UniProtKB/Swiss-Prot Q9C000: Variant p.Met1184Val

NACHT, LRR and PYD domains-containing protein 1
Gene: NLRP1
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Variant information Variant position:

1184 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Methionine (M) to Valine (V) at position 1184 (M1184V, p.Met1184Val). 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:

Increased autocatalytic processing and IL1B release. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs11651270 [ dbSNP | Ensembl ]

Sequence information Variant position:

1184 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1473 The length of the canonical sequence.
Location on the sequence:

VHLPHFVALQGGHVDTSLFQ M AHFKEEGMLLEKPARVELHH 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                         VHLPHFVAL-QGGHVDTSLFQMAHFKEEGMLLEKPARVELHH

Zebrafish                     AHLPHYMCLAESDPALTNAVKLLSVEDEGISLESVELTRFH

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 – 1473	NACHT, LRR and PYD domains-containing protein 1
Chain	1 – 1212	NACHT, LRR and PYD domains-containing protein 1, N-terminus
Domain	1079 – 1364	FIIND
Region	1079 – 1212	ZU5
Mutagenesis	1168 – 1168	H -> A. Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine.
Mutagenesis	1186 – 1186	H -> A. Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing can be restored by treatment with hydroxylamine.
Beta strand	1184 – 1188

Literature citations
The PYRIN domain: a novel motif found in apoptosis and inflammation proteins.
Bertin J.; DiStefano P.S.;
Cell Death Differ. 7:1273-1274(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); VARIANTS HIS-155; SER-246; MET-878; VAL-1119; VAL-1184; LEU-1241 AND CYS-1366; The full-ORF clone resource of the German cDNA consortium.
Bechtel S.; Rosenfelder H.; Duda A.; Schmidt C.P.; Ernst U.; Wellenreuther R.; Mehrle A.; Schuster C.; Bahr A.; Bloecker H.; Heubner D.; Hoerlein A.; Michel G.; Wedler H.; Koehrer K.; Ottenwaelder B.; Poustka A.; Wiemann S.; Schupp I.;
BMC Genomics 8:399-399(2007)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 282-1473 (ISOFORM 1); VARIANT VAL-1184; Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity.
Finger J.N.; Lich J.D.; Dare L.C.; Cook M.N.; Brown K.K.; Duraiswami C.; Bertin J.J.; Bertin J.; Gough P.J.;
J. Biol. Chem. 287:25030-25037(2012)
Cited for: PROTEIN SEQUENCE OF 1213-1224; FUNCTION; INTERACTION WITH PYCARD; INVOLVEMENT IN INFLAMMASOME COMPLEX; AUTOCATALYTIC CLEAVAGE; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS VAL-1119 AND VAL-1184; MUTAGENESIS OF HIS-1168; HIS-1186; SER-1211; PHE-1212; SER-1213; PRO-1214 AND HIS-1249;

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.