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FLASH GENE

Symbol

SYNE2

contributors: mct - updated : 04-07-2015

HGNC name	spectrin repeat containing, nuclear envelope 2
HGNC id	17084

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	373.49 kb     116 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	alternative promoter usage and splicing produces shorter forms containing spectrin repeats and the KASH domain (PMID: 19008300)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015180 115 - 21816 NP_055995 796.4 6884 - 2007 17881656 N2G, scaffold protein (nesprin-2 giant/NUANCE) essential for emerin anchorage to the inner nuclear membrane composed of an N-terminal -actinin type actin-binding domain (ABD), followed by a long spectrin-repeat-containing rod and a C-terminal KASH domain larger nesprin forms are thought to reside in the outer nuclear membrane FHOD1 is an interaction partner of N2G NM_182910 9 - 2586 NP_878914 48.2 429 - 2007 17462627 NM_182913 11 - 2694 NP_878917 62.2 556 - 2007 17462627 NM_182914 116 - 21882 NP_878918 798.9 6907 - 2009 19008300 Nesprin-2-giant larger nesprin forms are thought to reside in the outer nuclear membrane nesprin-2-epsilon 1 - - - 120 - . located at the nuclear envelope . strongly expressed in ovary, but absent from human skin fibroblasts . strongly in Ntera-2 cells (testicular embryonal carcinoma cell line) 2011 21820406 may have a role in very early development or in some ovary-specific function lacking the actin-binding N-terminus

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 Digestive liver       moderately Homo sapiens Reproductive female system placenta     highly Homo sapiens   female system ovary     highly Homo sapiens   male system testis     highly Homo sapiens Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	eye, dominant isoform in fetal brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal CH domain, and an actin-binding site
	two spectrin repeats
	a luminal domain binding directly to SUN proteins
	a region in the rod domain of SYNE2 that is predicted as SMC domain (AA 1436-1766)that can interact with itself, and has the capacity to bind to SMC2 and SMC4, the core subunits of condensin
	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

intraspecies

homolog to SYNE1

Homologene

FAMILY	alpha-actinin type actin-binding proteins family
	giant spectrin-repeat containing proteins family

CATEGORY

motor/contractile

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
	intracellular,nuclear envelope,ext
	intracellular,nuclear envelope,lumen
text	sarcoplasmic RE, nuclear membrane
	associate with the NE by virtue of their highly conserved type II transmembrane domain (KASH domain)
	relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum
	connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes

basic FUNCTION	acting as an adapter for assembling multiprotein complexes
	having a scaffolding function at the nuclear membrane and may be involved in human disease
	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
	implicated in nuclear envelope organization and the physical integration of the nucleus with cytoskeletal filaments
	multifunctional actin-binding and nuclear-envelope-associated protein
	important scaffold protein implicated in the maintenance of nuclear envelope architecture
	participate in the LINC complex that links the cytoplasm to the nucleus
	having potential novel SYNE2 functions in cellular signaling, and positive regulator of the Wnt signaling pathway
	giant nesprins form a link between the nuclear envelope and the cytoskeleton
	SYNE2 and SUN1 are involved in an early retinal developmental stage and the loss of function of these proteins eventually leads to an increase in cell death linked to apoptosis
	SYNE1, SYNE2 act as highly versatile tissue specific intracellular protein scaffolds
	SYNE2 may have an impact on chromosomes which might be due to its interaction with condensins or to indirect mechanisms provided by its interactions at the nuclear envelope

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	part of the LINC complex with the nesprin and SUN proteins
	SYNE2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina
	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	binds directly to emerin and the C-terminal common region of lamin A/C (LMNA is necessary for the nuclear envelope localization of Nesprin-2)
	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)
	interacting with UNC84A, and UNC84B
	interacting with EMD (Nesprin-2 and emerin localize to the nuclear enveloppe)
	SYNE2 interacts with FSCN1 through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery

cell & other	interacting with both dynein/dynactin and kinesin complexes for interkinetic nuclear migration and nuclear migration of photoreceptors during retinal development

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

EMD5

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

Marker

Therapy target

ANIMAL & CELL MODELS

	mice lacking the actin-binding domain of Nesprin-2 (Nesprin-2DeltaABD), have significant thickening of the epidermis, which is a consequence of the increased epithelial nuclear size
	Syne-2-/- and Sun1-/- mice exhibit excessive apoptosis in the retina