UniProtKB/Swiss-Prot P26678: Variant p.Arg9Cys

Cardiac phospholamban
Gene: PLN
Chromosomal location: 6q22.1
Variant information

Variant position:  9
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Cysteine (C) at position 9 (R9C, p.Arg9Cys).
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 large size and basic (R) to medium size and polar (C)
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:  In CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake.
Any additional useful information about the variant.



Sequence information

Variant position:  9
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  52
The length of the canonical sequence.

Location on the sequence:   MEKVQYLT  R SAIRRASTIEMPQQARQKLQ
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                         MEKVQYLTRSAIRRASTIEMPQQARQKLQ

Mouse                         MEKVQYLTRSAIRRASTIEMPQQARQNLQ

Rat                           MEKVQYLTRSAIRRASTIEMPQQARQNLQ

Pig                           MDKVQYLTRSAIRRASTIEMPQQARQNLQ

Bovine                        MDKVQYLTRSAIRRASTIEMPQQARQNLQ

Rabbit                        MEKVQYLTRSAIRRASTIEMPQQARQNLQ

Dog                           MDKVQYLTRSAIRRASTIEMPQQARQNLQ

Chicken                       MEKVQYITRSALRRASTLEVNPQARQRLQ

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.

TypePositionsDescription
Chain 1 – 52 Cardiac phospholamban
Topological domain 1 – 31 Cytoplasmic
Modified residue 1 – 1 N-acetylmethionine
Modified residue 16 – 16 Phosphoserine; by PKA and DMPK
Modified residue 17 – 17 Phosphothreonine; by CaMK2
Mutagenesis 9 – 9 R -> HL. Impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake.
Mutagenesis 13 – 13 R -> A. Abolishes phosphorylation by PKA.
Mutagenesis 14 – 14 R -> A. Abolishes phosphorylation by PKA.
Mutagenesis 16 – 16 S -> A. Abolishes phosphorylation by PKA.
Mutagenesis 17 – 17 T -> A. No effect on phosphorylation by PKA.
Helix 4 – 14


Literature citations

Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A.
Ceholski D.K.; Trieber C.A.; Holmes C.F.; Young H.S.;
J. Biol. Chem. 287:26596-26605(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-16; MUTAGENESIS OF ARG-9; ARG-13; ARG-14; SER-16 AND THR-17;

Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.
Schmitt J.P.; Kamisago M.; Asahi M.; Li G.H.; Ahmad F.; Mende U.; Kranias E.G.; MacLennan D.H.; Seidman J.G.; Seidman C.E.;
Science 299:1410-1413(2003)
Cited for: VARIANT CMD1P CYS-9; CHARACTERIZATION OF VARIANT CMD1P CYS-9;

Hydrophobic imbalance in the cytoplasmic domain of phospholamban is a determinant for lethal dilated cardiomyopathy.
Ceholski D.K.; Trieber C.A.; Young H.S.;
J. Biol. Chem. 287:16521-16529(2012)
Cited for: CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL; FUNCTION; SUBCELLULAR LOCATION;

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.