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UniProtKB/Swiss-Prot Q16832: Variant p.Ile726Arg

Discoidin domain-containing receptor 2
Gene: DDR2
Variant information

Variant position:  726
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 Isoleucine (I) to Arginine (R) at position 726 (I726R, p.Ile726Arg).
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 hydrophobic (I) to large size and basic (R)
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.



Sequence information

Variant position:  726
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:   FVHRDLATRNCLVGKNYTIK  I ADFGMSRNLYSGDYYRIQGR
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                         FVHRDLATRNCLVGKNYTIKIADFGMSRNLYSGDYYRIQGR

Mouse                         FVHRDLATRNCLVGKNYTIKIADFGMSRNLYSGDYYRIQGR

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.

TypePositionsDescription
Chain 22 – 855 Discoidin domain-containing receptor 2
Topological domain 422 – 855 Cytoplasmic
Domain 563 – 849 Protein kinase
Active site 710 – 710 Proton acceptor
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.
Beta strand 724 – 726


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;

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.