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2.A.29.7.2
Citrate/malate exchange carrier CIC (CTP); tricarboxylate carrier (citrate·H+/malate, PEP) (SLC25A1). Missense mutations in the SLC25A1 gene lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Majd et al. 2018 measured the effect of all twelve known pathogenic mutations on  transport activity. These mutations abolished transport of citrate completely, or reduced the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. The human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes (Majd et al. 2018). The prostate produces and releases large amounts of citrate. Mazurek et al. 2010 cloned the citrate transporter from human prostate epithelial cell plasma membranes.The prostatic carrier is an isoform of the mitochondrial transporter SLC25A1 with a different first exon. The cloned protein is the main prostatic transporter responsible for citrate release.

Accession Number:P53007
Protein Name:Citrate carrier CIC (CTP) aka tricarboxylate carrier (citrate┬ĚH+/malate, PEP) (SLC25A1)
Length:311
Molecular Weight:34013.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Mitochondrion inner membrane1 / Multi-pass membrane protein2
Substrate Citrate, malate, PEP, H+

Cross database links:

RefSeq: NP_005975.1   
Entrez Gene ID: 6576   
Pfam: PF00153   
OMIM: 190315  gene
KEGG: hsa:6576    hsa:6576   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005743 C:mitochondrial inner membrane
GO:0015137 F:citrate transmembrane transporter activity
GO:0005515 F:protein binding
GO:0006843 P:mitochondrial citrate transport
GO:0055085 P:transmembrane transport
GO:0006094 P:gluconeogenesis
GO:0035338 P:long-chain fatty-acyl-CoA biosynthetic process
GO:0019432 P:triglyceride biosynthetic process

References (11)

[1] “Localization of the human mitochondrial citrate transporter protein gene to chromosome 22q11 in the DiGeorge syndrome critical region.”  Heisterkamp N.et.al.   8666394
[2] “Cloning, genomic organization, and chromosomal localization of human citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal critical region.”  Goldmuntz E.et.al.   8660975
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[6] “Localization of the human mitochondrial citrate transporter protein gene to chromosome 22q11 in the DiGeorge syndrome critical region.”  Heisterkamp N.et.al.   8666394
[7] “Cloning, genomic organization, and chromosomal localization of human citrate transport protein to the DiGeorge/velocardiofacial syndrome minimal critical region.”  Goldmuntz E.et.al.   8660975
[8] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[9] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[10] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[11] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460

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FASTA formatted sequence
1:	MPAPRAPRAL AAAAPASGKA KLTHPGKAIL AGGLAGGIEI CITFPTEYVK TQLQLDERSH 
61:	PPRYRGIGDC VRQTVRSHGV LGLYRGLSSL LYGSIPKAAV RFGMFEFLSN HMRDAQGRLD 
121:	STRGLLCGLG AGVAEAVVVV CPMETIKVKF IHDQTSPNPK YRGFFHGVRE IVREQGLKGT 
181:	YQGLTATVLK QGSNQAIRFF VMTSLRNWYR GDNPNKPMNP LITGVFGAIA GAASVFGNTP 
241:	LDVIKTRMQG LEAHKYRNTW DCGLQILKKE GLKAFYKGTV PRLGRVCLDV AIVFVIYDEV 
301:	VKLLNKVWKT D