Q9UJS0 (CMC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium-binding mitochondrial carrier protein Aralar2

Alternative name(s):
Citrin
Mitochondrial aspartate glutamate carrier 2
Solute carrier family 25 member 13

Gene names

Name:	SLC25A13
Synonyms:	ARALAR2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	675 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.6
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein Ref.2.
Tissue specificity	High levels in liver and low levels in kidney, pancreas, placenta, heart and brain. Ref.1 Ref.2
Involvement in disease	Defects in SLC25A13 are the cause of citrullinemia type 2 (CTLN2) [MIM:603471]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN2 is characterized by neuropsychiatric symptoms including abnormal behaviors, loss of memory, seizures and coma. Death can result from brain edema. Onset is sudden and usually between the ages of 20 and 50 years. Ref.1 Ref.5 Defects in SLC25A13 are the cause of neonatal intrahepatic cholestasis due to citrin deficiency (NICCD) [MIM:605814]. NICCD is a form of citrullinemia type 2 with neonatal onset. NICCD is characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. NICCD is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms. Ref.9
Miscellaneous	Binds calcium.
Sequence similarities	Belongs to the mitochondrial carrier family. Contains 4 EF-hand domains. Contains 3 Solcar repeats.
Sequence caution	The sequence AAB67049.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAB70112.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Intrahepatic cholestasis
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ATP biosynthetic process Inferred from direct assay. Source: UniProtKB gluconeogenesis Traceable author statement. Source: Reactome malate-aspartate shuttle Inferred from direct assay Ref.6. Source: UniProtKB response to calcium ion Inferred from direct assay Ref.6. Source: UniProtKB
Cellular component	integral to plasma membrane Non-traceable author statement Ref.2. Source: UniProtKB mitochondrial inner membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	L-aspartate transmembrane transporter activity Inferred from direct assay Ref.6. Source: UniProtKB L-glutamate transmembrane transporter activity Inferred from direct assay Ref.6. Source: UniProtKB calcium ion binding Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 675	675	Calcium-binding mitochondrial carrier protein Aralar2		PRO_0000090600
Regions
	Transmembrane	332 – 349	18	Helical; Name=1; Potential
	Transmembrane	393 – 412	20	Helical; Name=2; Potential
	Transmembrane	436 – 449	14	Helical; Name=3; Potential
	Transmembrane	485 – 504	20	Helical; Name=4; Potential
	Transmembrane	524 – 541	18	Helical; Name=5; Potential
	Transmembrane	581 – 600	20	Helical; Name=6; Potential
	Domain	51 – 86	36	EF-hand 1
	Domain	87 – 122	36	EF-hand 2
	Domain	125 – 157	33	EF-hand 3
	Domain	158 – 193	36	EF-hand 4
	Repeat	326 – 418	93	Solcar 1
	Repeat	426 – 510	85	Solcar 2
	Repeat	518 – 606	89	Solcar 3
	Calcium binding	66 – 77	12	1 Ref.2
	Calcium binding	100 – 111	12	2 Ref.2
	Calcium binding	171 – 182	12	3 Ref.2
Amino acid modifications
	Modified residue	484	1	N6-acetyllysine Ref.7
Natural variations
	Natural variant	141	1	E → K. Corresponds to variant rs1131697 [ dbSNP | Ensembl ].		VAR_050126
	Natural variant	232	1	L → I. Corresponds to variant rs10255762 [ dbSNP | Ensembl ].		VAR_050127
	Natural variant	601	1	E → K in NICCD. Ref.9		VAR_016601
Experimental info
	Sequence conflict	231 – 232	2	EL → VH in CAB62206. Ref.2
	Sequence conflict	311	1	Q → QQ in AAB67049. Ref.3
	Sequence conflict	532	1	M → T in CAB62206. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UJS0 [UniParc]. Last modified February 21, 2001. Version 2. Checksum: AD07EDBC6C68989B	FASTA	675	74,176
	10 20 30 40 50 60 MAAAKVALTK RADPAELRTI FLKYASIEKN GEFFMSPNDF VTRYLNIFGE SQPNPKTVEL 70 80 90 100 110 120 LSGVVDQTKD GLISFQEFVA FESVLCAPDA LFMVAFQLFD KAGKGEVTFE DVKQVFGQTT 130 140 150 160 170 180 IHQHIPFNWD SEFVQLHFGK ERKRHLTYAE FTQFLLEIQL EHAKQAFVQR DNARTGRVTA 190 200 210 220 230 240 IDFRDIMVTI RPHVLTPFVE ECLVAAAGGT TSHQVSFSYF NGFNSLLNNM ELIRKIYSTL 250 260 270 280 290 300 AGTRKDVEVT KEEFVLAAQK FGQVTPMEVD ILFQLADLYE PRGRMTLADI ERIAPLEEGT 310 320 330 340 350 360 LPFNLAEAQR QKASGDSARP VLLQVAESAY RFGLGSVAGA VGATAVYPID LVKTRMQNQR 370 380 390 400 410 420 STGSFVGELM YKNSFDCFKK VLRYEGFFGL YRGLLPQLLG VAPEKAIKLT VNDFVRDKFM 430 440 450 460 470 480 HKDGSVPLAA EILAGGCAGG SQVIFTNPLE IVKIRLQVAG EITTGPRVSA LSVVRDLGFF 490 500 510 520 530 540 GIYKGAKACF LRDIPFSAIY FPCYAHVKAS FANEDGQVSP GSLLLAGAIA GMPAASLVTP 550 560 570 580 590 600 ADVIKTRLQV AARAGQTTYS GVIDCFRKIL REEGPKALWK GAGARVFRSS PQFGVTLLTY 610 620 630 640 650 660 ELLQRWFYID FGGVKPMGSE PVPKSRINLP APNPDHVGGY KLAVATFAGI ENKFGLYLPL 670 FKPSVSTSKA IGGGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INVOLVEMENT IN CTLN2, TISSUE SPECIFICITY.
[2]	"Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues." Del Arco A., Agudo M., Satrustegui J. Biochem. J. 345:725-732(2000) [PubMed: 10642534] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CALCIUM-BINDING. Tissue: Liver.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Uterus.
[5]	"Genomic structure of the adult-onset type II citrullinemia gene, SLC25A13, and cloning and expression of its mouse homologue." Sinasac D.S., Crackower M.A., Lee J.R., Kobayashi K., Saheki T., Scherer S.W., Tsui L.-C. Genomics 62:289-292(1999) [PubMed: 10610724] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 6-251, INVOLVEMENT IN CTLN2.
[6]	"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: FUNCTION.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-484, MASS SPECTROMETRY.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations." Yamaguchi N., Kobayashi K., Yasuda T., Nishi I., Iijima M., Nakagawa M., Osame M., Kondo I., Saheki T. Hum. Mutat. 19:122-130(2002) [PubMed: 11793471] [Abstract] Cited for: VARIANT NICCD LYS-601.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF118838 mRNA. Translation: AAD38501.1. Y17571 mRNA. Translation: CAB62206.1. AF164530 , AF164525, AF164526, AF164527, AF164528, AF164529 Genomic DNA. Translation: AAF28473.1. AC002540 Genomic DNA. Translation: AAB70112.1. Sequence problems. AC002450 Genomic DNA. Translation: AAB67049.1. Sequence problems. AC084368 Genomic DNA. No translation available. AC096775 Genomic DNA. No translation available. BC006566 mRNA. Translation: AAH06566.1.
IPI	IPI00007084.
RefSeq	NP_055066.1. NM_014251.2.
UniGene	Hs.489190.
3D structure databases
ProteinModelPortal	Q9UJS0.
SMR	Q9UJS0. Positions 13-224, 329-609.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UJS0. 11 interactions.
STRING	Q9UJS0.
Protein family/group databases
TCDB	2.A.29.14.2. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	Q9UJS0.
Polymorphism databases
DMDM	13124095.
Proteomic databases
PRIDE	Q9UJS0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265631; ENSP00000265631; ENSG00000004864.
GeneID	10165.
KEGG	hsa:10165.
UCSC	uc003uof.2. human.
Organism-specific databases
CTD	10165.
GeneCards	GC07M095749.
H-InvDB	HIX0006866.
HGNC	HGNC:10983. SLC25A13.
HPA	HPA018997.
MIM	603471. phenotype. 603859. gene. 605814. phenotype.
neXtProt	NX_Q9UJS0.
Orphanet	247585. Citrullinemia type II.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18042.
GeneTree	ENSGT00530000062944.
HOVERGEN	HBG005350.
InParanoid	Q9UJS0.
OrthoDB	EOG4BVRT4.
PhylomeDB	Q9UJS0.
Enzyme and pathway databases
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	Q9UJS0.
Bgee	Q9UJS0.
CleanEx	HS_SLC25A13.
Genevestigator	Q9UJS0.
GermOnline	ENSG00000004864. Homo sapiens.
Family and domain databases
InterPro	IPR011992. EF-hand-like_dom. IPR018249. EF_HAND_2. IPR002048. EF_hand_Ca-bd. IPR002067. Mit_carrier. IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 4 hits. G3DSA:1.50.40.10. G3DSA:1.50.40.10. 1 hit.
KO	K15105.
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00926. MITOCARRIER.
SMART	SM00054. EFh. 2 hits. [Graphical view]
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS00018. EF_HAND_1. False negative. PS50222. EF_HAND_2. 2 hits. PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00128. L-Aspartic Acid.
NextBio	38486.
SOURCE	Search...

Entry information

Entry name

CMC2_HUMAN

Accession

Primary (citable) accession number: Q9UJS0
Secondary accession number(s): O14566 , O14575, Q9NZW1, Q9UNI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	February 21, 2001
Last modified:	January 25, 2012
This is version 119 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.