UniProtKB - O75746 (CMC1_HUMAN)
Calcium-binding mitochondrial carrier protein Aralar1
SLC25A12
Functioni
Mitochondrial and calcium-binding carrier that catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane (PubMed:11566871, PubMed:25410934).
May have a function in the urea cycle (PubMed:11566871).
2 PublicationsMiscellaneous
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 65 | Calcium 1Combined sources1 Publication | 1 | |
Metal bindingi | 67 | Calcium 1Combined sources1 Publication | 1 | |
Metal bindingi | 69 | Calcium 1Combined sources | 1 | |
Metal bindingi | 71 | Calcium 1; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 76 | Calcium 1Combined sources1 Publication | 1 | |
Metal bindingi | 99 | Calcium 2Curated | 1 | |
Metal bindingi | 101 | Calcium 2Curated | 1 | |
Metal bindingi | 103 | Calcium 2Curated | 1 | |
Metal bindingi | 105 | Calcium 2Curated | 1 | |
Metal bindingi | 170 | Calcium 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 172 | Calcium 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 174 | Calcium 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 176 | Calcium 3PROSITE-ProRule annotation | 1 | |
Metal bindingi | 181 | Calcium 3PROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- acidic amino acid transmembrane transporter activity Source: Reactome
- calcium ion binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- L-aspartate transmembrane transporter activity Source: UniProtKB
- L-glutamate transmembrane transporter activity Source: UniProtKB
- transmembrane transporter activity Source: GO_Central
GO - Biological processi
- aspartate family amino acid metabolic process Source: Reactome
- aspartate transmembrane transport Source: UniProtKB
- gluconeogenesis Source: Reactome
- glutamate biosynthetic process Source: Ensembl
- L-glutamate transmembrane transport Source: UniProtKB
- malate-aspartate shuttle Source: UniProtKB
- negative regulation of glucose catabolic process to lactate via pyruvate Source: Ensembl
- positive regulation of ATP biosynthetic process Source: Ensembl
- positive regulation of glucose metabolic process Source: Ensembl
- positive regulation of myelination Source: Ensembl
- response to calcium ion Source: UniProtKB
Keywordsi
Biological process | Transport |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | O75746 |
Reactomei | R-HSA-1268020, Mitochondrial protein import R-HSA-70263, Gluconeogenesis R-HSA-8963693, Aspartate and asparagine metabolism |
SignaLinki | O75746 |
SIGNORi | O75746 |
Protein family/group databases
TCDBi | 2.A.29.14.1, the mitochondrial carrier (mc) family |
Names & Taxonomyi
Protein namesi | Recommended name: Calcium-binding mitochondrial carrier protein Aralar1Alternative name(s): Mitochondrial aspartate glutamate carrier 1 Solute carrier family 25 member 12 |
Gene namesi | Name:SLC25A12 Synonyms:ARALAR1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10982, SLC25A12 |
MIMi | 603667, gene |
neXtProti | NX_O75746 |
VEuPathDBi | HostDB:ENSG00000115840 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 1 Publication; Multi-pass membrane protein 1 Publication
Mitochondrion
- mitochondrial inner membrane Source: Reactome
- mitochondrion Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 330 – 347 | Helical; Name=11 PublicationAdd BLAST | 18 | |
Transmembranei | 391 – 410 | Helical; Name=21 PublicationAdd BLAST | 20 | |
Transmembranei | 434 – 447 | Helical; Name=31 PublicationAdd BLAST | 14 | |
Transmembranei | 483 – 502 | Helical; Name=41 PublicationAdd BLAST | 20 | |
Transmembranei | 522 – 539 | Helical; Name=51 PublicationAdd BLAST | 18 | |
Transmembranei | 579 – 598 | Helical; Name=61 PublicationAdd BLAST | 20 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Involvement in diseasei
Developmental and epileptic encephalopathy 39 (DEE39)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071976 | 353 | R → Q in DEE39; significant loss in ability to transport aspartate or glutamate. 1 PublicationCorresponds to variant dbSNP:rs886037851EnsemblClinVar. | 1 | |
Natural variantiVAR_063253 | 590 | Q → R in DEE39; the mutant protein is unable to transport aspartate or glutamate although it is able to integrate normally into the inner mitochondrial membrane. 1 PublicationCorresponds to variant dbSNP:rs121434396EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 8604 |
MalaCardsi | SLC25A12 |
MIMi | 612949, phenotype |
OpenTargetsi | ENSG00000115840 |
Orphaneti | 353217, Epileptic encephalopathy with global cerebral demyelination |
PharmGKBi | PA35858 |
Miscellaneous databases
Pharosi | O75746, Tbio |
Chemistry databases
DrugBanki | DB00128, Aspartic acid |
DrugCentrali | O75746 |
Genetic variation databases
BioMutai | SLC25A12 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000090598 | 2 – 678 | Calcium-binding mitochondrial carrier protein Aralar1Add BLAST | 677 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources1 Publication | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | O75746 |
jPOSTi | O75746 |
MassIVEi | O75746 |
MaxQBi | O75746 |
PaxDbi | O75746 |
PeptideAtlasi | O75746 |
PRIDEi | O75746 |
ProteomicsDBi | 3583 50177 [O75746-1] |
PTM databases
GlyGeni | O75746, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O75746 |
PhosphoSitePlusi | O75746 |
SwissPalmi | O75746 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000115840, Expressed in muscle of leg and 239 other tissues |
ExpressionAtlasi | O75746, baseline and differential |
Genevisiblei | O75746, HS |
Organism-specific databases
HPAi | ENSG00000115840, Tissue enhanced (skeletal) |
Interactioni
Subunit structurei
Homodimer (via N-terminus).
1 PublicationBinary interactionsi
O75746
With | #Exp. | IntAct |
---|---|---|
MAVS [Q7Z434] | 3 | EBI-1047585,EBI-995373 |
GO - Molecular functioni
- identical protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114164, 223 interactors |
IntActi | O75746, 61 interactors |
MINTi | O75746 |
STRINGi | 9606.ENSP00000388658 |
Miscellaneous databases
RNActi | O75746, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O75746 |
SMRi | O75746 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 65 – 76 | EF-hand 1CuratedAdd BLAST | 12 | |
Domaini | 86 – 121 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 125 – 155 | EF-hand 3CuratedAdd BLAST | 31 | |
Domaini | 157 – 192 | EF-hand 4PROSITE-ProRule annotationAdd BLAST | 36 | |
Repeati | 324 – 416 | Solcar 1PROSITE-ProRule annotationAdd BLAST | 93 | |
Repeati | 424 – 508 | Solcar 2PROSITE-ProRule annotationAdd BLAST | 85 | |
Repeati | 516 – 604 | Solcar 3PROSITE-ProRule annotationAdd BLAST | 89 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 294 | N-terminal domain1 PublicationAdd BLAST | 293 | |
Regioni | 295 – 310 | Linker loop domain1 PublicationAdd BLAST | 16 | |
Regioni | 320 – 612 | Carrier domain1 PublicationAdd BLAST | 293 | |
Regioni | 613 – 675 | C-terminal domain1 PublicationAdd BLAST | 63 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0751, Eukaryota |
GeneTreei | ENSGT00940000155963 |
HOGENOMi | CLU_014931_3_0_1 |
InParanoidi | O75746 |
OMAi | DWDCEWA |
OrthoDBi | 1007928at2759 |
PhylomeDBi | O75746 |
TreeFami | TF313209 |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR002067, Mit_carrier IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00926, MITOCARRIER |
SMARTi | View protein in SMART SM00054, EFh, 3 hits |
SUPFAMi | SSF103506, SSF103506, 1 hit SSF47473, SSF47473, 2 hits |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 1 hit PS50222, EF_HAND_2, 2 hits PS50920, SOLCAR, 3 hits |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAVKVQTTKR GDPHELRNIF LQYASTEVDG ERYMTPEDFV QRYLGLYNDP
60 70 80 90 100
NSNPKIVQLL AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK
110 120 130 140 150
SGNGEVTFEN VKEIFGQTII HHHIPFNWDC EFIRLHFGHN RKKHLNYTEF
160 170 180 190 200
TQFLQELQLE HARQAFALKD KSKSGMISGL DFSDIMVTIR SHMLTPFVEE
210 220 230 240 250
NLVSAAGGSI SHQVSFSYFN AFNSLLNNME LVRKIYSTLA GTRKDVEVTK
260 270 280 290 300
EEFAQSAIRY GQVTPLEIDI LYQLADLYNA SGRLTLADIE RIAPLAEGAL
310 320 330 340 350
PYNLAELQRQ QSPGLGRPIW LQIAESAYRF TLGSVAGAVG ATAVYPIDLV
360 370 380 390 400
KTRMQNQRGS GSVVGELMYK NSFDCFKKVL RYEGFFGLYR GLIPQLIGVA
410 420 430 440 450
PEKAIKLTVN DFVRDKFTRR DGSVPLPAEV LAGGCAGGSQ VIFTNPLEIV
460 470 480 490 500
KIRLQVAGEI TTGPRVSALN VLRDLGIFGL YKGAKACFLR DIPFSAIYFP
510 520 530 540 550
VYAHCKLLLA DENGHVGGLN LLAAGAMAGV PAASLVTPAD VIKTRLQVAA
560 570 580 590 600
RAGQTTYSGV IDCFRKILRE EGPSAFWKGT AARVFRSSPQ FGVTLVTYEL
610 620 630 640 650
LQRWFYIDFG GLKPAGSEPT PKSRIADLPP ANPDHIGGYR LATATFAGIE
660 670
NKFGLYLPKF KSPSVAVVQP KAAVAATQ
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB4DGK6 | B4DGK6_HUMAN | Calcium-binding mitochondrial carri... | SLC25A12 | 210 | Annotation score: | ||
H0YFB2 | H0YFB2_HUMAN | Calcium-binding mitochondrial carri... | SLC25A12 | 175 | Annotation score: | ||
F8W9J0 | F8W9J0_HUMAN | Calcium-binding mitochondrial carri... | SLC25A12 | 87 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 596 – 597 | VT → AH in CAA74834 (PubMed:9722566).Curated | 2 | |
Sequence conflicti | 600 | L → V in CAA74834 (PubMed:9722566).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071976 | 353 | R → Q in DEE39; significant loss in ability to transport aspartate or glutamate. 1 PublicationCorresponds to variant dbSNP:rs886037851EnsemblClinVar. | 1 | |
Natural variantiVAR_047917 | 473 | R → Q. Corresponds to variant dbSNP:rs35565687EnsemblClinVar. | 1 | |
Natural variantiVAR_063253 | 590 | Q → R in DEE39; the mutant protein is unable to transport aspartate or glutamate although it is able to integrate normally into the inner mitochondrial membrane. 1 PublicationCorresponds to variant dbSNP:rs121434396EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054469 | 1 – 108 | MAVKV…GEVTF → M in isoform 2. 1 PublicationAdd BLAST | 108 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y14494 mRNA Translation: CAA74834.1 AJ496568 mRNA Translation: CAD43090.1 AK091071 mRNA Translation: BAG52276.1 AC015976 Genomic DNA No translation available. AC068039 Genomic DNA Translation: AAY24134.1 AC114745 Genomic DNA No translation available. CH471058 Genomic DNA Translation: EAX11196.1 BC016932 mRNA Translation: AAH16932.1 |
CCDSi | CCDS33327.1 [O75746-1] |
RefSeqi | NP_003696.2, NM_003705.4 [O75746-1] |
Genome annotation databases
Ensembli | ENST00000422440.7; ENSP00000388658.2; ENSG00000115840.14 |
GeneIDi | 8604 |
KEGGi | hsa:8604 |
MANE-Selecti | ENST00000422440.7; ENSP00000388658.2; NM_003705.5; NP_003696.2 |
UCSCi | uc002uhh.4, human [O75746-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y14494 mRNA Translation: CAA74834.1 AJ496568 mRNA Translation: CAD43090.1 AK091071 mRNA Translation: BAG52276.1 AC015976 Genomic DNA No translation available. AC068039 Genomic DNA Translation: AAY24134.1 AC114745 Genomic DNA No translation available. CH471058 Genomic DNA Translation: EAX11196.1 BC016932 mRNA Translation: AAH16932.1 |
CCDSi | CCDS33327.1 [O75746-1] |
RefSeqi | NP_003696.2, NM_003705.4 [O75746-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4P5X | X-ray | 2.26 | A | 2-311 | [»] | |
4P60 | X-ray | 2.40 | A/B | 2-311 | [»] | |
AlphaFoldDBi | O75746 | |||||
SMRi | O75746 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114164, 223 interactors |
IntActi | O75746, 61 interactors |
MINTi | O75746 |
STRINGi | 9606.ENSP00000388658 |
Chemistry databases
DrugBanki | DB00128, Aspartic acid |
DrugCentrali | O75746 |
Protein family/group databases
TCDBi | 2.A.29.14.1, the mitochondrial carrier (mc) family |
PTM databases
GlyGeni | O75746, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O75746 |
PhosphoSitePlusi | O75746 |
SwissPalmi | O75746 |
Genetic variation databases
BioMutai | SLC25A12 |
Proteomic databases
EPDi | O75746 |
jPOSTi | O75746 |
MassIVEi | O75746 |
MaxQBi | O75746 |
PaxDbi | O75746 |
PeptideAtlasi | O75746 |
PRIDEi | O75746 |
ProteomicsDBi | 3583 50177 [O75746-1] |
Protocols and materials databases
Antibodypediai | 33855, 226 antibodies from 26 providers |
DNASUi | 8604 |
Genome annotation databases
Ensembli | ENST00000422440.7; ENSP00000388658.2; ENSG00000115840.14 |
GeneIDi | 8604 |
KEGGi | hsa:8604 |
MANE-Selecti | ENST00000422440.7; ENSP00000388658.2; NM_003705.5; NP_003696.2 |
UCSCi | uc002uhh.4, human [O75746-1] |
Organism-specific databases
CTDi | 8604 |
DisGeNETi | 8604 |
GeneCardsi | SLC25A12 |
HGNCi | HGNC:10982, SLC25A12 |
HPAi | ENSG00000115840, Tissue enhanced (skeletal) |
MalaCardsi | SLC25A12 |
MIMi | 603667, gene 612949, phenotype |
neXtProti | NX_O75746 |
OpenTargetsi | ENSG00000115840 |
Orphaneti | 353217, Epileptic encephalopathy with global cerebral demyelination |
PharmGKBi | PA35858 |
VEuPathDBi | HostDB:ENSG00000115840 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0751, Eukaryota |
GeneTreei | ENSGT00940000155963 |
HOGENOMi | CLU_014931_3_0_1 |
InParanoidi | O75746 |
OMAi | DWDCEWA |
OrthoDBi | 1007928at2759 |
PhylomeDBi | O75746 |
TreeFami | TF313209 |
Enzyme and pathway databases
PathwayCommonsi | O75746 |
Reactomei | R-HSA-1268020, Mitochondrial protein import R-HSA-70263, Gluconeogenesis R-HSA-8963693, Aspartate and asparagine metabolism |
SignaLinki | O75746 |
SIGNORi | O75746 |
Miscellaneous databases
BioGRID-ORCSi | 8604, 9 hits in 1076 CRISPR screens |
ChiTaRSi | SLC25A12, human |
GeneWikii | SLC25A12 |
GenomeRNAii | 8604 |
Pharosi | O75746, Tbio |
PROi | PR:O75746 |
RNActi | O75746, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115840, Expressed in muscle of leg and 239 other tissues |
ExpressionAtlasi | O75746, baseline and differential |
Genevisiblei | O75746, HS |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR002067, Mit_carrier IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00926, MITOCARRIER |
SMARTi | View protein in SMART SM00054, EFh, 3 hits |
SUPFAMi | SSF103506, SSF103506, 1 hit SSF47473, SSF47473, 2 hits |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 1 hit PS50222, EF_HAND_2, 2 hits PS50920, SOLCAR, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | CMC1_HUMAN | |
Accessioni | O75746Primary (citable) accession number: O75746 Secondary accession number(s): B3KR64, Q96AM8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2001 |
Last sequence update: | September 23, 2008 | |
Last modified: | May 25, 2022 | |
This is version 201 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families