SpermatogenesisOnline 1.0

Tag Content
SG ID
SG00010425 
UniProt Accession
Theoretical PI
8.9  
Molecular Weight
20895 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Csrp3 
Gene Synonyms/Alias
Clp, Mlp 
Protein Name
Cysteine and glycine-rich protein 3 
Protein Synonyms/Alias
Cysteine-rich protein 3;CRP3 LIM domain protein, cardiac; Muscle LIM protein; 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:7;56085768-56103400;-1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.176270245 
The probability was calculated by GAS algorithm, ranging from 0 to 1. The closer it is to 1, the more possibly it functions in spermatogenesis.
Description
Temporarily unavailable 
Abstract of related literatures
1. Differential display reverse transcription polymerase chain reaction (DD RT-PRC) was used to isolate cDNA clones of mRNA expressed in particular compartments of the developing murine head. One clone has been characterized and found to be the murine homologue of the MLP genes. In other species the LIM-domain containing MLPs are expressed specifically in muscle. In situ hybridization and RT-PCR have confirmed that the murine gene is expressed during both cardiac and skeletal myogenesis. Our data show that DD RT-PCR is a valuable technique to clone cDNA clones from minute tissue samples by virtue of the gene's expression pattern rather than by a process of library screening by homology. PMID: [8773898] 

2. The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID: [15489334] 

3. MLP is a LIM-only protein of terminally differentiated striated muscle cells, where it accumulates at actin-based structures involved in cytoarchitecture organization. To assess its role in muscle differentiation, we disrupted the MLP gene in mice. MLP (-/-) mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts were not hypertrophic, but already abnormally soft, with cell-autonomous and MLP-sensitive alterations in cytoarchitecture. Thus, MLP promotes proper cardiomyocyte cytoarchitecture, whose perturbation can lead to dilated cardiomyopathy. In vivo analysis revealed that MLP-deficient mice reproduce the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans, providing the first model for this condition in a genetically manipulatable organism. PMID: [9039266] 

4. Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause for heart failure. Molecular modifiers of the remodeling process remain poorly defined. Patients with heart failure after MI have reduced LV expression levels of muscle LIM protein (MLP), a component of the sarcomeric Z-disk that is involved in the integration of stress signals in cardiomyocytes. By using heterozygous MLP mutant (MLP+/-) mice, we explored the role of MLP in post-MI remodeling. LV dimensions and function were similar in sham-operated WT and MLP+/- mice. After MI, however, MLP+/- mice displayed more pronounced LV dilatation and systolic dysfunction and decreased survival compared with WT mice, indicating that reduced MLP levels predispose to adverse LV remodeling. LV dilatation in MLP+/- mice was associated with reduced thickening but enhanced elongation of cardiomyocytes. Activation of the stress-responsive, prohypertrophic calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway was reduced in MLP+/- mice after MI, as shown by a blunted transcriptional activation of NFAT in cardiomyocytes isolated from MLP+/-/NFAT-luciferase reporter gene transgenic mice. Calcineurin was colocalized with MLP at the Z-disk in WT mice but was displaced from the Z-disk in MLP+/- mice, indicating that MLP is essential for calcineurin anchorage to the Z-disk. In vitro assays in cardiomyocytes with down-regulated MLP confirmed that MLP is required for stress-induced calcineurin-NFAT activation. Our study reveals a link between the stress sensor MLP and the calcineurin-NFAT pathway at the sarcomeric Z-disk in cardiomyocytes and indicates that reduced MLP-calcineurin signaling predisposes to adverse remodeling after MI. PMID: [15665106] 

5. PICOT (protein kinase C-interacting cousin of thioredoxin) was previously shown to inhibit pressure overload-induced cardiac hypertrophy, concomitant with an increase in ventricular function and cardiomyocyte contractility. The combined analyses of glutathione S-transferase pull-down experiments and mass spectrometry enabled us to determine that PICOT directly interacts with muscle LIM protein (MLP) via its carboxyl-terminal half (PICOT-C). It was also shown that PICOT colocalizes with MLP in the Z-disc. MLP is known to play a role in anchoring calcineurin to the Z-disc in the sarcomere, which is critical for calcineurin-NFAT (nuclear factor of activated T cells) signaling. We, therefore, suggested that PICOT may affect calcineurin-NFAT signaling through its interaction with MLP. Consistent with this hypothesis, PICOT, or more specifically PICOT-C, abrogated phenylephrine-induced increases in calcineurin phosphatase activity, NFAT dephosphorylation/nuclear translocation, and NFAT-dependent transcriptional activation in neonatal cardiomyocytes. In addition, pressure overload-induced upregulation of NFAT target genes was significantly diminished in the hearts of PICOT-overexpressing transgenic mice. PICOT interfered with MLP-calcineurin interactions in a dose-dependent manner. Moreover, calcineurin was displaced from the Z-disc, concomitant with an abrogated interaction between calcineurin and MLP, in the hearts of PICOT transgenic mice. Replenishment of MLP restored the hypertrophic responses and the increase in calcineurin phosphatase activity that was inhibited by PICOT in phenylephrine-treated cardiomyocytes. Finally, PICOT-C inhibited cardiac hypertrophy to an extent that was comparable to that of full-length PICOT. Taken together, these data suggest that PICOT inhibits cardiac hypertrophy largely by negatively regulating calcineurin-NFAT signaling via disruption of the MLP-calcineurin interaction. PMID: [18258855] 

6.

RATIONALE:

We previously discovered the human 10T-->C (Trp4Arg) missense mutation in exon 2 of the muscle LIM protein (MLP, CSRP3) gene. PMID: [20044516] 

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Function
Positive regulator of myogenesis. Plays a crucial andspecific role in the organization of cytosolic structures incardiomyocytes. Could play a role in mechanical stretch sensing.May be a scaffold protein that promotes the assembly ofinteracting proteins at Z-line structures. It is essential forcalcineurin anchorage to the Z line. Required for stress-inducedcalcineurin-NFAT activation. 
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Subcellular Location
Nucleus (Potential). Cytoplasm. Cytoplasm,cytoskeleton (Potential). Cytoplasm, myofibril, sarcomere, Z line.Note=Mainly cytoplasmic. In the nucleus it associates with theactin cytoskeleton (Potential). In the Z line, found associatedwith GLRX3 (via C-terminus). 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005856 C:cytoskeleton IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IEA:UniProtKB-SubCell.
GO:0030018 C:Z disc IDA:MGI.
GO:0008270 F:zinc ion binding IEA:InterPro.
GO:0001974 P:blood vessel remodeling IEA:Compara.
GO:0048738 P:cardiac muscle tissue development IGI:MGI.
GO:0030154 P:cell differentiation IEA:UniProtKB-KW.
GO:0006874 P:cellular calcium ion homeostasis IGI:MGI.
GO:0007517 P:muscle organ development IEA:UniProtKB-KW.
GO:0002026 P:regulation of the force of heart contraction IGI:MGI.
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Interpro
IPR001781;    Znf_LIM.
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Pfam
PF00412;    LIM;    2.
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SMART
SM00132;    LIM;    2.
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PROSITE
PS00478;    LIM_DOMAIN_1;    2.
PS50023;    LIM_DOMAIN_2;    2.
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PRINTS
Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
CHAIN         1    194       Cysteine and glycine-rich protein 3.
                             /FTId=PRO_0000075728.
DOMAIN       10     61       LIM zinc-binding 1.
DOMAIN      120    171       LIM zinc-binding 2.
MOTIF        64     69       Nuclear localization signal (Potential).
COMPBIAS     63     78       Gly-rich.
COMPBIAS    177    185       Gly-rich.
MUTAGEN       4      4       W->R: Mice develop an age- and gene
                             dosage-dependent hypertrophic
                             cardiomyopathy and heart failure
                             phenotype, characterized by almost
                             complete loss of contractile reserve
                             under catecholamine induced stress. They
                             display increased in septum wall
                             thickness, fractional shortening, and
                             wall thickness per diameter (h/r). There
                             is also evidence for skeletal muscle
                             pathology. In addition, homozygous
                             mutants show increased left ventricle
                             (LC) mass per body weight (BW) and
                             significantly reduced body weight. An
                             increased nuclear localization of Csrp3
                             is also observed.
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Nucleotide Sequence
Length: 720 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 194 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
PrkceIntAct 
Other Protein-Protein interaction resources
String database  
View Microarray data
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