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UniProtKB/Swiss-Prot P00325: Variant p.Arg48His

All-trans-retinol dehydrogenase [NAD(+)] ADH1B
Gene: ADH1B
Variant information

Variant position:  48
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 Arginine (R) to Histidine (H) at position 48 (R48H, p.Arg48His).
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 basic (R) to medium size and polar (H)
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:  Three alleles are known: ADH1B*1 (ADH2*1) corresponding to variant beta-1, ADH1B*2 (ADH2*2) corresponding to variant beta-2, ADH1B*3 (ADH2*3) corresponding to variant beta-3. The sequence shown is that of allele ADH1B*1. The ADH1B*2 allele frequency in orientals is approximately 75%, whereas it is less than 5% in most Caucasian populations. ADH1B variations have been associated with protection against alcohol dependence and alcohol-related aerodigestive tract cancer [MIM:103720].
Additional information on the polymorphism described.

Variant description:  In beta-2; allele ADH1B*2; common in Asian populations; associated with a lower risk of alcoholism.
Any additional useful information about the variant.

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



Sequence information

Variant position:  48
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  375
The length of the canonical sequence.

Location on the sequence:   EVAPPKAYEVRIKMVAVGIC  R TDDHVVSGNLVTPLPVILGH
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                         EVAPPKAYEVRIKMVAVGICRTDDHVVSGNLVTPLPVILGH

Chimpanzee                    EVAPPKAYEVRIKMVAVGICRTDDHVVSGNLVTPLPAILGH

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 2 – 375 All-trans-retinol dehydrogenase [NAD(+)] ADH1B
Metal binding 47 – 47 Zinc 1; catalytic
Metal binding 68 – 68 Zinc 1; catalytic
Modified residue 35 – 35 Phosphotyrosine
Helix 48 – 54


Literature citations

Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit.
Carr L.G.; Xu Y.; Ho W.H.; Edenberg H.J.;
Alcohol. Clin. Exp. Res. 13:594-596(1989)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HIS-48; LYS-57 AND CYS-370; POLYMORPHISM;

The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide.
Matsuo Y.; Yokoyama R.; Yokoyama S.;
Eur. J. Biochem. 183:317-320(1989)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT HIS-48; POLYMORPHISM;

Submission
Polin L.; Hey-Chi H.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT HIS-48;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HIS-48; SER-60 AND CYS-370;

Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
Hillier L.W.; Graves T.A.; Fulton R.S.; Fulton L.A.; Pepin K.H.; Minx P.; Wagner-McPherson C.; Layman D.; Wylie K.; Sekhon M.; Becker M.C.; Fewell G.A.; Delehaunty K.D.; Miner T.L.; Nash W.E.; Kremitzki C.; Oddy L.; Du H.; Sun H.; Bradshaw-Cordum H.; Ali J.; Carter J.; Cordes M.; Harris A.; Isak A.; van Brunt A.; Nguyen C.; Du F.; Courtney L.; Kalicki J.; Ozersky P.; Abbott S.; Armstrong J.; Belter E.A.; Caruso L.; Cedroni M.; Cotton M.; Davidson T.; Desai A.; Elliott G.; Erb T.; Fronick C.; Gaige T.; Haakenson W.; Haglund K.; Holmes A.; Harkins R.; Kim K.; Kruchowski S.S.; Strong C.M.; Grewal N.; Goyea E.; Hou S.; Levy A.; Martinka S.; Mead K.; McLellan M.D.; Meyer R.; Randall-Maher J.; Tomlinson C.; Dauphin-Kohlberg S.; Kozlowicz-Reilly A.; Shah N.; Swearengen-Shahid S.; Snider J.; Strong J.T.; Thompson J.; Yoakum M.; Leonard S.; Pearman C.; Trani L.; Radionenko M.; Waligorski J.E.; Wang C.; Rock S.M.; Tin-Wollam A.-M.; Maupin R.; Latreille P.; Wendl M.C.; Yang S.-P.; Pohl C.; Wallis J.W.; Spieth J.; Bieri T.A.; Berkowicz N.; Nelson J.O.; Osborne J.; Ding L.; Meyer R.; Sabo A.; Shotland Y.; Sinha P.; Wohldmann P.E.; Cook L.L.; Hickenbotham M.T.; Eldred J.; Williams D.; Jones T.A.; She X.; Ciccarelli F.D.; Izaurralde E.; Taylor J.; Schmutz J.; Myers R.M.; Cox D.R.; Huang X.; McPherson J.D.; Mardis E.R.; Clifton S.W.; Warren W.C.; Chinwalla A.T.; Eddy S.R.; Marra M.A.; Ovcharenko I.; Furey T.S.; Miller W.; Eichler E.E.; Bork P.; Suyama M.; Torrents D.; Waterston R.H.; Wilson R.K.;
Nature 434:724-731(2005)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT HIS-48;

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
Bian Y.; Song C.; Cheng K.; Dong M.; Wang F.; Huang J.; Sun D.; Wang L.; Ye M.; Zou H.;
J. Proteomics 96:253-262(2014)
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND TYR-35; VARIANT [LARGE SCALE ANALYSIS] HIS-48; IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];

Human liver alcohol dehydrogenase: amino acid substitution in the beta 2 beta 2 Oriental isozyme explains functional properties, establishes an active site structure, and parallels mutational exchanges in the yeast enzyme.
Joernvall H.; Hempel J.; Vallee B.L.; Bosron W.F.; Li T.-K.;
Proc. Natl. Acad. Sci. U.S.A. 81:3024-3028(1984)
Cited for: VARIANT HIS-48; POLYMORPHISM;

Genetic polymorphism of alcohol dehydrogenase in Europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.
Borras E.; Coutelle C.; Rosell A.; Fernandez-Muixi F.; Broch M.; Crosas B.; Hjelmqvist L.; Lorenzo A.; Gutierrez C.; Santos M.; Szczepanek M.; Heilig M.; Quattrocchi P.; Farres J.; Vidal F.; Richart C.; Mach T.; Bogdal J.; Joernvall H.; Seitz H.K.; Couzigou P.; Pares X.;
Hepatology 31:984-989(2000)
Cited for: ASSOCIATION OF VARIANT HIS-48 WITH LOWER RISK OF ALCOHOLISM; POLYMORPHISM;

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.