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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H040: Variant p.Tyr117Cys

DNA-dependent metalloprotease SPRTN
Gene: SPRTN
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Variant information Variant position: help 117 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 Tyrosine (Y) to Cysteine (C) at position 117 (Y117C, p.Tyr117Cys). 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 large size and aromatic (Y) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 RJALS; impaired metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs); cells are completely unable to restore DNA replication fork progression. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 117 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 489 The length of the canonical sequence.
Location on the sequence: help LKLRPRKDLVETLLHEMIHA Y LFVTNNDKDREGHGPEFCKH 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                         LKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKH

Mouse                         LKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKH

Rat                           LKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKH

Bovine                        LKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKH

Xenopus laevis                LKLRPRKDLVETLLHEMIHALLFVTHNNKDHDSHGPEFCKH

Xenopus tropicalis            LKLRPRKDLVQTLLHEMIHALLFVTHNNKDHDSHGPEFCKH

Zebrafish                     LKLRPRKDLVQTLLHEMIHALLFVTQNNRDRDGHGPEFCKH

Caenorhabditis elegans        LTLRPRSDLVETLLHEMIHAYLFVKERNRDRDGHGPQFQAH
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 – 489 DNA-dependent metalloprotease SPRTN
Domain 45 – 212 SprT-like
Active site 112 – 112
Binding site 111 – 111
Binding site 115 – 115
Binding site 130 – 130
Alternative sequence 108 – 150 Missing. In isoform 3.
Mutagenesis 112 – 112 E -> AQ. Abolished metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs). Abolished ability to cleave CHEK1 during physiological DNA replication.
Helix 102 – 120



Literature citations
Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.
Lessel D.; Vaz B.; Halder S.; Lockhart P.J.; Marinovic-Terzic I.; Lopez-Mosqueda J.; Philipp M.; Sim J.C.; Smith K.R.; Oehler J.; Cabrera E.; Freire R.; Pope K.; Nahid A.; Norris F.; Leventer R.J.; Delatycki M.B.; Barbi G.; von Ameln S.; Hoegel J.; Degoricija M.; Fertig R.; Burkhalter M.D.; Hofmann K.; Thiele H.; Altmueller J.; Nuernberg G.; Nuernberg P.; Bahlo M.; Martin G.M.; Aalfs C.M.; Oshima J.; Terzic J.; Amor D.J.; Dikic I.; Ramadan K.; Kubisch C.;
Nat. Genet. 46:1239-1244(2014)
Cited for: INVOLVEMENT IN RJALS; VARIANT RJALS CYS-117; CHARACTERIZATION OF VARIANT RJALS CYS-117; SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks.
Lopez-Mosqueda J.; Maddi K.; Prgomet S.; Kalayil S.; Marinovic-Terzic I.; Terzic J.; Dikic I.;
Elife 5:0-0(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; COFACTOR; PROTEOLYTIC CLEAVAGE; ACTIVE SITE; MUTAGENESIS OF GLU-112 AND 408-ARG--LEU-411; CHARACTERIZATION OF VARIANT RJALS CYS-117; Metalloprotease SPRTN/DVC1 orchestrates replication-coupled DNA-protein crosslink repair.
Vaz B.; Popovic M.; Newman J.A.; Fielden J.; Aitkenhead H.; Halder S.; Singh A.N.; Vendrell I.; Fischer R.; Torrecilla I.; Drobnitzky N.; Freire R.; Amor D.J.; Lockhart P.J.; Kessler B.M.; McKenna G.W.; Gileadi O.; Ramadan K.;
Mol. Cell 64:704-719(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; PROTEOLYTIC CLEAVAGE; ACTIVE SITE; MUTAGENESIS OF GLU-112; CHARACTERIZATION OF VARIANT RJALS CYS-117; Mechanism and regulation of DNA-protein crosslink repair by the DNA-dependent metalloprotease SPRTN.
Stingele J.; Bellelli R.; Alte F.; Hewitt G.; Sarek G.; Maslen S.L.; Tsutakawa S.E.; Borg A.; Kjaer S.; Tainer J.A.; Skehel J.M.; Groll M.; Boulton S.J.;
Mol. Cell 64:688-703(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; PROTEOLYTIC CLEAVAGE; UBIQUITINATION AT LYS-341; LYS-376; LYS-414 AND LYS-435; ACTIVE SITE; MUTAGENESIS OF GLU-112; LYS-341; LYS-376; LYS-414 AND LYS-435; CHARACTERIZATION OF VARIANT RJALS CYS-117;
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.