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Protein

McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin

Gene

MKKS

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

Functioni

Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis (PubMed:20080638). Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). May play a role in protein processing in limb, cardiac and reproductive system development. May play a role in cytokinesis (PubMed:28753627).2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi192 – 199ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • RNA polymerase II repressing transcription factor binding Source: MGI
  • unfolded protein binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionChaperone
Biological processSensory transduction, Vision
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-5620922 BBSome-mediated cargo-targeting to cilium

Names & Taxonomyi

Protein namesi
Recommended name:
McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin
Alternative name(s):
Bardet-Biedl syndrome 6 protein
Gene namesi
Name:MKKSImported
Synonyms:BBS61 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000125863.17
HGNCiHGNC:7108 MKKS
MIMi604896 gene
neXtProtiNX_Q9NPJ1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

McKusick-Kaufman syndrome (MKKS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive developmental disorder. It is characterized by hydrometrocolpos, postaxial polydactyly and congenital heart defects.
See also OMIM:236700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00986684H → Y in MKKS; associated with S-242; decreased interaction with BBS12; no effect on ciliogenesis; disrupts import to the nucleus; no effect on interaction with SMARCC1; may affect modulation of SMARCC1 subcellular location. 3 PublicationsCorresponds to variant dbSNP:rs281797258EnsemblClinVar.1
Bardet-Biedl syndrome 6 (BBS6)17 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:605231
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01703532I → M in BBS6. 1 Publication1
Natural variantiVAR_08022340 – 570Missing in BBS6. 1 PublicationAdd BLAST531
Natural variantiVAR_06626241G → R in BBS6. 1 PublicationCorresponds to variant dbSNP:rs766132697Ensembl.1
Natural variantiVAR_00988252G → D in BBS6; fails to associate with centrosome. 3 PublicationsCorresponds to variant dbSNP:rs28937875EnsemblClinVar.1
Natural variantiVAR_00988357T → A in BBS6; found in a patient also carrying A-155 in TMEM237; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Y-84 mutant; greatly reduces the ability to interact with BBS12. 5 PublicationsCorresponds to variant dbSNP:rs74315399EnsemblClinVar.1
Natural variantiVAR_06626399C → R in BBS6. 1 Publication1
Natural variantiVAR_017040155R → L in BBS6; increases MKKS protein degradation; localizes properly to the centrosome. 2 PublicationsCorresponds to variant dbSNP:rs138111422Ensembl.1
Natural variantiVAR_038898181A → P in BBS6. 1 Publication1
Natural variantiVAR_017036236S → P in BBS6. 3 Publications1
Natural variantiVAR_038899237T → A in BBS6. 1 PublicationCorresponds to variant dbSNP:rs760185677Ensembl.1
Natural variantiVAR_038900237T → P in BBS6. 2 Publications1
Natural variantiVAR_009884277L → P in BBS6; moderately affects interaction with BBS2; greatly reduces the ability to interact with BBS12. 2 PublicationsCorresponds to variant dbSNP:rs74315398EnsemblClinVar.1
Natural variantiVAR_017037286D → A in BBS6; fails to associate with centrosome. 2 Publications1
Natural variantiVAR_066264299P → L in BBS6. 1 PublicationCorresponds to variant dbSNP:rs756083063Ensembl.1
Natural variantiVAR_017042345G → E in BBS6; increases MKKS protein degradation; fails to associate with centrosome; the mutant is highly polyubiquitinated and rapidly degraded by the ubiquitin-proteasome protein degradation pathway. 3 PublicationsCorresponds to variant dbSNP:rs779116830Ensembl.1
Natural variantiVAR_077208395H → R in BBS6; atypical mild phenotype consisting of retinitis pigmentosa and polydactyly without other signs of Bardet-Biedl syndrome; results in decreased interaction with BBS12. 1 PublicationCorresponds to variant dbSNP:rs912923677Ensembl.1
Natural variantiVAR_038902460S → P in BBS6. 1 Publication1
Natural variantiVAR_038903492D → N in BBS6. 1 PublicationCorresponds to variant dbSNP:rs142327258EnsemblClinVar.1
Natural variantiVAR_013161499C → S in BBS6; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Tyr-84 mutant; localizes properly to the centrosome. 4 PublicationsCorresponds to variants dbSNP:rs281797259 and dbSNP:rs137853155EnsemblClinVarEnsembl.1
Natural variantiVAR_017038511S → A in BBS6. 1 Publication1
Natural variantiVAR_017039518R → H in BBS6. 1 PublicationCorresponds to variant dbSNP:rs149051148EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi454L → P: No effect on import to the nucleus. 1 Publication1

Keywords - Diseasei

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

Organism-specific databases

DisGeNETi8195
GeneReviewsiMKKS
MalaCardsiMKKS
MIMi236700 phenotype
605231 phenotype
OpenTargetsiENSG00000125863
Orphaneti110 Bardet-Biedl syndrome
2473 McKusick-Kaufman syndrome
PharmGKBiPA30826

Polymorphism and mutation databases

BioMutaiMKKS
DMDMi11133565

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001284151 – 570McKusick-Kaufman/Bardet-Biedl syndromes putative chaperoninAdd BLAST570

Proteomic databases

EPDiQ9NPJ1
PaxDbiQ9NPJ1
PeptideAtlasiQ9NPJ1
PRIDEiQ9NPJ1
ProteomicsDBi82024

PTM databases

iPTMnetiQ9NPJ1
PhosphoSitePlusiQ9NPJ1

Expressioni

Tissue specificityi

Widely expressed in adult and fetal tissues.

Gene expression databases

BgeeiENSG00000125863 Expressed in 219 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_MKKS
GenevisibleiQ9NPJ1 HS

Organism-specific databases

HPAiHPA041071
HPA044233

Interactioni

Subunit structurei

Component of a complex composed at least of MKKS, BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 AND CCT8 (PubMed:20080638). Interacts with STUB1 (PubMed:18094050). Interacts with BBS2 (via coiled coil domain) (PubMed:20080638). Interacts with CCDC28B (PubMed:16327777). Interacts with BBS12 (PubMed:26900326). Interacts with SMARCC1, a component of the SWI/SNF complexes; the interaction takes place predominantly in the cytoplasm and may modulate SMARCC1 location (PubMed:28753627).5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113837, 11 interactors
CORUMiQ9NPJ1
DIPiDIP-60349N
IntActiQ9NPJ1, 10 interactors
STRINGi9606.ENSP00000246062

Structurei

3D structure databases

ProteinModelPortaliQ9NPJ1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni198 – 370Substrate-binding apical domainAdd BLAST173

Domaini

The substrate-binding apical domain region is sufficient for centrosomal association.

Sequence similaritiesi

Belongs to the TCP-1 chaperonin family.Curated

Phylogenomic databases

eggNOGiKOG0360 Eukaryota
COG0459 LUCA
GeneTreeiENSGT00390000007214
HOGENOMiHOG000013131
HOVERGENiHBG005055
InParanoidiQ9NPJ1
KOiK09492
OMAiTSKPACM
OrthoDBiEOG091G0VW9
PhylomeDBiQ9NPJ1
TreeFamiTF329106

Family and domain databases

Gene3Di1.10.560.10, 1 hit
3.30.260.10, 1 hit
3.50.7.10, 1 hit
InterProiView protein in InterPro
IPR002423 Cpn60/TCP-1
IPR027409 GroEL-like_apical_dom_sf
IPR027413 GROEL-like_equatorial_sf
IPR028790 MKKS
IPR027410 TCP-1-like_intermed_sf
PANTHERiPTHR11353:SF77 PTHR11353:SF77, 1 hit
PfamiView protein in Pfam
PF00118 Cpn60_TCP1, 1 hit
SUPFAMiSSF48592 SSF48592, 1 hit
SSF52029 SSF52029, 1 hit

Sequencei

Sequence statusi: Complete.

Q9NPJ1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSRLEAKKPS LCKSEPLTTE RVRTTLSVLK RIVTSCYGPS GRLKQLHNGF
60 70 80 90 100
GGYVCTTSQS SALLSHLLVT HPILKILTAS IQNHVSSFSD CGLFTAILCC
110 120 130 140 150
NLIENVQRLG LTPTTVIRLN KHLLSLCISY LKSETCGCRI PVDFSSTQIL
160 170 180 190 200
LCLVRSILTS KPACMLTRKE TEHVSALILR AFLLTIPENA EGHIILGKSL
210 220 230 240 250
IVPLKGQRVI DSTVLPGILI EMSEVQLMRL LPIKKSTALK VALFCTTLSG
260 270 280 290 300
DTSDTGEGTV VVSYGVSLEN AVLDQLLNLG RQLISDHVDL VLCQKVIHPS
310 320 330 340 350
LKQFLNMHRI IAIDRIGVTL MEPLTKMTGT QPIGSLGSIC PNSYGSVKDV
360 370 380 390 400
CTAKFGSKHF FHLIPNEATI CSLLLCNRND TAWDELKLTC QTALHVLQLT
410 420 430 440 450
LKEPWALLGG GCTETHLAAY IRHKTHNDPE SILKDDECTQ TELQLIAEAF
460 470 480 490 500
CSALESVVGS LEHDGGEILT DMKYGHLWSV QADSPCVANW PDLLSQCGCG
510 520 530 540 550
LYNSQEELNW SFLRSTRRPF VPQSCLPHEA VGSASNLTLD CLTAKLSGLQ
560 570
VAVETANLIL DLSYVIEDKN
Length:570
Mass (Da):62,342
Last modified:October 1, 2000 - v1
Checksum:i14BA57FF8AEA0AF7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01703532I → M in BBS6. 1 Publication1
Natural variantiVAR_00986437Y → C in MKKS and BBS6; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Tyr-84 mutant; the mutant is immobilized at the centrosome even in the absence of proteasome inhibition; the mutant is also highly polyubiquitinated; no effect on import to the nucleus. 6 PublicationsCorresponds to variant dbSNP:rs74315396EnsemblClinVar.1
Natural variantiVAR_08022340 – 570Missing in BBS6. 1 PublicationAdd BLAST531
Natural variantiVAR_06626241G → R in BBS6. 1 PublicationCorresponds to variant dbSNP:rs766132697Ensembl.1
Natural variantiVAR_00986549G → V1 PublicationCorresponds to variant dbSNP:rs528833454Ensembl.1
Natural variantiVAR_00988252G → D in BBS6; fails to associate with centrosome. 3 PublicationsCorresponds to variant dbSNP:rs28937875EnsemblClinVar.1
Natural variantiVAR_00988357T → A in BBS6; found in a patient also carrying A-155 in TMEM237; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Y-84 mutant; greatly reduces the ability to interact with BBS12. 5 PublicationsCorresponds to variant dbSNP:rs74315399EnsemblClinVar.1
Natural variantiVAR_00986684H → Y in MKKS; associated with S-242; decreased interaction with BBS12; no effect on ciliogenesis; disrupts import to the nucleus; no effect on interaction with SMARCC1; may affect modulation of SMARCC1 subcellular location. 3 PublicationsCorresponds to variant dbSNP:rs281797258EnsemblClinVar.1
Natural variantiVAR_06626399C → R in BBS6. 1 Publication1
Natural variantiVAR_017040155R → L in BBS6; increases MKKS protein degradation; localizes properly to the centrosome. 2 PublicationsCorresponds to variant dbSNP:rs138111422Ensembl.1
Natural variantiVAR_038898181A → P in BBS6. 1 Publication1
Natural variantiVAR_017036236S → P in BBS6. 3 Publications1
Natural variantiVAR_038899237T → A in BBS6. 1 PublicationCorresponds to variant dbSNP:rs760185677Ensembl.1
Natural variantiVAR_038900237T → P in BBS6. 2 Publications1
Natural variantiVAR_009867242A → S in MKKS and BBS6; associated with Y-84 in MKKS; unknown pathological significance; increases MKKS protein degradation; no effect on ciliogenesis; disrupts import to the nucleus; no effect on interaction with SMARCC1; may affect modulation of SMARCC1 subcellular location. 8 PublicationsCorresponds to variant dbSNP:rs74315394EnsemblClinVar.1
Natural variantiVAR_009884277L → P in BBS6; moderately affects interaction with BBS2; greatly reduces the ability to interact with BBS12. 2 PublicationsCorresponds to variant dbSNP:rs74315398EnsemblClinVar.1
Natural variantiVAR_017037286D → A in BBS6; fails to associate with centrosome. 2 Publications1
Natural variantiVAR_066264299P → L in BBS6. 1 PublicationCorresponds to variant dbSNP:rs756083063Ensembl.1
Natural variantiVAR_038901325T → P Has a modifier effect on BBS; causes a mislocalization of the protein; fails to associate with centrosome. 3 PublicationsCorresponds to variant dbSNP:rs137853156EnsemblClinVar.1
Natural variantiVAR_017041339I → V3 PublicationsCorresponds to variant dbSNP:rs137853909EnsemblClinVar.1
Natural variantiVAR_017042345G → E in BBS6; increases MKKS protein degradation; fails to associate with centrosome; the mutant is highly polyubiquitinated and rapidly degraded by the ubiquitin-proteasome protein degradation pathway. 3 PublicationsCorresponds to variant dbSNP:rs779116830Ensembl.1
Natural variantiVAR_077208395H → R in BBS6; atypical mild phenotype consisting of retinitis pigmentosa and polydactyly without other signs of Bardet-Biedl syndrome; results in decreased interaction with BBS12. 1 PublicationCorresponds to variant dbSNP:rs912923677Ensembl.1
Natural variantiVAR_038902460S → P in BBS6. 1 Publication1
Natural variantiVAR_066265488A → T in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS12; uncertain pathological role. 1 PublicationCorresponds to variant dbSNP:rs61734546EnsemblClinVar.1
Natural variantiVAR_038903492D → N in BBS6. 1 PublicationCorresponds to variant dbSNP:rs142327258EnsemblClinVar.1
Natural variantiVAR_013161499C → S in BBS6; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Tyr-84 mutant; localizes properly to the centrosome. 4 PublicationsCorresponds to variants dbSNP:rs281797259 and dbSNP:rs137853155EnsemblClinVarEnsembl.1
Natural variantiVAR_017038511S → A in BBS6. 1 Publication1
Natural variantiVAR_009868517R → C4 PublicationsCorresponds to variant dbSNP:rs1547EnsemblClinVar.1
Natural variantiVAR_017039518R → H in BBS6. 1 PublicationCorresponds to variant dbSNP:rs149051148EnsemblClinVar.1
Natural variantiVAR_009869532G → V3 PublicationsCorresponds to variant dbSNP:rs1545EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF221992 mRNA Translation: AAF73872.1
AF221993 mRNA Translation: AAF73873.1
AK291925 mRNA Translation: BAF84614.1
AL157427 mRNA Translation: CAB75652.1
AL034430 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10344.1
CH471133 Genomic DNA Translation: EAX10345.1
CCDSiCCDS13111.1
PIRiT46911
RefSeqiNP_061336.1, NM_018848.3
NP_740754.1, NM_170784.2
UniGeneiHs.472119
Hs.741430

Genome annotation databases

EnsembliENST00000347364; ENSP00000246062; ENSG00000125863
ENST00000399054; ENSP00000382008; ENSG00000125863
GeneIDi8195
KEGGihsa:8195
UCSCiuc002wnt.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Mutations of the MKKS gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF221992 mRNA Translation: AAF73872.1
AF221993 mRNA Translation: AAF73873.1
AK291925 mRNA Translation: BAF84614.1
AL157427 mRNA Translation: CAB75652.1
AL034430 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10344.1
CH471133 Genomic DNA Translation: EAX10345.1
CCDSiCCDS13111.1
PIRiT46911
RefSeqiNP_061336.1, NM_018848.3
NP_740754.1, NM_170784.2
UniGeneiHs.472119
Hs.741430

3D structure databases

ProteinModelPortaliQ9NPJ1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113837, 11 interactors
CORUMiQ9NPJ1
DIPiDIP-60349N
IntActiQ9NPJ1, 10 interactors
STRINGi9606.ENSP00000246062

PTM databases

iPTMnetiQ9NPJ1
PhosphoSitePlusiQ9NPJ1

Polymorphism and mutation databases

BioMutaiMKKS
DMDMi11133565

Proteomic databases

EPDiQ9NPJ1
PaxDbiQ9NPJ1
PeptideAtlasiQ9NPJ1
PRIDEiQ9NPJ1
ProteomicsDBi82024

Protocols and materials databases

DNASUi8195
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000347364; ENSP00000246062; ENSG00000125863
ENST00000399054; ENSP00000382008; ENSG00000125863
GeneIDi8195
KEGGihsa:8195
UCSCiuc002wnt.3 human

Organism-specific databases

CTDi8195
DisGeNETi8195
EuPathDBiHostDB:ENSG00000125863.17
GeneCardsiMKKS
GeneReviewsiMKKS
HGNCiHGNC:7108 MKKS
HPAiHPA041071
HPA044233
MalaCardsiMKKS
MIMi236700 phenotype
604896 gene
605231 phenotype
neXtProtiNX_Q9NPJ1
OpenTargetsiENSG00000125863
Orphaneti110 Bardet-Biedl syndrome
2473 McKusick-Kaufman syndrome
PharmGKBiPA30826
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0360 Eukaryota
COG0459 LUCA
GeneTreeiENSGT00390000007214
HOGENOMiHOG000013131
HOVERGENiHBG005055
InParanoidiQ9NPJ1
KOiK09492
OMAiTSKPACM
OrthoDBiEOG091G0VW9
PhylomeDBiQ9NPJ1
TreeFamiTF329106

Enzyme and pathway databases

ReactomeiR-HSA-5620922 BBSome-mediated cargo-targeting to cilium

Miscellaneous databases

ChiTaRSiMKKS human
GeneWikiiMKKS
GenomeRNAii8195
PROiPR:Q9NPJ1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125863 Expressed in 219 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_MKKS
GenevisibleiQ9NPJ1 HS

Family and domain databases

Gene3Di1.10.560.10, 1 hit
3.30.260.10, 1 hit
3.50.7.10, 1 hit
InterProiView protein in InterPro
IPR002423 Cpn60/TCP-1
IPR027409 GroEL-like_apical_dom_sf
IPR027413 GROEL-like_equatorial_sf
IPR028790 MKKS
IPR027410 TCP-1-like_intermed_sf
PANTHERiPTHR11353:SF77 PTHR11353:SF77, 1 hit
PfamiView protein in Pfam
PF00118 Cpn60_TCP1, 1 hit
SUPFAMiSSF48592 SSF48592, 1 hit
SSF52029 SSF52029, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMKKS_HUMAN
AccessioniPrimary (citable) accession number: Q9NPJ1
Secondary accession number(s): A8K7B0, D3DW18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 170 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
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