UniProtKB/SwissProt variant VAR

Variant information

Variant position:

254

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 Isoleucine (I) to Valine (V) at position 254 (I254V, p.Ile254Val).

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

Variant description:

May influence susceptibility to juvenile rheumatoid arthritis; increased adenosine deaminase activity and decreased adenosine phosphorylase activity; reduced ability to promote pattern recognition receptor (PRR)-induced cytokines; reduced NOD2-induced signaling; does not change interaction with FASN.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs3764147 [ dbSNP | Ensembl ]

Sequence information

Variant position:

254

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

Protein sequence length:

430

The length of the canonical sequence.

Location on the sequence:

NAAGFNVEKFYRIKTHHSND I WIMGRKEPDSYDGITTNQRG

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                         NAAGFNVEKFYRIKTHHSNDIWIMGRKEPDSYDGITTNQRG

Mouse                         NAAGFNAEKFYRIKTDHASEVWVMGKKEPESYDGIVTNQRG

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 – 430	Purine nucleoside phosphorylase LACC1
Metal binding	250 – 250	Zinc; catalytic
Modified residue	247 – 247	N6-acetyllysine
Mutagenesis	247 – 247	K -> A. Decreased acetylation; does not affect ability to promote pattern recognition receptor (PRR)-induced cytokines in macrophages.
Mutagenesis	265 – 265	Y -> A. Does not affect ability to promote pattern recognition receptor (PRR)-induced cytokines in macrophages; when associated with A-52 and A-89.

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]; VARIANT VAL-254;

C13orf31 (FAMIN) is a central regulator of immunometabolic function.
Cader M.Z.; Boroviak K.; Zhang Q.; Assadi G.; Kempster S.L.; Sewell G.W.; Saveljeva S.; Ashcroft J.W.; Clare S.; Mukhopadhyay S.; Brown K.P.; Tschurtschenthaler M.; Raine T.; Doe B.; Chilvers E.R.; Griffin J.L.; Kaneider N.C.; Floto R.A.; D'Amato M.; Bradley A.; Wakelam M.J.; Dougan G.; Kaser A.;
Nat. Immunol. 17:1046-1056(2016)
Cited for: SUBCELLULAR LOCATION; INTERACTION WITH FASN; CHARACTERIZATION OF VARIANT VAL-254;

Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes.
Lahiri A.; Hedl M.; Yan J.; Abraham C.;
Nat. Commun. 8:15614-15614(2017)
Cited for: FUNCTION; INTERACTION WITH SDHA; PHOSPHORYLATION; ACETYLATION AT LYS-247; TISSUE SPECIFICITY; INDUCTION; CHARACTERIZATION OF VARIANT VAL-254; MUTAGENESIS OF TYR-52; TYR-89; LYS-247; 249-HIS-HIS-250 AND TYR-265;

LACC1 gene defects in familial form of juvenile arthritis.
Karacan I.; Ugurlu S.; Sahin S.; Everest E.; Kasapcopur O.; Tolun A.; Oezdogan H.; Turanli E.T.;
J. Rheumatol. 45:726-728(2018)
Cited for: INVOLVEMENT IN JUVAR; VARIANT VAL-254; VARIANT JUVAR 414-ARG--GLU-430 DEL;

FAMIN is a multifunctional purine enzyme enabling the purine nucleotide cycle.
Cader M.Z.; de Almeida Rodrigues R.P.; West J.A.; Sewell G.W.; Md-Ibrahim M.N.; Reikine S.; Sirago G.; Unger L.W.; Inglesias-Romero A.B.; Ramshorn K.; Haag L.M.; Saveljeva S.; Ebel J.F.; Rosenstiel P.; Kaneider N.C.; Lee J.C.; Lawley T.D.; Bradley A.; Dougan G.; Modis Y.; Griffin J.L.; Kaser A.;
Cell 180:278-295(2020)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANT VAL-254;

LACC1 required for NOD2-induced, ER stress-mediated innate immune outcomes in human macrophages and LACC1 risk variants modulate these outcomes.
Huang C.; Hedl M.; Ranjan K.; Abraham C.;
Cell Rep. 29:4525-4539(2019)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH ATF6; EIF2AK3 AND ERN1; CHARACTERIZATION OF VARIANT VAL-254; CHARACTERIZATION OF VARIANT JUVAR ARG-284;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8IV20: Variant p.Ile254Val