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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P28482: Variant p.Ala174Val

Mitogen-activated protein kinase 1
Gene: MAPK1
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Variant information Variant position: help 174 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 Alanine (A) to Valine (V) at position 174 (A174V, p.Ala174Val). 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 small size and hydrophobic (A) to medium size and hydrophobic (V) 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 NS13; results in increased MAPK signaling; increased translocation to the nucleus; reduced interaction with DUSP6; no effect on interaction with MAP2K1. Any additional useful information about the variant.


Sequence information Variant position: help 174 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 360 The length of the canonical sequence.
Location on the sequence: help NLLLNTTCDLKICDFGLARV A DPDHDHTGFLTEYVATRWYR 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                         NLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYR

Mouse                         NLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYR

Rat                           NLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYR

Bovine                        NLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYR

Xenopus laevis                NLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYR
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 2 – 360 Mitogen-activated protein kinase 1
Domain 25 – 313 Protein kinase
Modified residue 185 – 185 Phosphothreonine; by MAP2K1 and MAP2K2
Modified residue 187 – 187 Phosphotyrosine; by MAP2K1 and MAP2K2
Modified residue 190 – 190 Phosphothreonine; by autocatalysis
Mutagenesis 185 – 185 T -> A. Inhibits interaction with TPR; when associated with A-187.
Mutagenesis 187 – 187 Y -> A. Inhibits interaction with TPR; when associated with A-185.



Literature citations
Enhanced MAPK1 function causes a neurodevelopmental disorder within the RASopathy clinical spectrum.
Motta M.; Pannone L.; Pantaleoni F.; Bocchinfuso G.; Radio F.C.; Cecchetti S.; Ciolfi A.; Di Rocco M.; Elting M.W.; Brilstra E.H.; Boni S.; Mazzanti L.; Tamburrino F.; Walsh L.; Payne K.; Fernandez-Jaen A.; Ganapathi M.; Chung W.K.; Grange D.K.; Dave-Wala A.; Reshmi S.C.; Bartholomew D.W.; Mouhlas D.; Carpentieri G.; Bruselles A.; Pizzi S.; Bellacchio E.; Piceci-Sparascio F.; Lissewski C.; Brinkmann J.; Waclaw R.R.; Waisfisz Q.; van Gassen K.; Wentzensen I.M.; Morrow M.M.; Alvarez S.; Martinez-Garcia M.; De Luca A.; Memo L.; Zampino G.; Rossi C.; Seri M.; Gelb B.D.; Zenker M.; Dallapiccola B.; Stella L.; Prada C.E.; Martinelli S.; Flex E.; Tartaglia M.;
Am. J. Hum. Genet. 107:499-513(2020)
Cited for: VARIANTS NS13 ASN-74; TYR-80; VAL-174; ASN-318; GLY-318; GLN-322 AND ARG-323; INVOLVEMENT IN NS13; CHARACTERIZATION OF VARIANTS NS13 ASN-74; TYR-80; VAL-174; ASN-318; GLY-318 AND ARG-323; SUBCELLULAR LOCATION; FUNCTION; INTERACTION WITH MAP2K1 AND DUSP6;
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.