Mkks McKusick-Kaufman syndrome [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mkksprovided by MGI
Official Full Name: McKusick-Kaufman syndromeprovided by MGI
Primary source: MGI:MGI:1891836
See related: Ensembl:ENSMUSG00000027274 AllianceGenome:MGI:1891836
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Bbs6; 1300013E18Rik
Summary: This gene encodes a protein which shares sequence similarity with other members of the type II chaperonin family. The encoded protein is a centrosome-shuttling protein and plays an important role in cytokinesis. This protein also interacts with other type II chaperonin members to form a complex known as the BBSome, which involves ciliary membrane biogenesis. This protein is encoded by a downstream open reading frame (dORF). Several upstream open reading frames (uORFs) have been identified, which repress the translation of the dORF, and two of which can encode small mitochondrial membrane proteins. Alternatively spliced transcripts encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
Expression: Ubiquitous expression in heart adult (RPKM 8.1), bladder adult (RPKM 6.4) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 F3; 2 67.64 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (136715700..136733422, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (136873780..136891406, complement)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Loss of Bardet-Biedl Syndrome proteins (BBS) proteins Bbs6 and Bbs8 affects ciliated retinal pigment epithelium (RPE).
Title: Bardet-Biedl Syndrome proteins regulate cilia disassembly during tissue maturation.
Three uORFs (uMKKS0, uMKKS1 and uMKKS2) are reported, and they can repress the translation of the downstream MKKS ORF. uMKKS1 and uMKKS2 are highly conserved in mammals and they encode two different mitochondrial membrane proteins respectively.
Title: Translational repression of the McKusick-Kaufman syndrome transcript by unique upstream open reading frames encoding mitochondrial proteins with alternative polyadenylation sites.
Combinations of Cep290rd16 & Mkksko alleles improved ciliogenesis & sensory functions vs either mutant alone. Altered association of CEP290 & MKKS affects multiprotein complex integrity at the cilia transition zone & basal body.
Title: Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.
Data implicate Bardet-Biedl syndrome genes in the regulation of vascular function and demonstrate that disrupting Bbs2 and Bbs6 genes affect differentially the vascular function.
Title: Contrasting vascular effects caused by loss of Bardet-Biedl syndrome genes.
Bardet-Biedl syndrome (BBS) proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS.
Title: Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling.
These results indicate that the MKKS mutants have an abnormal conformation and that chaperone-dependent degradation mediated by CHIP is a key feature of McKusick-Kaufman syndrome/Bardet-Biedl syndrome diseases.
Title: MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.
Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in a fraction of cilia covering mouse airway epithelia in Bbs1, Bbs2, Bbs4, and Bbs6 mutant mice.
Title: Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.
MKKS/BBS6 is a novel centrosomal component required for cytokinesis
Title: MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis.
Mutations in Mkks are the basis of the BBS-like syndrome in knockout mice.
Title: Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (1) 1 citation
Gene trapped (1) 1 citation

General gene information

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Markers

AI463362 (e-PCR)
- UniSTS:178724

AI957237 (e-PCR)
- UniSTS:164182

Mkks (e-PCR), detects polymorphism
- UniSTS:525920

RH137166 (e-PCR)
- UniSTS:219254

MARC_17187-17188:1021314368:3 (e-PCR)
- UniSTS:268244

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables unfolded protein binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within artery smooth muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within brain morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cartilage development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cerebral cortex development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chaperone-mediated protein complex assembly	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within chaperone-mediated protein complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cilium assembly	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cilium assembly	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within detection of mechanical stimulus involved in sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in developmental process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within face development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fat cell differentiation	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hippocampus development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within leptin-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of appetite by leptin-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within non-motile cilium assembly	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within non-motile cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within photoreceptor cell maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein folding	IEA Inferred from Electronic Annotation more info
involved_in regulation of cilium beat frequency involved in ciliary motility	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of stress fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to leptin	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sensory perception of smell	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within spermatid development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within striatum development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vasodilation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in ciliary basal body	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in kinociliary basal body	IBA Inferred from Biological aspect of Ancestor more info
located_in kinociliary basal body	IDA Inferred from Direct Assay more info	PubMed
located_in motile cilium	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: molecular chaperone MKKS

Names: McKusick-Kaufman syndrome protein; McKusick-Kaufman syndrome protein; MKKS protein; mcKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin; protein Bbs6 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001141946.1 → NP_001135418.1 molecular chaperone MKKS isoform 1

See identical proteins and their annotated locations for NP_001135418.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

BC080765, BY735964

Consensus CDS

CCDS16794.1

UniProtKB/Swiss-Prot

Q8BGQ3, Q9JI70

Related

ENSMUSP00000028730.7, ENSMUST00000028730.13

Conserved Domains (1) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family
NM_001286981.1 → NP_001273910.1 molecular chaperone MKKS isoform 2

See identical proteins and their annotated locations for NP_001273910.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame segment in the coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AI662260, AK004987, AK008406, BY735964, CJ157733

UniProtKB/TrEMBL

Q9DBF3

Conserved Domains (2) summary

pfam00118
Location:29 → 501

Cpn60_TCP1; TCP-1/cpn60 chaperonin family

cl02777
Location:32 → 401

chaperonin_like; chaperonin_like superfamily. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I ...
NM_001286983.1 → NP_001273912.1 molecular chaperone MKKS isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an internal exon, which results in a downstream start codon compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

BC100336, BY735964, CJ157733

Conserved Domains (1) summary

cl02777
Location:3 → 73

chaperonin_like; chaperonin_like superfamily. Chaperonins are involved in productive folding of proteins. They share a common general morphology, a double toroid of 2 stacked rings, each composed of 7-9 subunits. There are 2 main chaperonin groups. The symmetry of type I ...
NM_021527.2 → NP_067502.2 molecular chaperone MKKS isoform 1

See identical proteins and their annotated locations for NP_067502.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC080765, BY735964, CJ157733

Consensus CDS

CCDS16794.1

UniProtKB/Swiss-Prot

Q8BGQ3, Q9JI70

Related

ENSMUSP00000105716.3, ENSMUST00000110089.9

Conserved Domains (1) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

136715700..136733422 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036162438.1 → XP_036018331.1 molecular chaperone MKKS isoform X1

UniProtKB/Swiss-Prot

Q8BGQ3, Q9JI70

Conserved Domains (1) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family
XM_036162437.1 → XP_036018330.1 molecular chaperone MKKS isoform X1

UniProtKB/Swiss-Prot

Q8BGQ3, Q9JI70

Conserved Domains (1) summary

pfam00118
Location:29 → 569

Cpn60_TCP1; TCP-1/cpn60 chaperonin family