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Protein

Calcium uptake protein 1, mitochondrial

Gene

Micu1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains (PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU1 acts both as an activator or inhibitor of mitochondrial calcium uptake (By similarity). Acts as a gatekeeper of MCU at low concentration of calcium, preventing channel opening (By similarity). Enhances MCU opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm (PubMed:24560927). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi233 – 24411 PublicationAdd BLAST12
Calcium bindingi423 – 43421 PublicationAdd BLAST12

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • identical protein binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-8949215 Mitochondrial calcium ion transport
R-MMU-8949664 Processing of SMDT1

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium uptake protein 1, mitochondrial
Alternative name(s):
Calcium-binding atopy-related autoantigen 1 homolog
Gene namesi
Name:Micu1
Synonyms:Cbara1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2384909 Micu1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei34 – 52HelicalSequence analysisAdd BLAST19
Topological domaini53 – 477Mitochondrial intermembraneBy similarityAdd BLAST425

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Disruption phenotypei

Lethality during the first hours after birth: embryos are at the expected Mendelian ratio and death takes place only after birth.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi62C → A: No effect. 1
Mutagenesisi203C → A: No effect. 1
Mutagenesisi233D → A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-244; A-423 and A-434. 1
Mutagenesisi244E → A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-423 and A-434. 1
Mutagenesisi277C → A: No effect. 1
Mutagenesisi423D → A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-244 and A-434. 1
Mutagenesisi434E → A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-244 and A-423. 1
Mutagenesisi465C → A: Abolishes interaction with MICU2. 1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionSequence analysisAdd BLAST33
ChainiPRO_000032299234 – 477Calcium uptake protein 1, mitochondrialAdd BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi465Interchain (with C-410 in MICU2)1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ8VCX5
PaxDbiQ8VCX5
PeptideAtlasiQ8VCX5
PRIDEiQ8VCX5

PTM databases

iPTMnetiQ8VCX5
PhosphoSitePlusiQ8VCX5

Expressioni

Tissue specificityi

Expressed in skeletal muscle, heart, kidney, liver, brain, lung, fat and spleen.2 Publications

Gene expression databases

BgeeiENSMUSG00000020111 Expressed in 274 organ(s), highest expression level in colon
CleanExiMM_CBARA1
ExpressionAtlasiQ8VCX5 baseline and differential
GenevisibleiQ8VCX5 MM

Interactioni

Subunit structurei

Homohexamer; in absence of calcium (By similarity). Forms a homohexamer in absence of calcium and rearranges into a heterodimer in presence of calcium (By similarity). Heterodimer; disulfide-linked; heterodimerizes with MICU2 (PubMed:23409044, PubMed:24560927). The heterodimer formed with MICU2 associates with MCU at low calcium concentration and dissociates from MCU at high calcium level (By similarity). Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (By similarity). Interacts (via polybasic region) with EMRE/SMDT1; the interaction is direct (By similarity). Interacts (via polybasic region) with MCU (via coiled coil domains); the interaction is direct and precedes formation of the heterodimer with MICU2 (PubMed:23409044). Interacts with SLC25A23 (By similarity). Interacts with CHCHD4/MIA40; which introduces the interchain disulfide bond with MICU2 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000126597

Structurei

3D structure databases

ProteinModelPortaliQ8VCX5
SMRiQ8VCX5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini220 – 255EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini342 – 376EF-hand 2PROSITE-ProRule annotationAdd BLAST35
Domaini410 – 445EF-hand 3PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni101 – 112Polybasic regionBy similarityAdd BLAST12
Regioni457 – 467C-helix regionBy similarityAdd BLAST11

Domaini

The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels.1 Publication
The C-helix is required for assembling the Ca2+-free homohexamer. It also plays a key role in mitochondrial calcium uptake, probably by mediating interaction with MICU2.By similarity
The EF-hand domains have high affinity for calcium and act as sensors of calcium levels.By similarity

Sequence similaritiesi

Belongs to the MICU1 family. MICU1 subfamily.Curated

Keywords - Domaini

Repeat, Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2643 Eukaryota
ENOG410ZSC1 LUCA
GeneTreeiENSGT00530000063089
HOVERGENiHBG107586
InParanoidiQ8VCX5
KOiK22827
OMAiERKEPNE
OrthoDBiEOG091G05UE
PhylomeDBiQ8VCX5
TreeFamiTF313815

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR039800 MICU1/2/3
PANTHERiPTHR12294 PTHR12294, 1 hit
PfamiView protein in Pfam
PF13202 EF-hand_5, 1 hit
PF13833 EF-hand_8, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 2 hits
SUPFAMiSSF47473 SSF47473, 2 hits
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits

Sequences (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8VCX5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MFRLNTLSAL AELAVGSRWY HGASQPTQTK RRLMLVAFLG ASAVTASTGL
60 70 80 90 100
LWKKAHAESP PCVNSKKPDT EDKERNKDSG EVSSREGRAA DAAAEPYPED
110 120 130 140 150
KKKKRSGFRD RKVMEYENRI RAYSTPDKIF RYFATLKVIN EPGETEVFMT
160 170 180 190 200
PQDFVRSITP NEKQPEHLGL DQYIIKRFDG KKIAQEREKF ADEGSIFYSL
210 220 230 240 250
GECGLISFSD YIFLTTVLST PQRNFEIAFK MFDLNGDGEV DMEEFEQVQS
260 270 280 290 300
IIRSQTSMGM RHRDRPTTGN TLKSGLCSAL TTYFFGADLK GKLTIKNFLE
310 320 330 340 350
FQRKLQHDVL KLEFERHDPV DGRISERQFG GMLLAYSGVQ SKKLTAMQRQ
360 370 380 390 400
LKKHFKDGKG LTFQEVENFF TFLKNINDVD TALSFYHMAG ASLDKVTMQQ
410 420 430 440 450
VARTVAKVEL SDHVCDVVFA LFDCDGNGEL SNKEFVSIMK QRLMRGLEKP
460 470
KDMGFTRLMQ AMWKCAQETA WDFALPK
Length:477
Mass (Da):54,353
Last modified:March 1, 2002 - v1
Checksum:iD4088D7540E70E5D
GO
Isoform 2 (identifier: Q8VCX5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-181: K → KEFWQTE

Note: No experimental confirmation available.
Show »
Length:483
Mass (Da):55,174
Checksum:i5618EBC4D78FB97E
GO
Isoform 3 (identifier: Q8VCX5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-181: K → KEFWQ

Note: No experimental confirmation available.
Show »
Length:481
Mass (Da):54,944
Checksum:i6DB742577FAEAE0D
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q9E0E9Q9E0_MOUSE
Calcium uptake protein 1, mitochond...
Micu1
234Annotation score:
F6Z1Z9F6Z1Z9_MOUSE
Calcium uptake protein 1, mitochond...
Micu1
78Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19W → C in BAC36895 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_031982181K → KEFWQTE in isoform 2. 1 Publication1
Alternative sequenceiVSP_031983181K → KEFWQ in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046049 mRNA Translation: BAC32581.1
AK049521 mRNA Translation: BAC33792.1
AK050113 mRNA Translation: BAC34073.1
AK052485 mRNA Translation: BAC35013.1
AK077605 mRNA Translation: BAC36895.1
BC018320 mRNA Translation: AAH18320.1
BC023022 mRNA Translation: AAH23022.1
BC023042 mRNA Translation: AAH23042.1
BC026566 mRNA Translation: AAH26566.1
CCDSiCCDS35909.1 [Q8VCX5-1]
CCDS78817.1 [Q8VCX5-2]
CCDS78818.1 [Q8VCX5-3]
RefSeqiNP_001278371.1, NM_001291442.1 [Q8VCX5-2]
NP_001278372.1, NM_001291443.1 [Q8VCX5-3]
NP_659071.1, NM_144822.3 [Q8VCX5-1]
UniGeneiMm.27199

Genome annotation databases

EnsembliENSMUST00000020311; ENSMUSP00000020311; ENSMUSG00000020111 [Q8VCX5-2]
ENSMUST00000092508; ENSMUSP00000090166; ENSMUSG00000020111 [Q8VCX5-3]
ENSMUST00000165563; ENSMUSP00000126597; ENSMUSG00000020111 [Q8VCX5-1]
ENSMUST00000179709; ENSMUSP00000136567; ENSMUSG00000020111 [Q8VCX5-1]
GeneIDi216001
KEGGimmu:216001
UCSCiuc007fdx.2 mouse [Q8VCX5-1]
uc007fdy.2 mouse [Q8VCX5-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046049 mRNA Translation: BAC32581.1
AK049521 mRNA Translation: BAC33792.1
AK050113 mRNA Translation: BAC34073.1
AK052485 mRNA Translation: BAC35013.1
AK077605 mRNA Translation: BAC36895.1
BC018320 mRNA Translation: AAH18320.1
BC023022 mRNA Translation: AAH23022.1
BC023042 mRNA Translation: AAH23042.1
BC026566 mRNA Translation: AAH26566.1
CCDSiCCDS35909.1 [Q8VCX5-1]
CCDS78817.1 [Q8VCX5-2]
CCDS78818.1 [Q8VCX5-3]
RefSeqiNP_001278371.1, NM_001291442.1 [Q8VCX5-2]
NP_001278372.1, NM_001291443.1 [Q8VCX5-3]
NP_659071.1, NM_144822.3 [Q8VCX5-1]
UniGeneiMm.27199

3D structure databases

ProteinModelPortaliQ8VCX5
SMRiQ8VCX5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000126597

PTM databases

iPTMnetiQ8VCX5
PhosphoSitePlusiQ8VCX5

Proteomic databases

EPDiQ8VCX5
PaxDbiQ8VCX5
PeptideAtlasiQ8VCX5
PRIDEiQ8VCX5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020311; ENSMUSP00000020311; ENSMUSG00000020111 [Q8VCX5-2]
ENSMUST00000092508; ENSMUSP00000090166; ENSMUSG00000020111 [Q8VCX5-3]
ENSMUST00000165563; ENSMUSP00000126597; ENSMUSG00000020111 [Q8VCX5-1]
ENSMUST00000179709; ENSMUSP00000136567; ENSMUSG00000020111 [Q8VCX5-1]
GeneIDi216001
KEGGimmu:216001
UCSCiuc007fdx.2 mouse [Q8VCX5-1]
uc007fdy.2 mouse [Q8VCX5-3]

Organism-specific databases

CTDi10367
MGIiMGI:2384909 Micu1

Phylogenomic databases

eggNOGiKOG2643 Eukaryota
ENOG410ZSC1 LUCA
GeneTreeiENSGT00530000063089
HOVERGENiHBG107586
InParanoidiQ8VCX5
KOiK22827
OMAiERKEPNE
OrthoDBiEOG091G05UE
PhylomeDBiQ8VCX5
TreeFamiTF313815

Enzyme and pathway databases

ReactomeiR-MMU-8949215 Mitochondrial calcium ion transport
R-MMU-8949664 Processing of SMDT1

Miscellaneous databases

PROiPR:Q8VCX5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020111 Expressed in 274 organ(s), highest expression level in colon
CleanExiMM_CBARA1
ExpressionAtlasiQ8VCX5 baseline and differential
GenevisibleiQ8VCX5 MM

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR039800 MICU1/2/3
PANTHERiPTHR12294 PTHR12294, 1 hit
PfamiView protein in Pfam
PF13202 EF-hand_5, 1 hit
PF13833 EF-hand_8, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 2 hits
SUPFAMiSSF47473 SSF47473, 2 hits
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiMICU1_MOUSE
AccessioniPrimary (citable) accession number: Q8VCX5
Secondary accession number(s): Q8BK07, Q8BL84, Q8R1W0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2002
Last modified: November 7, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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