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UniProtKB/Swiss-Prot Q9Y2K2: Variant p.Arg187Cys

Serine/threonine-protein kinase SIK3
Gene: SIK3
Variant information

Variant position:  187
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Cysteine (C) at position 187 (R187C, p.Arg187Cys).
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:  Change from large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Involvement in disease:  Spondyloepimetaphyseal dysplasia, Krakow type (SEMDK) [MIM:618162]: An autosomal recessive skeletal disorder characterized by severe spondyloepimetaphyseal dysplasia, rhizomelia, mesomelia with significant anterior bowing of all limbs, severe immunodeficiency, and developmental delay. {ECO:0000269|PubMed:30232230}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In SEMDK; decreased protein expression; decreased kinase activity; no effect on the interaction with DEPTOR, MLST8/GbetaL, RICTOR and RPTOR.
Any additional useful information about the variant.



Sequence information

Variant position:  187
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1321
The length of the canonical sequence.

Location on the sequence:   RKFKQIVTAVYFCHCRNIVH  R DLKAENLLLDANLNIKIADF
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLNIKIADF

Mouse                         RKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLNIKIADF

Zebrafish                     RKFKQIVAAVYFCHCRSIVHRDLKAENLLLDHNLNIKIADF

Sequence annotation in neighborhood:  
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 – 1321 Serine/threonine-protein kinase SIK3
Domain 66 – 317 Protein kinase
Active site 188 – 188 Proton acceptor
Alternative sequence 1 – 760 MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYEIDRTIGKGNFAVVKRATHLVTKAKVAIKIIDKTQLDEENLKKIFREVQIMKMLCHPHIIRLYQVMETERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLNIKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPFDGSTLQNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQLKEERQVDPLNEDVLLAMEDMGLDKEQTLQSLRSDAYDHYSAIYSLLCDRHKRHKTLRLGALPSMPRALAFQAPVNIQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDEGEEPSPEALVRYLSMRRHTVGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQNLQPTGQLEYKEQSLLQPPTLQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTMTPAVPAVTPVDEESSDGEPDQEAVQSSTYKDSNTLHLPTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQLQQECEQLQKMYGGQIDERTLEKTQQQHMLYQQEQHHQILQQQIQDSICPPQPSPPLQAACENQPALLTHQLQRLRIQPSSPPPNHPNNHLFRQPSNSPPPMSSAMIQPH -> MACSTPHGSNRRLPRKCHFSLPTRTPTLCTSLRSVSPLCAGSQMGLRASRPSKLTWKKWATTAASNSCSRSVSSCRRCTGGRLMKEPWRRPSSSICYTSRSSTIKFSSNKFKTLSVLLSHLHLFRLHVKISQPSLPISSR. In isoform 2.


Literature citations

The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling.
Csukasi F.; Duran I.; Barad M.; Barta T.; Gudernova I.; Trantirek L.; Martin J.H.; Kuo C.Y.; Woods J.; Lee H.; Cohn D.H.; Krejci P.; Krakow D.;
Sci. Transl. Med. 10:0-0(2018)
Cited for: INVOLVEMENT IN SEMDK; VARIANT SEMDK CYS-187; CHARACTERIZATION OF VARIANT SEMDK CYS-187; FUNCTION; INTERACTION WITH DEPTOR; MLST8; RICTOR AND RPTOR; CATALYTIC ACTIVITY; TISSUE SPECIFICITY; PHOSPHORYLATION AT THR-221;

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.