UniProtKB/SwissProt variant VAR

Variant information

Variant position:

120

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Aspartate (D) to Glycine (G) at position 120 (D120G, p.Asp120Gly).

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 medium size and acidic (D) to glycine (G)

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

Involvement in disease:

MASP2 deficiency (MASPD) [MIM:613791]: A disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease. {ECO:0000269|PubMed:12904520, ECO:0000269|PubMed:17252003}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In MASPD; found in a patient suffering from frequent infections and chronic inflammatory disease; strongly decreases affinity for MBL2 and FCN2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72550870 [ dbSNP | Ensembl ]

Sequence information

Variant position:

120

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

686

The length of the canonical sequence.

Location on the sequence:

APGKDTFYSLGSSLDITFRS D YSNEKPFTGFEAFYAAEDID

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                         APGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYAAEDID

Mouse                         APGNDTFYSLGPSLKVTFHSDYSNEKPFTGFEAFYAAEDVD

Rat                           APGNDTFYSLGPSLKVTFHSDYSNEKPFTGFEAFYAAEDVD

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	16 – 686	Mannan-binding lectin serine protease 2
Chain	16 – 444	Mannan-binding lectin serine protease 2 A chain
Domain	16 – 137	CUB 1
Metal binding	120 – 120	Calcium 1
Metal binding	122 – 122	Calcium 1; via carbonyl oxygen
Metal binding	123 – 123	Calcium 1
Metal binding	138 – 138	Calcium 2
Metal binding	139 – 139	Calcium 2; via carbonyl oxygen
Mutagenesis	121 – 121	Y -> A. Strongly decreases affinity for MBL2, but not for FCN2.
Mutagenesis	124 – 124	E -> A. Decreases affinity for MBL2. Slight decrease in affinity for FCN2.

Literature citations

The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.
Gregory L.A.; Thielens N.M.; Matsushita M.; Sorensen R.; Arlaud G.J.; Fontecilla-Camps J.-C.; Gaboriaud C.;
J. Biol. Chem. 279:29391-29397(2004)
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 16-181 (ISOFORM 2); CHARACTERIZATION OF VARIANT GLY-120; CALCIUM-BINDING SITES; DIMERIZATION; MUTAGENESIS OF TYR-74; TYR-121 AND GLU-124; INTERACTION WITH MBL2 AND FCN2; DISULFIDE BONDS;

Inherited deficiency of mannan-binding lectin-associated serine protease 2.
Stengaard-Pedersen K.; Thiel S.; Gadjeva M.; Moller-Kristensen M.; Sorensen R.; Jensen L.T.; Sjoeholm A.G.; Fugger L.; Jensenius J.C.;
N. Engl. J. Med. 349:554-560(2003)
Cited for: VARIANT MASPD GLY-120; CHARACTERIZATION OF VARIANT MASPD GLY-120;

Novel MASP2 variants detected among North African and Sub-Saharan individuals.
Lozano F.; Suarez B.; Munoz A.; Jensenius J.C.; Mensa J.; Vives J.; Horcajada J.P.;
Tissue Antigens 66:131-135(2005)
Cited for: VARIANTS GLN-99; CYS-118; GLY-120 AND LEU-126;

Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms.
Thiel S.; Steffensen R.; Christensen I.J.; Ip W.K.; Lau Y.L.; Reason I.J.; Eiberg H.; Gadjeva M.; Ruseva M.; Jensenius J.C.;
Genes Immun. 8:154-163(2007)
Cited for: VARIANTS MASPD GLY-120; LEU-126 AND HIS-ASN-HIS-156 INS; VARIANTS GLN-99; CYS-118 AND ALA-377; CHARACTERIZATION OF VARIANT ALA-377;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00187: Variant p.Asp120Gly