Reviewed, UniProtKB/Swiss-Prot O75746 (CMC1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	678 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium-dependent mitochondrial aspartate and glutamate carrier. 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
Miscellaneous	Binds calcium.
Sequence similarities	Belongs to the mitochondrial carrier family. 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
Domain	Repeat Transmembrane
Ligand	Calcium
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	L-glutamate transport Ref.2 Inferred from direct assay. Source: UniProtKB aspartate transport Ref.2 Inferred from direct assay. Source: UniProtKB malate-aspartate shuttle Ref.2 Inferred from direct assay. Source: UniProtKB response to calcium ion Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	L-aspartate transmembrane transporter activity Ref.2 Inferred from direct assay. Source: UniProtKB L-glutamate transmembrane transporter activity Ref.2 Inferred from direct assay. Source: UniProtKB calcium ion binding Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C20orf24	Q9BUV8	1	EBI-1047585,EBI-1050079
PELO	Q9BRX2	1	EBI-1047585,EBI-1043580
PHLDA3	Q9Y5J5	1	EBI-1047585,EBI-1055859
PNKP	Q96T60	1	EBI-1047585,EBI-1045072

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	1 Potential
	Transmembrane	391 – 410	20	2 Potential
	Transmembrane	434 – 447	14	3 Potential
	Transmembrane	483 – 502	20	4 Potential
	Transmembrane	522 – 539	18	5 Potential
	Transmembrane	579 – 598	20	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: dbSNP rs35565687.		VAR_047917
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)
	O75746-1 [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: 9722566] [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: 11566871] [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: 15815621] [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: 15489334] [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: 10369257] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.470608
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O75746. 5 interactions.
Protein family/group databases
TCDB	2.A.29.14.1. mitochondrial carrier (MC) family.
Proteomic databases
PRIDE	O75746.
Genome annotation databases
Ensembl	ENSG00000115840. Homo sapiens. [Contig view]
GeneID	8604.
KEGG	hsa:8604.
Organism-specific databases
GeneCards	GC02M172349.
H-InvDB	HIX0002590.
HGNC	HGNC:10982. SLC25A12.
MIM	603667. gene.
PharmGKB	PA35858.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O75746.
HOVERGEN	O75746.
OMA	O75746. QELRNIF.
Enzyme and pathway databases
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	O75746.
Bgee	O75746.
CleanEx	HS_SLC25A12.
GermOnline	ENSG00000115840. Homo sapiens.
Family and domain databases
InterPro	IPR002113. Aden_trnslctor. IPR011992. EF-Hand_type. IPR018247. EF_HAND_1. IPR018249. EF_HAND_2. IPR002048. EF_hand_Ca_bd. IPR002067. Mit_carrier. IPR001993. Mitochondria_substrate_carrier. IPR018108. Mitochondrial_sb/sol_carrier. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
PANTHER	PTHR11896. Mitoch_carrier. 1 hit.
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00927. ADPTRNSLCASE. PR00926. MITOCARRIER.
SMART	SM00054. EFh. 3 hits. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 2 hits. PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00128. L-Aspartic Acid.
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:	July 7, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)