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UniProtKB/Swiss-Prot Q14653: Variant p.Leu401Val

Interferon regulatory factor 3
Gene: IRF3
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.

TypePositionsDescription
Chain 1 – 427 Interferon regulatory factor 3
Region 141 – 427 Mediates interaction with ZDHHC11
Modified residue 385 – 385 Phosphoserine
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 -> ADE. Complete loss of viral infection induced phosphorylation.
Mutagenesis 386 – 386 S -> E. Phosphomimetic mutant; interacts with CREBBP; when associated with E-396.
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.