UniProtKB/SwissProt variant VAR

Variant information

Variant position:

752

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 Arginine (R) to Cysteine (C) at position 752 (R752C, p.Arg752Cys).

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 (R) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. {ECO:0000269|PubMed:19110212, ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:26463668}. 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 SEMD-SL; causes retention in an intracellular compartment and thereby abolishes signaling in response collagen binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121964863 [ dbSNP | Ensembl ]

Sequence information

Variant position:

752

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

Protein sequence length:

855

The length of the canonical sequence.

Location on the sequence:

SRNLYSGDYYRIQGRAVLPI R WMSWESILLGKFTTASDVWA

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                         SRNLYSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWA

Mouse                         SRNLYSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWA

Baker's yeast                 -----------------------------------------

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	22 – 855	Discoidin domain-containing receptor 2
Topological domain	422 – 855	Cytoplasmic
Domain	563 – 849	Protein kinase
Modified residue	736 – 736	Phosphotyrosine; by SRC and autocatalysis
Modified residue	740 – 740	Phosphotyrosine; by SRC and autocatalysis
Modified residue	741 – 741	Phosphotyrosine; by SRC and autocatalysis
Mutagenesis	736 – 736	Y -> F. Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-740 and F-741.
Mutagenesis	740 – 740	Y -> F. Promotes autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-741.
Mutagenesis	741 – 741	Y -> F. Reduces autophosphorylation. Abolishes phosphorylation by SRC; when associated with F-736 and F-740.

Literature citations

Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.
Bargal R.; Cormier-Daire V.; Ben-Neriah Z.; Le Merrer M.; Sosna J.; Melki J.; Zangen D.H.; Smithson S.F.; Borochowitz Z.; Belostotsky R.; Raas-Rothschild A.;
Am. J. Hum. Genet. 84:80-84(2009)
Cited for: VARIANTS SEMD-SL ILE-713; ARG-726 AND CYS-752;

Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients.
Ali B.R.; Xu H.; Akawi N.A.; John A.; Karuvantevida N.S.; Langer R.; Al-Gazali L.; Leitinger B.;
Hum. Mol. Genet. 19:2239-2250(2010)
Cited for: VARIANT SEMD-SL LYS-113; CHARACTERIZATION OF VARIANTS SEMD-SL LYS-113; ILE-713; ARG-726 AND CYS-752; MUTAGENESIS OF TRP-52; GLYCOSYLATION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q16832: Variant p.Arg752Cys