UniProtKB/Swiss-Prot O15244: Variant p.Ser270Ala

Solute carrier family 22 member 2
Gene: SLC22A2
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Variant information Variant position:

270 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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:

From Serine (S) to Alanine (A) at position 270 (S270A, p.Ser270Ala). 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 small size and polar (S) to small size and hydrophobic (A) 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
Variant description:

Decreased Ki value for TBA inhibition of MPP(+); no change in transport efficiency (Vmax/Km) and clearance of cyclo(his-pro) and salsolinol. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs316019 [ dbSNP | Ensembl ]

Sequence information Variant position:

270 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

555 The length of the canonical sequence.
Location on the sequence:

LVLAGVAYALPHWRWLQFTV S LPNFFFLLYYWCIPESPRWL 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                         LVLAGVAYALPHWRWLQFTVSLPNFFFLLYYWCIPESPRWL

Mouse                         LILAGVAYALPNWRWLQFAVTLPNFCFLLYFWCIPESPRWL

Rat                           LILAGVAYVIPNWRWLQFAVTLPNFCFLLYFWCIPESPRWL

Pig                           LVLAGVAYALPHWRWLQFTVTLPNFCFLFYYWCVPESPRWL

Rabbit                        LVLAGVAYALPRWRWLQLTVTLPYFCFLLYYWCIPESPRWL

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.

Type	Positions	Description
Chain	1 – 555	Solute carrier family 22 member 2
Transmembrane	264 – 284	Helical
Alternative sequence	243 – 555	Missing. In isoform 3.
Mutagenesis	257 – 257	Y -> F. No change in TEA uptake.
Mutagenesis	279 – 279	Y -> F. No change in TEA uptake.
Mutagenesis	280 – 280	Y -> F. No change in TEA uptake.
Mutagenesis	284 – 284	P -> A. Decreased TEA and metformin uptake. Decreased tyrosine phosphorylation.
Mutagenesis	286 – 286	S -> A. No change in TEA and metformin uptake. No change in tyrosine phosphorylation.
Mutagenesis	287 – 287	P -> A. Decreased TEA and metformin uptake. Decreased tyrosine phosphorylation.

Literature citations
Cloning and characterization of two human polyspecific organic cation transporters.
Gorboulev V.; Ulzheimer J.C.; Akhoundova A.; Ulzheimer-Teuber I.; Karbach U.; Quester S.; Baumann C.; Lang F.; Busch A.E.; Koepsell H.;
DNA Cell Biol. 16:871-881(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; TRANSPORTER ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; MISCELLANEOUS; VARIANT ALA-270; cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney.
Urakami Y.; Akazawa M.; Saito H.; Okuda M.; Inui K.;
J. Am. Soc. Nephrol. 13:1703-1710(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); FUNCTION; TRANSPORTER ACTIVITY; TISSUE SPECIFICITY; MISCELLANEOUS; VARIANT ALA-270; 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] (ISOFORM 1); VARIANT ALA-270; 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] (ISOFORMS 1 AND 3); VARIANT ALA-270; Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function.
Leabman M.K.; Huang C.C.; Kawamoto M.; Johns S.J.; Stryke D.; Ferrin T.E.; DeYoung J.; Taylor T.; Clark A.G.; Herskowitz I.; Giacomini K.M.;
Pharmacogenetics 12:395-405(2002)
Cited for: VARIANT SER-54; CHARACTERIZATION OF VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432; Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.
Shikata E.; Yamamoto R.; Takane H.; Shigemasa C.; Ikeda T.; Otsubo K.; Ieiri I.;
J. Hum. Genet. 52:117-122(2007)
Cited for: VARIANTS MET-201 AND ALA-270; Identification of the endogenous key substrates of the human organic cation transporter OCT2 and their implication in function of dopaminergic neurons.
Taubert D.; Grimberg G.; Stenzel W.; Schoemig E.;
PLoS ONE 2:e385-e385(2007)
Cited for: VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432; CHARACTERIZATION OF VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432; FUNCTION; TRANSPORTER ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; TISSUE SPECIFICITY;

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.