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FLASH GENE

Symbol

LMNB1

contributors: mct/npt/pgu - updated : 04-05-2017

HGNC name	lamin B1
HGNC id	6637

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ADLD leukodystrophy, adult-onset type MCPH28 microcephaly 28, primary
Location	5q23.2      Physical location : 126.112.832 - 126.172.709
Synonym symbol(s)	LMN, LMN2, LMNB, MGC111419, ADLD, LB1

DNA

TYPE	functioning gene
STRUCTURE	60.40 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005573 11 - 3420 66.4 586 - 2008 18334554 NM_001198557 11 - 2267 - 376 - 2008 18334554

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Lymphoid/Immune thymus       highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal head domain
	a central rod domain
	a nuclear localization signal (NLS)
	C-terminal CAAX motif (posttranslationally modified by farnesylation, endoproteolysis, and carboxymethylation at the CAAX motif)

mono polymer

homomer , heteromer , tetramer

HOMOLOGY

Homologene

FAMILY

intermediate filament family, type V

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nuclear envelope,int
	intracellular,nuclear envelope,lamina
	intracellular,nuclear envelope,matrix attachement regions
text	major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions

basic FUNCTION	involved in nuclear stability, chromatin structure and gene expression
	LAMB1-nucleoskeleton is required to maintain RNA synthesis and ongoing synthesis is a fundamental determinant of global nuclear architecture in cells
	expressed on the cell surface of 24-h aged neutrophils, and apoptotic neutrophils express cytoskeletal proteins on their surface (these cells may participate in the development of autoantibodies directed against cytoskeletal proteins, a condition frequently reported in several inflammatory diseases)
	lamin B1-containing nucleoskeleton is required to maintain RNA synthesis and ongoing synthesis is a fundamental determinant of global nuclear architecture in mammalian cells
	maintains the functional plasticity of nucleoli
	helps to anchor the nucleus to the cytoskeleton
	could function to sequester microtubule polymerization activities within the spindle
	component of nuclear lamina which is a filamentous meshwork of proteins underlying the inner nuclear membrane
	importance of LMNB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway
	LMNB1 mRNA, and subsequent protein, decline in senescent cells is likely due at least in part to reduced LMNB1 mRNA stability
	farnesylation of LMNB1--but not LMNB2--is crucial for brain development and for retaining chromatin within the bounds of the nuclear lamina during neuronal migration
	may contribute to senescence in at least two ways due to its uneven genome-wide redistribution: first, through the spatial reorganization of chromatin and, second, through gene repression
	constitutes one of the major structural proteins in the lamina mesh
	is likely required to maintain chromatin condensation in interphase nuclei
	maintenance of LMNB1 levels is required for DNA replication and repair through regulation of the expression of key factors involved in these essential nuclear functions
	component of the nuclear lamina that plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning
	LMNA, LMNB1, LMNB2 not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains
	LMNB1 is required for neural stem cells (NSCs) to differentiate in proper numbers of neurons and express cell-type specific genes during corticogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

coiled coil dimers associated to form a tetrameric subunit from which Ifs assemble

INTERACTION

DNA

RNA

small molecule

protein	interacting with POU2F1 (POU2F1 has previously been shown to colocalize partly with B-type lamins and is essential for transcriptional regulation of oxidative stress response genes)
	interaction with KIF11 (LMNB1 only very weakly antagonizes KIF11 in mediating poleward microtubule-flux (
	only LMNB1 overexpression induced senescence, which was prevented by telomerase expression or inactivation of TP53
	interacts directly with the promoters of some genes associated with DNA damage response and repair, including BRCA1 and RAD51
	autophagy protein MAP1LC3A/Atg8 directly interacts with the nuclear lamina protein LMNB1 (lamin B1), and binds to LMN/lamin-associated chromatin domains (LADs)

cell & other

REGULATION

Other

diassembly at the start and reassembly at the end of mitosis mediated by phosphorylation,dephosphorylation

ASSOCIATED DISORDERS

corresponding disease(s)

ADLD , MCPH28

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   depletion of LMNB1 or LMNA/Cwas sufficient to recapitulate some oncogene-induced senescence (OIS) features, including cell cycle exit and downregulation of nuclear envelope (NE) proteins 7) tumoral     --over   is directly associated with low-grade differentiation, increased incidence of distant metastasis, and poor prognosis of patients with pancreatic cancer constitutional       loss of function significantly impairs corticogenesis and neurogenesis during embryonic development

Susceptibility

to multiple sclerosis

Variant & Polymorphism other	linked to the autoimmune attack that occurs in multiple sclerosis

Candidate gene
Marker	lamin B1 loss can serve as biomarker of senescence, and LMNB1 decline may be useful as an early senescence–associated marker
Therapy target
	System Type Disorder Pubmed cancer endocrine pancreas is a novel therapeutic target of betulinic acid treatment in pancreatic carcinoma

ANIMAL & CELL MODELS

	mice that lack a functional Lmnb1 gene die minutes after birth, and fibroblasts from these mice have misshapen nuclei and undergo premature senescence in culture
	mice expressing nonfarnesylated LmnB1 died soon after birth, with severe neurodevelopmental defects and striking nuclear abnormalities in neurons