UniProtKB/SwissProt variant VAR

Variant information

Variant position:

637

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 Lysine (K) to Glutamate (E) at position 637 (K637E, p.Lys637Glu).

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 basic (K) to medium size and acidic (E)

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:

In IMD31A; affects both phosphorylation and DNA-binding activity; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs587777705 [ dbSNP | Ensembl ]

Sequence information

Variant position:

637

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:

VERSQNGGEPDFHAVEPYTK K ELSAVTFPDIIRNYKVMAAE

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                         VERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAE

Mouse                         VERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAE

Pig                           VERSQNGGEPYFHAVEPYTKKELSAVTFPDIIRNYKVMAAE

Caenorhabditis elegans        VCEEADGQKIPFH-LAPFTIKDLDQLSLASRIASCPQL---

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	2 – 750	Signal transducer and activator of transcription 1-alpha/beta
Domain	573 – 670	SH2
Modified residue	637 – 637	N6-methyllysine
Modified residue	657 – 657	ADP-ribosyl glutamic acid; by PARP14
Mutagenesis	636 – 637	KK -> AA. No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation.
Mutagenesis	657 – 657	E -> Q. Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-705.
Helix	636 – 640

Literature citations

Dominant-negative STAT1 SH2 domain mutations in unrelated patients with Mendelian susceptibility to mycobacterial disease.
Tsumura M.; Okada S.; Sakai H.; Yasunaga S.; Ohtsubo M.; Murata T.; Obata H.; Yasumi T.; Kong X.F.; Abhyankar A.; Heike T.; Nakahata T.; Nishikomori R.; Al-Muhsen S.; Boisson-Dupuis S.; Casanova J.L.; Alzahrani M.; Shehri M.A.; Elghazali G.; Takihara Y.; Kobayashi M.;
Hum. Mutat. 33:1377-1387(2012)
Cited for: VARIANTS IMD31A GLU-637 AND ARG-673; CHARACTERIZATION OF VARIANTS IMD31A GLU-637 AND ARG-673;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P42224: Variant p.Lys637Glu