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Protein

Mitochondrial proton/calcium exchanger protein

Gene

LETM1

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

Functioni

Mitochondrial proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (PubMed:18628306). Required for the maintenance of the tubular shape and cristae organization (PubMed:18628306). In contrast to SLC8B1/NCLX, does not constitute the major factor for mitochondrial calcium extrusion (PubMed:24898248).3 Publications

Activity regulationi

Inhibited by ruthenium red or its derivative Ru360.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi676 – 688PROSITE-ProRule annotationAdd BLAST13

GO - Molecular functioni

  • calcium:proton antiporter activity Source: UniProtKB
  • calcium ion binding Source: ProtInc
  • ribosome binding Source: InterPro

GO - Biological processi

Keywordsi

Biological processAntiport, Calcium transport, Ion transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-8949215 Mitochondrial calcium ion transport

Protein family/group databases

TCDBi2.A.97.1.1 the mitochondrial inner membrane k(+)/h(+) and ca(2+)/h(+) exchanger (letm1) family

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial proton/calcium exchanger proteinCurated
Alternative name(s):
Leucine zipper-EF-hand-containing transmembrane protein 1
Gene namesi
Name:LETM1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000168924.14
HGNCiHGNC:6556 LETM1
MIMi604407 gene
neXtProtiNX_O95202

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
Topological domaini116 – 208Mitochondrial intermembraneBy similarityAdd BLAST93
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 739Mitochondrial matrixBy similarityAdd BLAST510

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3954
MalaCardsiLETM1
OpenTargetsiENSG00000168924
Orphaneti280 Wolf-Hirschhorn syndrome
PharmGKBiPA30335

Polymorphism and mutation databases

BioMutaiLETM1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 115MitochondrionSequence analysisAdd BLAST115
ChainiPRO_0000017694116 – 739Mitochondrial proton/calcium exchanger proteinAdd BLAST624

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei597N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO95202
MaxQBiO95202
PaxDbiO95202
PeptideAtlasiO95202
PRIDEiO95202
ProteomicsDBi50710
50711 [O95202-2]
50712 [O95202-3]

PTM databases

iPTMnetiO95202
PhosphoSitePlusiO95202
SwissPalmiO95202

Expressioni

Gene expression databases

BgeeiENSG00000168924 Expressed in 206 organ(s), highest expression level in vagina
CleanExiHS_LETM1
GenevisibleiO95202 HS

Organism-specific databases

HPAiHPA011029
HPA011100

Interactioni

Subunit structurei

Homohexamer (By similarity). Can form 2 complexes: a major (300 kDa) and a minor complex (500-600 kDa) (PubMed:18628306). Interacts with BCS1L (PubMed:18628306).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PSMA3P257883EBI-1052895,EBI-348380

Protein-protein interaction databases

BioGridi110145, 30 interactors
IntActiO95202, 25 interactors
MINTiO95202
STRINGi9606.ENSP00000305653

Structurei

3D structure databases

ProteinModelPortaliO95202
SMRiO95202
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini252 – 537Letm1 RBDPROSITE-ProRule annotationAdd BLAST286
Domaini663 – 698EF-handPROSITE-ProRule annotationAdd BLAST36

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili115 – 136Sequence analysisAdd BLAST22
Coiled coili462 – 490Sequence analysisAdd BLAST29
Coiled coili537 – 627Sequence analysisAdd BLAST91
Coiled coili708 – 739Sequence analysisAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi18 – 21Poly-Pro4

Sequence similaritiesi

Belongs to the LETM1 family.Curated

Keywords - Domaini

Coiled coil, Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1043 Eukaryota
ENOG410XRSP LUCA
GeneTreeiENSGT00390000011225
HOGENOMiHOG000290246
HOVERGENiHBG052322
InParanoidiO95202
KOiK17800
OMAiARMTTEQ
OrthoDBiEOG091G034T
PhylomeDBiO95202
TreeFamiTF316321

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR011685 LETM1
IPR033122 LETM1_RBD
PfamiView protein in Pfam
PF07766 LETM1, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 1 hit
PS50222 EF_HAND_2, 1 hit
PS51758 LETM1_RBD, 1 hit

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
Isoform 1 (identifier: O95202-1) [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
MASILLRSCR GRAPARLPPP PRYTVPRGSP GDPAHLSCAS TLGLRNCLNV
60 70 80 90 100
PFGCCTPIHP VYTSSRGDHL GCWALRPECL RIVSRAPWTS TSVGFVAVGP
110 120 130 140 150
QCLPVRGWHS SRPVRDDSVV EKSLKSLKDK NKKLEEGGPV YSPPAEVVVK
160 170 180 190 200
KSLGQRVLDE LKHYYHGFRL LWIDTKIAAR MLWRILNGHS LTRRERRQFL
210 220 230 240 250
RICADLFRLV PFLVFVVVPF MEFLLPVAVK LFPNMLPSTF ETQSLKEERL
260 270 280 290 300
KKELRVKLEL AKFLQDTIEE MALKNKAAKG SATKDFSVFF QKIRETGERP
310 320 330 340 350
SNEEIMRFSK LFEDELTLDN LTRPQLVALC KLLELQSIGT NNFLRFQLTM
360 370 380 390 400
RLRSIKADDK LIAEEGVDSL NVKELQAACR ARGMRALGVT EDRLRGQLKQ
410 420 430 440 450
WLDLHLHQEI PTSLLILSRA MYLPDTLSPA DQLKSTLQTL PEIVAKEAQV
460 470 480 490 500
KVAEVEGEQV DNKAKLEATL QEEAAIQQEH REKELQKRSE VAKDFEPERV
510 520 530 540 550
VAAPQRPGTE PQPEMPDTVL QSETLKDTAP VLEGLKEEEI TKEEIDILSD
560 570 580 590 600
ACSKLQEQKK SLTKEKEELE LLKEDVQDYS EDLQEIKKEL SKTGEEKYVE
610 620 630 640 650
ESKASKRLTK RVQQMIGQID GLISQLEMDQ QAGKLAPANG MPTGENVISV
660 670 680 690 700
AELINAMKQV KHIPESKLTS LAAALDENKD GKVNIDDLVK VIELVDKEDV
710 720 730
HISTSQVAEI VATLEKEEKV EEKEKAKEKA EKEVAEVKS
Length:739
Mass (Da):83,354
Last modified:May 1, 1999 - v1
Checksum:i942E9138F299D94F
GO
Isoform 2 (identifier: O95202-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: MASILLRSCRGRAPARLPPPPRYTVPRGSPGDPAHLSCASTLGLRNCL → MRHTWPFR
     292-294: KIR → QVL
     295-739: Missing.

Note: May be due to intron retention. No experimental confirmation available.
Show »
Length:254
Mass (Da):29,291
Checksum:i5510CB4D93FFDDDE
GO
Isoform 3 (identifier: O95202-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     292-294: KIR → QVL
     295-739: Missing.

Note: May be due to intron retention.
Show »
Length:294
Mass (Da):33,245
Checksum:i5C8B98ECA4D20E42
GO

Sequence cautioni

The sequence CAB63769 differs from that shown. Reason: Erroneous translation. Incomplete prediction of CDS at the C-terminus.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0378141 – 48MASIL…LRNCL → MRHTWPFR in isoform 2. 2 PublicationsAdd BLAST48
Alternative sequenceiVSP_037815292 – 294KIR → QVL in isoform 2 and isoform 3. 2 Publications3
Alternative sequenceiVSP_037816295 – 739Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST445

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061025 mRNA Translation: AAD13138.1
AK293572 mRNA Translation: BAG57043.1
AK310563 mRNA No translation available.
AL133650 mRNA Translation: CAB63769.2 Sequence problems.
BC014500 mRNA Translation: AAH14500.1
BC021208 mRNA Translation: AAH21208.1
CCDSiCCDS3355.1 [O95202-1]
PIRiT43494
RefSeqiNP_036450.1, NM_012318.2 [O95202-1]
UniGeneiHs.120165

Genome annotation databases

EnsembliENST00000302787; ENSP00000305653; ENSG00000168924 [O95202-1]
GeneIDi3954
KEGGihsa:3954
UCSCiuc003gdv.3 human [O95202-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061025 mRNA Translation: AAD13138.1
AK293572 mRNA Translation: BAG57043.1
AK310563 mRNA No translation available.
AL133650 mRNA Translation: CAB63769.2 Sequence problems.
BC014500 mRNA Translation: AAH14500.1
BC021208 mRNA Translation: AAH21208.1
CCDSiCCDS3355.1 [O95202-1]
PIRiT43494
RefSeqiNP_036450.1, NM_012318.2 [O95202-1]
UniGeneiHs.120165

3D structure databases

ProteinModelPortaliO95202
SMRiO95202
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110145, 30 interactors
IntActiO95202, 25 interactors
MINTiO95202
STRINGi9606.ENSP00000305653

Protein family/group databases

TCDBi2.A.97.1.1 the mitochondrial inner membrane k(+)/h(+) and ca(2+)/h(+) exchanger (letm1) family

PTM databases

iPTMnetiO95202
PhosphoSitePlusiO95202
SwissPalmiO95202

Polymorphism and mutation databases

BioMutaiLETM1

Proteomic databases

EPDiO95202
MaxQBiO95202
PaxDbiO95202
PeptideAtlasiO95202
PRIDEiO95202
ProteomicsDBi50710
50711 [O95202-2]
50712 [O95202-3]

Protocols and materials databases

DNASUi3954
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302787; ENSP00000305653; ENSG00000168924 [O95202-1]
GeneIDi3954
KEGGihsa:3954
UCSCiuc003gdv.3 human [O95202-1]

Organism-specific databases

CTDi3954
DisGeNETi3954
EuPathDBiHostDB:ENSG00000168924.14
GeneCardsiLETM1
HGNCiHGNC:6556 LETM1
HPAiHPA011029
HPA011100
MalaCardsiLETM1
MIMi604407 gene
neXtProtiNX_O95202
OpenTargetsiENSG00000168924
Orphaneti280 Wolf-Hirschhorn syndrome
PharmGKBiPA30335
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1043 Eukaryota
ENOG410XRSP LUCA
GeneTreeiENSGT00390000011225
HOGENOMiHOG000290246
HOVERGENiHBG052322
InParanoidiO95202
KOiK17800
OMAiARMTTEQ
OrthoDBiEOG091G034T
PhylomeDBiO95202
TreeFamiTF316321

Enzyme and pathway databases

ReactomeiR-HSA-8949215 Mitochondrial calcium ion transport

Miscellaneous databases

ChiTaRSiLETM1 human
GeneWikiiLETM1
GenomeRNAii3954
PROiPR:O95202
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168924 Expressed in 206 organ(s), highest expression level in vagina
CleanExiHS_LETM1
GenevisibleiO95202 HS

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR011685 LETM1
IPR033122 LETM1_RBD
PfamiView protein in Pfam
PF07766 LETM1, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 1 hit
PS50222 EF_HAND_2, 1 hit
PS51758 LETM1_RBD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLETM1_HUMAN
AccessioniPrimary (citable) accession number: O95202
Secondary accession number(s): B4DED2, Q9UF65
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: May 1, 1999
Last modified: October 10, 2018
This is version 158 of the entry and version 1 of the sequence. See 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 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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