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FLASH GENE

Symbol

NEB

contributors: mct/npt/pgu - updated : 23-11-2013

HGNC name	nebulin
HGNC id	7720

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	NEM2 nemaline myopathy 2
Location	2q23.3      Physical location : 152.341.854 - 152.591.001
Synonym symbol(s)	NEM2, NEB177D, FLJ39568, FLJ39584, DKFZp686C1456, FLJ11505, FLJ36536

DNA

TYPE	functioning gene
STRUCTURE	249.15 kb     181 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D2S381 - D2S151 - NEB /D2S2236 - D2S356 - D2S321 - D2S141 - qter

RNA

TRANSCRIPTS	type	messenger

text	complex splicing resulting in isoform with different number of repeats tissue and stage specific

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004543 149 - 20644 NP_004534 - 6669 - 2004 15266303 NM_001164508 181 - 26202 NP_001157980 - 8525 - 2004 15266303 exchange of exon 143 for exon 144 NM_001164507 181 - 26202 NP_001157979 - 8525 - 2004 15266303

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       highly Digestive mouth       highly Endocrine neuroendocrine pituitary     highly Respiratory respiratory tract larynx     highly

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an acidic N-terminal domain
	35-AAs module repeats (185 small tandem repeats of approximately 35 AA, differentially expressed)
	a linker domain
	a glutamic acid-rich domain
	a serine-rich domain
	a SH3 domain at the C terminus localized within the IZI junction (SSVLYKEN motif), binding to desmin and may directly connect the titin and nebulin filament systems via an interaction with the spring-like PEVK domain from the I-band region of titin (C-terminal region of nebulin interacted with the C-terminus of archvillin , that is a novel ligand of proline-rich regions of XIRP1 and XIRP2

HOMOLOGY

Homologene

FAMILY

CATEGORY

regulatory , structural protein

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microfilament
text	C terminal integrating into the Z disc lattice and a N terminus projecting into the I-band

basic FUNCTION	involved in the length regulation of the thin filament
	giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils
	bind and stabilize f-actin
	giant filamentous protein extending along the entire length of the thin filament, providing a blueprint for muscle thin filament assembly
	can be considered as a fourth filament system of the sarcomere (after thin, thick and titin filaments)
	as in skeletal muscle, may have a role as an actin filament stabilizer or length regulator in neurons of the human brain, although patients with NEB mutations usually have normal cognition
	giant sarcomeric protein that plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function
	nebulin SH3 domain plays a role in bearing high active stress and perhaps in fine-tuning the excitation-contraction coupling mechanism

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	nebulin–WASL complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex
	both DES and NEB form complex filament systems in muscle cells that synergistically collaborate to integrate the myofibril contractile machinery to the IF cytoskeletal network

INTERACTION

DNA

RNA

small molecule

protein	binding to actin
	interacting with titin (TTN)
	interaction with SVIL (may provide a direct link between the sarcolemma and myofibrillar Z-lines)
	WASL binds to the nebulin C-terminal region by IGF1 stimulation
	interacts with desmin DES) through multiple sites to provide efficient stability to satisfy the dynamic contractile activity of myocytes
	temporally restricted interaction of Xin-repeat proteins (XIRP1, XIRP2) with nebulin/nebulette during early stages of myofibril development that is lost upon further maturation

cell & other

15 helical actin binding

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

NEM2

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

in Neb(deltaExon55) mice the regulation of contraction is impaired, as evidenced by marked changes in crossbridge cycling kinetics and by a reduction of the calcium sensitivity of force generation