Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcium-binding mitochondrial carrier protein Aralar1

Gene

SLC25A12

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

Functioni

Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane. May have a function in the urea cycle.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi65 – 761Add BLAST12
Calcium bindingi99 – 1102Add BLAST12
Calcium bindingi170 – 1813Add BLAST12

GO - Molecular functioni

  • acidic amino acid transmembrane transporter activity Source: Reactome
  • calcium ion binding Source: UniProtKB
  • L-aspartate transmembrane transporter activity Source: UniProtKB
  • L-glutamate transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  • aspartate transport Source: UniProtKB
  • gluconeogenesis Source: Reactome
  • L-glutamate transport Source: UniProtKB
  • malate-aspartate shuttle Source: UniProtKB
  • response to calcium ion Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115840-MONOMER.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-70263. Gluconeogenesis.

Protein family/group databases

TCDBi2.A.29.14.1. the mitochondrial carrier (mc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-binding mitochondrial carrier protein Aralar1
Alternative name(s):
Mitochondrial aspartate glutamate carrier 1
Solute carrier family 25 member 12
Gene namesi
Name:SLC25A12
Synonyms:ARALAR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:10982. SLC25A12.

Subcellular locationi

  • Mitochondrion inner membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei330 – 347Helical; Name=1Sequence analysisAdd BLAST18
Transmembranei391 – 410Helical; Name=2Sequence analysisAdd BLAST20
Transmembranei434 – 447Helical; Name=3Sequence analysisAdd BLAST14
Transmembranei483 – 502Helical; Name=4Sequence analysisAdd BLAST20
Transmembranei522 – 539Helical; Name=5Sequence analysisAdd BLAST18
Transmembranei579 – 598Helical; Name=6Sequence analysisAdd BLAST20

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
  • mitochondrial inner membrane Source: Reactome
  • mitochondrion Source: UniProtKB
  • myelin sheath Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Epileptic encephalopathy, early infantile, 39 (EIEE39)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE39 is characterized by global hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected. Inheritance is autosomal recessive.
See also OMIM:612949
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071976353R → Q in EIEE39; significant loss in ability to transport aspartate or glutamate. 1 Publication1
Natural variantiVAR_063253590Q → R in EIEE39; 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 rs121434396dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8604.
MalaCardsiSLC25A12.
MIMi612949. phenotype.
OpenTargetsiENSG00000115840.
Orphaneti353217. Epileptic encephalopathy with global cerebral demyelination.
PharmGKBiPA35858.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

Polymorphism and mutation databases

BioMutaiSLC25A12.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000905982 – 678Calcium-binding mitochondrial carrier protein Aralar1Add BLAST677

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO75746.
MaxQBiO75746.
PaxDbiO75746.
PeptideAtlasiO75746.
PRIDEiO75746.

PTM databases

iPTMnetiO75746.
PhosphoSitePlusiO75746.
SwissPalmiO75746.

Expressioni

Tissue specificityi

High levels in heart and skeletal muscle, low in brain and very low in kidney.2 Publications

Gene expression databases

BgeeiENSG00000115840.
CleanExiHS_SLC25A12.
ExpressionAtlasiO75746. baseline and differential.
GenevisibleiO75746. HS.

Organism-specific databases

HPAiHPA035333.
HPA035334.

Interactioni

Protein-protein interaction databases

BioGridi114164. 32 interactors.
IntActiO75746. 26 interactors.
STRINGi9606.ENSP00000388658.

Structurei

Secondary structure

1678
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 23Combined sources9
Beta strandi26 – 28Combined sources3
Beta strandi31 – 34Combined sources4
Helixi36 – 40Combined sources5
Turni41 – 43Combined sources3
Helixi54 – 64Combined sources11
Beta strandi69 – 71Combined sources3
Helixi74 – 84Combined sources11
Helixi89 – 98Combined sources10
Helixi108 – 117Combined sources10
Beta strandi128 – 130Combined sources3
Helixi131 – 137Combined sources7
Turni138 – 141Combined sources4
Helixi147 – 169Combined sources23
Beta strandi174 – 177Combined sources4
Helixi179 – 189Combined sources11
Helixi191 – 193Combined sources3
Helixi196 – 200Combined sources5
Helixi202 – 205Combined sources4
Turni206 – 210Combined sources5
Beta strandi212 – 215Combined sources4
Helixi216 – 227Combined sources12
Helixi229 – 238Combined sources10
Helixi250 – 257Combined sources8
Turni258 – 261Combined sources4
Helixi265 – 276Combined sources12
Beta strandi282 – 284Combined sources3
Helixi286 – 292Combined sources7
Beta strandi300 – 302Combined sources3
Turni305 – 307Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4P5XX-ray2.26A2-311[»]
4P60X-ray2.40A/B2-311[»]
ProteinModelPortaliO75746.
SMRiO75746.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 76EF-hand 1PROSITE-ProRule annotationAdd BLAST12
Domaini86 – 121EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini125 – 155EF-hand 3PROSITE-ProRule annotationAdd BLAST31
Domaini157 – 192EF-hand 4PROSITE-ProRule annotationAdd BLAST36
Repeati324 – 416Solcar 1Add BLAST93
Repeati424 – 508Solcar 2Add BLAST85
Repeati516 – 604Solcar 3Add BLAST89

Sequence similaritiesi

Contains 4 EF-hand domains.PROSITE-ProRule annotation
Contains 3 Solcar repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0751. Eukaryota.
ENOG410XNRM. LUCA.
GeneTreeiENSGT00530000062944.
HOGENOMiHOG000180633.
HOVERGENiHBG005350.
InParanoidiO75746.
KOiK15105.
OMAiDGYNHPL.
OrthoDBiEOG091G08GT.
PhylomeDBiO75746.
TreeFamiTF313209.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
1.50.40.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PfamiPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSiPR00926. MITOCARRIER.
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF103506. SSF103506. 1 hit.
SSF47473. SSF47473. 2 hits.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
PS50920. SOLCAR. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75746-1) [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
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
Length:678
Mass (Da):74,762
Last modified:September 23, 2008 - v2
Checksum:iD00A7D3D4244539F
GO
Isoform 2 (identifier: O75746-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: MAVKVQTTKR...DKSGNGEVTF → M

Note: No experimental confirmation available.
Show »
Length:571
Mass (Da):62,720
Checksum:i76841A88D6370748
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti596 – 597VT → AH in CAA74834 (PubMed:9722566).Curated2
Sequence conflicti600L → V in CAA74834 (PubMed:9722566).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071976353R → Q in EIEE39; significant loss in ability to transport aspartate or glutamate. 1 Publication1
Natural variantiVAR_047917473R → Q.Corresponds to variant rs35565687dbSNPEnsembl.1
Natural variantiVAR_063253590Q → R in EIEE39; 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 rs121434396dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0544691 – 108MAVKV…GEVTF → M in isoform 2. 1 PublicationAdd BLAST108

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.
CCDSiCCDS33327.1. [O75746-1]
RefSeqiNP_003696.2. NM_003705.4. [O75746-1]
UniGeneiHs.470608.

Genome annotation databases

EnsembliENST00000422440; ENSP00000388658; ENSG00000115840. [O75746-1]
GeneIDi8604.
KEGGihsa:8604.
UCSCiuc002uhh.4. human. [O75746-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS33327.1. [O75746-1]
RefSeqiNP_003696.2. NM_003705.4. [O75746-1]
UniGeneiHs.470608.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4P5XX-ray2.26A2-311[»]
4P60X-ray2.40A/B2-311[»]
ProteinModelPortaliO75746.
SMRiO75746.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114164. 32 interactors.
IntActiO75746. 26 interactors.
STRINGi9606.ENSP00000388658.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

Protein family/group databases

TCDBi2.A.29.14.1. the mitochondrial carrier (mc) family.

PTM databases

iPTMnetiO75746.
PhosphoSitePlusiO75746.
SwissPalmiO75746.

Polymorphism and mutation databases

BioMutaiSLC25A12.

Proteomic databases

EPDiO75746.
MaxQBiO75746.
PaxDbiO75746.
PeptideAtlasiO75746.
PRIDEiO75746.

Protocols and materials databases

DNASUi8604.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000422440; ENSP00000388658; ENSG00000115840. [O75746-1]
GeneIDi8604.
KEGGihsa:8604.
UCSCiuc002uhh.4. human. [O75746-1]

Organism-specific databases

CTDi8604.
DisGeNETi8604.
GeneCardsiSLC25A12.
H-InvDBHIX0002590.
HGNCiHGNC:10982. SLC25A12.
HPAiHPA035333.
HPA035334.
MalaCardsiSLC25A12.
MIMi603667. gene.
612949. phenotype.
neXtProtiNX_O75746.
OpenTargetsiENSG00000115840.
Orphaneti353217. Epileptic encephalopathy with global cerebral demyelination.
PharmGKBiPA35858.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0751. Eukaryota.
ENOG410XNRM. LUCA.
GeneTreeiENSGT00530000062944.
HOGENOMiHOG000180633.
HOVERGENiHBG005350.
InParanoidiO75746.
KOiK15105.
OMAiDGYNHPL.
OrthoDBiEOG091G08GT.
PhylomeDBiO75746.
TreeFamiTF313209.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115840-MONOMER.
ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-70263. Gluconeogenesis.

Miscellaneous databases

ChiTaRSiSLC25A12. human.
GeneWikiiSLC25A12.
GenomeRNAii8604.
PROiO75746.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115840.
CleanExiHS_SLC25A12.
ExpressionAtlasiO75746. baseline and differential.
GenevisibleiO75746. HS.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
1.50.40.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PfamiPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSiPR00926. MITOCARRIER.
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF103506. SSF103506. 1 hit.
SSF47473. SSF47473. 2 hits.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
PS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCMC1_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 162 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

Miscellaneous

Binds calcium.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.