANT VAL-123.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANT VAL-123.
[13]	"Bardet-Biedl syndrome in Denmark -- report of 13 novel sequence variations in six genes." Hjortshoj T.D., Gronskov K., Philp A.R., Nishimura D.Y., Riise R., Sheffield V.C., Rosenberg T., Brondum-Nielsen K. Hum. Mutat. 31:429-436(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LYS-629.
[14]	"BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition." Deveault C., Billingsley G., Duncan J.L., Bin J., Theal R., Vincent A., Fieggen K.J., Gerth C., Noordeh N., Traboulsi E.I., Fishman G.A., Chitayat D., Knueppel T., Millan J.M., Munier F.L., Kennedy D., Jacobson S.G., Innes A.M. , Mitchell G.A., Boycott K., Heon E. Hum. Mutat. 32:610-619(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BBS2 CYS-81; ALA-104; ARG-125; PRO-136; TRP-307; CYS-317 AND PRO-632.
+	Additional computationally mapped references.

Web resources

Mutations of the BBS2 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF342736 mRNA. Translation: AAK28552.1. AK027635 mRNA. Translation: BAB55252.1. BC014140 mRNA. Translation: AAH14140.1.
IPI	IPI00306961.
RefSeq	NP_114091.3. NM_031885.3.
UniGene	Hs.333738.
3D structure databases
ProteinModelPortal	Q9BXC9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BXC9. 29 interactions.
MINT	MINT-1454659.
STRING	9606.ENSP00000245157.
PTM databases
PhosphoSite	Q9BXC9.
Polymorphism databases
DMDM	20454827.
Proteomic databases
PaxDb	Q9BXC9.
PRIDE	Q9BXC9.
Protocols and materials databases
DNASU	583.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245157; ENSP00000245157; ENSG00000125124.
GeneID	583.
KEGG	hsa:583.
UCSC	uc002ejd.2. human.
Organism-specific databases
CTD	583.
GeneCards	GC16M056569.
HGNC	HGNC:967. BBS2.
HPA	HPA041315.
MIM	209900. phenotype. 606151. gene.
neXtProt	NX_Q9BXC9.
Orphanet	110. Bardet-Biedl syndrome.
PharmGKB	PA25276.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG87621.
HOGENOM	HOG000007549.
HOVERGEN	HBG031114.
InParanoid	Q9BXC9.
KO	K16747.
OrthoDB	EOG4V9TQ3.
Gene expression databases
ArrayExpress	Q9BXC9.
Bgee	Q9BXC9.
CleanEx	HS_BBS2.
Genevestigator	Q9BXC9.
GermOnline	ENSG00000125124. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 2 hits.
InterPro	IPR016616. Bardet-Biedl_syndrome_2_prot. IPR015943. WD40/YVTN_repeat-like_dom. IPR017986. WD40_repeat_dom. [Graphical view]
PIRSF	PIRSF013684. BBS2. 1 hit.
SUPFAM	SSF50978. WD40_like. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	583.
NextBio	2387.
SOURCE	Search...

Entry information

Entry name

BBS2_HUMAN

Accession

Primary (citable) accession number: Q9BXC9
Secondary accession number(s): Q96CM0, Q96SN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.