This gene encodes a core regulatory component of a calcium channel in the mitochondrial inner membrane. [provided by RefSeq, Apr 2017] See more...

Aliases for SMDT1 Gene

Aliases for SMDT1 Gene

  • Single-Pass Membrane Protein With Aspartate Rich Tail 1 2 3 5
  • Single-Pass Membrane Protein With Aspartate-Rich Tail 1, Mitochondrial 3 4
  • Essential MCU Regulator, Mitochondrial 3 4
  • C22orf32 3 4
  • EMRE 3 4
  • UPF0466 Protein C22orf32, Mitochondrial 3
  • Chromosome 22 Open Reading Frame 32 2
  • Essential MCU Regulator 2
  • DDDD 3

External Ids for SMDT1 Gene

Previous HGNC Symbols for SMDT1 Gene

  • C22orf32

Previous GeneCards Identifiers for SMDT1 Gene

  • GC22P042476

Summaries for SMDT1 Gene

Entrez Gene Summary for SMDT1 Gene

  • This gene encodes a core regulatory component of a calcium channel in the mitochondrial inner membrane. [provided by RefSeq, Apr 2017]

GeneCards Summary for SMDT1 Gene

SMDT1 (Single-Pass Membrane Protein With Aspartate Rich Tail 1) is a Protein Coding gene. Diseases associated with SMDT1 include Retinitis Pigmentosa 4 and Brachydactyly, Type D.

UniProtKB/Swiss-Prot Summary for SMDT1 Gene

  • Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU (PubMed:24231807). Plays a central role in regulating the uniplex complex response to intracellular calcium signaling (PubMed:27099988). Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (PubMed:27099988).

Additional gene information for SMDT1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMDT1 Gene

Genomics for SMDT1 Gene

GeneHancer (GH) Regulatory Elements for SMDT1 Gene

Promoters and enhancers for SMDT1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH22J042077 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 585.7 -0.4 -429 3.9 ZBTB40 EP300 SIN3A NRF1 TCF12 POLR2G SP1 NCOR1 GTF2E2 PHF8 SMDT1 lnc-NDUFA6-2 CYP2D6 XRCC6 EP300 PHF5A RPL5P34 EP300-AS1 ZC3H7B NDUFA6-DT
GH22J042069 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 85.4 -8.7 -8743 3.3 EP300 TCF12 NRF1 POLR2G SP1 ZFX ZIC2 POLR2A ZBTB10 ZBTB11 ENSG00000286659 NAGA SMDT1 CYP2D6 WBP2NL NDUFA6-DT
GH22J042088 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 73 +10.6 10589 3.1 RXRA EP300 FOXK2 ZBTB40 CTCF SIN3A TCF12 NRF1 USF1 POLR2G NDUFA6 NDUFA6-DT ENSG00000270083 SMDT1 CYP2D6 NFAM1 CENPM CCDC134
GH22J042073 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE CraniofacialAtlas 81.1 -5.4 -5366 3.1 CTCF ZNF274 POLR2A ZNF341 YY1 PHF8 NR2F1 RAD21 TAF1 ZFP36 PHETA2 RF01210-253 SNORD13P1 SMDT1 CYP2D6 NAGA NDUFA6-DT
GH22J042120 Promoter/Enhancer 1.1 Ensembl ENCODE 78.3 +41.3 41278 1.5 ZNF282 ZNF316 GABPA NFE2 NR2F1 ELF1 HDAC2 ZFP91 ZNF384 EGR1 SMDT1 CYP2D6 NDUFA6-DT L3MBTL2 LOC105373047 OLA1P1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMDT1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMDT1

Genomic Locations for SMDT1 Gene

Genomic Locations for SMDT1 Gene
chr22:42,079,691-42,084,284
(GRCh38/hg38)
Size:
4,594 bases
Orientation:
Plus strand
chr22:42,475,695-42,480,288
(GRCh37/hg19)
Size:
4,594 bases
Orientation:
Plus strand

Genomic View for SMDT1 Gene

Genes around SMDT1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMDT1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMDT1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMDT1 Gene

Proteins for SMDT1 Gene

  • Protein details for SMDT1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H4I9-EMRE_HUMAN
    Recommended name:
    Essential MCU regulator, mitochondrial
    Protein Accession:
    Q9H4I9
    Secondary Accessions:
    • B2R5D1
    • Q8TAB9

    Protein attributes for SMDT1 Gene

    Size:
    107 amino acids
    Molecular mass:
    11441 Da
    Quaternary structure:
    • Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807). Interacts (via the transmembrane region) with MCU (via the first transmembrane region); the interaction is direct (PubMed:27099988). Interacts (via the poly-Asp region) with MICU1 (via polybasic region); the interaction is direct (PubMed:27099988). Interacts (via its C-terminal poly-Asp tail) with MCUR1; the interaction is direct (PubMed:27184846). Unprocessed form interacts (via transit peptide) with MAIP1 (PubMed:27642048).

    Three dimensional structures from OCA and Proteopedia for SMDT1 Gene

neXtProt entry for SMDT1 Gene

Post-translational modifications for SMDT1 Gene

  • Undergoes proteolytic degradation in neurons: degraded by AFG3L2 before SMDT1/EMRE assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048).

Other Protein References for SMDT1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SMDT1 Gene

Domains & Families for SMDT1 Gene

Gene Families for SMDT1 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters

Protein Domains for SMDT1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SMDT1 Gene

GenScript: Design optimal peptide antigens:
  • UPF0466 protein C22orf32, mitochondrial (CV032_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H4I9

UniProtKB/Swiss-Prot:

EMRE_HUMAN :
  • The GXXXX[G/A/S] motif at the C-terminal part of the transmembrane region mediates interaction with MCU and is required to activate the calcium-conducting pore in the uniporter complex.
  • Belongs to the SMDT1/EMRE family.
Domain:
  • The GXXXX[G/A/S] motif at the C-terminal part of the transmembrane region mediates interaction with MCU and is required to activate the calcium-conducting pore in the uniporter complex.
  • The poly-Asp region at the C-terminus mediates interaction with the polybasic region of MICU1.
Family:
  • Belongs to the SMDT1/EMRE family.
genes like me logo Genes that share domains with SMDT1: view

Function for SMDT1 Gene

Molecular function for SMDT1 Gene

UniProtKB/Swiss-Prot Function:
Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU (PubMed:24231807). Plays a central role in regulating the uniplex complex response to intracellular calcium signaling (PubMed:27099988). Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (PubMed:27099988).

Phenotypes From GWAS Catalog for SMDT1 Gene

Gene Ontology (GO) - Molecular Function for SMDT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 27099988
genes like me logo Genes that share ontologies with SMDT1: view
genes like me logo Genes that share phenotypes with SMDT1: view

Animal Models for SMDT1 Gene

MGI Knock Outs for SMDT1:
  • Smdt1 Smdt1<tm1b(EUCOMM)Wtsi>

Animal Model Products

  • Taconic Biosciences Mouse Models for SMDT1

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMDT1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SMDT1 Gene

Localization for SMDT1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMDT1 Gene

Mitochondrion inner membrane; Single-pass membrane protein. Note=MAIP1 is required to assist sorting of EMRE/SMDT1 into mitochondrion by protecting EMRE/SMDT1 against protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation by the mitochondrial processing peptidase (PMPCA and PMPCB) (PubMed:27642048). {ECO:0000269 PubMed:27642048}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMDT1 gene
Compartment Confidence
mitochondrion 5
nucleus 5
plasma membrane 2
extracellular 2
cytosol 2
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMDT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005739 mitochondrion IEA,IDA --
GO:0005743 mitochondrial inner membrane TAS --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with SMDT1: view

Pathways & Interactions for SMDT1 Gene

PathCards logo

SuperPathways for SMDT1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SMDT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006816 calcium ion transport IEA --
GO:0006851 mitochondrial calcium ion transmembrane transport TAS,IBA --
GO:0036444 calcium import into the mitochondrion IMP,IEA 22925203
GO:0051560 mitochondrial calcium ion homeostasis IMP,IEA 24231807
genes like me logo Genes that share ontologies with SMDT1: view

No data available for Pathways by source and SIGNOR curated interactions for SMDT1 Gene

Drugs & Compounds for SMDT1 Gene

No Compound Related Data Available

Transcripts for SMDT1 Gene

mRNA/cDNA for SMDT1 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SMDT1

Alternative Splicing Database (ASD) splice patterns (SP) for SMDT1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b
SP1: - -
SP2: -
SP3:

Relevant External Links for SMDT1 Gene

GeneLoc Exon Structure for
SMDT1

Expression for SMDT1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SMDT1 Gene

Protein differential expression in normal tissues from HIPED for SMDT1 Gene

This gene is overexpressed in Nasal epithelium (58.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SMDT1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SMDT1

SOURCE GeneReport for Unigene cluster for SMDT1 Gene:

Hs.306083

Evidence on tissue expression from TISSUES for SMDT1 Gene

  • Nervous system(4.3)
  • Muscle(2.5)
genes like me logo Genes that share expression patterns with SMDT1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for SMDT1 Gene

Orthologs for SMDT1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SMDT1 Gene

Organism Taxonomy Gene Similarity Type Details
platypus
(Ornithorhynchus anatinus)
Mammalia SMDT1 31
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia C22H22orf32 30
  • 98.35 (n)
SMDT1 31
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SMDT1 31 30
  • 91.09 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SMDT1 31 30
  • 90.43 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Smdt1 17 31 30
  • 85.15 (n)
rat
(Rattus norvegicus)
Mammalia Smdt1 30
  • 85.15 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 79 (a)
OneToMany
-- 31
  • 48 (a)
OneToMany
chicken
(Gallus gallus)
Aves SMDT1 31
  • 67 (a)
OneToOne
C22ORF32 30
  • 66.67 (n)
lizard
(Anolis carolinensis)
Reptilia SMDT1 31
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia smdt1 30
  • 62.72 (n)
Str.8588 30
zebrafish
(Danio rerio)
Actinopterygii smdt1 31
  • 47 (a)
OneToOne
Dr.29472 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13565 30
fruit fly
(Drosophila melanogaster)
Insecta CG17680 31
  • 43 (a)
OneToOne
Species where no ortholog for SMDT1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SMDT1 Gene

ENSEMBL:
Gene Tree for SMDT1 (if available)
TreeFam:
Gene Tree for SMDT1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMDT1: view image

Paralogs for SMDT1 Gene

No data available for Paralogs for SMDT1 Gene

Variants for SMDT1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMDT1 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
rs17852210 - p.Arg46Gly

Additional dbSNP identifiers (rs#s) for SMDT1 Gene

Structural Variations from Database of Genomic Variants (DGV) for SMDT1 Gene

Variant ID Type Subtype PubMed ID
nsv508737 CNV insertion 20534489
nsv834210 CNV loss 17160897

Variation tolerance for SMDT1 Gene

Residual Variation Intolerance Score: 35.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.47; 10.26% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMDT1 Gene

Human Gene Mutation Database (HGMD)
SMDT1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMDT1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMDT1 Gene

Disorders for SMDT1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SMDT1 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search SMDT1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SMDT1

genes like me logo Genes that share disorders with SMDT1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SMDT1 Gene

Publications for SMDT1 Gene

  1. EMRE is an essential component of the mitochondrial calcium uniporter complex. (PMID: 24231807) Sancak Y … Mootha VK (Science (New York, N.Y.) 2013) 2 3 4 54
  2. The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria. (PMID: 27642048) König T … Langer T (Molecular cell 2016) 3 4 54
  3. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics. (PMID: 27184846) Tomar D … Madesh M (Cell reports 2016) 3 4 54
  4. Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex. (PMID: 27099988) Tsai MF … Miller C (eLife 2016) 3 4 54
  5. EMRE Is a Matrix Ca(2+) Sensor that Governs Gatekeeping of the Mitochondrial Ca(2+) Uniporter. (PMID: 26774479) Vais H … Foskett JK (Cell reports 2016) 3 4 54

Products for SMDT1 Gene

Sources for SMDT1 Gene