UniProtKB/SwissProt variant VAR

Variant information

Variant position:

358

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 Aspartate (D) to Alanine (A) at position 358 (D358A, p.Asp358Ala).

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 medium size and acidic (D) to small size and hydrophobic (A)

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 variations in IL6R determine soluble IL6R serum levels [MIM:614689].Genetic variations in IL6R define the IL6 serum level quantitative trait locus [MIM:614752]. -

Additional information on the polymorphism described.

Variant description:

Significantly associated with circulating levels of IL6 and soluble IL6R.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs2228145 [ dbSNP | Ensembl ]

Sequence information

Variant position:

358

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

Protein sequence length:

468

The length of the canonical sequence.

Location on the sequence:

KDDDNILFRDSANATSLPVQ D SSSVPLPTFLVAGGSLAFGT

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                         KDDDNILFRDSANATSL--PVQDSSSVPLPTFLVAGGSLAFGT

Mouse                         SANHEDQYESSTEATSVLAPVQESSSMSLPTFLVAGGSLAF

Rat                           YDNHEDQYGSSTEATSVLAPVQGSSPIPLPTFLVAGGSLAF

Pig                           EDDEDISSKESANATSL--PVQDSASVPLPTFLVAGGSLAF

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	20 – 468	Interleukin-6 receptor subunit alpha
Topological domain	20 – 365	Extracellular
Alternative sequence	356 – 365	VQDSSSVPLP -> GSRRRGSCGL. In isoform 2.

Literature citations

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] (ISOFORMS 1 AND 2); VARIANT ALA-358;

Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
Reich D.; Patterson N.; Ramesh V.; De Jager P.L.; McDonald G.J.; Tandon A.; Choy E.; Hu D.; Tamraz B.; Pawlikowska L.; Wassel-Fyr C.; Huntsman S.; Waliszewska A.; Rossin E.; Li R.; Garcia M.; Reiner A.; Ferrell R.; Cummings S.; Kwok P.Y.; Harris T.; Zmuda J.M.; Ziv E.;
Am. J. Hum. Genet. 80:716-726(2007)
Cited for: POLYMORPHISM; VARIANT ALA-358; ASSOCIATION OF VARIANT ALA-358 WITH IL6 AND SOLUBLE IL6R SERUM LEVELS;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08887: Variant p.Asp358Ala