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O75746 (CMC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium-binding mitochondrial carrier protein Aralar1
Alternative name(s):
Mitochondrial aspartate glutamate carrier 1
Solute carrier family 25 member 12
Gene names
Name:SLC25A12
Synonyms:ARALAR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length678 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane. May have a function in the urea cycle. Ref.2

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

High levels in heart and skeletal muscle, low in brain and very low in kidney. Ref.1 Ref.6

Involvement in disease

Global cerebral hypomyelination (GCHM) [MIM:612949]: A disorder with onset in infancy and characterized by severe psychomotor retardation, hypotonia, seizures, hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Miscellaneous

Binds calcium.

Sequence similarities

Belongs to the mitochondrial carrier (TC 2.A.29) family. [View classification]

Contains 4 EF-hand domains.

Contains 3 Solcar repeats.

Ontologies

Keywords
   Biological processTransport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processL-glutamate transport

Inferred from direct assay Ref.2. Source: UniProtKB

aspartate transport

Inferred from direct assay Ref.2. Source: UniProtKB

carbohydrate metabolic process

Traceable author statement. Source: Reactome

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

malate-aspartate shuttle

Inferred from direct assay Ref.2. Source: UniProtKB

response to calcium ion

Inferred from direct assay Ref.2. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of membrane

Non-traceable author statement Ref.1. Source: UniProtKB

mitochondrial inner membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay Ref.2Ref.1. Source: UniProtKB

   Molecular_functionL-aspartate transmembrane transporter activity

Inferred from direct assay Ref.2. Source: UniProtKB

L-glutamate transmembrane transporter activity

Inferred from direct assay Ref.2. Source: UniProtKB

calcium ion binding

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 678677Calcium-binding mitochondrial carrier protein Aralar1
PRO_0000090598

Regions

Transmembrane330 – 34718Helical; Name=1; Potential
Transmembrane391 – 41020Helical; Name=2; Potential
Transmembrane434 – 44714Helical; Name=3; Potential
Transmembrane483 – 50220Helical; Name=4; Potential
Transmembrane522 – 53918Helical; Name=5; Potential
Transmembrane579 – 59820Helical; Name=6; Potential
Domain65 – 7612EF-hand 1
Domain86 – 12136EF-hand 2
Domain125 – 15531EF-hand 3
Domain157 – 19236EF-hand 4
Repeat324 – 41693Solcar 1
Repeat424 – 50885Solcar 2
Repeat516 – 60489Solcar 3
Calcium binding65 – 76121 Ref.1
Calcium binding99 – 110122 Ref.1
Calcium binding170 – 181123 Ref.1

Amino acid modifications

Modified residue21N-acetylalanine Ref.8

Natural variations

Natural variant4731R → Q.
Corresponds to variant rs35565687 [ dbSNP | Ensembl ].
VAR_047917
Natural variant5901Q → R in GCHM; the mutant protein is unable to transport aspartate or glutamate although it is able to integrate normally into the inner mitochondrial membrane. Ref.9
VAR_063253

Experimental info

Sequence conflict596 – 5972VT → AH in CAA74834. Ref.1
Sequence conflict6001L → V in CAA74834. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O75746 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: D00A7D3D4244539F

FASTA67874,762
        10         20         30         40         50         60 
MAVKVQTTKR GDPHELRNIF LQYASTEVDG ERYMTPEDFV QRYLGLYNDP NSNPKIVQLL 

        70         80         90        100        110        120 
AGVADQTKDG LISYQEFLAF ESVLCAPDSM FIVAFQLFDK SGNGEVTFEN VKEIFGQTII 

       130        140        150        160        170        180 
HHHIPFNWDC EFIRLHFGHN RKKHLNYTEF TQFLQELQLE HARQAFALKD KSKSGMISGL 

       190        200        210        220        230        240 
DFSDIMVTIR SHMLTPFVEE NLVSAAGGSI SHQVSFSYFN AFNSLLNNME LVRKIYSTLA 

       250        260        270        280        290        300 
GTRKDVEVTK EEFAQSAIRY GQVTPLEIDI LYQLADLYNA SGRLTLADIE RIAPLAEGAL 

       310        320        330        340        350        360 
PYNLAELQRQ QSPGLGRPIW LQIAESAYRF TLGSVAGAVG ATAVYPIDLV KTRMQNQRGS 

       370        380        390        400        410        420 
GSVVGELMYK NSFDCFKKVL RYEGFFGLYR GLIPQLIGVA PEKAIKLTVN DFVRDKFTRR 

       430        440        450        460        470        480 
DGSVPLPAEV LAGGCAGGSQ VIFTNPLEIV KIRLQVAGEI TTGPRVSALN VLRDLGIFGL 

       490        500        510        520        530        540 
YKGAKACFLR DIPFSAIYFP VYAHCKLLLA DENGHVGGLN LLAAGAMAGV PAASLVTPAD 

       550        560        570        580        590        600 
VIKTRLQVAA RAGQTTYSGV IDCFRKILRE EGPSAFWKGT AARVFRSSPQ FGVTLVTYEL 

       610        620        630        640        650        660 
LQRWFYIDFG GLKPAGSEPT PKSRIADLPP ANPDHIGGYR LATATFAGIE NKFGLYLPKF 

       670 
KSPSVAVVQP KAAVAATQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain."
Del Arco A., Satrustegui J.
J. Biol. Chem. 273:23327-23334(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CALCIUM-BINDING.
Tissue: Heart.
[2]"Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria."
Palmieri L., Pardo B., Lasorsa F.M., del Arco A., Kobayashi K., Iijima M., Runswick M.J., Walker J.E., Saheki T., Satrustegui J., Palmieri F.
EMBO J. 20:5060-5069(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Heart.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph.
[6]"The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein."
Kobayashi K., Sinasac D.S., Iijima M., Boright A.P., Begum L., Lee J.R., Yasuda T., Ikeda S., Hirano R., Terazono H., Crackower M.A., Kondo I., Tsui L.-C., Scherer S.W., Saheki T.
Nat. Genet. 22:159-163(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"AGC1 deficiency associated with global cerebral hypomyelination."
Wibom R., Lasorsa F.M., Tohonen V., Barbaro M., Sterky F.H., Kucinski T., Naess K., Jonsson M., Pierri C.L., Palmieri F., Wedell A.
N. Engl. J. Med. 361:489-495(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GCHM ARG-590, CHARACTERIZATION OF VARIANT GCHM ARG-590.
[10]Erratum
Wibom R., Lasorsa F.M., Tohonen V., Barbaro M., Sterky F.H., Kucinski T., Naess K., Jonsson M., Pierri C.L., Palmieri F., Wedell A.
N. Engl. J. Med. 361:731-731(2009)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y14494 mRNA. Translation: CAA74834.1.
AJ496568 mRNA. Translation: CAD43090.1.
AC068039 Genomic DNA. Translation: AAY24134.1.
CH471058 Genomic DNA. Translation: EAX11196.1.
BC016932 mRNA. Translation: AAH16932.1.
RefSeqNP_003696.2. NM_003705.4.
UniGeneHs.470608.

3D structure databases

ProteinModelPortalO75746.
SMRO75746. Positions 14-223, 330-602.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114164. 15 interactions.
IntActO75746. 10 interactions.
STRING9606.ENSP00000388658.

Chemistry

DrugBankDB00128. L-Aspartic Acid.

Protein family/group databases

TCDB2.A.29.14.1. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteO75746.

Proteomic databases

PaxDbO75746.
PRIDEO75746.

Protocols and materials databases

DNASU8604.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000422440; ENSP00000388658; ENSG00000115840.
GeneID8604.
KEGGhsa:8604.
UCSCuc002uhh.3. human.

Organism-specific databases

CTD8604.
GeneCardsGC02M172604.
H-InvDBHIX0002590.
HGNCHGNC:10982. SLC25A12.
HPAHPA035333.
MIM603667. gene.
612949. phenotype.
neXtProtNX_O75746.
Orphanet353217. Epileptic encephalopathy with global cerebral demyelination.
PharmGKBPA35858.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG292991.
HOGENOMHOG000180633.
HOVERGENHBG005350.
InParanoidO75746.
KOK15105.
OMAAQTMSQI.
OrthoDBEOG70GMF1.
PhylomeDBO75746.
TreeFamTF313209.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressO75746.
BgeeO75746.
CleanExHS_SLC25A12.
GenevestigatorO75746.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
1.50.40.10. 1 hit.
InterProIPR011992. 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]
PfamPF13405. EF-hand_6. 1 hit.
PF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSPR00926. MITOCARRIER.
SMARTSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMSSF103506. SSF103506. 1 hit.
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
PS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC25A12.
GenomeRNAi8604.
NextBio32241.
PROO75746.
SOURCESearch...

Entry information

Entry nameCMC1_HUMAN
AccessionPrimary (citable) accession number: O75746
Secondary accession number(s): Q96AM8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: September 23, 2008
Last modified: April 16, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM