UniProtKB/Swiss-Prot P41220: Variant p.Asp40Tyr

Regulator of G-protein signaling 2
Gene: RGS2
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Variant information Variant position:

40 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 Aspartate (D) to Tyrosine (Y) at position 40 (D40Y, p.Asp40Tyr). 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 large size and aromatic (Y) 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:

Decreased down-regulation of angiotensin-activated signaling pathway; reduced localization at the cell membrane. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs201233692 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

AGSGHKSEEKREKMKRTLLK D WKTRLSYFLQNSSTPGKPKT 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                         AGSGHKSEEKREKMKRTLLKDWKTRLSYFLQNSSTPGKPKT

Mouse                         AGNGPKVEEKREKMKRTLLKDWKTRLSYFLQNSSAPGKPKT

Rat                           AGNGPKVEEKREKMKRTLLKDWKTRLSYFLQNSSTPGKPKT

Pig                           AGTGPKSEEKREKMKRTLLKDWKTRLSYFLQNSSSPGKPKT

Bovine                        AGTGPKNEEKREKMKRTLLKDWKSRLSYFLQNSSSPGKPKT

Caenorhabditis elegans        HSGSVSVEKKN-------------------QENDGP-----

Baker's yeast                 SRSDGDAESSN-----TVLIQLR------------------

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 – 211	Regulator of G-protein signaling 2
Region	32 – 66	Necessary for membrane association
Mutagenesis	33 – 33	M -> L. Loss of isoform 4 expression.
Mutagenesis	37 – 37	L -> D. Impairs association with plasma membrane.
Mutagenesis	38 – 38	L -> D. Impairs association with plasma membrane.
Mutagenesis	41 – 41	W -> D. Impairs association with plasma membrane.
Mutagenesis	45 – 45	L -> D. Impairs association with plasma membrane.
Mutagenesis	48 – 48	F -> D. Impairs association with plasma membrane.
Mutagenesis	49 – 49	L -> D. Impairs association with plasma membrane.

Literature citations
Human missense mutations in regulator of G protein signaling 2 affect the protein function through multiple mechanisms.
Phan H.T.N.; Sjoegren B.; Neubig R.R.;
Mol. Pharmacol. 92:451-458(2017)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH GNAQ; CHARACTERIZATION OF VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; HIS-44; LYS-50; LEU-55; HIS-78; GLY-99; VAL-110; HIS-188 AND ARG-196; Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; HIS-44; LYS-50; LEU-55; GLY-99; VAL-110; HIS-188 AND ARG-196;

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.