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UniProtKB/Swiss-Prot P43403: Variant p.Arg360Pro

Tyrosine-protein kinase ZAP-70
Gene: ZAP70
Chromosomal location: 2q11-q13
Variant information

Variant position:  360
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 Proline (P) at position 360 (R360P, p.Arg360Pro).
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 hydrophobic (P)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Autoimmune disease, multisystem, infantile-onset, 2 (ADMIO2) [MIM:617006]: An autosomal recessive, autoimmune disorder characterized by systemic manifestations including blistering skin disease, uncontrollable bullous pemphigoid, inflammatory colitis, autoimmune hypothyroidism, proteinuria and nephrotic syndrome. {ECO:0000269|PubMed:26783323}. 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 ADMIO2; no effect on interaction with phosphorylated CD247; increases TCR-induced Y-319 and Y-493 phosphorylation of ZAP70 and phosphorylation of LAT and LCP2; increases subcellular localization of CD69 at the cell surface; weakly decreases autoinhibition conformation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  360
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  619
The length of the canonical sequence.

Location on the sequence:   ADIELGCGNFGSVRQGVYRM  R KKQIDVAIKVLKQGTEKADT
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                         ADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADT

Mouse                         ADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADK

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 – 619 Tyrosine-protein kinase ZAP-70
Domain 338 – 600 Protein kinase
Binding site 369 – 369 ATP
Mutagenesis 362 – 362 K -> E. Increases constitutive kinase activity on LAT phosphorylation, strongly increases subcellular localization of CD69 at the cell surface and decreases autoinhibition conformation.


Literature citations

A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70.
Chan A.Y.; Punwani D.; Kadlecek T.A.; Cowan M.J.; Olson J.L.; Mathes E.F.; Sunderam U.; Fu S.M.; Srinivasan R.; Kuriyan J.; Brenner S.E.; Weiss A.; Puck J.M.;
J. Exp. Med. 213:155-165(2016)
Cited for: VARIANTS ADMIO2 TRP-192 AND PRO-360; CHARACTERIZATION OF VARIANTS ADMIO2 TRP-192 AND PRO-360; INVOLVEMENT IN ADMIO2; INTERACTION WITH CD247; MUTAGENESIS OF ARG-37; ARG-190; 315-TYR--TYR-319; ASP-327 AND LYS-362;

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.