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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NPJ1: Variant p.Thr57Ala

Molecular chaperone MKKS
Gene: MKKS
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Variant information Variant position: help 57 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Threonine (T) to Alanine (A) at position 57 (T57A, p.Thr57Ala). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help 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. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 57 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 570 The length of the canonical sequence.
Location on the sequence: help YGPSGRLKQLHNGFGGYVCT T SQSSALLSHLLVTHPILKIL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         YGPSGRLKQLHNGFGGYVCTTSQSSALLSHLLVTHPILKIL

Mouse                         YGPSGRLKQLHNGLGGCVYTTSQSSALLRNLSVTHPVLKIL
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 570 Molecular chaperone MKKS



Literature citations
MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.
Hirayama S.; Yamazaki Y.; Kitamura A.; Oda Y.; Morito D.; Okawa K.; Kimura H.; Cyr D.M.; Kubota H.; Nagata K.;
Mol. Biol. Cell 19:899-911(2008)
Cited for: SUBCELLULAR LOCATION; INTERACTION WITH STUB1; CHARACTERIZATION OF VARIANTS BBS6 CYS-37; ALA-57; SER-242; GLU-345 AND SER-499; 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)
Cited for: FUNCTION; IDENTIFICATION IN A MULTIPROTEIN COMPLEX; INTERACTION WITH BBS2; CHARACTERIZATION OF VARIANTS BBS6 CYS-37; ASP-52; ALA-57; TYR-84; PRO-236 AND PRO-277; Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.
Katsanis N.; Beales P.L.; Woods M.O.; Lewis R.A.; Green J.S.; Parfrey P.S.; Ansley S.J.; Davidson W.S.; Lupski J.R.;
Nat. Genet. 26:67-70(2000)
Cited for: VARIANTS BBS6 CYS-37; ALA-57 AND PRO-277; Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.
Beales P.L.; Katsanis N.; Lewis R.A.; Ansley S.J.; Elcioglu N.; Raza J.; Woods M.O.; Green J.S.; Parfrey P.S.; Davidson W.S.; Lupski J.R.;
Am. J. Hum. Genet. 68:606-616(2001)
Cited for: VARIANTS BBS6 MET-32; ALA-57; PRO-236; ALA-286; SER-499; ALA-511 AND HIS-518; VARIANT SER-242; TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.
Huang L.; Szymanska K.; Jensen V.L.; Janecke A.R.; Innes A.M.; Davis E.E.; Frosk P.; Li C.; Willer J.R.; Chodirker B.N.; Greenberg C.R.; McLeod D.R.; Bernier F.P.; Chudley A.E.; Muller T.; Shboul M.; Logan C.V.; Loucks C.M.; Beaulieu C.L.; Bowie R.V.; Bell S.M.; Adkins J.; Zuniga F.I.; Ross K.D.; Wang J.; Ban M.R.; Becker C.; Nurnberg P.; Douglas S.; Craft C.M.; Akimenko M.A.; Hegele R.A.; Ober C.; Utermann G.; Bolz H.J.; Bulman D.E.; Katsanis N.; Blacque O.E.; Doherty D.; Parboosingh J.S.; Leroux M.R.; Johnson C.A.; Boycott K.M.;
Am. J. Hum. Genet. 89:713-730(2011)
Cited for: VARIANT BBS6 ALA-57;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.