Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 220

(5) LIM domain-only protein LMO7. 53 Actinin-associated LIM protein is expressed
at lower levels in the heart than skeletal muscles.
Group- 2 PDZ-LIM proteins are represented by 2 protein kinases: LIM kinase
LIMK1 and LIMK2. They contain a PDZ domain, 2 LIM regions, and a Tyr kinase
sequence.
Group- 3 PDZ-LIM proteins - the Enigma subfamily - include 4 members that
possess a single N-terminal PDZ domain and 3 tandem C-terminal LIM domains.
This class encompasses: (1) Enigma, 54 (2) Enigma homolog (EnH or EnH1), 55
(3) Cypher, 56 and (4) LMP4 scaffold proteins.

Enigma Group

In humans, 4 spliced variants of the Enh transcript produce 4 isoforms
(EnH1-EnH4). Isoform EnH1 is expressed in embryonic and neonatal hearts,
whereas, in adults, EnH2 to EnH4 are predominant [ 384 ]. Isotype EnH1 possesses
an N-terminal PDZ domain and 3 C-terminal LIM domains, whereas EnH2 to EnH4
do not have LIM domains, but retain the N-terminal PDZ domain.
Enigma is able to bind actin,

β

-tropomyosin, and protein kinases. Agent EnH1
is an adaptor for protein kinase-C. It also links to protein kinase-D1 to regulate the
activity of Ca V 1 channels. In normal adult hearts, EnH4 does not recruit PKC and
PKD enzymes. During sustained arterial hypertension, EnH1 can be re-expressed
and scaffold PKC and PKD kinases [ 384 ]. Subtype EnH1 promotes hypertrophy,
whereas other isotypes prevent hypertrophy.
Cypher interacts also with

α

-actinin-2. Its isoform Cypher-2 binds to various, but
not all types of protein kinase-C.
LIM-PDZ domain-containing protein LMP4 is coexpressed with and directly
binds to heart-specific T-box TBx5 transcription factor. Unbound to LMP4, Tbx5
shuttles between the nucleus and cytoplasm; in a complex with LMP4, it localizes to
actin filaments [ 385 ]. The TBx5-LMP4 complex undergoes assembly-disassembly
cycles in response to external stimuli. Protein LMP4 represses TBx5 activity.

5.3.5.7 Four-and-a-Half LIM-Only Proteins

The family of four-and-a-half LIM (abnormal cell lineage LIN11, insulin gene
enhancer protein Islet-1 (Isl1), and mechanosensory abnormality protein MEC3)-

53 A.k.a. F-box-only protein FBx20.
54 A.k.a. PDZ and LIM domain-containing protein PDLIM7 and LIM domain-containing protein
LMP1.
55 A.k.a. PDLIM5.
56 A.k.a. PDLIM6, Z-band alternatively spliced protein (ZASP), LIM domain-binding protein
LDB3, and Oracle.