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UniProtKB/Swiss-Prot P42224: Variant p.Tyr701Cys

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

Variant position:  701
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 Tyrosine (Y) to Cysteine (C) at position 701 (Y701C, p.Tyr701Cys).
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 aromatic (Y) to medium size and polar (C)
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 IMD31B; disrupts transactivation activity in response to IFNG.
Any additional useful information about the variant.



Sequence information

Variant position:  701
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:   YSRPKEAPEPMELDGPKGTG  Y IKTELISVSEVHPSRLQTTD
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                         YSRPKEAPEPMELDGPKGTGYIKTELISVSEVH-----------------PSRLQTT------------D

Mouse                         YSRPKEAPEPMELDDPKRTGYIKTELISVSEVH--------

Pig                           YSRPKEAPEPMELDGPKGTGYIKTELISVSEVH--------

Caenorhabditis elegans        ESEERHRVG----GGDSPTGYIQSEIVMVAKTNGNFRRMSN

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

New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe.
Soltesz B.; Toth B.; Shabashova N.; Bondarenko A.; Okada S.; Cypowyj S.; Abhyankar A.; Csorba G.; Tasko S.; Sarkadi A.K.; Mehes L.; Rozsival P.; Neumann D.; Chernyshova L.; Tulassay Z.; Puel A.; Casanova J.L.; Sediva A.; Litzman J.; Marodi L.;
J. Med. Genet. 50:567-578(2013)
Cited for: VARIANTS IMD31C GLY-165; LYS-179; GLN-274; TRP-274; ARG-285 AND MET-385; CHARACTERIZATION OF VARIANTS IMD31C LYS-179; GLN-274; TRP-274; ARG-285 AND MET-385; CHARACTERIZATION OF VARIANT IMD31B CYS-701;

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.