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UniProtKB/Swiss-Prot P01024: Variant p.Asp1115Asn

Complement C3
Gene: C3
Variant information

Variant position:  1115
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 Asparagine (N) at position 1115 (D1115N, p.Asp1115Asn).
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 medium size and polar (N)
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:  Hemolytic uremic syndrome atypical 5 (AHUS5) [MIM:612925]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:18796626, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
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 AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1115
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1663
The length of the canonical sequence.

Location on the sequence:   IDSQVLCGAVKWLILEKQKP  D GVFQEDAPVIHQEMIGGLRN
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                         IDSQVLCGAVKWLILEKQKPDGVFQEDAPVIHQEMIGGLRN

Mouse                         IDSHVLCGAVKWLILEKQKPDGVFQEDGPVIHQEMIGGFRN

Rat                           IDSQVLCGAVKWLILEKQKPDGVFQEDGPVIHQEMIGGFRN

Pig                           IDSQVLCGAVKWLILEKQKPDGVFEENGPVIHQEMIGGFKN

Bovine                        IDSKDLCETVKWLILEKQKPDGIFQEDGPVIHQEMIGGFRD

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 23 – 1663 Complement C3
Chain 672 – 1663 Complement C3 alpha chain
Chain 749 – 1663 Complement C3b alpha' chain
Chain 955 – 1303 Complement C3dg fragment
Chain 1002 – 1303 Complement C3d fragment
Disulfide bond 873 – 1513
Disulfide bond 1101 – 1158
Mutagenesis 1110 – 1110 E -> A. No effect on binding of C3d to CR2.
Mutagenesis 1115 – 1115 D -> A. No effect on binding of C3d to CR2.
Mutagenesis 1121 – 1121 D -> A. No effect on binding of C3d to CR2.
Turn 1114 – 1116


Literature citations

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.
Fremeaux-Bacchi V.; Miller E.C.; Liszewski M.K.; Strain L.; Blouin J.; Brown A.L.; Moghal N.; Kaplan B.S.; Weiss R.A.; Lhotta K.; Kapur G.; Mattoo T.; Nivet H.; Wong W.; Gie S.; Hurault de Ligny B.; Fischbach M.; Gupta R.; Hauhart R.; Meunier V.; Loirat C.; Dragon-Durey M.A.; Fridman W.H.; Janssen B.J.; Goodship T.H.; Atkinson J.P.;
Blood 112:4948-4952(2008)
Cited for: VARIANTS AHUS5 GLN-592; TRP-592; TRP-735; VAL-1094; ASN-1115; TRP-1158; LYS-1161 AND ASP-1464; CHARACTERIZATION OF VARIANTS AHUS5 GLN-592; TRP-592; VAL-1094; ASN-1115 AND LYS-1161;

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.