LDB3 LIM domain binding 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LDB3provided by HGNC
Official Full Name: LIM domain binding 3provided by HGNC
Primary source: HGNC:HGNC:15710
See related: Ensembl:ENSG00000122367 MIM:605906; AllianceGenome:HGNC:15710
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MFM4; ZASP; CMD1C; CMH24; CMPD3; LVNC3; CYPHER; LDB3Z1; LDB3Z4; ORACLE; PDLIM6
Summary: This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]
Annotation information: Note: LDB3 (Gene ID: 11155) and ZASP (Gene ID: 101927655) share the ZASP alias/unofficial symbol in common. [01 Jun 2018]
Expression: Biased expression in heart (RPKM 95.5), prostate (RPKM 11.4) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 10q23.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (86666788..86736072)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (87550947..87620190)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (88426545..88495829)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy.
Title: Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy.
Protein aggregates and autophagy involvement in a family with a mutation in Z-band alternatively spliced PDZ-motif protein.
Title: Protein aggregates and autophagy involvement in a family with a mutation in Z-band alternatively spliced PDZ-motif protein.
Alterations of protein expression of phospholamban, ZASP and plakoglobin in human atria in subgroups of seniors.
Title: Alterations of protein expression of phospholamban, ZASP and plakoglobin in human atria in subgroups of seniors.
The rs4468255 of LIM domain binding 3 (LDB3) is significantly correlated with idiopathic dilated cardiomyopathy of Chinese Han population
Title: Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy.
p.(D117N) variant in Cypher/ZASP is not a causative mutation for dilated cardiomyopathy and ventricular arrhythmias.
Title: D117N in Cypher/ZASP may not be a causative mutation for dilated cardiomyopathy and ventricular arrhythmias.
A novel heterozygous missense mutation (p.N155H) in a highly conserved PDZ-like motif of ZASP was identified. The results indicate that typical ZASP-MFM presenting with late-onset distal myopathy is commonly associated with mutations in PDZ-like motif of ZASP.
Title: A novel mutation in the PDZ-like motif of ZASP causes distal ZASP-related myofibrillar myopathy.
The molecular basis for high-affinity binding of ZASP to G-Actin has been described.
Title: Expression and Purification of ZASP Subdomains and Clinically Important Isoforms: High-Affinity Binding to G-Actin.
this is the first family with Arrhythmogenic right ventricular cardiomyopathy where a mutation in LDB3 is associated with Arrhythmogenic right ventricular cardiomyopathy
Title: A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy.
Study identified abnormal inclusion of LDB3 exon 11 specific to myotonic dystrophy type at the RNA and protein level; inclusion changed the affinity of LDB3 for PKC, indicating that exon 11 may contribute to the activation of PKC in DM1
Title: LDB3 splicing abnormalities are specific to skeletal muscles of patients with myotonic dystrophy type 1 and alter its PKC binding affinity.
results show that MFM-associated ZASP mutations in the actin-binding domain have deleterious effects on the core structure of the Z-discs in skeletal muscle.
Title: Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP) mutations in the actin-binding domain cause disruption of skeletal muscle actin filaments in myofibrillar myopathy.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dilated cardiomyopathy 1C MedGen: C1832244 OMIM: 601493 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs
Myofibrillar myopathy 4 MedGen: C4721886 OMIM: 609452 GeneReviews: Not available	Compare labs
Primary dilated cardiomyopathy MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48664 (e-PCR)
- UniSTS:83202

RH122045 (e-PCR)
- UniSTS:134681

D10S1290E (e-PCR)
- UniSTS:151324

D10S1307E (e-PCR)
- UniSTS:151339

LDB3 (e-PCR)
- UniSTS:511832

D11S3430 (e-PCR)
- UniSTS:152671

RH41795 (e-PCR)
- UniSTS:65120

SHGC-57810 (e-PCR)
- UniSTS:94305

D1S1423 (e-PCR)
- UniSTS:149619

RH118568 (e-PCR)
- UniSTS:137967

Ldb3 (e-PCR), detects polymorphism
- UniSTS:515316

SHGC-154028 (e-PCR)
- UniSTS:182267

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cytoskeletal protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables muscle alpha-actinin binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in heart development	IBA Inferred from Biological aspect of Ancestor more info
involved_in muscle structure development	IBA Inferred from Biological aspect of Ancestor more info
involved_in sarcomere organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in Z disc	IBA Inferred from Biological aspect of Ancestor more info
located_in Z disc	IDA Inferred from Direct Assay more info	PubMed
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
part_of filamentous actin	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in pseudopodium	IEA Inferred from Electronic Annotation more info
is_active_in stress fiber	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: LIM domain-binding protein 3

Names: PDZ and LIM domain 6; Z-band alternatively spliced PDZ-motif protein; cardiomyopathy, dilated 1C (autosomal dominant); protein cypher

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008876.1 RefSeqGene

Range

4886..72505

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_385

mRNA and Protein(s)

NM_001080114.2 → NP_001073583.1 LIM domain-binding protein 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 2, which is shorter but with the same N- and C-termini, when it is compared to isoform 1.

Source sequence(s)

AB014513, AC067750, AL601484, DA762127

Consensus CDS

CCDS41544.1

UniProtKB/TrEMBL

B4DGP4

Related

ENSP00000401437.3, ENST00000429277.7

Conserved Domains (6) summary

cd09362
Location:500 → 551

LIM2_Enigma_like; The second LIM domain of Enigma-like family

cd09363
Location:559 → 612

LIM3_Enigma_like; The third LIM domain of Enigma-like family

cd09454
Location:441 → 492

LIM1_ZASP_Cypher; The first LIM domain of ZASP/Cypher family

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:148 → 238

DUF4749; Domain of unknown function (DUF4749)

cl26464
Location:272 → 439

Atrophin-1; Atrophin-1 family
NM_001080115.2 → NP_001073584.1 LIM domain-binding protein 3 isoform 3

See identical proteins and their annotated locations for NP_001073584.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks several segments and uses a different 3' segment in its coding region, compared to variant 1. The resulting protein (isoform 3) is shorter with a distinct C-terminus when it is compared to isoform 1. Variants 3 and 7 encode isoform 3.

Source sequence(s)

AC067750, AF276807, BC010929, F33274

Consensus CDS

CCDS44450.1

UniProtKB/TrEMBL

A0A0S2Z501, A0A8I5KX76

Related

ENSP00000485389.1, ENST00000623007.3

Conserved Domains (3) summary

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:194 → 285

DUF4749; Domain of unknown function (DUF4749)

cl25751
Location:77 → 180

DUF4045; Domain of unknown function (DUF4045)
NM_001080116.1 → NP_001073585.1 LIM domain-binding protein 3 isoform 4

See identical proteins and their annotated locations for NP_001073585.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences, including a different 3' segment, in its coding region, compared to variant 1. The resulting protein (isoform 4) is shorter and has a distinct C-terminus when it is compared to isoform 1. Variants 4, 11, and 12 encode isoform 4.

Source sequence(s)

AJ133766, BC010929, DA898241, F33274

Consensus CDS

CCDS41545.1

UniProtKB/TrEMBL

A0A0S2Z530, B4DUL3

Related

ENSP00000361136.3, ENST00000372066.8

Conserved Domains (2) summary

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:148 → 249

DUF4749; Domain of unknown function (DUF4749)
NM_001171610.2 → NP_001165081.1 LIM domain-binding protein 3 isoform 5

See identical proteins and their annotated locations for NP_001165081.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) has multiple differences in the coding region, compared to variant 1. The encoded isoform (5) is longer than isoform 1.

Source sequence(s)

AC067750, AK304760

Consensus CDS

CCDS53550.1

UniProtKB/TrEMBL

B4DGP4

Related

ENSP00000485500.1, ENST00000623056.4

Conserved Domains (8) summary

smart00735
Location:189 → 214

ZM; ZASP-like motif

cd09362
Location:615 → 666

LIM2_Enigma_like; The second LIM domain of Enigma-like family

cd09363
Location:674 → 727

LIM3_Enigma_like; The third LIM domain of Enigma-like family

cd09454
Location:556 → 607

LIM1_ZASP_Cypher; The first LIM domain of ZASP/Cypher family

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:263 → 353

DUF4749; Domain of unknown function (DUF4749)

cl25751
Location:77 → 180

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:387 → 554

Atrophin-1; Atrophin-1 family
NM_001171611.2 → NP_001165082.1 LIM domain-binding protein 3 isoform 6

See identical proteins and their annotated locations for NP_001165082.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 3' UTR and has multiple differences in the coding region, compared to variant 1. The encoded isoform (6) is shorter and has a distinct C-terminus, compared to isoform (1).

Source sequence(s)

AC067750, AF276809

Consensus CDS

CCDS53549.1

UniProtKB/Swiss-Prot

O75112

Related

ENSP00000361126.4, ENST00000372056.8

Conserved Domains (4) summary

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:263 → 353

DUF4749; Domain of unknown function (DUF4749)

cl25751
Location:77 → 180

DUF4045; Domain of unknown function (DUF4045)

cl25776
Location:189 → 214

DUF4749; Domain of unknown function (DUF4749)
NM_001368063.1 → NP_001354992.1 LIM domain-binding protein 3 isoform 3

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS44450.1

UniProtKB/TrEMBL

A0A0S2Z501, A0A8I5KX76
NM_001368064.1 → NP_001354993.1 LIM domain-binding protein 3 isoform 7

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS91289.1

UniProtKB/TrEMBL

B4DGP4, V5T7C5

Related

ENSP00000508987.1, ENST00000688001.1
NM_001368065.1 → NP_001354994.1 LIM domain-binding protein 3 isoform 7

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS91289.1

UniProtKB/TrEMBL

B4DGP4, V5T7C5

Related

ENSP00000510609.1, ENST00000689296.1
NM_001368066.1 → NP_001354995.1 LIM domain-binding protein 3 isoform 8

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS91290.1

UniProtKB/TrEMBL

A0A8I5KV04

Related

ENSP00000509539.1, ENST00000693680.1
NM_001368067.1 → NP_001354996.1 LIM domain-binding protein 3 isoform 4

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS41545.1

UniProtKB/TrEMBL

A0A0S2Z530, B4DUL3

Related

ENSP00000263066.7, ENST00000263066.11

Conserved Domains (2) summary

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:148 → 249

DUF4749; Domain of unknown function (DUF4749)
NM_001368068.1 → NP_001354997.1 LIM domain-binding protein 3 isoform 4

Status: REVIEWED

Source sequence(s)

AC067750

Consensus CDS

CCDS41545.1

UniProtKB/TrEMBL

A0A0S2Z530, B4DUL3

Conserved Domains (2) summary

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:148 → 249

DUF4749; Domain of unknown function (DUF4749)
NM_007078.3 → NP_009009.1 LIM domain-binding protein 3 isoform 1

See identical proteins and their annotated locations for NP_009009.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AB014513, AC067750, BC010929

Consensus CDS

CCDS7377.1

UniProtKB/Swiss-Prot

A2TDB7, A6NIV4, B4E3K3, O75112, Q5K6N9, Q5K6P0, Q5K6P1, Q96FH2, Q9Y4Z3, Q9Y4Z4, Q9Y4Z5

UniProtKB/TrEMBL

B4DGP4

Related

ENSP00000355296.3, ENST00000361373.9

Conserved Domains (6) summary

cd09362
Location:610 → 661

LIM2_Enigma_like; The second LIM domain of Enigma-like family

cd09363
Location:669 → 722

LIM3_Enigma_like; The third LIM domain of Enigma-like family

cd09454
Location:551 → 602

LIM1_ZASP_Cypher; The first LIM domain of ZASP/Cypher family

cd00992
Location:5 → 81

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam15936
Location:194 → 285

DUF4749; Domain of unknown function (DUF4749)

cl26386
Location:352 → 550

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III