UniProtKB/Swiss-Prot Q9Y616: Variant p.Pro111Ala

Interleukin-1 receptor-associated kinase 3
Gene: IRAK3
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Variant information Variant position:

111 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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:

From Proline (P) to Alanine (A) at position 111 (P111A, p.Pro111Ala). 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 medium size and hydrophobic (P) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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:

Probable risk factor for ASRT5; abolishes phosphorylation of Ser-110; abolishes interaction with PIN1; no effect on cytoplasmic localization; reduces protein stability. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs373806603 [ dbSNP | Ensembl ]

Sequence information Variant position:

111 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

596 The length of the canonical sequence.
Location on the sequence:

QEMGHRRAIHLITNYGAVLS P SEKSYQEGGFPNILFKETAN 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                         QEMGHRRAIHLITNYGAVLSPSEKSYQEGGFPNILFK-------------ETAN

Mouse                         QDMGHQRAIHLIINYGVSWTPSVQTHHELPFPSFPPEVKHA

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.

Type	Positions	Description
Chain	1 – 596	Interleukin-1 receptor-associated kinase 3
Site	110 – 111	Cis/trans isomerization of proline peptide bond; by PIN1; dependent on Ser-110 phosphorylation
Modified residue	110 – 110	Phosphoserine; by IRAK1
Mutagenesis	110 – 110	S -> A. Abolishes phosphorylation. Abolishes interaction with PIN1. Reduces protein stability.
Mutagenesis	110 – 110	S -> E. Phosphomimic. Slight decrease in the interaction with PIN1. Weak interaction with PIN1 in absence of IL33-mediated dendritic cell stimulation. Increases resistant to degradation. Localizes to the nucleus in absence of stimulus. Does not affect isomerization of Pro-111 peptide bond.

Literature citations
IRAK-M is involved in the pathogenesis of early-onset persistent asthma.
Balaci L.; Spada M.C.; Olla N.; Sole G.; Loddo L.; Anedda F.; Naitza S.; Zuncheddu M.A.; Maschio A.; Altea D.; Uda M.; Pilia S.; Sanna S.; Masala M.; Crisponi L.; Fattori M.; Devoto M.; Doratiotto S.; Rassu S.; Mereu S.; Giua E.; Cadeddu N.G.; Atzeni R.; Pelosi U.; Corrias A.; Perra R.; Torrazza P.L.; Pirina P.; Ginesu F.; Marcias S.; Schintu M.G.; Del Giacco G.S.; Manconi P.E.; Malerba G.; Bisognin A.; Trabetti E.; Boner A.; Pescollderungg L.; Pignatti P.F.; Schlessinger D.; Cao A.; Pilia G.;
Am. J. Hum. Genet. 80:1103-1114(2007)
Cited for: INVOLVEMENT IN ASRT5; VARIANTS LEU-22; ALA-111; MET-134; VAL-400 AND GLN-429; The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.
Nechama M.; Kwon J.; Wei S.; Kyi A.T.; Welner R.S.; Ben-Dov I.Z.; Arredouani M.S.; Asara J.M.; Chen C.H.; Tsai C.Y.; Nelson K.F.; Kobayashi K.S.; Israel E.; Zhou X.Z.; Nicholson L.K.; Lu K.P.;
Nat. Commun. 9:1603-1603(2018)
Cited for: STRUCTURE BY NMR OF 1-119 OF MUTANTS ASP-56 AND GLU-61; FUNCTION; INTERACTION WITH PIN1; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; PHOSPHORYLATION AT SER-110; ISOMERIZATION AT 110-SER-PRO-111; MUTAGENESIS OF SER-110 AND SER-467; VARIANT ALA-111;

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.