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UniProtKB/Swiss-Prot P31213: Variant p.Val89Leu

3-oxo-5-alpha-steroid 4-dehydrogenase 2
Gene: SRD5A2
Variant information

Variant position:  89
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 Valine (V) to Leucine (L) at position 89 (V89L, p.Val89Leu).
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:  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:  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

Polymorphism:  Individuals with Thr-49 have an increased risk of prostate cancer (PubMed:10501358). The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme (PubMed:10501358).
Additional information on the polymorphism described.

Variant description:  No effect on affinity for testosterone; no effect on affinity for NADPH; decreased Vmax; no effect on affinity for testosterone when associated with T-49; no effect on affinity for NADPH when associated with T-49; increased Vmax when associated with T-49; decreased affinity for testosterone when associated with M-187; increased affinity for NADPH when associated with M-187; decreased Vmax when associated with M-187; no effect on affinity for testosterone when associated with L-234; increased affinity for NADPH when associated with L-234; decreased Vmax when associated with L-234.
Any additional useful information about the variant.

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



Sequence information

Variant position:  89
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  254
The length of the canonical sequence.

Location on the sequence:   ARQPLSLFGPPGTVLLGLFC  V HYFHRTFVYSLLNRGRPYPA
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                         ARQPLSLFGPPGTVLLGLFCVHYFHRTFVYSLLNRGRPYPA

Mouse                         AWQPRSLFGPPGNVLLGLFSAHYFHRTFIYSLLTRGRPLSA

Rat                           AWQPRSLFGPPGNVLLALFSAHYFHRTFIYSLLTRGRPFPA

Pig                           AGQPRSLFGPPATVLLGLFCAHYFHRTFVYSLLTRGRPFPV

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 – 254 3-oxo-5-alpha-steroid 4-dehydrogenase 2
Transmembrane 72 – 92 Helical


Literature citations

Submission
Schupp I.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT LEU-89;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS THR-49; LEU-89 AND VAL-113;

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT LEU-89;

Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II.
Makridakis N.M.; di Salle E.; Reichardt J.K.;
Pharmacogenetics 10:407-413(2000)
Cited for: VARIANTS ARG-5; LEU-30; ARG-48; THR-49; THR-51; LEU-89; MET-187; LEU-194 AND LEU-234; VARIANT PPSH GLN-227; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;

Steroid 5-alpha reductase type II V89L substitution is not associated with risk of prostate cancer in a multiethnic population study.
Pearce C.L.; Makridakis N.M.; Ross R.K.; Pike M.C.; Kolonel L.N.; Henderson B.E.; Reichardt J.K.V.;
Cancer Epidemiol. Biomarkers Prev. 11:417-418(2002)
Cited for: VARIANT LEU-89;

Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients.
Sasaki G.; Ogata T.; Ishii T.; Kosaki K.; Sato S.; Homma K.; Takahashi T.; Hasegawa T.; Matsuo N.;
J. Clin. Endocrinol. Metab. 88:3431-3436(2003)
Cited for: VARIANT PPSH GLN-227; VARIANT LEU-89;

SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects.
Nicoletti A.; Baldazzi L.; Balsamo A.; Barp L.; Pirazzoli P.; Gennari M.; Radetti G.; Cacciari E.; Cicognani A.;
Clin. Endocrinol. (Oxf.) 63:375-380(2005)
Cited for: VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246; VARIANTS THR-49 AND LEU-89;

New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2.
Hackel C.; Oliveira L.E.; Ferraz L.F.; Tonini M.M.; Silva D.N.; Toralles M.B.; Stuchi-Perez E.G.; Guerra-Junior G.;
J. Mol. Med. 83:569-576(2005)
Cited for: VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246; VARIANTS THR-49 AND LEU-89;

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.