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Protein

Bardet-Biedl syndrome 4 protein

Gene

BBS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. 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. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization. Required for microtubule anchoring at the centrosome but not for microtubule nucleation. May be required for the dynein-mediated transport of pericentriolar proteins to the centrosome.3 Publications

GO - Molecular functioni

  • alpha-tubulin binding Source: BHF-UCL
  • beta-tubulin binding Source: BHF-UCL
  • dynactin binding Source: BHF-UCL
  • microtubule motor activity Source: UniProtKB
  • RNA polymerase II repressing transcription factor binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Protein transport, Sensory transduction, Transport, Vision

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140463-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Names & Taxonomyi

Protein namesi
Recommended name:
Bardet-Biedl syndrome 4 protein
Gene namesi
Name:BBS4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:969. BBS4.

Subcellular locationi

GO - Cellular componenti

  • BBSome Source: UniProtKB
  • centriolar satellite Source: UniProtKB
  • centriole Source: BHF-UCL
  • centrosome Source: UniProtKB
  • ciliary basal body Source: BHF-UCL
  • ciliary membrane Source: BHF-UCL
  • ciliary transition zone Source: GO_Central
  • cilium Source: UniProtKB
  • cytosol Source: Reactome
  • motile cilium Source: BHF-UCL
  • non-motile cilium Source: BHF-UCL
  • nucleus Source: GOC
  • pericentriolar material Source: UniProtKB
  • photoreceptor connecting cilium Source: Ensembl
  • photoreceptor inner segment Source: Ensembl
  • photoreceptor outer segment Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Bardet-Biedl syndrome 4 (BBS4)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615982
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017049165N → H in BBS4. 1 Publication1
Natural variantiVAR_013170295R → P in BBS4. 1 PublicationCorresponds to variant rs121434632dbSNPEnsembl.1
Natural variantiVAR_017050327L → P in BBS4. 1 Publication1
Natural variantiVAR_038895351L → R in BBS4. 1 Publication1
Natural variantiVAR_017051364A → E in BBS4. 1 PublicationCorresponds to variant rs28938468dbSNPEnsembl.1
Natural variantiVAR_038896368D → G in BBS4. 1 PublicationCorresponds to variant rs772548770dbSNPEnsembl.1
Natural variantiVAR_017052457S → I in BBS4. 1 Publication1
Natural variantiVAR_017053472M → V in BBS4. 2 PublicationsCorresponds to variant rs2277596dbSNPEnsembl.1
Natural variantiVAR_038897503P → L in BBS4. Corresponds to variant rs756419611dbSNPEnsembl.1

Keywords - Diseasei

Bardet-Biedl syndrome, Ciliopathy, Disease mutation, Mental retardation, Obesity

Organism-specific databases

DisGeNETi585.
MalaCardsiBBS4.
MIMi615982. phenotype.
OpenTargetsiENSG00000140463.
Orphaneti110. Bardet-Biedl syndrome.
PharmGKBiPA25278.

Polymorphism and mutation databases

BioMutaiBBS4.
DMDMi160359000.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001062631 – 519Bardet-Biedl syndrome 4 proteinAdd BLAST519

Proteomic databases

EPDiQ96RK4.
MaxQBiQ96RK4.
PaxDbiQ96RK4.
PeptideAtlasiQ96RK4.
PRIDEiQ96RK4.

PTM databases

iPTMnetiQ96RK4.
PhosphoSitePlusiQ96RK4.

Expressioni

Tissue specificityi

Ubiquitously expressed. The highest level of expression is found in the kidney.

Gene expression databases

BgeeiENSG00000140463.
CleanExiHS_BBS4.
ExpressionAtlasiQ96RK4. baseline and differential.
GenevisibleiQ96RK4. HS.

Organism-specific databases

HPAiHPA039418.
HPA040386.

Interactioni

Subunit structurei

Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1 and DCTN1. Interacts with DC28B. Interacts with ALDOB and C2CD3. Interacts with PKD1 (PubMed:24939912). Interacts with CEP290 (PubMed:23943788).7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ALDOBP050624EBI-1805814,EBI-1045507
BBIP1A8MTZ03EBI-1805814,EBI-2892417
BBS1Q8NFJ97EBI-1805814,EBI-1805484
CEP290O150782EBI-1805814,EBI-1811944
DCTN1Q142033EBI-1805814,EBI-724352
EPAS1Q998142EBI-1805814,EBI-447470
IQCB1Q150515EBI-1805814,EBI-2805823
MYOGP151733EBI-1805814,EBI-3906629
PCM1Q1515416EBI-1805814,EBI-741421

GO - Molecular functioni

  • alpha-tubulin binding Source: BHF-UCL
  • beta-tubulin binding Source: BHF-UCL
  • dynactin binding Source: BHF-UCL
  • RNA polymerase II repressing transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi107060. 31 interactors.
DIPiDIP-46540N.
IntActiQ96RK4. 50 interactors.
STRINGi9606.ENSP00000268057.

Structurei

3D structure databases

ProteinModelPortaliQ96RK4.
SMRiQ96RK4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati67 – 100TPR 1Add BLAST34
Repeati101 – 134TPR 2Add BLAST34
Repeati135 – 168TPR 3Add BLAST34
Repeati169 – 201TPR 4Add BLAST33
Repeati203 – 235TPR 5Add BLAST33
Repeati237 – 269TPR 6Add BLAST33
Repeati270 – 303TPR 7Add BLAST34
Repeati304 – 337TPR 8Add BLAST34
Repeati339 – 371TPR 9Add BLAST33
Repeati373 – 408TPR 10Add BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 66Required for localization to centrosomesAdd BLAST66
Regioni101 – 337Interaction with PCM11 PublicationAdd BLAST237
Regioni338 – 519Required for localization to centrosomesAdd BLAST182

Sequence similaritiesi

Belongs to the BBS4 family.Curated
Contains 10 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00530000063455.
HOGENOMiHOG000261391.
HOVERGENiHBG024456.
InParanoidiQ96RK4.
KOiK16531.
OMAiQETHGLC.
OrthoDBiEOG091G09T3.
PhylomeDBiQ96RK4.
TreeFamiTF324966.

Family and domain databases

Gene3Di1.25.40.10. 3 hits.
InterProiIPR028786. BBS4.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR23083:SF398. PTHR23083:SF398. 1 hit.
PfamiPF13414. TPR_11. 2 hits.
PF13181. TPR_8. 3 hits.
[Graphical view]
SMARTiSM00028. TPR. 8 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50005. TPR. 8 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96RK4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEERVATRT QFPVSTESQK PRQKKAPEFP ILEKQNWLIH LHYIRKDYEA
60 70 80 90 100
CKAVIKEQLQ ETQGLCEYAI YVQALIFRLE GNIQESLELF QTCAVLSPQS
110 120 130 140 150
ADNLKQVARS LFLLGKHKAA IEVYNEAAKL NQKDWEISHN LGVCYIYLKQ
160 170 180 190 200
FNKAQDQLHN ALNLNRHDLT YIMLGKIHLL EGDLDKAIEV YKKAVEFSPE
210 220 230 240 250
NTELLTTLGL LYLQLGIYQK AFEHLGNALT YDPTNYKAIL AAGSMMQTHG
260 270 280 290 300
DFDVALTKYR VVACAVPESP PLWNNIGMCF FGKKKYVAAI SCLKRANYLA
310 320 330 340 350
PFDWKILYNL GLVHLTMQQY ASAFHFLSAA INFQPKMGEL YMLLAVALTN
360 370 380 390 400
LEDIENAKRA YAEAVHLDKC NPLVNLNYAV LLYNQGEKKN ALAQYQEMEK
410 420 430 440 450
KVSLLKDNSS LEFDSEMVEM AQKLGAALQV GEALVWTKPV KDPKSKHQTT
460 470 480 490 500
STSKPASFQQ PLGSNQALGQ AMSSAAAYRT LPSGAGGTSQ FTKPPSLPLE
510
PEPAVESSPT ETSEQIREK
Length:519
Mass (Da):58,282
Last modified:October 23, 2007 - v2
Checksum:i59BC9B29355C8E3C
GO
Isoform 2 (identifier: Q96RK4-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:527
Mass (Da):59,084
Checksum:i09A45FF715582D14
GO
Isoform 3 (identifier: Q96RK4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: Missing.

Note: No experimental confirmation available.
Show »
Length:347
Mass (Da):38,282
Checksum:i22AAB3D93C36F0E9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03889446K → R.2 PublicationsCorresponds to variant rs75295839dbSNPEnsembl.1
Natural variantiVAR_06628761E → K Found in patients with Bardet-Biedl syndrome carrying mutations in other BBS genes; uncertain pathological role. 1 Publication1
Natural variantiVAR_017049165N → H in BBS4. 1 Publication1
Natural variantiVAR_028722268E → K.Corresponds to variant rs11638283dbSNPEnsembl.1
Natural variantiVAR_013170295R → P in BBS4. 1 PublicationCorresponds to variant rs121434632dbSNPEnsembl.1
Natural variantiVAR_017050327L → P in BBS4. 1 Publication1
Natural variantiVAR_038895351L → R in BBS4. 1 Publication1
Natural variantiVAR_017054354I → T.3 PublicationsCorresponds to variant rs2277598dbSNPEnsembl.1
Natural variantiVAR_017051364A → E in BBS4. 1 PublicationCorresponds to variant rs28938468dbSNPEnsembl.1
Natural variantiVAR_038896368D → G in BBS4. 1 PublicationCorresponds to variant rs772548770dbSNPEnsembl.1
Natural variantiVAR_028723393A → V.1 PublicationCorresponds to variant rs17852452dbSNPEnsembl.1
Natural variantiVAR_066288412E → D in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS1; uncertain pathological role. 1 PublicationCorresponds to variant rs147202164dbSNPEnsembl.1
Natural variantiVAR_017052457S → I in BBS4. 1 Publication1
Natural variantiVAR_017053472M → V in BBS4. 2 PublicationsCorresponds to variant rs2277596dbSNPEnsembl.1
Natural variantiVAR_066289488T → K in a patient with Bardet-Biedl syndrome homozygous for a mutation in BBS12; uncertain pathological role. 1 PublicationCorresponds to variant rs561284402dbSNPEnsembl.1
Natural variantiVAR_038897503P → L in BBS4. Corresponds to variant rs756419611dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0475071 – 172Missing in isoform 3. 1 PublicationAdd BLAST172
Alternative sequenceiVSP_0244101 – 8MAEERVAT → MALTVVPSFSVSGVWK in isoform 2. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF359281 mRNA. Translation: AAK58868.1.
AY457143 mRNA. Translation: AAS13441.1.
AK075321 mRNA. Translation: BAC11547.1.
AK303706 mRNA. Translation: BAG64690.1.
AC009712 Genomic DNA. No translation available.
BC008923 mRNA. Translation: AAH08923.2.
BC027624 mRNA. Translation: AAH27624.1.
CCDSiCCDS10246.1. [Q96RK4-1]
CCDS58377.1. [Q96RK4-3]
RefSeqiNP_001239607.1. NM_001252678.1. [Q96RK4-3]
NP_001307594.1. NM_001320665.1.
NP_149017.2. NM_033028.4. [Q96RK4-1]
XP_011520150.1. XM_011521848.1. [Q96RK4-3]
XP_011520151.1. XM_011521849.1. [Q96RK4-3]
XP_016877940.1. XM_017022451.1. [Q96RK4-3]
XP_016877941.1. XM_017022452.1. [Q96RK4-3]
XP_016877942.1. XM_017022453.1. [Q96RK4-3]
XP_016877943.1. XM_017022454.1. [Q96RK4-3]
UniGeneiHs.208681.

Genome annotation databases

EnsembliENST00000268057; ENSP00000268057; ENSG00000140463. [Q96RK4-1]
ENST00000395205; ENSP00000378631; ENSG00000140463. [Q96RK4-3]
GeneIDi585.
KEGGihsa:585.
UCSCiuc002avb.4. human. [Q96RK4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Mutations of the BBS4 gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF359281 mRNA. Translation: AAK58868.1.
AY457143 mRNA. Translation: AAS13441.1.
AK075321 mRNA. Translation: BAC11547.1.
AK303706 mRNA. Translation: BAG64690.1.
AC009712 Genomic DNA. No translation available.
BC008923 mRNA. Translation: AAH08923.2.
BC027624 mRNA. Translation: AAH27624.1.
CCDSiCCDS10246.1. [Q96RK4-1]
CCDS58377.1. [Q96RK4-3]
RefSeqiNP_001239607.1. NM_001252678.1. [Q96RK4-3]
NP_001307594.1. NM_001320665.1.
NP_149017.2. NM_033028.4. [Q96RK4-1]
XP_011520150.1. XM_011521848.1. [Q96RK4-3]
XP_011520151.1. XM_011521849.1. [Q96RK4-3]
XP_016877940.1. XM_017022451.1. [Q96RK4-3]
XP_016877941.1. XM_017022452.1. [Q96RK4-3]
XP_016877942.1. XM_017022453.1. [Q96RK4-3]
XP_016877943.1. XM_017022454.1. [Q96RK4-3]
UniGeneiHs.208681.

3D structure databases

ProteinModelPortaliQ96RK4.
SMRiQ96RK4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107060. 31 interactors.
DIPiDIP-46540N.
IntActiQ96RK4. 50 interactors.
STRINGi9606.ENSP00000268057.

PTM databases

iPTMnetiQ96RK4.
PhosphoSitePlusiQ96RK4.

Polymorphism and mutation databases

BioMutaiBBS4.
DMDMi160359000.

Proteomic databases

EPDiQ96RK4.
MaxQBiQ96RK4.
PaxDbiQ96RK4.
PeptideAtlasiQ96RK4.
PRIDEiQ96RK4.

Protocols and materials databases

DNASUi585.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000268057; ENSP00000268057; ENSG00000140463. [Q96RK4-1]
ENST00000395205; ENSP00000378631; ENSG00000140463. [Q96RK4-3]
GeneIDi585.
KEGGihsa:585.
UCSCiuc002avb.4. human. [Q96RK4-1]

Organism-specific databases

CTDi585.
DisGeNETi585.
GeneCardsiBBS4.
GeneReviewsiBBS4.
H-InvDBHIX0012411.
HGNCiHGNC:969. BBS4.
HPAiHPA039418.
HPA040386.
MalaCardsiBBS4.
MIMi600374. gene.
615982. phenotype.
neXtProtiNX_Q96RK4.
OpenTargetsiENSG00000140463.
Orphaneti110. Bardet-Biedl syndrome.
PharmGKBiPA25278.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00530000063455.
HOGENOMiHOG000261391.
HOVERGENiHBG024456.
InParanoidiQ96RK4.
KOiK16531.
OMAiQETHGLC.
OrthoDBiEOG091G09T3.
PhylomeDBiQ96RK4.
TreeFamiTF324966.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140463-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Miscellaneous databases

GeneWikiiBBS4.
GenomeRNAii585.
PROiQ96RK4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140463.
CleanExiHS_BBS4.
ExpressionAtlasiQ96RK4. baseline and differential.
GenevisibleiQ96RK4. HS.

Family and domain databases

Gene3Di1.25.40.10. 3 hits.
InterProiIPR028786. BBS4.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR23083:SF398. PTHR23083:SF398. 1 hit.
PfamiPF13414. TPR_11. 2 hits.
PF13181. TPR_8. 3 hits.
[Graphical view]
SMARTiSM00028. TPR. 8 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50005. TPR. 8 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBBS4_HUMAN
AccessioniPrimary (citable) accession number: Q96RK4
Secondary accession number(s): B4E178
, Q53DZ5, Q8NHU9, Q96H45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: October 23, 2007
Last modified: November 30, 2016
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.