UniProtKB/Swiss-Prot Q5S007: Variant p.Lys1906Met

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
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Variant information Variant position:

1906 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Methionine (M) at position 1906 (K1906M, p.Lys1906Met). 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 hydrophobic (M) 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:

Does not inhibit interaction with RAB29; shows a progressive increase in neurite length and branching. Any additional useful information about the variant.

Sequence information Variant position:

1906 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2527 The length of the canonical sequence.
Location on the sequence:

GDGSFGSVYRAAYEGEEVAV K IFNKHTSLRLLRQELVVLCH 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                         GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCH

Mouse                         GDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCH

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 – 2527	Leucine-rich repeat serine/threonine-protein kinase 2
Domain	1879 – 2138	Protein kinase
Binding site	1906 – 1906
Mutagenesis	1906 – 1906	K -> A. Loss of kinase activity. Decreases proteasomal degradation of MAPT; when associated with N-1994 and A-2017.
Mutagenesis	1906 – 1906	K -> M. Loss of kinase activity and ability to enhance NOD2 signaling.
Beta strand	1901 – 1906

Literature citations
The familial Parkinsonism gene LRRK2 regulates neurite process morphology.
MacLeod D.; Dowman J.; Hammond R.; Leete T.; Inoue K.; Abeliovich A.;
Neuron 52:587-593(2006)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020; VARIANT MET-1906; RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk.
MacLeod D.A.; Rhinn H.; Kuwahara T.; Zolin A.; Di Paolo G.; McCabe B.D.; MacCabe B.D.; Marder K.S.; Honig L.S.; Clark L.N.; Small S.A.; Abeliovich A.;
Neuron 77:425-439(2013)
Cited for: FUNCTION IN RETROGRADE TRANSPORT; INTERACTION WITH RAB29 AND VPS35; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT PARK8 SER-2019; CHARACTERIZATION OF VARIANT MET-1906;

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.