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UniProtKB/Swiss-Prot Q04609: Variant p.Tyr75His

Glutamate carboxypeptidase 2
Gene: FOLH1
Variant information

Variant position:  75
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 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 Tyrosine (Y) to Histidine (H) at position 75 (Y75H, p.Tyr75His).
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 large size and aromatic (Y) to medium size and polar (H)
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

Polymorphism:  Genetic variation in FOLH1 may be associated with low folate levels and consequent hyperhomocysteinemia. This condition can result in increased risk of cardiovascular disease, neural tube defects, and cognitive deficits.
Additional information on the polymorphism described.

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



Sequence information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  750
The length of the canonical sequence.

Location on the sequence:   KHNMKAFLDELKAENIKKFL  Y NFTQIPHLAGTEQNFQLAKQ
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                         KHNMK-AFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQ

Mouse                         HSGMKKEFLHELKAENIKKFLYNFTRTPHLAGTQNNFELAK

Rat                           YPGMKKAFLQELKAENIKKFLYNFTRTPHLAGTQHNFELAK

Pig                           QHNVKKAFLDELKAENIKTFLYNFTRIPHLAGTEQNFQLAK

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 1 – 750 Glutamate carboxypeptidase 2
Topological domain 44 – 750 Extracellular
Glycosylation 76 – 76 N-linked (GlcNAc...) asparagine
Alternative sequence 1 – 585 Missing. In isoform PSMA-3.
Alternative sequence 1 – 308 Missing. In isoform 10.
Alternative sequence 1 – 159 Missing. In isoform PSMA-4.
Mutagenesis 76 – 76 N -> A. Loss of glycosylation. Reduces enzyme activity.
Helix 67 – 77


Literature citations

Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene.
O'Keefe D.S.; Su S.L.; Bacich D.J.; Horiguchi Y.; Luo Y.; Powell C.T.; Zandvliet D.; Russell P.J.; Molloy P.L.; Nowak N.J.; Shows T.B.; Mullins C.; Vonder Haar R.A.; Fair W.R.; Heston W.D.W.;
Biochim. Biophys. Acta 1443:113-127(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PSMA-1); VARIANT HIS-75;

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.