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UniProtKB/Swiss-Prot P22760: Variant p.Val281Ile

Arylacetamide deacetylase
Gene: AADAC
Variant information

Variant position:  281
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 Isoleucine (I) at position 281 (V281I, p.Val281Ile).
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:  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

Polymorphism:  Three alleles are known: AADAC*1, AADAC*2 and AADAC*3. The sequence shown is that of AADAC*1 which is found in European American, African American, Japanese and Korean populations at allelic frequencies of 39.3 to 47.4%. The AADAC*2 allele is found in European American, African American, Korean, and Japanese populations at allelic frequencies of 52.6 to 63.5% whereas the AADAC*3 allele is found in European American (1.3%) and African American (2.0%) samples but not in Japanese or Korean samples.
Additional information on the polymorphism described.

Variant description:  In alleles AADAC*2 and AADAC*3; mildly decreased enzyme activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  281
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  399
The length of the canonical sequence.

Location on the sequence:   EKAMLSRQHVPVESSHLFKF  V NWSSLLPERFIKGHVYNNPN
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                         EKAMLSRQHVPVESSHLFKFVNWSSLLPERFIKGHVYNNPN

Mouse                         EKAMLLNQHVPMESSHLLQFVNWSSLLPERYKKSPVYKNPT

Rat                           EKAMLLNQHVPVEFSHLLQFVNWSSLLPQRYKKGYFYKTPT

Bovine                        KKAMLSNQHIPLESSNLFKFVNWSSLLPEKFKKGHIYKTPT

Rabbit                        EKAMLLNQHVPVESSHLFKFTNWSSLLPEKFKKGHVYNTPT

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 – 399 Arylacetamide deacetylase
Topological domain 24 – 399 Lumenal
Glycosylation 282 – 282 N-linked (GlcNAc...) asparagine
Disulfide bond 116 – 340
Mutagenesis 282 – 282 N -> Q. Abolishes glycosylation at this site and causes substantial decrease in activity and reduced substrate affinity.


Literature citations

Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.
Probst M.R.; Beer M.; Beer D.; Jenoe P.; Meyer U.A.; Gasser R.;
J. Biol. Chem. 269:21650-21656(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; PARTIAL PROTEIN SEQUENCE; VARIANT ILE-281;

Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T.; Suzuki Y.; Nishikawa T.; Otsuki T.; Sugiyama T.; Irie R.; Wakamatsu A.; Hayashi K.; Sato H.; Nagai K.; Kimura K.; Makita H.; Sekine M.; Obayashi M.; Nishi T.; Shibahara T.; Tanaka T.; Ishii S.; Yamamoto J.; Saito K.; Kawai Y.; Isono Y.; Nakamura Y.; Nagahari K.; Murakami K.; Yasuda T.; Iwayanagi T.; Wagatsuma M.; Shiratori A.; Sudo H.; Hosoiri T.; Kaku Y.; Kodaira H.; Kondo H.; Sugawara M.; Takahashi M.; Kanda K.; Yokoi T.; Furuya T.; Kikkawa E.; Omura Y.; Abe K.; Kamihara K.; Katsuta N.; Sato K.; Tanikawa M.; Yamazaki M.; Ninomiya K.; Ishibashi T.; Yamashita H.; Murakawa K.; Fujimori K.; Tanai H.; Kimata M.; Watanabe M.; Hiraoka S.; Chiba Y.; Ishida S.; Ono Y.; Takiguchi S.; Watanabe S.; Yosida M.; Hotuta T.; Kusano J.; Kanehori K.; Takahashi-Fujii A.; Hara H.; Tanase T.-O.; Nomura Y.; Togiya S.; Komai F.; Hara R.; Takeuchi K.; Arita M.; Imose N.; Musashino K.; Yuuki H.; Oshima A.; Sasaki N.; Aotsuka S.; Yoshikawa Y.; Matsunawa H.; Ichihara T.; Shiohata N.; Sano S.; Moriya S.; Momiyama H.; Satoh N.; Takami S.; Terashima Y.; Suzuki O.; Nakagawa S.; Senoh A.; Mizoguchi H.; Goto Y.; Shimizu F.; Wakebe H.; Hishigaki H.; Watanabe T.; Sugiyama A.; Takemoto M.; Kawakami B.; Yamazaki M.; Watanabe K.; Kumagai A.; Itakura S.; Fukuzumi Y.; Fujimori Y.; Komiyama M.; Tashiro H.; Tanigami A.; Fujiwara T.; Ono T.; Yamada K.; Fujii Y.; Ozaki K.; Hirao M.; Ohmori Y.; Kawabata A.; Hikiji T.; Kobatake N.; Inagaki H.; Ikema Y.; Okamoto S.; Okitani R.; Kawakami T.; Noguchi S.; Itoh T.; Shigeta K.; Senba T.; Matsumura K.; Nakajima Y.; Mizuno T.; Morinaga M.; Sasaki M.; Togashi T.; Oyama M.; Hata H.; Watanabe M.; Komatsu T.; Mizushima-Sugano J.; Satoh T.; Shirai Y.; Takahashi Y.; Nakagawa K.; Okumura K.; Nagase T.; Nomura N.; Kikuchi H.; Masuho Y.; Yamashita R.; Nakai K.; Yada T.; Nakamura Y.; Ohara O.; Isogai T.; Sugano S.;
Nat. Genet. 36:40-45(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT ILE-281;

Submission
Mural R.J.; Istrail S.; Sutton G.G.; Florea L.; Halpern A.L.; Mobarry C.M.; Lippert R.; Walenz B.; Shatkay H.; Dew I.; Miller J.R.; Flanigan M.J.; Edwards N.J.; Bolanos R.; Fasulo D.; Halldorsson B.V.; Hannenhalli S.; Turner R.; Yooseph S.; Lu F.; Nusskern D.R.; Shue B.C.; Zheng X.H.; Zhong F.; Delcher A.L.; Huson D.H.; Kravitz S.A.; Mouchard L.; Reinert K.; Remington K.A.; Clark A.G.; Waterman M.S.; Eichler E.E.; Adams M.D.; Hunkapiller M.W.; Myers E.W.; Venter J.C.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT ILE-281;

A novel polymorphic allele of human arylacetamide deacetylase leads to decreased enzyme activity.
Shimizu M.; Fukami T.; Kobayashi Y.; Takamiya M.; Aoki Y.; Nakajima M.; Yokoi T.;
Drug Metab. Dispos. 40:1183-1190(2012)
Cited for: FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; BIOPHYSICOCHEMICAL PROPERTIES; VARIANTS ILE-281 AND GLN-399 EXT; CHARACTERIZATION OF VARIANTS ILE-281 AND GLN-399 EXT;

Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population.
Saito S.; Iida A.; Sekine A.; Kawauchi S.; Higuchi S.; Ogawa C.; Nakamura Y.;
J. Hum. Genet. 48:249-270(2003)
Cited for: VARIANT ILE-281;

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.