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UniProtKB/Swiss-Prot P42224: Variant p.Leu706Ser

Signal transducer and activator of transcription 1-alpha/beta
Gene: STAT1
Variant information

Variant position:  706
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Leucine (L) to Serine (S) at position 706 (L706S, p.Leu706Ser).
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 (L) to small size and polar (S)
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

Variant description:  In IMD31A; loss of GAF and ISGF3 activation; impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs; affects phosphorylation of the protein.
Any additional useful information about the variant.

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



Sequence information

Variant position:  706
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  750
The length of the canonical sequence.

Location on the sequence:   EAPEPMELDGPKGTGYIKTE  L ISVSEVHPSRLQTTDNLLPM
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                         EAPEPMELDGPKGTGYIKTELISVSEVH-----------------PSRLQTT------------DNLLPM

Mouse                         EAPEPMELDDPKRTGYIKTELISVSEVH-------------

Pig                           EAPEPMELDGPKGTGYIKTELISVSEVH-------------

Caenorhabditis elegans        HRVG----GGDSPTGYIQSEIVMVAKTNGNFRRMSNAPSMF

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 2 – 750 Signal transducer and activator of transcription 1-alpha/beta
Modified residue 701 – 701 Phosphotyrosine; by JAK1, JAK2 or TYK2
Modified residue 705 – 705 ADP-ribosyl glutamic acid; by PARP14
Modified residue 708 – 708 Phosphoserine; by IKKE
Cross 703 – 703 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Cross 703 – 703 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Mutagenesis 701 – 701 Y -> E. Not phosphorylated at S-708 upon IFNB induction.
Mutagenesis 701 – 701 Y -> F. No effect on basal sumoylation. Enhances sumoylation in the presence of MAPK stimulation. Phosphorylated at S-708 upon IFNB induction.
Mutagenesis 703 – 703 K -> R. Abolishes sumoylation by SUMO1. Increased IFN-gamma-mediated transactivation.
Mutagenesis 705 – 705 E -> Q. Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-657.
Mutagenesis 708 – 708 S -> A. Phosphorylated at Y-701 upon IFNB induction.
Mutagenesis 708 – 708 S -> D. Not phosphorylated at Y-701 upon IFNB induction.


Literature citations

Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation.
Dupuis S.; Dargemont C.; Fieschi C.; Thomassin N.; Rosenzweig S.; Harris J.; Holland S.M.; Schreiber R.D.; Casanova J.-L.;
Science 293:300-303(2001)
Cited for: VARIANT IMD31A SER-706;

Novel STAT1 alleles in otherwise healthy patients with mycobacterial disease.
Chapgier A.; Boisson-Dupuis S.; Jouanguy E.; Vogt G.; Feinberg J.; Prochnicka-Chalufour A.; Casrouge A.; Yang K.; Soudais C.; Fieschi C.; Santos O.F.; Bustamante J.; Picard C.; de Beaucoudrey L.; Emile J.F.; Arkwright P.D.; Schreiber R.D.; Rolinck-Werninghaus C.; Rosen-Wolff A.; Magdorf K.; Roesler J.; Casanova J.L.;
PLoS Genet. 2:E131-E131(2006)
Cited for: VARIANTS IMD31A GLN-320 AND HIS-463; CHARACTERIZATION OF VARIANTS GLN-320; HIS-463 AND SER-706;

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.