LETM1 leucine zipper-EF-hand containing transmembrane protein 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: LETM1provided by HGNC
Official Full Name: leucine zipper-EF-hand containing transmembrane protein 1provided by HGNC
Primary source: HGNC:6556
See related: Ensembl:ENSG00000168924; HPRD:05101; MIM:604407; Vega:OTTHUMG00000121149
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
Summary: This gene encodes a protein that is localized to the inner mitochondrial membrane. The protein functions to maintain the mitochondrial tubular shapes and is required for normal mitochondrial morphology and cellular viability. Mutations in this gene cause Wolf-Hirschhorn syndrome, a complex malformation syndrome caused by the deletion of parts of the distal short arm of chromosome 4. Related pseudogenes have been identified on chromosomes 8, 15 and 19. [provided by RefSeq, Oct 2009]

Genomic context

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Location :: 4p16.3

Sequence :: Chromosome: 4; NC_000004.11 (1813206..1857974, complement)

See LETM1 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Summarizes the current state of the art about the functions of LETM1 and its role in pathophysiology, with some emphasis on whether it is a feasible candidate for regulation of mitochondrial Ca2+ homeostasis.
Title: Perspectives on: SGP symposium on mitochondrial physiology and medicine: the pathophysiology of LETM1.
Letm1 and UCP2/3 independently contribute to two distinct, mitochondrial Ca(2+) uptake pathways in intact endothelial cells.
Title: Leucine zipper EF hand-containing transmembrane protein 1 (Letm1) and uncoupling proteins 2 and 3 (UCP2/3) contribute to two distinct mitochondrial Ca2+ uptake pathways.
we have identified a novel submicroscopic duplication involving dosage sensitive genes TACC3, FGFR3, and LETM1.
Title: A novel 4p16.3 microduplication distal to WHSC1 and WHSC2 characterized by oligonucleotide array with new phenotypic features.
LETM1 suppressed lung cancer cell growth in vitro and in vivo.
Title: Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Letm1, was found to specifically mediate coupled Ca2+/H+ exchange; RNAi knockdown, overexpression, and liposome reconstitution of the purified Letm1 protein demonstrate that Letm1 is a mitochondrial Ca2+/H+ antiporter
Title: Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter.
Data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. Increased expression of LETM1 in human cancer suggests that dysregulation of LETM1 features in tumorigenesis.
Title: Association of LETM1 and MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death.
LETM1 protein is a novel binding partner for Carboxyl-terminal modulator protein that may play an important role in mitochondrial fragmentation via optic atrophy type 1-cleavage.
Title: Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis.
the LETM1-mediated regulation of the mitochondrial volume and its interaction with the mitochondrial AAA-ATPase BCS1L that is responsible for three different human disorders
Title: Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L.
Study shows that human LETM1 is located in the inner membrane, exposed to the matrix and oligomerized in higher molecular weight complexes of unknown composition; down-regulation of LETM1 caused 'necrosis-like' death, without activation of caspases.
Title: LETM1, deleted in Wolf-Hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability.

Submit: New GeneRIF Correction See all (12)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:110145	BioGRID:125237	C12orf57	BioGRID	PubMed	Co-fractionation
BioGRID:110145	BioGRID:109622	ICT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110145	BioGRID:109822	ILF3	BioGRID	PubMed	Co-fractionation
BioGRID:110145	BioGRID:115755	SYNCRIP	BioGRID	PubMed	Co-fractionation
BioGRID:110145	BioGRID:118878	TBK1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110145	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

General gene information

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Markers

RH41928 (e-PCR)
- UniSTS:77928

D1S1425 (e-PCR)
- UniSTS:149621

SHGC-24744 (e-PCR)
- UniSTS:60573

Homology

Homologs of the LETM1 gene: The LETM1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cristae formation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
integral to membrane	IEA Inferred from Electronic Annotation more info
mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info
mitochondrion	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: LETM1 and EF-hand domain-containing protein 1, mitochondrial

Names: LETM1 and EF-hand domain-containing protein 1, mitochondrial; Mdm38 homolog; leucine zipper-EF-hand-containing transmembrane protein 1

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_013063.1 RefSeqGene

Range

5001..49769

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_012318.2 → NP_036450.1 LETM1 and EF-hand domain-containing protein 1, mitochondrial precursor

Status: REVIEWED

Source sequence(s)

AC105448, AF061025

Consensus CDS

CCDS3355.1

UniProtKB/Swiss-Prot

O95202

Related

ENSP00000305653, OTTHUMP00000149960, ENST00000302787, OTTHUMT00000241634

Conserved Domains (1) summary

pfam07766
Location:150 – 418
Blast Score: 917

LETM1; LETM1-like protein

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

1813206..1857974, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

1756076..1799634, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

1795734..1839373, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01029525.1 (14707..21062)	None
genomic	ABBA01029526.1	None
genomic	ABBA01029527.1	None
genomic	AC105448.5 (431..45198)	None
genomic	AMYH01013872.1 (17685..61324)	None
genomic	CH471131.2	EAW82560.1
		EAW82561.1
mRNA	AF061025.1	AAD13138.1
mRNA	AK293572.1	BAG57043.1
mRNA	AK310563.1	None
mRNA	AL133650.1	CAB63769.2
mRNA	BC014500.1	AAH14500.1
mRNA	BC021208.1	AAH21208.1
other-genetic	DQ893606.2	ABM84532.1