O75746 (CMC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 110.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames 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 |
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| 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 | 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 | Defects in SLC25A12 are the cause of aspartate-glutamate carrier 1 deficiency (AGC1D) [MIM:612949]; also called global cerebral hypomyelination. This syndrome consists of a child severe psychomotor retardation, hypotonia and hypomyelination of the central nervous system. Ref.8 |
| 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 |
| Disease | Disease mutation |
| Domain | Repeat Transmembrane Transmembrane helix |
| Ligand | Calcium |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | gluconeogenesis Traceable author statement. Source: Reactome malate-aspartate shuttleInferred from direct assay Ref.2. Source: UniProtKB response to calcium ionInferred from direct assay Ref.2. Source: UniProtKB |
| Cellular component | integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB mitochondrial inner membraneTraceable author statement. Source: Reactome |
| Molecular function | L-aspartate transmembrane transporter activity Inferred from direct assay Ref.2. Source: UniProtKB L-glutamate transmembrane transporter activityInferred from direct assay Ref.2. Source: UniProtKB calcium ion bindingInferred 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 AGC1D; 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
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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: 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. 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. 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] | "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]. |
| [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: 19641205] [Abstract] Cited for: VARIANT AGC1D ARG-590, CHARACTERIZATION OF VARIANT AGC1D 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_003705.3. |
| UniGene | Hs.470608. |
3D structure databases | |
| ProteinModelPortal | O75746. |
| SMR | O75746. Positions 14-293, 327-607. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O75746. 5 interactions. |
| STRING | O75746. |
Protein family/group databases | |
| TCDB | 2.A.29.14.1. mitochondrial carrier (MC) family. |
Proteomic databases | |
| PRIDE | O75746. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000422440; ENSP00000388658; ENSG00000115840. |
| GeneID | 8604. |
| KEGG | hsa:8604. |
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 | prNOG04936. |
| GeneTree | ENSGT00530000062944. |
| HOGENOM | HBG357440. |
| HOVERGEN | HBG005350. |
| InParanoid | O75746. |
| OMA | AQNAIRY. |
| OrthoDB | EOG4BVRT4. |
| PhylomeDB | O75746. |
Enzyme and pathway databases | |
| Reactome | REACT_474. Metabolism of carbohydrates. |
Gene expression databases | |
| ArrayExpress | O75746. |
| Bgee | O75746. |
| CleanEx | HS_SLC25A12. |
| Genevestigator | O75746. |
| GermOnline | ENSG00000115840. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. 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. 2 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. 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. |
| SOURCE | Search... |
Entry information
| Entry name | CMC1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O75746 Secondary accession number(s): Q96AM8 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with