UniProtKB/Swiss-Prot O60494: Variant p.Asn1545Tyr

Cubilin
Gene: CUBN
Chromosomal location: 10p12
Variant information

Variant position:  1545
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Asparagine (N) to Tyrosine (Y) at position 1545 (N1545Y, p.Asn1545Tyr).
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 (N) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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



Sequence information

Variant position:  1545
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  3623
The length of the canonical sequence.

Location on the sequence:   NYPSPYRSNTDCSWVIRVDR  N HRVLLNFTDFDLEPQDSCIM
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                         NYPSPYRSNTDCSWVIRVDRNHRVLLNFTDF------------------DLEPQDSC----------IM

Mouse                         NYPNNYRANTECSWIIQVEKYHRVLLNITDF----------

Rat                           NYPNNYRANTECSWIIQVERHHRVLLNITDF----------

Dog                           NYPSPYRGNTDCSWVIRVERNHRILLNFTDF----------

Caenorhabditis elegans        GYPSAYLPGIKCNFLINAPPGYHIEYALEKYYSPYYHDDRK

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 36 – 3623 Cubilin
Domain 1510 – 1619 CUB 10
Glycosylation 1551 – 1551 N-linked (GlcNAc...)


Literature citations

The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region.
Kozyraki R.; Kristiansen M.; Silahtaroglu A.; Hansen C.; Jacobsen C.; Tommerup N.; Verroust P.J.; Moestrup S.K.;
Blood 91:3593-3600(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; PROTEIN SEQUENCE OF 36-41; FUNCTION; BINDING TO THE GIF-COBALAMIN COMPLEX; PROTEOLYTIC PROCESSING; VARIANTS SER-253; TYR-1545; ILE-1769; TYR-2162 AND TRP-2717;

Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.
Aminoff M.; Carter J.E.; Chadwick R.B.; Johnson C.; Graesbeck R.; Abdelaal M.A.; Broch H.; Jenner L.B.; Verroust P.J.; Moestrup S.K.; de la Chapelle A.; Krahe R.;
Nat. Genet. 21:309-313(1999)
Cited for: VARIANT RH-MGA1 LEU-1297; VARIANTS ILE-124; SER-253; THR-389; HIS-1032; TYR-1545; SER-1559; ILE-1769; PHE-2153; ARG-2575; ARG-2691; ILE-2879; VAL-2984; GLY-3002; ILE-3422 AND LYS-3552;

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.