Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9UJS0 (CMC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length675 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.3

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

Citrullinemia 2 (CTLN2) [MIM:603471]: A form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. Citrullinemia type 2 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7

Cholestasis, neonatal intrahepatic, caused by citrin deficiency (NICCD) [MIM:605814]: A form of citrullinemia type 2 with neonatal onset, characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. Neonatal intrahepatic cholestasis due to citrin deficiency 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

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.

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 processTransport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Intrahepatic cholestasis
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP biosynthetic process

Inferred from direct assay PubMed 12851387. Source: UniProtKB

L-glutamate transport

Inferred from direct assay Ref.3. Source: UniProtKB

aspartate transport

Inferred from direct assay Ref.3. Source: UniProtKB

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular respiration

Inferred from direct assay PubMed 12851387. Source: UniProtKB

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

malate-aspartate shuttle

Inferred from direct assay Ref.3. Source: UniProtKB

response to calcium ion

Inferred from direct assay Ref.3. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

transport

Non-traceable author statement Ref.2. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

Non-traceable author statement Ref.2. Source: UniProtKB

mitochondrial inner membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.2Ref.3. Source: UniProtKB

   Molecular_functionL-aspartate transmembrane transporter activity

Inferred from direct assay Ref.3. Source: UniProtKB

L-glutamate transmembrane transporter activity

Inferred from direct assay Ref.3. Source: UniProtKB

calcium ion binding

Inferred from direct assay Ref.2. Source: UniProtKB

transporter activity

Non-traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UJS0-1)

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.
Isoform 2 (identifier: Q9UJS0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     311-311: Q → QQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 675674Calcium-binding mitochondrial carrier protein Aralar2
PRO_0000090600

Regions

Transmembrane332 – 34918Helical; Name=1; Potential
Transmembrane393 – 41220Helical; Name=2; Potential
Transmembrane436 – 44914Helical; Name=3; Potential
Transmembrane485 – 50420Helical; Name=4; Potential
Transmembrane524 – 54118Helical; Name=5; Potential
Transmembrane581 – 60020Helical; Name=6; Potential
Domain51 – 8636EF-hand 1
Domain87 – 12236EF-hand 2
Domain125 – 15733EF-hand 3
Domain158 – 19336EF-hand 4
Repeat326 – 41893Solcar 1
Repeat426 – 51085Solcar 2
Repeat518 – 60689Solcar 3
Calcium binding66 – 77121 Ref.2
Calcium binding100 – 111122 Ref.2
Calcium binding171 – 182123 Ref.2

Amino acid modifications

Modified residue21N-acetylalanine Ref.9
Modified residue3531N6-acetyllysine By similarity
Modified residue3721N6-acetyllysine By similarity
Modified residue4841N6-acetyllysine; alternate By similarity
Modified residue4841N6-succinyllysine; alternate By similarity
Modified residue5801N6-succinyllysine By similarity
Modified residue6621N6-acetyllysine By similarity

Natural variations

Alternative sequence3111Q → QQ in isoform 2.
VSP_043747
Natural variant1411E → K.
Corresponds to variant rs1131697 [ dbSNP | Ensembl ].
VAR_050126
Natural variant2321L → I.
Corresponds to variant rs10255762 [ dbSNP | Ensembl ].
VAR_050127
Natural variant6011E → K in NICCD. Ref.10
VAR_016601

Experimental info

Sequence conflict231 – 2322EL → VH in CAB62206. Ref.2
Sequence conflict5321M → T in CAB62206. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: AD07EDBC6C68989B

FASTA67574,176
        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 

« Hide

Isoform 2 [UniParc].

Checksum: DE2CB869F95E5238
Show »

FASTA67674,304

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CALCIUM-BINDING.
Tissue: Liver.
[3]"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] (ISOFORM 2), FUNCTION.
[4]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton 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].
[6]"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] (ISOFORM 1).
Tissue: Uterus.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 6-251, INVOLVEMENT IN CTLN2.
[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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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].
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANT NICCD LYS-601.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF118838 mRNA. Translation: AAD38501.1.
Y17571 mRNA. Translation: CAB62206.1.
AJ496569 mRNA. Translation: CAD43091.1.
AC002540 Genomic DNA. Translation: AAB70112.1. Sequence problems.
AC002450 Genomic DNA. Translation: AAB67049.1. Sequence problems.
AC004458 Genomic DNA. No translation available.
AC084368 Genomic DNA. No translation available.
AC096775 Genomic DNA. No translation available.
CH471091 Genomic DNA. Translation: EAW76748.1.
BC006566 mRNA. Translation: AAH06566.1.
AH009104 Genomic DNA. Translation: AAF28473.1.
RefSeqNP_001153682.1. NM_001160210.1.
NP_055066.1. NM_014251.2.
UniGeneHs.489190.

3D structure databases

ProteinModelPortalQ9UJS0.
SMRQ9UJS0. Positions 13-223, 332-604.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115467. 24 interactions.
IntActQ9UJS0. 28 interactions.
MINTMINT-3081120.
STRING9606.ENSP00000265631.

Chemistry

DrugBankDB00128. L-Aspartic Acid.

Protein family/group databases

TCDB2.A.29.14.2. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteQ9UJS0.

Polymorphism databases

DMDM13124095.

Proteomic databases

PaxDbQ9UJS0.
PRIDEQ9UJS0.

Protocols and materials databases

DNASU10165.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265631; ENSP00000265631; ENSG00000004864. [Q9UJS0-1]
ENST00000416240; ENSP00000400101; ENSG00000004864. [Q9UJS0-2]
GeneID10165.
KEGGhsa:10165.
UCSCuc003uof.4. human. [Q9UJS0-1]
uc003uog.4. human. [Q9UJS0-2]

Organism-specific databases

CTD10165.
GeneCardsGC07M095749.
H-InvDBHIX0167840.
HGNCHGNC:10983. SLC25A13.
HPAHPA018997.
MIM603471. phenotype.
603859. gene.
605814. phenotype.
neXtProtNX_Q9UJS0.
Orphanet247585. Citrullinemia type II.
247598. Neonatal intrahepatic cholestasis due to citrin deficiency.
PharmGKBPA35859.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG292991.
HOGENOMHOG000180633.
HOVERGENHBG005350.
InParanoidQ9UJS0.
KOK15105.
OMACDEFEAV.
OrthoDBEOG70GMF1.
PhylomeDBQ9UJS0.
TreeFamTF313209.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressQ9UJS0.
BgeeQ9UJS0.
CleanExHS_SLC25A13.
GenevestigatorQ9UJS0.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
1.50.40.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
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. 2 hits.
[Graphical view]
SUPFAMSSF103506. SSF103506. 1 hit.
PROSITEPS50222. EF_HAND_2. 2 hits.
PS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC25A13. human.
GenomeRNAi10165.
NextBio38486.
PROQ9UJS0.
SOURCESearch...

Entry information

Entry nameCMC2_HUMAN
AccessionPrimary (citable) accession number: Q9UJS0
Secondary accession number(s): O14566 expand/collapse secondary AC list , O14575, Q546F9, Q9NZW1, Q9UNI7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: April 16, 2014
This is version 142 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 7

Human chromosome 7: entries, gene names and cross-references to MIM