UniProtKB/Swiss-Prot P17405: Variant p.Gly508Arg

Sphingomyelin phosphodiesterase
Gene: SMPD1
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Variant information Variant position:

508 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 Glycine (G) to Arginine (R) at position 508 (G508R, p.Gly508Arg). 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 large size and basic (R) 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:

A common polymorphism arises from a variable number of hexanucleotide repeat sequence within the signal peptide region. Additional information on the polymorphism described.
Variant description:

Does not affect enzymatic activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1050239 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TTYIGLNPGYRVYQIDGNYS G SSHVVLDHETYILNLTQANI 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                         TTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANI

Mouse                         TTFINLNPGYRVYQIDGNYPGSSHVVLDHETYILNLTQANA

Bovine                        TTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYIMNLTEANE

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	47 – 631	Sphingomyelin phosphodiesterase
Chain	254 – 631	Sphingomyelin phosphodiesterase, processed form
Modified residue	510 – 510	Phosphoserine; by PKC/PRKCD
Glycosylation	505 – 505	N-linked (GlcNAc...) asparagine
Glycosylation	522 – 522	N-linked (GlcNAc...) asparagine
Mutagenesis	505 – 505	N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.
Mutagenesis	510 – 510	S -> A. Abolishes constitutive secretion and decreases secretion in response to IL1B. No effect on lysosomal targeting. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. Abolishes phosphorylation by PRKCD.
Mutagenesis	522 – 522	N -> G. Loss of sphingomyelin phosphodiesterase activity. Loss of secretion.

Literature citations
Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs.
Schuchman E.H.; Suchi M.; Takahashi T.; Sandhoff K.; Desnick R.J.;
J. Biol. Chem. 266:8531-8539(1991)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; FUNCTION; CATALYTIC ACTIVITY; ALTERNATIVE SPLICING; VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508; Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene.
Newrzella D.; Stoffel W.;
Biol. Chem. Hoppe-Seyler 373:1233-1238(1992)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS 48-ALA-LEU-49 DEL AND ARG-508; 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] (ISOFORM 4); VARIANTS 48-ALA-LEU-49 DEL AND ARG-508; Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts.
Quintern L.E.; Schuchman E.H.; Levran O.; Suchi M.; Ferlinz K.; Reinke H.; Sandhoff K.; Desnick R.J.;
EMBO J. 8:2469-2473(1989)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 130-631; PARTIAL PROTEIN SEQUENCE; ALTERNATIVE SPLICING; VARIANTS ILE-324 AND ARG-508; Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.
Pavluu-Pereira H.; Asfaw B.; Poupctova H.; Ledvinova J.; Sikora J.; Vanier M.T.; Sandhoff K.; Zeman J.; Novotna Z.; Chudoba D.; Elleder M.;
J. Inherit. Metab. Dis. 28:203-227(2005)
Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579; VARIANT ARG-508; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378; Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease.
Rhein C.; Muehle C.; Kornhuber J.; Reichel M.;
Int. J. Mol. Sci. 16:13649-13652(2015)
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325; CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508; CATALYTIC ACTIVITY;

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.