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Protein

Calcium uptake protein 2, mitochondrial

Gene

MICU2

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

Functioni

Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927).4 Publications

GO - Molecular functioni

  • calcium ion binding Source: Ensembl
  • protein heterodimerization activity Source: UniProtKB

GO - Biological processi

  • calcium ion transmembrane import into mitochondrion Source: UniProtKB
  • mitochondrial calcium ion homeostasis Source: UniProtKB
  • mitochondrial calcium ion transport Source: UniProtKB
  • negative regulation of mitochondrial calcium ion concentration Source: UniProtKB
  • positive regulation of mitochondrial calcium ion concentration Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:MONOMER66-34416.

Protein family/group databases

TCDBi8.A.44.1.2. the mitochondrial ef hand ca(2+) uniporter regulator (micu) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium uptake protein 2, mitochondrial
Alternative name(s):
EF-hand domain-containing family member A1
Gene namesi
Name:MICU2
Synonyms:EFHA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:31830. MICU2.

Subcellular locationi

GO - Cellular componenti

  • calcium channel complex Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleus Source: HPA
  • uniplex complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185D → A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-375 and A-386. 1 Publication1
Mutagenesisi375D → A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-185 and A-386. 1 Publication1
Mutagenesisi386E → A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-185 and A-375. 1 Publication1

Organism-specific databases

DisGeNETi221154.
OpenTargetsiENSG00000165487.
PharmGKBiPA134891566.

Polymorphism and mutation databases

BioMutaiMICU2.
DMDMi115502157.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 22MitochondrionSequence analysisAdd BLAST22
ChainiPRO_000025121723 – 434Calcium uptake protein 2, mitochondrialAdd BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei205PhosphoserineCombined sources1
Disulfide bondi413Interchain (with C-463 in MICU1)By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiQ8IYU8.
MaxQBiQ8IYU8.
PaxDbiQ8IYU8.
PeptideAtlasiQ8IYU8.
PRIDEiQ8IYU8.

PTM databases

iPTMnetiQ8IYU8.
PhosphoSitePlusiQ8IYU8.

Expressioni

Gene expression databases

BgeeiENSG00000165487.
CleanExiHS_EFHA1.
ExpressionAtlasiQ8IYU8. baseline and differential.
GenevisibleiQ8IYU8. HS.

Organism-specific databases

HPAiHPA045511.
HPA058790.

Interactioni

Subunit structurei

Heterodimer; disulfide-linked; heterodimerizes with MICU1 (PubMed:24560927). Interacts with MCU (PubMed:26341627). The heterodimer formed with MICU1 associates with MCU at low calcium concentration and dissociates from MCU at high calcium level (PubMed:26387864). Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807).4 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi128692. 24 interactors.
IntActiQ8IYU8. 2 interactors.
STRINGi9606.ENSP00000371811.

Structurei

3D structure databases

ProteinModelPortaliQ8IYU8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini172 – 207EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini227 – 262EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini293 – 328EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini362 – 397EF-hand 4PROSITE-ProRule annotationAdd BLAST36

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 50Ala-richAdd BLAST49

Domaini

The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels (PubMed:24503055). It is unclear which EF-hand binds calcium as none of the 4 EF-hand domains seem to contain a canonical calcium-binding site.1 Publication

Sequence similaritiesi

Belongs to the MICU1 family. MICU2 subfamily.Curated
Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transit peptide

Phylogenomic databases

eggNOGiKOG2643. Eukaryota.
ENOG410ZSC1. LUCA.
GeneTreeiENSGT00530000063089.
HOGENOMiHOG000007649.
HOVERGENiHBG054562.
InParanoidiQ8IYU8.
OMAiIQEMEFL.
OrthoDBiEOG091G0WLM.
PhylomeDBiQ8IYU8.
TreeFamiTF320374.

Family and domain databases

Gene3Di1.10.238.10. 4 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 4 hits.
PROSITEiPS50222. EF_HAND_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8IYU8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAAGSCAR VAAWGGKLRR GLAVSRQAVR SPGPLAAAVA GAALAGAGAA
60 70 80 90 100
WHHSRVSVAA RDGSFTVSAQ KNVEHGIIYI GKPSLRKQRF MQFSSLEHEG
110 120 130 140 150
EYYMTPRDFL FSVMFEQMER KTSVKKLTKK DIEDTLSGIQ TAGCGSTFFR
160 170 180 190 200
DLGDKGLISY TEYLFLLTIL TKPHSGFHVA FKMLDTDGNE MIEKREFFKL
210 220 230 240 250
QKIISKQDDL MTVKTNETGY QEAIVKEPEI NTTLQMRFFG KRGQRKLHYK
260 270 280 290 300
EFRRFMENLQ TEIQEMEFLQ FSKGLSFMRK EDFAEWLLFF TNTENKDIYW
310 320 330 340 350
KNVREKLSAG ESISLDEFKS FCHFTTHLED FAIAMQMFSL AHRPVRLAEF
360 370 380 390 400
KRAVKVATGQ ELSNNILDTV FKIFDLDGDE CLSHEEFLGV LKNRMHRGLW
410 420 430
VPQHQSIQEY WKCVKKESIK GVKEVWKQAG KGLF
Length:434
Mass (Da):49,666
Last modified:October 3, 2006 - v2
Checksum:i37F31B7BE2DE80E7
GO

Sequence cautioni

The sequence BAC03769 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti205S → N in AAH34965 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027662260Q → L.1 PublicationCorresponds to variant rs17853349dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL138680, AL136219 Genomic DNA. Translation: CAH70136.1.
AL136219, AL138680 Genomic DNA. Translation: CAH70594.1.
BC031089 mRNA. Translation: AAH31089.1.
BC034965 mRNA. Translation: AAH34965.1.
AK091907 mRNA. Translation: BAC03769.1. Different initiation.
CCDSiCCDS9297.1.
RefSeqiNP_689939.1. NM_152726.2.
UniGeneiHs.412103.

Genome annotation databases

EnsembliENST00000382374; ENSP00000371811; ENSG00000165487.
GeneIDi221154.
KEGGihsa:221154.
UCSCiuc001uof.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL138680, AL136219 Genomic DNA. Translation: CAH70136.1.
AL136219, AL138680 Genomic DNA. Translation: CAH70594.1.
BC031089 mRNA. Translation: AAH31089.1.
BC034965 mRNA. Translation: AAH34965.1.
AK091907 mRNA. Translation: BAC03769.1. Different initiation.
CCDSiCCDS9297.1.
RefSeqiNP_689939.1. NM_152726.2.
UniGeneiHs.412103.

3D structure databases

ProteinModelPortaliQ8IYU8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128692. 24 interactors.
IntActiQ8IYU8. 2 interactors.
STRINGi9606.ENSP00000371811.

Protein family/group databases

TCDBi8.A.44.1.2. the mitochondrial ef hand ca(2+) uniporter regulator (micu) family.

PTM databases

iPTMnetiQ8IYU8.
PhosphoSitePlusiQ8IYU8.

Polymorphism and mutation databases

BioMutaiMICU2.
DMDMi115502157.

Proteomic databases

EPDiQ8IYU8.
MaxQBiQ8IYU8.
PaxDbiQ8IYU8.
PeptideAtlasiQ8IYU8.
PRIDEiQ8IYU8.

Protocols and materials databases

DNASUi221154.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382374; ENSP00000371811; ENSG00000165487.
GeneIDi221154.
KEGGihsa:221154.
UCSCiuc001uof.4. human.

Organism-specific databases

CTDi221154.
DisGeNETi221154.
GeneCardsiMICU2.
HGNCiHGNC:31830. MICU2.
HPAiHPA045511.
HPA058790.
MIMi610632. gene.
neXtProtiNX_Q8IYU8.
OpenTargetsiENSG00000165487.
PharmGKBiPA134891566.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2643. Eukaryota.
ENOG410ZSC1. LUCA.
GeneTreeiENSGT00530000063089.
HOGENOMiHOG000007649.
HOVERGENiHBG054562.
InParanoidiQ8IYU8.
OMAiIQEMEFL.
OrthoDBiEOG091G0WLM.
PhylomeDBiQ8IYU8.
TreeFamiTF320374.

Enzyme and pathway databases

BioCyciZFISH:MONOMER66-34416.

Miscellaneous databases

GenomeRNAii221154.
PROiQ8IYU8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165487.
CleanExiHS_EFHA1.
ExpressionAtlasiQ8IYU8. baseline and differential.
GenevisibleiQ8IYU8. HS.

Family and domain databases

Gene3Di1.10.238.10. 4 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13833. EF-hand_8. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 4 hits.
PROSITEiPS50222. EF_HAND_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMICU2_HUMAN
AccessioniPrimary (citable) accession number: Q8IYU8
Secondary accession number(s): Q8N0T6, Q8NAX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: November 2, 2016
This is version 118 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: 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

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.