UniProtKB/Swiss-Prot Q86WV6: Variant p.His232Arg

Stimulator of interferon genes protein
Gene: STING1
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Variant information Variant position:

232 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 Histidine (H) to Arginine (R) at position 232 (H232R, p.His232Arg). 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 polar (H) to large size and basic (R) 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
Variant description:

Activated by both 2'-3' linked cGAMP and 3'-3' linked cGAMP. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1131769 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LSMADPNIRFLDKLPQQTGD H AGIKDRVYSNSIYELLENGQ 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                         LSMADPNIRFLDKLPQQTGDHAGIKDRVYSNSIYELLEN-GQ

Mouse                         LSVVDPNIRFRDMLPQQNIDRAGIKNRVYSNSVYEILEN-G

Rat                           LSVADPNIRFRDMLPQQNTDRAGVKNRAYSNSVYELLEN-G

Pig                           LSVADPNIRFLHELPQQSADRAGIKGRVYTNSIYELLEN-G

Bovine                        LNVADPNIRFLHELPQQSADRAGIKGRVYTNSIYELLEN-G

Chicken                       LEKADSNIQYLADLPETILTRAGIKRRVYKHSLYVIRDK-D

Xenopus tropicalis            LKDVDENITFLKEIPPLYIDRAGIKGRVFKNNVYRILDE-D

Zebrafish                     PEEEDTNVVFHENLPDLKLDRAGVRKRSYTNSVYKITHN-N

Drosophila                    LE--SHLLDKAEPLETQFINRAGVY-RPFKHDVYRMNKKVN

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 – 379	Stimulator of interferon genes protein
Topological domain	135 – 379	Cytoplasmic
Region	153 – 340	Cyclic dinucleotide-binding domain (CBD)
Binding site	238 – 238
Binding site	238 – 238
Modified residue	229 – 229	Phosphothreonine
Modified residue	241 – 241	Phosphoserine
Cross	236 – 236	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	230 – 230	G -> I. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway.
Mutagenesis	236 – 236	K -> R. Loss of deubiquitination by USP44.
Mutagenesis	238 – 238	R -> A. Abolished cGAMP-binding. Abolished ability to induce autophagy.
Mutagenesis	240 – 240	Y -> A. Abolished cGAMP-binding.
Mutagenesis	240 – 240	Y -> S. Strong decrease in c-di-GMP-binding.
Mutagenesis	242 – 242	N -> A. Strong decrease in c-di-GMP and cGAMP-binding.
Beta strand	228 – 232

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 ARG-232; Ancient origin of cGAS-STING reveals mechanism of universal 2',3' cGAMP signaling.
Kranzusch P.J.; Wilson S.C.; Lee A.S.; Berger J.M.; Doudna J.A.; Vance R.E.;
Mol. Cell 59:891-903(2015)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT ARG-232;

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.