UniProtKB/Swiss-Prot P61011: Variant p.Gly226Glu

Signal recognition particle subunit SRP54
Gene: SRP54
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Variant information Variant position:

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

LP/P [Disclaimer] 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 Glycine (G) to Glutamate (E) at position 226 (G226E, p.Gly226Glu). 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 glycine (G) to medium size and acidic (E) 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
Variant description:

In SCN8; decreases expression levels; decreases neutrophil numbers and migration capacity; faster dissociation of the interaction with the SRP receptor subunit SRPRA; reduced SR compaction; impaired interaction with SR; impaired detachment from ribosome; effects on enzymatic activity are unclear as both normal and reduced GTPase activity have been reported. Any additional useful information about the variant.

Sequence information Variant position:

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

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

LQVANAIQPDNIVYVMDASI G QACEAQAKAFKDKVDVASVI 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                         LQVANAIQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

                              LQVANAIQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

Mouse                         LQVSNAIQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

Rat                           LQVSNAIQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

Bovine                        LQVANAIQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

Zebrafish                     LQVSNAVQPDNIVYVMDASIGQACEAQAKAFKDKVDVASVI

Slime mold                    KQIETAVKPDNCIFVMDSSIGQAAYEQATAFRSSVKVGSII

Baker's yeast                 IEISNVIKPNQTIMVLDASIGQAAEQQSKAFKESSDFGAII

Fission yeast                 VEISDAIRPDQTIMILDASIGQAAESQSKAFKETADFGAVI

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 – 504	Signal recognition particle subunit SRP54
Region	1 – 295	NG domain
Helix	223 – 228

Literature citations
Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.
Carapito R.; Konantz M.; Paillard C.; Miao Z.; Pichot A.; Leduc M.S.; Yang Y.; Bergstrom K.L.; Mahoney D.H.; Shardy D.L.; Alsaleh G.; Naegely L.; Kolmer A.; Paul N.; Hanauer A.; Rolli V.; Mueller J.S.; Alghisi E.; Sauteur L.; Macquin C.; Morlon A.; Sancho C.S.; Amati-Bonneau P.; Procaccio V.; Mosca-Boidron A.L.; Marle N.; Osmani N.; Lefebvre O.; Goetz J.G.; Unal S.; Akarsu N.A.; Radosavljevic M.; Chenard M.P.; Rialland F.; Grain A.; Bene M.C.; Eveillard M.; Vincent M.; Guy J.; Faivre L.; Thauvin-Robinet C.; Thevenon J.; Myers K.; Fleming M.D.; Shimamura A.; Bottollier-Lemallaz E.; Westhof E.; Lengerke C.; Isidor B.; Bahram S.;
J. Clin. Invest. 127:4090-4103(2017)
Cited for: VARIANTS SCN8 ALA-115; THR-117 DEL AND GLU-226; CHARACTERIZATION OF VARIANTS SCN8 ALA-115; THR-117 DEL AND GLU-226; CATALYTIC ACTIVITY; FUNCTION; Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.
Bellanne-Chantelot C.; Schmaltz-Panneau B.; Marty C.; Fenneteau O.; Callebaut I.; Clauin S.; Docet A.; Damaj G.L.; Leblanc T.; Pellier I.; Stoven C.; Souquere S.; Antony-Debre I.; Beaupain B.; Aladjidi N.; Barlogis V.; Bauduer F.; Bensaid P.; Boespflug-Tanguy O.; Berger C.; Bertrand Y.; Carausu L.; Fieschi C.; Galambrun C.; Schmidt A.; Journel H.; Mazingue F.; Nelken B.; Quah T.C.; Oksenhendler E.; Ouachee M.; Pasquet M.; Saada V.; Suarez F.; Pierron G.; Vainchenker W.; Plo I.; Donadieu J.;
Blood 132:1318-1331(2018)
Cited for: FUNCTION; DEVELOPMENTAL STAGE; SUBCELLULAR LOCATION; VARIANTS SCN8 ARG-113; THR-117 DEL; TYR-118; TYR-136; ASP-223; GLU-226 AND ASP-274; CHARACTERIZATION OF VARIANTS SCN8 THR-117 DEL; TYR-118; TYR-136 AND ASP-223; Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.
Lee J.H.; Jomaa A.; Jomaa A.; Chung S.; Hwang Fu Y.H.; Qian R.; Sun X.; Hsieh H.H.; Chandrasekar S.; Bi X.; Mattei S.; Boehringer D.; Weiss S.; Ban N.; Shan S.O.;
Sci. Adv. 7:942-942(2021)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF SIGNAL RECOGNITION PARTICLE IN COMPLEX WITH RIBOSOME NASCENT CHAIN COMPLEX AND THE SRP RECEPTOR; FUNCTION; CATALYTIC ACTIVITY; INTERACTION WITH SRPRA; CHARACTERIZATION OF VARIANT SCN8 GLU-226; DOMAIN;

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.