Q6ZW61 (BBS12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bardet-Biedl syndrome 12 protein

Gene names

Name:	BBS12
Synonyms:	C4orf24

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	710 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable molecular chaperone. Assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation. Ref.6 Ref.7
Subunit structure	Component of the BBS/CCT complex composed at least of MKKS, BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 AND CCT8. Ref.7
Subcellular location	Cell projection › cilium. Note: Located within the basal body of the primary cilium of differentiating preadipocytes. Ref.6
Involvement in disease	Bardet-Biedl syndrome 12 (BBS12) [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.7 Ref.8 Ref.9 Ref.10
Miscellaneous	Adipocytes derived from BBS-patients' dermal fibroblasts in culture exhibit higher propensity for fat accumulation when compared to controls. This strongly suggests that a peripheral primary dysfunction of adipogenesis participates to the pathogenesis of obesity in BBS.
Sequence similarities	Belongs to the TCP-1 chaperonin family. BBS12 subfamily.
Sequence caution	The sequence BAC04006.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cell projection Cilium
Coding sequence diversity	Polymorphism
Disease	Bardet-Biedl syndrome Ciliopathy Disease mutation Mental retardation Obesity
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein metabolic process Inferred from electronic annotation. Source: InterPro chaperone-mediated protein complex assembly Inferred from mutant phenotype Ref.7. Source: MGI
Cellular_component	cilium Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BBS10	Q8TAM1	5	EBI-6128352,EBI-6128013
BBS7	Q8IWZ6	6	EBI-6128352,EBI-1806001
BBS9	Q3SYG4	2	EBI-6128352,EBI-2826852
MKKS	Q9NPJ1	10	EBI-6128352,EBI-721319

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 710	710	Bardet-Biedl syndrome 12 protein		PRO_0000301981
Natural variations
	Natural variant	39	1	I → T. Ref.8 Ref.9 Ref.10		VAR_034919
	Natural variant	88	1	L → R in BBS12. Ref.10		VAR_066266
	Natural variant	113	1	Missing in BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8		VAR_034920
	Natural variant	119	1	G → S Associated with H-263 in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS10. Ref.10 Corresponds to variant rs77731085 [ dbSNP | Ensembl ].		VAR_066267
	Natural variant	126	1	E → D. Corresponds to variant rs309369 [ dbSNP | Ensembl ].		VAR_034921
	Natural variant	159	1	P → L in BBS12; pathogenicity uncertain; significantly reduces the interaction with MKKS; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8		VAR_034922
	Natural variant	170	1	I → V. Ref.8		VAR_034923
	Natural variant	195	1	K → R. Ref.5 Corresponds to variant rs17854892 [ dbSNP | Ensembl ].		VAR_034924
	Natural variant	238	1	N → K. Corresponds to variant rs17006082 [ dbSNP | Ensembl ].		VAR_034925
	Natural variant	263	1	Y → H Associated with S-119 in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS10. Ref.10 Corresponds to variant rs150040166 [ dbSNP | Ensembl ].		VAR_066268
	Natural variant	289	1	A → P in BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8		VAR_034926
	Natural variant	293	1	Q → E in BBS12. Ref.10		VAR_066269
	Natural variant	346	1	I → T in BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8		VAR_062964
	Natural variant	355	1	R → Q in BBS12. Ref.10		VAR_066270
	Natural variant	386	1	R → Q. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs309370 [ dbSNP | Ensembl ].		VAR_034927
	Natural variant	400	1	V → M in BBS12. Ref.10		VAR_066271
	Natural variant	408	1	K → R in a patient with Bardet-Biedl syndrome compound heterozygote for BBS2 mutations; uncertain pathological role. Ref.9		VAR_066272
	Natural variant	429	1	S → T. Corresponds to variant rs7665271 [ dbSNP | Ensembl ].		VAR_034928
	Natural variant	461	1	N → H. Corresponds to variant rs10027479 [ dbSNP | Ensembl ].		VAR_034929
	Natural variant	467	1	D → N. Ref.1 Ref.5 Corresponds to variant rs13135778 [ dbSNP | Ensembl ].		VAR_034930
	Natural variant	484	1	R → K. Corresponds to variant rs35690634 [ dbSNP | Ensembl ].		VAR_034931
	Natural variant	501	1	T → M in BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8 Ref.10		VAR_062965
	Natural variant	511 – 513	3	Missing in BBS12.		VAR_066273
	Natural variant	524	1	Y → C in a patient with Bardet-Biedl syndrome homozygous for a mutation in BBS2; uncertain pathological role. Ref.9		VAR_066274
	Natural variant	525	1	R → H in BBS12. Ref.10		VAR_066275
	Natural variant	539	1	G → D in BBS12. Ref.10		VAR_066276
	Natural variant	540	1	G → V in BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation. Ref.7 Ref.8		VAR_034932
	Natural variant	615	1	A → V. Ref.5 Corresponds to variant rs17857451 [ dbSNP | Ensembl ].		VAR_034933
	Natural variant	674	1	R → C in BBS12. Ref.10		VAR_066277
Experimental info
	Sequence conflict	462	1	E → G in CAD98035. Ref.2
	Sequence conflict	597	1	K → R in BAC04006. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q6ZW61 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: F441A12526A23B40	FASTA	710	79,085
	10 20 30 40 50 60 MVMACRVVNK RRHMGLQQLS SFAETGRTFL GPLKSSKFII DEECHESVLI SSTVRLLESL 70 80 90 100 110 120 DLTSAVGQLL NEAVQAQNNT YRTGISTLLF LVGAWSSAVE ECLHLGVPIS IIVSVMSEGL 130 140 150 160 170 180 NFCSEEVVSL HVPVHNIFDC MDSTKTFSQL ETFSVSLCPF LQVPSDTDLI EELHGLKDVA 190 200 210 220 230 240 SQTLTISNLS GRPLKSYELF KPQTKVEADN NTSRTLKNSL LADTCCRQSI LIHSRHFNRT 250 260 270 280 290 300 DNTEGVSKPD GFQEHVTATH KTYRCNDLVE LAVGLSHGDH SSMKLVEEAV QLQYQNACVQ 310 320 330 340 350 360 QGNCTKPFMF DISRIFTCCL PGLPETSSCV CPGYITVVSV SNNPVIKELQ NQPVRIVLIE 370 380 390 400 410 420 GDLTENYRHL GFNKSANIKT VLDSMRLQED SSEELWANHV LQVLIQFKVN LVLVQGNVSE 430 440 450 460 470 480 RLIEKCINSK RLVIGSVNGS VMQAFAEAAG AVQVAYITQV NEDCVGDGVC VTFWRSSPLD 490 500 510 520 530 540 VVDRNNRIAI LLKTEGINLV TAVLTNPVTA QMQIKEDRFW TCAYRLYYAL KEEKVFLGGG 550 560 570 580 590 600 AVEFLCLSCL HILAEQSLKK ENHACSGWLH NTSSWLASSL AIYRPTVLKF LANGWQKYLS 610 620 630 640 650 660 TLLYNTANYS SEFEASTYIQ HHLQNATDSG SPSSYILNEY SKLNSRIFNS DISNKLEQIP 670 680 690 700 710 RVYDVVTPKI EAWRRALDLV LLVLQTDSEI ITGHGHTQIN SQELTGFLFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], VARIANTS GLN-386 AND ASN-467. Tissue: Spleen and Tongue.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-386. Tissue: Fetal kidney.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-386.
[5]	"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], VARIANTS ARG-195; GLN-386; ASN-467 AND VAL-615. Tissue: Brain.
[6]	"Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation." Marion V., Stoetzel C., Schlicht D., Messaddeq N., Koch M., Flori E., Danse J.M., Mandel J.-L., Dollfus H. Proc. Natl. Acad. Sci. U.S.A. 106:1820-1825(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"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: FUNCTION, IDENTIFICATION IN BBS/CCT COMPLEX, CHARACTERIZATION OF VARIANTS BBS12 VAL-113 DEL; LEU-159; PRO-289; THR-346; MET-501 AND VAL-540.
[8]	"Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome." Stoetzel C., Muller J., Laurier V., Davis E.E., Zaghloul N.A., Vicaire S., Jacquelin C., Plewniak F., Leitch C.C., Sarda P., Hamel C., de Ravel T.J., Lewis R.A., Friederich E., Thibault C., Danse J.-M., Verloes A., Bonneau D. , Katsanis N., Poch O., Mandel J.-L., Dollfus H. Am. J. Hum. Genet. 80:1-11(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BBS12 VAL-113 DEL; LEU-159; PRO-289; THR-346; MET-501 AND VAL-540, VARIANTS THR-39 AND VAL-170.
[9]	"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 BBS12 511-GLN--GLN-513 DEL, VARIANTS THR-39; ARG-408 AND CYS-524.
[10]	"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 THR-39; SER-119 AND HIS-263, VARIANTS BBS12 ARG-88; GLU-293; GLN-355; MET-400; MET-501; HIS-525; ASP-539 AND CYS-674.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK092949 mRNA. Translation: BAC04006.1. Different initiation. AK123553 mRNA. Translation: BAC85644.1. BX538148 mRNA. Translation: CAD98035.1. AC053545 Genomic DNA. No translation available. CH471056 Genomic DNA. Translation: EAX05223.1. CH471056 Genomic DNA. Translation: EAX05224.1. BC055426 mRNA. Translation: AAH55426.1.
IPI	IPI00470599.
RefSeq	NP_001171478.1. NM_001178007.1. NP_689831.2. NM_152618.2.
UniGene	Hs.400698.
3D structure databases
ProteinModelPortal	Q6ZW61.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6ZW61. 7 interactions.
STRING	9606.ENSP00000319062.
PTM databases
PhosphoSite	Q6ZW61.
Polymorphism databases
DMDM	296434408.
Proteomic databases
PaxDb	Q6ZW61.
PRIDE	Q6ZW61.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314218; ENSP00000319062; ENSG00000181004. ENST00000542236; ENSP00000438273; ENSG00000181004.
GeneID	166379.
KEGG	hsa:166379.
UCSC	uc003ieu.3. human.
Organism-specific databases
CTD	166379.
GeneCards	GC04P123653.
H-InvDB	HIX0018635.
HGNC	HGNC:26648. BBS12.
MIM	209900. phenotype. 610683. gene.
neXtProt	NX_Q6ZW61.
Orphanet	110. Bardet-Biedl syndrome.
PharmGKB	PA162377350.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39264.
HOGENOM	HOG000294113.
HOVERGEN	HBG107495.
InParanoid	Q6ZW61.
OMA	HESVLIS.
OrthoDB	EOG4F4S9G.
PhylomeDB	Q6ZW61.
Gene expression databases
ArrayExpress	Q6ZW61.
Bgee	Q6ZW61.
CleanEx	HS_BBS12.
Genevestigator	Q6ZW61.
Family and domain databases
InterPro	IPR002423. Cpn60/TCP-1. [Graphical view]
PANTHER	PTHR11353. PTHR11353. 1 hit.
Pfam	PF00118. Cpn60_TCP1. 2 hits. [Graphical view]
SUPFAM	SSF48592. GroEL-ATPase. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	166379.
NextBio	88593.
SOURCE	Search...

Entry information

Entry name

BBS12_HUMAN

Accession

Primary (citable) accession number: Q6ZW61
Secondary accession number(s): D3DNX5 , Q7Z342, Q7Z482, Q8NAB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 80 of the entry and version 2 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.