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FLASH GENE

Symbol

LDB3

contributors: mct/npt - updated : 25-06-2015

HGNC name	LIM domain binding 3
HGNC id	15710

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	69.36 kb     13 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_007078 13 splicing 5308 NP_009009 - 727 specifically expressed in skeletal muscle and heart 2011 2130382 variant 1 - CypherL Cypher long presence and absence of three C-terminal LIM domains unique roles for CypherL isoforms in maintaining Z-line ultrastructure and signaling NM_001080114 12 splicing 4978 NP_001073583 - 617 - 2011 2130382 NM_001080115 7 splicing 1695 NP_001073584 - 330 - 2011 2130382 NM_001080116 8 splicing 1659 NP_001073585 - 283 - 2011 2130382 Cypher short (CypherS) absence of three C-terminal LIM domains NM_001171611 6 - 1899 NP_001165082 - 398 - 2011 2130382

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 Mus musculus Nervous brain         Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac   highly Mus musculus Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text

muscle

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal PDZ domain, interacted with the L-type calcium channel through its C-terminal PDZ binding motif
	a PDZ/DHR domain
	a conserved sequence called the ZM-motif, important in targeting ALP to the alpha-actinin containing structures in cell (Klaavuniemi 2006)
	three LIM zinc-binding domains at its C terminus with a short ZASP motif (ZM, AA186–211) in the middle

conjugated

HemoP

mono polymer

monomer

HOMOLOGY

interspecies

homolog to murine Ldb3

intraspecies

homolog to enigma

Homologene

FAMILY	PDZ-LIM domain protein family
	ALP/Enigma subfamily of the PDZ-LIM domain protein family

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,microsome
	intracellular,cytoplasm,cytoskeleton
text	expressed in pseudopodia and in cytoplasm around the nucleus
	colocalized with actin in the I-band
	colocalizes with betaPS integrin in myotendinous junctions and with alpha-actinin in muscle Z lines(Jani 2007)
	cytoskeletal protein localized in the sarcomeric Z-line (Zheng 2009)
	localized predominantly at Z-lines together with sarcomeric alpha-actinin

basic FUNCTION	Z-disc associated protein,that may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain
	has an important role in maintaining Z-disc stability in striated and cardiac muscle (Klaavuniemi 2006)
	striated Z-line protein, which plays an important structural role in cardiac muscle in maintaining the integrity of sarcomeres under the stress of contraction force
	important function in the assembly of integrin adhesion sites both in cell culture and in tissues (Jani 2007)
	plays a pivotal role in maintaining adult cardiac structure and cardiac function through protein–protein interactions with other Z-line proteins (Zheng 2009)
	having a pivotal role in the structure and functions of striated muscles (Zheng 2009)
	plays an essential structural role in cardiac muscle
	cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines
	not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins
	LDB3 and PDLIM5 redundantly play an essential role in sustaining Z-line structure from the earliest stages of cardiac function, and are redundantly required to maintain normal embryonic heart function and embryonic viability

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	NADPH

protein	C terminus of alpha-actinin-2 (ACTN2)
	flavoprotein P450 oxidoreductase (POR)
	specific binding of its PDZ domain to the C-terminal region of both calsarcin-1 (MYOZ2) and myotilin (MYOT) within the Z-line
	physically interacts with alpha-actinin (Jani 2007)
	PGM1 bound to LDB3 at the domains encoded by exons 4 and 10, and LDB3 anchors PGM1 to Z-disc under conditions of stress
	specifically interacted with PRKAR2A and calcineurin
	interaction between LDB3 and CACNA1C that facilitated PRKA-mediated phosphorylation of the CACNA1C at Ser1928
	binds to alpha-actinin and the calcium voltage channels (LTCC) via its PDZ domain

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CMD1C , MFMZ

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   aberrant splicing of LDB3 exon 11 in DM1 skeletal muscle

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	cardiac-specific knockout of Cypher in mouse leads to severe cardiac dysfunction, including DCM and premature lethality from heart failure, with disrupted cellular architecture and altered activities of multiple cellular signaling pathways (Zheng 2009)
	Cypher global-null mice display postnatal death with cardiac and skeletal muscle defects