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lamin-A
Function:
- lamins are components of the nuclear lamina (see lamin)
- lamin A & lamin C filaments cross-link into an orthogonal lattice (nuclear lamina), which is attached via lamin B to the inner nuclear membrane through interactions with a lamin B receptor
- increased phosphorylation of the lamins occurs before nuclear envelope disintegration & probably plays a role in regulating lamin associations
- the C-terminal 18 residues are removed by proteolytic cleavage of lamin A; cleavage requires prior farnesylation
- proteolytically processed Lamin A interacts with NARF
Structure:
- belongs to the intermediate filament family
- a 2-3 kD fragment is cleaved from the C-terminus
- farnesylated
Compartment:
- nuclear lamina
Pathology:
- truncation of Lamin A associated with: [3] Hutchinson-Gilford Progeria syndrome
- unprocessed prelamin A & truncated lamin A act dominant negatively to perturb cell cycle checkpoint control, DNA damage response & DNA repair, resulting in genomic instability [3]
Properties
GENERAL: lamin-A/C
RELATED: lamin A/C gene
SIZE: entity length = 664 aa
MW = 74 kD
COMPARTMENT: nuclear membrane
MOTIF: MLIP interaction {1-130}
MOTIF: Head {1-33}
acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
Thr phosphorylation site {T10}
Ser phosphorylation site {S12}
Ser phosphorylation site {S18}
Thr phosphorylation site {T19}
Ser phosphorylation site {S22}
Thr phosphorylation site {T24}
Rod {34-383}
MOTIF: Coil 1A {34-70}
Linker 1 {71-80}
Coil 1B {81-218}
Linker 2 {219-242}
Coil 2 {243-383}
threonine residue {266}
Ser phosphorylation site {S277}
Ser phosphorylation site {S301}
aspartate residue {325}
glutamate residue {330}
Tail {384-664}
MOTIF: Ser phosphorylation site {S390}
Ser phosphorylation site {S392}
Thr phosphorylation site {T394}
Ser phosphorylation site {S395}
Ser phosphorylation site {S398}
Ser phosphorylation site {S403}
Ser phosphorylation site {S404}
Ser phosphorylation site {S406}
Ser phosphorylation site {S407}
Thr phosphorylation site {T409}
Ser phosphorylation site {S414}
Thr phosphorylation site {T416}
nuclear translocation signal {417-422}
Ser phosphorylation site {S423}
Thr phosphorylation site {T424}
Ser phosphorylation site {S458}
Thr phosphorylation site {T496}
Thr phosphorylation site {T505}
Ser phosphorylation site {S507}
Thr phosphorylation site {T510}
Ser phosphorylation site {S571}
Ser phosphorylation site {S573}
Ser phosphorylation site {S628}
Ser phosphorylation site {S632}
Ser phosphorylation site {S636}
proteolytic site {646-647}
Ser phosphorylation site {S652}
CaaX motif
SITE: C-TERMINUS
EFFECTOR-BOUND: farnesyl
Database Correlations
OMIM 150330
MORBIDMAP 150330
UniProt P02545
References
- Holtz D et al
The CaaX motif of lamin A functions in conjunction with
the nuclear localization signal to target assembly to the
nuclear envelope.
Cell 59:969 1989
PMID: 2557160
- Glomset JA et al
Prenyl proteins in eukaryotic cells: a new type of
membrane anchor.
TIBS 15(April):139 1990
PMID: 2187294
- Liu B et al
Genomic instability in laminopathy-based premature aging.
Nat Med. 2005 Jul;11(7):780-5. Epub 2005 Jun 26
PMID: 15980864
- UniProt :accession P02545