UniProtKB/Swiss-Prot Q14653: Variant p.Leu401Val

Interferon regulatory factor 3
Gene: IRF3
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Variant information Variant position:

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

US 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 Leucine (L) to Valine (V) at position 401 (L401V, p.Leu401Val). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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:

No effect on IFNB induction upon Sendai virus infection. Any additional useful information about the variant.

Sequence information Variant position:

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

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

VGGASSLENTVDLHISNSHP L SLTSDQYKAYLQDLVEGMDF 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                         VGGASSLEN-TVDLHISNSHPLSLTSDQYKAYLQDLVEGMDF

Mouse                         EGGASSLK--TVDLHISNSQPISLTSDQYKAYLQDLVEDMD

Pig                           DGGASSLEN-TVDLHISNSHPLSLTSDQYKACLRDLVEDMD

Bovine                        QGGASSLEN-TVDLHISNSDPLSLTPDQYMACLQDLAEDMD

Chicken                       RGGASSLNSGNVSLQLSDSFNLFELIEQYHMQTD-------

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 – 427	Interferon regulatory factor 3
Region	141 – 427	Mediates interaction with ZDHHC11
Modified residue	385 – 385	Phosphoserine
Modified residue	386 – 386	Diphosphoserine
Modified residue	386 – 386	Phosphoserine; by TBK1
Modified residue	396 – 396	Phosphoserine; by IKKE and TBK1
Modified residue	398 – 398	Phosphoserine
Modified residue	404 – 404	Phosphothreonine
Alternative sequence	105 – 427	Missing. In isoform 5.
Alternative sequence	328 – 427	DLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMDFQGPGES -> GSWAPRSDYLHGRKRTLTTLCPLVLCGGVMAPGPAVDQEARDGQGCAHVPQGLGRNGPGRGCLLPGEYCGPAHFQQPPTLPHLRPVQGLPAGLGGGHGFPGPWGELSPRSSWCASNPPVPHHLNQ. In isoform 4.
Mutagenesis	385 – 385	S -> ADE. Complete loss of viral infection induced phosphorylation.
Mutagenesis	386 – 386	S -> A. Complete loss of viral infection induced phosphorylation. Abolished pyrophosphorylation.
Mutagenesis	386 – 386	S -> E. Phosphomimetic mutant; interacts with CREBBP; when associated with E-396.
Mutagenesis	390 – 390	T -> A. Does not affect pyrophosphorylation.
Mutagenesis	396 – 405	SNSHPLSLTS -> ANAHPLALAA. Complete loss of viral infection induced phosphorylation.
Mutagenesis	396 – 405	SNSHPLSLTS -> DNDHPLDLDD. Acts as a constitutively activated IRF3.
Mutagenesis	396 – 396	S -> E. Phosphomimetic mutant; interacts with CREBBP; when associated with E-386.
Beta strand	401 – 404

Literature citations
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Zhang Q.; Bastard P.; Liu Z.; Le Pen J.; Moncada-Velez M.; Chen J.; Ogishi M.; Sabli I.K.D.; Hodeib S.; Korol C.; Rosain J.; Bilguvar K.; Ye J.; Bolze A.; Bigio B.; Yang R.; Arias A.A.; Zhou Q.; Zhang Y.; Onodi F.; Korniotis S.; Karpf L.; Philippot Q.; Chbihi M.; Bonnet-Madin L.; Dorgham K.; Smith N.; Schneider W.M.; Razooky B.S.; Hoffmann H.H.; Michailidis E.; Moens L.; Han J.E.; Lorenzo L.; Bizien L.; Meade P.; Neehus A.L.; Ugurbil A.C.; Corneau A.; Kerner G.; Zhang P.; Rapaport F.; Seeleuthner Y.; Manry J.; Masson C.; Schmitt Y.; Schlueter A.; Le Voyer T.; Khan T.; Li J.; Fellay J.; Roussel L.; Shahrooei M.; Alosaimi M.F.; Mansouri D.; Al-Saud H.; Al-Mulla F.; Almourfi F.; Al-Muhsen S.Z.; Alsohime F.; Al Turki S.; Hasanato R.; van de Beek D.; Biondi A.; Bettini L.R.; D'Angio' M.; Bonfanti P.; Imberti L.; Sottini A.; Paghera S.; Quiros-Roldan E.; Rossi C.; Oler A.J.; Tompkins M.F.; Alba C.; Vandernoot I.; Goffard J.C.; Smits G.; Migeotte I.; Haerynck F.; Soler-Palacin P.; Martin-Nalda A.; Colobran R.; Morange P.E.; Keles S.; Coelkesen F.; Ozcelik T.; Yasar K.K.; Senoglu S.; Karabela S.N.; Rodriguez-Gallego C.; Novelli G.; Hraiech S.; Tandjaoui-Lambiotte Y.; Duval X.; Laouenan C.; Snow A.L.; Dalgard C.L.; Milner J.D.; Vinh D.C.; Mogensen T.H.; Marr N.; Spaan A.N.; Boisson B.; Boisson-Dupuis S.; Bustamante J.; Puel A.; Ciancanelli M.J.; Meyts I.; Maniatis T.; Soumelis V.; Amara A.; Nussenzweig M.; Garcia-Sastre A.; Krammer F.; Pujol A.; Duffy D.; Lifton R.P.; Zhang S.Y.; Gorochov G.; Beziat V.; Jouanguy E.; Sancho-Shimizu V.; Rice C.M.; Abel L.; Notarangelo L.D.; Cobat A.; Su H.C.; Casanova J.L.;
Science 370:0-0(2020)
Cited for: VARIANTS GLU-49 DEL; 145-GLY--GLU-200 DEL; LYS-146; GLN-227; GLN-285 AND VAL-401; CHARACTERIZATION OF VARIANTS GLU-49 DEL; 145-GLY--GLU-200 DEL; LYS-146; GLN-227; GLN-285 AND VAL-401; 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.