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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07948: Variant p.Tyr508Phe

Tyrosine-protein kinase Lyn
Gene: LYN
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Variant information Variant position: help 508 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 Phenylalanine (F) at position 508 (Y508F, p.Tyr508Phe). 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 Similar physico-chemical property. Both residues are large size and aromatic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In SAIDV; pathogenic; increased kinase activity due to loss of autoinhibition resulting in constitutive activation; loss of Y-508 phosphorylation; increased Y-397 phosphorylation. Any additional useful information about the variant.


Sequence information Variant position: help 508 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 512 The length of the canonical sequence.
Location on the sequence: help PTFDYLQSVLDDFYTATEGQ Y QQQP 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                         PTFDYLQSVLDDFYTATEGQYQQQP

Mouse                         PTFDYLQSVLDDFYTATEGQYQQQP

Rat                           PTFDYLQSVLDDFYTATEGQYQQQP
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 – 512 Tyrosine-protein kinase Lyn
Modified residue 508 – 508 Phosphotyrosine; by autocatalysis, CSK and MATK
Mutagenesis 498 – 498 D -> A. Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-346; A-353 and A-499.
Mutagenesis 499 – 499 D -> A. Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-346; A-353 and A-498.



Literature citations
Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells.
Ingley E.; Schneider J.R.; Payne C.J.; McCarthy D.J.; Harder K.W.; Hibbs M.L.; Klinken S.P.;
J. Biol. Chem. 281:31920-31929(2006)
Cited for: INTERACTION WITH PAG1; MUTAGENESIS OF TYR-397; CHARACTERIZATION OF VARIANT SAIDV PHE-508; ACTIVITY REGULATION; UBIQUITINATION; De Novo Gain-Of-Function Variations in LYN Associated With an Early-Onset Systemic Autoinflammatory Disorder.
Louvrier C.; El Khouri E.; Grall Lerosey M.; Quartier P.; Guerrot A.M.; Bader Meunier B.; Chican J.; Mohammad M.; Assrawi E.; Daskalopoulou A.; Arenas Garcia A.; Copin B.; Piterboth W.; Dastot Le Moal F.; Karabina S.A.; Amselem S.; Giurgea I.;
Arthritis Rheumatol. 75:468-474(2023)
Cited for: VARIANT SAIDV HIS-508; CHARACTERIZATION OF VARIANTS SAIDV 508-TYR--PRO-512 DEL; HIS-508 AND PHE-508; FUNCTION; Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.
de Jesus A.A.; Chen G.; Yang D.; Brdicka T.; Ruth N.M.; Bennin D.; Cebecauerova D.; Malcova H.; Freeman H.; Martin N.; Svojgr K.; Passo M.H.; Bhuyan F.; Alehashemi S.; Rastegar A.T.; Uss K.; Kardava L.; Marrero B.; Duric I.; Omoyinmi E.; Peldova P.; Lee C.R.; Kleiner D.E.; Hadigan C.M.; Hewitt S.M.; Pittaluga S.; Carmona-Rivera C.; Calvo K.R.; Shah N.; Balascakova M.; Fink D.L.; Kotalova R.; Parackova Z.; Peterkova L.; Kuzilkova D.; Campr V.; Sramkova L.; Biancotto A.; Brooks S.R.; Manes C.; Meffre E.; Harper R.L.; Kuehn H.; Kaplan M.J.; Brogan P.; Rosenzweig S.D.; Merchant M.; Deng Z.; Huttenlocher A.; Moir S.L.; Kuhns D.B.; Boehm M.; Skvarova Kramarzova K.; Goldbach-Mansky R.;
Nat. Commun. 14:1502-1502(2023)
Cited for: VARIANTS SAIDV 507-GLN--PRO-512 DEL; 508-TYR--PRO-512 DEL AND PHE-508; CHARACTERIZATION OF VARIANTS SAIDV 507-GLN--PRO-512 DEL; 508-TYR--PRO-512 DEL AND PHE-508; FUNCTION;
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.