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Protein

Essential MCU regulator, mitochondrial

Gene

SMDT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 Publications

GO - Biological processi

  • calcium ion transmembrane import into mitochondrion Source: UniProtKB
  • mitochondrial calcium ion homeostasis Source: UniProtKB
  • mitochondrial calcium ion transport Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:G66-32316-MONOMER.
ZFISH:MONOMER66-34418.

Protein family/group databases

TCDBi8.A.45.1.1. the essential mcu regulator, emre (emre) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Essential MCU regulator, mitochondrial1 Publication
Alternative name(s):
Single-pass membrane protein with aspartate-rich tail 1, mitochondrialImported
Gene namesi
Name:SMDT1Imported
Synonyms:C22orf32Imported, EMRE1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:25055. SMDT1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini53 – 64Mitochondrial matrix2 PublicationsAdd BLAST12
Transmembranei65 – 84HelicalSequence analysisAdd BLAST20
Topological domaini85 – 107Mitochondrial intermembrane2 PublicationsAdd BLAST23

GO - Cellular componenti

  • integral component of mitochondrial inner membrane Source: UniProtKB
  • mitochondrion Source: HPA
  • nucleus Source: HPA
  • uniplex complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi81G → W: Abolishes calcium uptake into mitochondria. 1 Publication1
Mutagenesisi85S → W: Abolishes calcium uptake into mitochondria. 1 Publication1
Mutagenesisi101 – 107EDDDDDD → QNNNNNN: Abolishes regulation of calcium uptake into mitochondria. 1 Publication7

Organism-specific databases

OpenTargetsiENSG00000183172.
ENSG00000272835.
ENSG00000272901.
ENSG00000274112.
PharmGKBiPA145149451.

Polymorphism and mutation databases

BioMutaiSMDT1.
DMDMi74761431.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 52Mitochondrion1 PublicationAdd BLAST52
ChainiPRO_000029632053 – 107Essential MCU regulator, mitochondrialAdd BLAST55

Post-translational modificationi

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).1 Publication

Proteomic databases

EPDiQ9H4I9.
MaxQBiQ9H4I9.
PaxDbiQ9H4I9.
PeptideAtlasiQ9H4I9.
PRIDEiQ9H4I9.
TopDownProteomicsiQ9H4I9.

Expressioni

Gene expression databases

BgeeiENSG00000183172.
CleanExiHS_C22orf32.
ExpressionAtlasiQ9H4I9. baseline and differential.
GenevisibleiQ9H4I9. HS.

Organism-specific databases

HPAiHPA032117.
HPA060340.

Interactioni

Subunit structurei

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 C2orf47/MAIP1 (PubMed:27642048).4 Publications

Protein-protein interaction databases

BioGridi124866. 6 interactors.
STRINGi9606.ENSP00000327467.

Structurei

3D structure databases

ProteinModelPortaliQ9H4I9.
SMRiQ9H4I9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 52Interaction with C2orf47/MAIP11 PublicationAdd BLAST52

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi81 – 85GXXXX[G/A/S]1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi102 – 107Poly-AspSequence analysis6

Domaini

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.1 Publication
The poly-Asp region at the C-terminus mediates interaction with the polybasic region of MICU1.1 Publication

Sequence similaritiesi

Belongs to the SMDT1/EMRE family.Curated

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4542. Eukaryota.
ENOG4112ABK. LUCA.
GeneTreeiENSGT00390000017489.
HOGENOMiHOG000018296.
HOVERGENiHBG095170.
InParanoidiQ9H4I9.
OMAiWKENGAI.
OrthoDBiEOG091G13VT.
PhylomeDBiQ9H4I9.
TreeFamiTF314649.

Family and domain databases

InterProiIPR018782. MCU_reg.
[Graphical view]
PfamiPF10161. DDDD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9H4I9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGAARWLV LAPVRSGALR SGPSLRKDGD VSAAWSGSGR SLVPSRSVIV
60 70 80 90 100
TRSGAILPKP VKMSFGLLRV FSIVIPFLYV GTLISKNFAA LLEEHDIFVP

EDDDDDD
Length:107
Mass (Da):11,441
Last modified:March 1, 2001 - v1
Checksum:i4E00824D322AE99D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03462846R → G.1 PublicationCorresponds to variant rs17852210dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL449243 mRNA. Translation: CAC15000.1.
CR456453 mRNA. Translation: CAG30339.1.
AK312142 mRNA. Translation: BAG35078.1.
Z82192, AL021878 Genomic DNA. Translation: CAI19711.1.
CH471095 Genomic DNA. Translation: EAW60488.1.
BC024237 mRNA. Translation: AAH24237.1.
CCDSiCCDS14031.1.
RefSeqiNP_201575.3. NM_033318.4.
XP_011528811.1. XM_011530509.2.
UniGeneiHs.306083.

Genome annotation databases

EnsembliENST00000331479; ENSP00000327467; ENSG00000183172.
ENST00000571525; ENSP00000459368; ENSG00000272901.
ENST00000607293; ENSP00000475471; ENSG00000272835.
ENST00000615504; ENSP00000485029; ENSG00000274112.
GeneIDi91689.
KEGGihsa:91689.
UCSCiuc003bca.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL449243 mRNA. Translation: CAC15000.1.
CR456453 mRNA. Translation: CAG30339.1.
AK312142 mRNA. Translation: BAG35078.1.
Z82192, AL021878 Genomic DNA. Translation: CAI19711.1.
CH471095 Genomic DNA. Translation: EAW60488.1.
BC024237 mRNA. Translation: AAH24237.1.
CCDSiCCDS14031.1.
RefSeqiNP_201575.3. NM_033318.4.
XP_011528811.1. XM_011530509.2.
UniGeneiHs.306083.

3D structure databases

ProteinModelPortaliQ9H4I9.
SMRiQ9H4I9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124866. 6 interactors.
STRINGi9606.ENSP00000327467.

Protein family/group databases

TCDBi8.A.45.1.1. the essential mcu regulator, emre (emre) family.

Polymorphism and mutation databases

BioMutaiSMDT1.
DMDMi74761431.

Proteomic databases

EPDiQ9H4I9.
MaxQBiQ9H4I9.
PaxDbiQ9H4I9.
PeptideAtlasiQ9H4I9.
PRIDEiQ9H4I9.
TopDownProteomicsiQ9H4I9.

Protocols and materials databases

DNASUi91689.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331479; ENSP00000327467; ENSG00000183172.
ENST00000571525; ENSP00000459368; ENSG00000272901.
ENST00000607293; ENSP00000475471; ENSG00000272835.
ENST00000615504; ENSP00000485029; ENSG00000274112.
GeneIDi91689.
KEGGihsa:91689.
UCSCiuc003bca.4. human.

Organism-specific databases

CTDi91689.
GeneCardsiSMDT1.
H-InvDBHIX0019152.
HGNCiHGNC:25055. SMDT1.
HPAiHPA032117.
HPA060340.
MIMi615588. gene.
neXtProtiNX_Q9H4I9.
OpenTargetsiENSG00000183172.
ENSG00000272835.
ENSG00000272901.
ENSG00000274112.
PharmGKBiPA145149451.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4542. Eukaryota.
ENOG4112ABK. LUCA.
GeneTreeiENSGT00390000017489.
HOGENOMiHOG000018296.
HOVERGENiHBG095170.
InParanoidiQ9H4I9.
OMAiWKENGAI.
OrthoDBiEOG091G13VT.
PhylomeDBiQ9H4I9.
TreeFamiTF314649.

Enzyme and pathway databases

BioCyciZFISH:G66-32316-MONOMER.
ZFISH:MONOMER66-34418.

Miscellaneous databases

GenomeRNAii91689.
PROiQ9H4I9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183172.
CleanExiHS_C22orf32.
ExpressionAtlasiQ9H4I9. baseline and differential.
GenevisibleiQ9H4I9. HS.

Family and domain databases

InterProiIPR018782. MCU_reg.
[Graphical view]
PfamiPF10161. DDDD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEMRE_HUMAN
AccessioniPrimary (citable) accession number: Q9H4I9
Secondary accession number(s): B2R5D1, Q8TAB9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

A publication reports an opposite topology (PubMed:26774479). However, 3 different articles, 2 in human and one in mouse, confirm the topology shown in this entry (PubMed:27099988, PubMed:27642048).3 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
  6. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.