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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60494: Variant p.Pro1297Leu

Cubilin
Gene: CUBN
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Variant information Variant position: help 1297 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Proline (P) to Leucine (L) at position 1297 (P1297L, p.Pro1297Leu). 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: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In IGS1; decreases strongly the CBLIF binding affinity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1297 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 3623 The length of the canonical sequence.
Location on the sequence: help TCENVVIVNQTYGILESIGY P NPYSENQHCNWTIRATTGNT 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TCENVVIVNQTYGILESIGYPNPYSENQ--HCNWTIRATTGNT

                              TCRNVVIVNRNYGILESIHYPNPYSDNQ--RCNWTIQATTG

Mouse                         TCDNVVIVNKTSGILESINYPNPYDKDQ--RCNWTIQATTG

Rat                           RCDNVVIVNKTSGILESINYPNPYDKNQ--RCNWTIQATTG

Pig                           TCDNVVIVNRTYGILESIHYPKPYSVNQ--RCNWTIQATAG

Caenorhabditis elegans        LCNGIVHEAIS-GSIQSPGYPYKVYSNQ--FCTWTIKVPKG

Drosophila                    NC--IRNLTATTGTIESLNYMEPFWETIPINCSWTIRAPKG
Sequence annotation in neighborhood: help 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 1278 – 1389 CUB 8
Glycosylation 1285 – 1285 N-linked (GlcNAc...) asparagine
Glycosylation 1307 – 1307 N-linked (GlcNAc...) asparagine
Disulfide bond 1278 – 1306
Turn 1294 – 1297



Literature citations
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: INVOLVEMENT IN IGS1; VARIANT IGS1 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; Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin.
Kristiansen M.; Aminoff M.; Jacobsen C.; de La Chapelle A.; Krahe R.; Verroust P.J.; Moestrup S.K.;
Blood 96:405-409(2000)
Cited for: CHARACTERIZATION OF VARIANT IGS1 LEU-1297; Detailed investigations of proximal tubular function in Imerslund-Graesbeck syndrome.
Storm T.; Zeitz C.; Cases O.; Amsellem S.; Verroust P.J.; Madsen M.; Benoist J.F.; Passemard S.; Lebon S.; Joensson I.M.; Emma F.; Koldsoe H.; Hertz J.M.; Nielsen R.; Christensen E.I.; Kozyraki R.;
BMC Med. Genet. 14:111-111(2013)
Cited for: VARIANTS IGS1 GLU-1112 AND LEU-1297; CHARACTERIZATION OF VARIANT IGS1 GLU-1112;
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.