Q9HC21 (TPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial thiamine pyrophosphate carrier

Alternative name(s):
Mitochondrial uncoupling protein 1
Solute carrier family 25 member 19

Gene names

Name:	SLC25A19
Synonyms:	DNC, MUP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	320 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mitochondrial transporter mediating uptake of thiamine pyrophosphate (ThPP) into mitochondria. Ref.4
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in all tissues examined except for placenta. Highest levels in colon, kidney, lung, testis, spleen, and brain. Ref.1
Involvement in disease	Microcephaly, Amish type (MCPHA) [MIM:607196]: A disorder characterized by severe congenital microcephaly and severe 2-ketoglutaric aciduria leading to death within the first year. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Thiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type (THMD4) [MIM:613710]: A disease characterized by recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Miscellaneous	The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue By similarity.
Sequence similarities	Belongs to the mitochondrial carrier (TC 2.A.29) family. [View classification] Contains 3 Solcar repeats.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Disease mutation Neuropathy
Domain	Repeat Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Non-traceable author statement. Source: UniProtKB
Molecular_function	deoxynucleotide transmembrane transporter activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	Mitochondrial thiamine pyrophosphate carrier		PRO_0000090611
Regions
	Transmembrane	19 – 39	21	Helical; Name=1; Potential
	Transmembrane	87 – 107	21	Helical; Name=2; Potential
	Transmembrane	122 – 142	21	Helical; Name=3; Potential
	Transmembrane	173 – 193	21	Helical; Name=4; Potential
	Transmembrane	220 – 240	21	Helical; Name=5; Potential
	Transmembrane	293 – 313	21	Helical; Name=6; Potential
	Repeat	13 – 106	94	Solcar 1
	Repeat	116 – 202	87	Solcar 2
	Repeat	214 – 309	96	Solcar 3
	Motif	241 – 246	6	Substrate recognition By similarity
Natural variations
	Natural variant	125	1	G → S in THMD4; affects function as shown by complementation studies in yeast. Ref.7		VAR_065125
	Natural variant	177	1	G → A in MCPHA. Ref.6		VAR_014103

Sequences

	Sequence		Length	Mass (Da)
	Q9HC21 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 57CE0F01D538B1BE	FASTA	320	35,511
	10 20 30 40 50 60 MVGYDPKPDG RNNTKFQVAV AGSVSGLVTR ALISPFDVIK IRFQLQHERL SRSDPSAKYH 70 80 90 100 110 120 GILQASRQIL QEEGPTAFWK GHVPAQILSI GYGAVQFLSF EMLTELVHRG SVYDAREFSV 130 140 150 160 170 180 HFVCGGLAAC MATLTVHPVD VLRTRFAAQG EPKVYNTLRH AVGTMYRSEG PQVFYKGLAP 190 200 210 220 230 240 TLIAIFPYAG LQFSCYSSLK HLYKWAIPAE GKKNENLQNL LCGSGAGVIS KTLTYPLDLF 250 260 270 280 290 300 KKRLQVGGFE HARAAFGQVR RYKGLMDCAK QVLQKEGALG FFKGLSPSLL KAALSTGFMF 310 320 FSYEFFCNVF HCMNRTASQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals." Dolce V., Fiermonte G., Runswick M.J., Palmieri F., Walker J.E. Proc. Natl. Acad. Sci. U.S.A. 98:2284-2288(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"MUP 1, a mitochondrial uncoupling protein." Renard S., Mondesert G., Besnard F. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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]. Tissue: Lung.
[4]	"The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier." Kang J., Samuels D.C. Mitochondrion 8:103-108(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"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].
[6]	"Mutant deoxynucleotide carrier is associated with congenital microcephaly." Rosenberg M.J., Agarwala R., Bouffard G., Davis J., Fiermonte G., Hilliard M.S., Koch T., Kalikin L.M., Makalowska I., Morton D.H., Petty E.M., Weber J.L., Palmieri F., Kelley R.I., Schaeffer A.A., Biesecker L.G. Nat. Genet. 32:175-179(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MCPHA ALA-177.
[7]	"SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis." Spiegel R., Shaag A., Edvardson S., Mandel H., Stepensky P., Shalev S.A., Horovitz Y., Pines O., Elpeleg O. Ann. Neurol. 66:419-424(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THMD4 SER-125, CHARACTERIZATION OF VARIANT THMD4 SER-125.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ251857 mRNA. Translation: CAC27560.1. AJ301616 Genomic DNA. Translation: CAC37793.1. AF182404 mRNA. Translation: AAG16903.1. BC001075 mRNA. Translation: AAH01075.1. BC005120 mRNA. Translation: AAH05120.1.
IPI	IPI00028068.
RefSeq	NP_001119593.1. NM_001126121.1. NP_001119594.1. NM_001126122.1. NP_068380.3. NM_021734.4.
UniGene	Hs.514470.
3D structure databases
ProteinModelPortal	Q9HC21.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HC21. 1 interaction.
STRING	9606.ENSP00000319574.
Protein family/group databases
TCDB	2.A.29.16.1. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	Q9HC21.
Polymorphism databases
DMDM	20137652.
Proteomic databases
PaxDb	Q9HC21.
PRIDE	Q9HC21.
Protocols and materials databases
DNASU	60386.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320362; ENSP00000319574; ENSG00000125454. ENST00000402418; ENSP00000385312; ENSG00000125454. ENST00000416858; ENSP00000397818; ENSG00000125454. ENST00000442286; ENSP00000402202; ENSG00000125454. ENST00000580994; ENSP00000463795; ENSG00000125454.
GeneID	60386.
KEGG	hsa:60386.
UCSC	uc002jns.4. human.
Organism-specific databases
CTD	60386.
GeneCards	GC17M073266.
HGNC	HGNC:14409. SLC25A19.
MIM	606521. gene. 607196. phenotype. 613710. phenotype.
neXtProt	NX_Q9HC21.
Orphanet	99742. Amish lethal microcephaly. 217396. Progressive demyelinating neuropathy with bilateral striatal necrosis.
PharmGKB	PA37879.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310116.
HOGENOM	HOG000165726.
HOVERGEN	HBG105731.
InParanoid	Q9HC21.
KO	K15108.
OMA	FSFYERF.
OrthoDB	EOG46WZ8Z.
PhylomeDB	Q9HC21.
Gene expression databases
ArrayExpress	Q9HC21.
Bgee	Q9HC21.
CleanEx	HS_SLC25A19.
Genevestigator	Q9HC21.
GermOnline	ENSG00000125454. Homo sapiens.
Family and domain databases
Gene3D	1.50.40.10. 1 hit.
InterPro	IPR002067. Mit_carrier. IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00926. MITOCARRIER.
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	60386.
NextBio	65310.
SOURCE	Search...

Entry information

Entry name

TPC_HUMAN

Accession

Primary (citable) accession number: Q9HC21

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 11, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 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.