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FLASH GENE

Symbol

SYNE1

contributors: mct/npt - updated : 23-12-2016

HGNC name	spectrin repeat containing, nuclear envelope 1
HGNC id	17089

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AMCN3 arthrogryposis multiplex congenita neurogenic 3 EMD4 Emery-Dreifuss muscular dystrophy 4 SCAR8 spinocerebellar autosomal recesssive 8
Location	6q25.1      Physical location : 152.442.822 - 152.958.534
Synonym name	synaptic nuclei expressed gene 1
	nesprin 1
	enaptin
	myocyte nuclear envelope
	Nuclear envelope spectrin-repeat proteins
Synonym symbol(s)	CPG2, MYNE1, SYNE-1, SYNE-1B, KIAA0796, KIAA1262, KIAA1756, C6orf98, 8B, dJ45H2.2

DNA

TYPE	functioning gene
STRUCTURE	515.71 kb     146 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	have multiple alternative start and termination sites throughout their genes allowing the generation of smaller isoforms (PMID: 22768332)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed SYNE1-VB - - 10835 NP_056108 - 3321 - 2005 15749817 NM_033071 135 - 27436 NP_149062 - 8749 - 2005 15749817 also called SYNE1-VL larger nesprin forms are thought to reside in the outer nuclear membrane SYNE1-VA 19 - 3894 - 982 highly in skeletal and cardiac muscle 2005 15749817 shorter forms are tethered to the inner nuclear membrane p50(Nesp1) - - - 50 - - 2014 24862572 localizes to processing bodies (PBs), where it acts as a microtubule-associated protein capable of linking mRNP complexes to microtubules is a multi-functional processing bodies (PBs) component and microtubule scaffold necessary for RNA granule dynamics and provides evidence for PB and stress granules (SGs) micro-heterogeneity NM_182961 145 - 27745 NP_892006 1000 8797 - 2005 15749817 variant 1

EXPRESSION

Type	ubiquitous

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 Endocrine adrenal gland       highly   neuroendocrine pituitary     highly   thyroid       highly Lymphoid/Immune thymus       highly Nervous brain hindbrain cerebellum     Urinary kidney       lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth       Muscular striatum cardiac     Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal calponin domains, binding filamentous actin, an actin-binding site
	a large central spectrin-like rod domain
	one interrupted LEM domain
	a luminal domain binding directly to SUN proteins
	a transmembrane anchor that tethers to the nuclear membrane
	a short domain that resides within the lumen between the inner and outer nuclear membrane (Puckelwartz 2009)
	C-terminal single transmembrane domain (KASH domain) spanning the outer nuclear membrane, which mediates nuclear membrane localization, and/or N-terminal paired calponin-homology domains that bind actin

mono polymer

trimer

HOMOLOGY

interspecies

ortholog to drosophila Msp900

Homologene

FAMILY	giant spectrin-repeat containing proteins family
	nesprin family

CATEGORY

motor/contractile

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus,nucleoplasm,nuclear bodies
	intracellular,nuclear envelope,ext
text	sarcomeric Z-line of skeletal and cardiac muscle
	at the nuclear envelope of synaptic nuclei
	outer nuclear membrane protein that is thought to link the nucleus to the actin cytoskeleton (Zhang 2010)
	localizes to processing bodies (PBs), where it acts as a microtubule-associated protein capable of linking mRNP complexes to microtubules

basic FUNCTION	playing an important role in muscle function
	functioning at both the Golgi and the nuclear envelope, perhaps linking the two organelles during muscle differentiation
	having an important function in muscle development and maintenance (Attali 2009)
	playing a role in anchoring nuclei at the neuromuscular junction
	multi-isomeric, spectrin-repeat proteins that bind both emerin and lamins A/C and form a network in muscle linking the nucleoskeleton to the inner nuclear membrane, the outer nuclear membrane, membraneous organelles, the sarcomere and the actin cytoskeleton
	in combination with two SUN-domain proteins, UNC84A and UNC84B, form a linking complex that couples the nucleoskeleton to the cytoskeleton
	participate in the LINC complex that links the cytoplasm to the nucleus (Puckelwartz 2009)
	involved in anchoring specialized myonuclei underneath neuromuscular junctions (Attali 2009)
	essential for normal positioning and anchorage of nuclei in skeletal muscle
	may be forming the critical link between the nucleus and the myofibers, without which nuclear attachment to myofibers is completely abolished
	is not a structural component of the nucleus, but is rather a coupling element that mediates interactions between F-actin and the nucleus
	SYNE1, SYNE2 act as highly versatile tissue specific intracellular protein scaffolds
	plays an important role in the proliferation and apoptosis of mesenchymal stem cells
	SUN1, SUN2, SYNE1 (LINC complex) have emerged as a key regulators of actin cytoskeletal organisation
	LINC complex exists in a mechanical feedback circuit with RHOA to regulate Vascular smooth muscle cells (VSMCs) actomyosin activity and morphology
	mislocalization of LINC complex proteins (SUN1, SUN2, LMNA, EMD, SYNE1) is a significant characteristic of cellular senescence phenotypes and may influence complex events at the nuclear membrane, including trafficking and heterochromatin attachment

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	part of the LINC complex with the nesprin and SUN proteins (Puckelwartz 2009)
	SUN2 must form a trimer to bind to SYNE1, SYNE2, and this trimerization is mediated through two predicted coiled-coil regions of the protein, CC1 and CC2, which precede the SUN domain

INTERACTION

DNA

RNA

small molecule

protein	emerin and lamin A
	interacting with TOR1A through the KASH domain (role for torsinA in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the nuclear envelope, with torsinA influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement) (Nery 2008)
	F-actin bound to SYNE1 and the actin cortical layer are considered to be involved in mechanical interaction with the nucleus

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SCAR8 , AMCN3 , EMD4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in Emery-Dreyfuss muscular dystrophy caused, in part, by uncoupling of the nucleoskeleton and cytoskeleton because of perturbed nesprin/emerin/lamin interactions)

Susceptibility

Variant & Polymorphism

Candidate gene	for Emery-Dreifuss muscular dystrophy (Zhang 2010)
Marker
Therapy target

ANIMAL & CELL MODELS

	mice with deletion of the C-terminus of nesprin-1 (homozygous for this mutation) exhibit lethality with approximately half dying at or near birth from respiratory failure; surviving mice display hindlimb weakness and an abnormal gait (Puckelwartz 2009)
	young Nesprin 1–/– mice of both sexes experienced growth retardation, increased variability in body weight and decreased exercise tolerance compared with wild-type animals (Zhang 2010)