UniProtKB/Swiss-Prot P17927: Variant p.Thr1969Ala

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1969 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Threonine (T) to Alanine (A) at position 1969 (T1969A, p.Thr1969Ala). 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 polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 0 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
Polymorphism: CR1 contains a system of antigens called the Knops blood group system. Polymorphisms within this system are involved in malarial rosetting, a process associated with cerebral malaria, the major cause of mortality in Plasmodium falciparum malaria. Common Knops system antigens include McCoy (McC) and Sl(a)/Vil (Kn4, or Swain-Langley; Vil or Villien). Sl(a-) phenotype is more common in persons of African descent and may protect against fatal malaria.Other polymorphic forms of CR1 contain 23, 37 or 44 Sushi (CCP/SCR) domains instead of the 30 Sushi (CCP/SCR) domains. The most frequent alleles are the F allotype (shown here) and the S allotype (37 repeat Sushi domains). The gene frequencies of the F allotype and S allotype are 0.87 and 0.11 in Caucasians, 0.82 and 0.11 in African Americans, 0.89 and 0.11 in Mexicans. - Genetic variations in CR1 resulting in CR1 deficiency are involved in protection against severe malaria [MIM:611162]. Parasitized red blood cells (RBCs) from children suffering from severe malaria often adhere to complement receptor 1 (CR1) on uninfected RBCs to form clumps of cells known as rosettes. CR1-deficient red blood cells show greatly reduced rosetting and CR1 deficiency occurs in healthy individuals from malaria-endemic regions. - Additional information on the polymorphism described.
Other resources: Links to websites of interest for the variant.

• Variant rs2296160 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1969 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 2039 The length of the canonical sequence.
Location on the sequence: WSQCQADDRWDPPLAKCTSR T HDALIVGTLSGTIFFILLII 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.
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	42 – 2039	Complement receptor type 1
Topological domain	42 – 1971	Extracellular

Literature citations

Structure of the gene for the F allele of complement receptor type 1 and sequence of the coding region unique to the S allele.
Vik D.P.; Wong W.W.;
J. Immunol. 151:6214-6224(1993)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE S AND ALLELE F); VARIANTS VAL-1615; ARG-1827; ASP-1850 AND ALA-1969; Human C3b/C4b receptor (CR1). Demonstration of long homologous repeating domains that are composed of the short consensus repeats characteristics of C3/C4 binding proteins.
Klickstein L.B.; Wong W.W.; Smith J.A.; Weis J.H.; Wilson J.G.; Fearon D.T.;
J. Exp. Med. 165:1095-1112(1987)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 503-2039; VARIANT ALA-1969;