O75746 (CMC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	678 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8
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 process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gluconeogenesis 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_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB mitochondrial inner membrane Traceable author statement. Source: Reactome
Molecular_function	L-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 678	678	Calcium-binding mitochondrial carrier protein Aralar1		PRO_0000090598
Regions
	Transmembrane	330 – 347	18	Helical; Name=1; Potential
	Transmembrane	391 – 410	20	Helical; Name=2; Potential
	Transmembrane	434 – 447	14	Helical; Name=3; Potential
	Transmembrane	483 – 502	20	Helical; Name=4; Potential
	Transmembrane	522 – 539	18	Helical; Name=5; Potential
	Transmembrane	579 – 598	20	Helical; Name=6; Potential
	Domain	65 – 76	12	EF-hand 1
	Domain	86 – 121	36	EF-hand 2
	Domain	125 – 155	31	EF-hand 3
	Domain	157 – 192	36	EF-hand 4
	Repeat	324 – 416	93	Solcar 1
	Repeat	424 – 508	85	Solcar 2
	Repeat	516 – 604	89	Solcar 3
	Calcium binding	65 – 76	12	1 Ref.1
	Calcium binding	99 – 110	12	2 Ref.1
	Calcium binding	170 – 181	12	3 Ref.1
Natural variations
	Natural variant	473	1	R → Q. Corresponds to variant rs35565687 [ dbSNP | Ensembl ].		VAR_047917
	Natural variant	590	1	Q → 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.8		VAR_063253
Experimental info
	Sequence conflict	596 – 597	2	VT → AH in CAA74834. Ref.1
	Sequence conflict	600	1	L → V in CAA74834. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75746 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: D00A7D3D4244539F	FASTA	678	74,762
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
[9]	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.
IPI	IPI00386271.
RefSeq	NP_003696.2. NM_003705.4.
UniGene	Hs.470608.
3D structure databases
ProteinModelPortal	O75746.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75746. 7 interactions.
STRING	9606.ENSP00000388658.
Protein family/group databases
TCDB	2.A.29.14.1. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	O75746.
Proteomic databases
PaxDb	O75746.
PRIDE	O75746.
Protocols and materials databases
DNASU	8604.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000422440; ENSP00000388658; ENSG00000115840.
GeneID	8604.
KEGG	hsa:8604.
UCSC	uc002uhh.2. human.
Organism-specific databases
CTD	8604.
GeneCards	GC02M172604.
H-InvDB	HIX0002590.
HGNC	HGNC:10982. SLC25A12.
HPA	HPA035333.
MIM	603667. gene. 612949. phenotype.
neXtProt	NX_O75746.
PharmGKB	PA35858.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG292991.
HOGENOM	HOG000180633.
HOVERGEN	HBG005350.
InParanoid	O75746.
KO	K15105.
OMA	DPQELRN.
OrthoDB	EOG4BVRT4.
PhylomeDB	O75746.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	O75746.
Bgee	O75746.
CleanEx	HS_SLC25A12.
Genevestigator	O75746.
GermOnline	ENSG00000115840. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 2 hits. 1.50.40.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR002067. Mit_carrier. IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Pfam	PF13405. EF_hand_4. 1 hit. PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00926. MITOCARRIER.
SMART	SM00054. EFh. 3 hits. [Graphical view]
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 2 hits. PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00128. L-Aspartic Acid.
GenomeRNAi	8604.
NextBio	32241.
SOURCE	Search...

Entry information

Entry name

CMC1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.