unc-45 UNC-45/Cro1/She4 central domain-containing protein [Caenorhabditis elegans] - Gene

Summary

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Official Symbol: unc-45
Official Full Name: UNC-45/Cro1/She4 central domain-containing protein
Primary source: WormBase:WBGene00006781
Locus tag: CELE_F30H5.1
See related: AllianceGenome:WB:WBGene00006781
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Caenorhabditis elegans (strain: Bristol N2)
Lineage: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
Summary: Enables identical protein binding activity; protein folding chaperone; and ubiquitin protein ligase binding activity. Involved in several processes, including chaperone-mediated protein folding; egg-laying behavior; and sarcomere organization. Located in cell cortex and cleavage furrow. Is expressed in body wall musculature and non-striated muscle. Human ortholog(s) of this gene implicated in cataract 43 and myofibrillar myopathy 11. Orthologous to several human genes including UNC45B (unc-45 myosin chaperone B). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See unc-45 in Genome Data Viewer

Location:: chromosome: III

Exon count:: 11

Sequence:: Chromosome: III; NC_003281.10 (491547..502625)

Chromosome III - NC_003281.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003281.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.
Title: The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.
Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity.
Title: Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity.
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores.
Title: Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores.
Data highlight the importance of utilizing a flexible myosin-binding domain. This so-called UCS domain can adopt discrete conformations to efficiently bind and fold substrate. Moreover, our data uncover the molecular basis of temperature-sensitive UNC-45 mutations underlying one of the most prominent motility defects in C. elegans.
Title: Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.
UNC-45 chaperone can serve as an adaptor protein of UFD-2 to poly-ubiquitinate unfolded myosin, pointing to a possible role of the UFD-2/UNC-45 pair in maintaining proteostasis in muscle cells.
Title: UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins.
Biochemical and structural analyses with in vivo studies of the C. elegans UNC-45 protein reveal a chaperone chain in which UNC-45 tandem modules assemble a multisite docking platform that enforces collaboration with Hsp70 and Hsp90 in a precisely defined pattern to assemble myosin filaments.
Title: The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.
UNC-45 is not required to fold or maintain the actin binding domain but is still required for myosin function.
Title: UNC-45 is required for NMY-2 contractile function in early embryonic polarity establishment and germline cellularization in C. elegans.
Study reports that transgenic worms overexpressing UNC-45 display defects in myosin assembly, with decreased myosin content and a mild paralysis phenotype.
Title: The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans.
UNC-45 interacts with more than one type of myosin and functions in the embryo to regulate cytoplasmic myosin assembly and/or stability during cytokinesis
Title: Maternal UNC-45 is involved in cytokinesis and colocalizes with non-muscle myosin in the early Caenorhabditis elegans embryo.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

F30H5.1 (e-PCR)
- UniSTS:313109

Y55B1A_115.e (e-PCR)
- UniSTS:323108

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
enables Hsp90 protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein folding chaperone	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in chaperone-mediated protein folding	IBA Inferred from Biological aspect of Ancestor more info
involved_in chaperone-mediated protein folding	IDA Inferred from Direct Assay more info	PubMed
involved_in egg-laying behavior	IGI Inferred from Genetic Interaction more info	PubMed
involved_in egg-laying behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryo development ending in birth or egg hatching	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in locomotion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in sarcomere organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell cortex	IDA Inferred from Direct Assay more info	PubMed
located_in cleavage furrow	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: UNC-45/Cro1/She4 central domain-containing protein

NP_497205.1

Confirmed by transcript evidence

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_003281.10 Reference assembly

Range

491547..502625

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_064804.9 → NP_497205.1 UNC-45/Cro1/She4 central domain-containing protein [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_497205.1

Status: REVIEWED

UniProtKB/TrEMBL

G5EG62

Conserved Domains (3) summary

TIGR00990
Location:4 → 190

3a0801s09; mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70)

sd00006
Location:8 → 36

TPR; TPR repeat [structural motif]

pfam11701
Location:359 → 507

UNC45-central; Myosin-binding striated muscle assembly central