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FLASH GENE
Symbol LDB3 contributors: mct/npt - updated : 25-06-2015
HGNC name LIM domain binding 3
HGNC id 15710
Corresponding disease
CMD1C cardiomyopathy, dilated 1C
MFMZ myofibrillar myopathy ZASP-related
Location 10q23.2      Physical location : 88.428.205 - 88.495.822
Synonym name
  • Z-band alternatively spliced PDZ-motif
  • cDNA sequence,expressed in brain, >100kDa,related to enigma
  • PDZ and LIM domain 6
  • cypher
  • oracle
  • Synonym symbol(s) ZASP, CYPHER, KIAA0613, ORACLE, PDLIM6, FLJ35865, KIAA01613, KIAA0613
    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
    Physical map
    LOC387696 10 hypothetical gene supported by L13802; NM_001006 GRID1 10q22 glutamate receptor, ionotropic, delta 1 KIAA0261 10q23.31 KIAA0261 LOC340749 10q23.31 similar to Rpl7a protein OPN4 10q22 opsin 4 (melanopsin) LDB3 10q22.3-q23.2 LIM domain binding 3 BMPR1A 10q22.3-q23.2 bone morphogenetic protein receptor, type IA EMILIN3 10q23.31 elastin microfibril interfacer 3 SNCG 10q26.2-q23.3 synuclein, gamma (breast cancer-specific protein 1) APM2 10q23.31 adipose specific 2 KIAA1975 10q23.31 KIAA1975 protein similar to MRIP2 GLUD1 10q23.3 glutamate dehydrogenase 1 MGC5560 10q23.31 hypothetical protein MGC5560 LOC389991 10 similar to synaptotagmin XV isoform a; chr10 synaptotagmin FAM22A 10q23.31 family with sequence similarity 22, member A LOC387697 10 LOC387697 LOC387698 10 similar to KIAA2020 protein LOC118945 10q23.31 similar to Cathepsin L preproprotein MINPP1 10q23.3 multiple inositol polyphosphate histidine phosphatase, 1 PAPSS2 10q23-q23.2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 FLJ14600 10q23.31 hypothetical protein FLJ14600 MGC35136 10q23.31 hypothetical protein MGC35136 PTEN 10q23.3 phosphatase and tensin homolog (mutated in multiple advanced cancers 1) FLJ11218 10q23.31 hypothetical protein FLJ11218 LOC142910 10q23.31 similar to Triacylglycerol lipase, gastric precursor (Gastric lipase) (GL) LOC389992 10 similar to ribosomal protein L7 LIPF 10q23.33 lipase, gastric
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 splicing 5308 - 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
  • 12 splicing 4978 - 617 - 2011 2130382
    7 splicing 1695 - 330 - 2011 2130382
    8 splicing 1659 - 283 - 2011 2130382
  • Cypher short (CypherS)
  • absence of three C-terminal LIM domains
  • 6 - 1899 - 398 - 2011 2130382
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Mus musculus
    Nervousbrain    
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac highly Mus musculus
    Muscularstriatumskeletal 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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