UniProtKB/Swiss-Prot P02545: Variant p.Arg644Cys

Prelamin-A/C
Gene: LMNA
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Variant information Variant position:

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

US 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 Arginine (R) to Cysteine (C) at position 644 (R644C, p.Arg644Cys). 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 HGPS and EDMD2; uncertain significance; partially inhibits tail cleavage. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs142000963 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

RSYRSVGGSGGGSFGDNLVT R SYLLGNSSPRTQSPQNCSIM 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                         RSYRSVGGSGGGS-FGDNLVTRSYLLGNSSPRTQ--SPQNCSIM

Mouse                         RSFRSVGGSGGGS-FGDNLVTRSYLLGNSSPRSQ--SSQNC

Rat                           RSFRSVGGSGGGS-FGDNLVTRSYLLGNSSPRTQ--SSQNC

Pig                           RSYRSVGGSGGGS-FGDNLVTRSYLLGNSRPRTQ--SPQNC

Chicken                       RGYR----SSGGG-IGEGLLGRSYVLGGAGPRRQAPAPQGC

Xenopus laevis                RTYRSTGGTSGGSGLGESPVTRNFIVGNGQRAQV--APQNC

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 – 661	Prelamin-A/C
Chain	1 – 646	Lamin-A/C
Region	384 – 664	Tail
Modified residue	628 – 628	Phosphoserine
Modified residue	632 – 632	Phosphoserine
Modified residue	636 – 636	Phosphoserine
Modified residue	652 – 652	Phosphoserine
Modified residue	661 – 661	Cysteine methyl ester
Lipidation	661 – 661	S-farnesyl cysteine
Glycosylation	625 – 625	O-linked (GlcNAc) serine
Glycosylation	628 – 628	O-linked (GlcNAc) serine
Alternative sequence	573 – 664	Missing. In isoform C.
Alternative sequence	607 – 656	Missing. In isoform 6.
Alternative sequence	664 – 664	M -> IQEMGMRWEVEEGRRKVSLSCLP. In isoform 4.
Mutagenesis	628 – 628	S -> D. Mimics phosphorylation; causes redistribution between the nucleus and the cytoplasm during interphase; when associated with D-22 and D-392.
Mutagenesis	644 – 644	R -> A. Does not affect tail cleavage.
Mutagenesis	647 – 647	L -> R. Completely inhibits tail cleavage.
Mutagenesis	648 – 648	L -> A. Completely inhibits tail cleavage.
Mutagenesis	650 – 650	N -> A. Partially inhibits tail cleavage.
Mutagenesis	661 – 661	C -> S. Loss of interaction with NARF. Abolishes farnesylation.

Literature citations
Requirements for efficient proteolytic cleavage of prelamin A by ZMPSTE24.
Barrowman J.; Hamblet C.; Kane M.S.; Michaelis S.;
PLoS ONE 7:E32120-E32120(2012)
Cited for: MUTAGENESIS OF ARG-644; LEU-647; LEU-648; ASN-650 AND CYS-661; CHARACTERIZATION OF VARIANT HGPS CYS-644; Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.
Csoka A.B.; Cao H.; Sammak P.J.; Constantinescu D.; Schatten G.P.; Hegele R.A.;
J. Med. Genet. 41:304-308(2004)
Cited for: VARIANT HGPS CYS-644; VARIANTS ILE-10 AND VAL-578; Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.
Scharner J.; Brown C.A.; Bower M.; Iannaccone S.T.; Khatri I.A.; Escolar D.; Gordon E.; Felice K.; Crowe C.A.; Grosmann C.; Meriggioli M.N.; Asamoah A.; Gordon O.; Gnocchi V.F.; Ellis J.A.; Mendell J.R.; Zammit P.S.;
Hum. Mutat. 32:152-167(2011)
Cited for: VARIANTS EDMD2 SER-39; CYS-45; PRO-150; PRO-189; ARG-190 INS; LEU-206; TRP-249; GLN-249; PRO-268; PRO-271; PRO-294; PRO-295; PRO-303; GLN-355 DEL; LYS-358; LYS-361; LYS-386; ASP-449; TRP-453; PRO-454; TYR-461; ARG-467; PRO-527; LYS-528; ARG-528; SER-541; PRO-541; SER-602 AND CYS-644; CHARACTERIZATION OF VARIANTS EDMD2 PRO-25; TRP-249; ILE-456 AND PRO-541;

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.