UniProtKB/Swiss-Prot P30043: Variant p.Ser111Leu

Flavin reductase (NADPH)
Gene: BLVRB
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Variant information Variant position:

111 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 Serine (S) to Leucine (L) at position 111 (S111L, p.Ser111Leu). 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 small size and polar (S) to medium size and hydrophobic (L) 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:

Risk factor for thrombocytosis; enhanced generation of reactive oxygen species (ROS) leading to impaired megakaryocyte differentiation; abolished NAD(P)H-dependent reductase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs149698066 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

ARNIVAAMKAHGVDKVVACT S AFLLWDPTKVPPRLQAVTDD 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                         ARNIVAAMKAHGVDKVVACTSAFLLWDPTKVPPRLQAVTDD

Mouse                         TRNIVTAMKAHGVDKVVACTSAFLLWDPTKVPPRLQDVTDD

Bovine                        AQNIVAAMKAHGVDKVVACTSAFLLWDPSKVPPRLQDVTDD

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 – 206	Flavin reductase (NADPH)
Active site	109 – 109	S-nitroso-cysteine intermediate; for S-nitroso-CoA-dependent nitrosyltransferase activity
Binding site	109 – 109
Mutagenesis	109 – 109	C -> R. Abolished S-nitroso-CoA-dependent nitrosyltransferase activity; when associated with R-188.
Mutagenesis	111 – 111	S -> A. Abolished NAD(P)H-dependent reductase activity.

Literature citations
BLVRB redox mutation defines heme degradation in a metabolic pathway of enhanced thrombopoiesis in humans.
Wu S.; Li Z.; Gnatenko D.V.; Zhang B.; Zhao L.; Malone L.E.; Markova N.; Mantle T.J.; Nesbitt N.M.; Bahou W.F.;
Blood 128:699-709(2016)
Cited for: FUNCTION; VARIANT LEU-111; CHARACTERIZATION OF VARIANT LEU-111; Enzymatic Activity and Thermodynamic Stability of Biliverdin IXbeta Reductase Are Maintained by an Active Site Serine.
Chu W.T.; Nesbitt N.M.; Gnatenko D.V.; Li Z.; Zhang B.; Seeliger M.A.; Browne S.; Mantle T.J.; Bahou W.F.; Wang J.;
Chemistry 23:1891-1900(2017)
Cited for: CHARACTERIZATION OF VARIANT LEU-111; MUTAGENESIS OF SER-111;

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.