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Q9HC21 (TPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

Protein attributes

Sequence length320 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mitochondrial transporter mediating uptake of thiamine pyrophosphate (ThPP) into mitochondria. Ref.6

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.8

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.9

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HC21-1)

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: Q9HC21-2)

The sequence of this isoform differs from the canonical sequence as follows:
     97-153: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 320320Mitochondrial thiamine pyrophosphate carrier
PRO_0000090611

Regions

Transmembrane19 – 3921Helical; Name=1; Potential
Transmembrane87 – 10721Helical; Name=2; Potential
Transmembrane122 – 14221Helical; Name=3; Potential
Transmembrane173 – 19321Helical; Name=4; Potential
Transmembrane220 – 24021Helical; Name=5; Potential
Transmembrane293 – 31321Helical; Name=6; Potential
Repeat13 – 10694Solcar 1
Repeat116 – 20287Solcar 2
Repeat214 – 30996Solcar 3
Motif241 – 2466Substrate recognition By similarity

Natural variations

Alternative sequence97 – 15357Missing in isoform 2.
VSP_053908
Natural variant1251G → S in THMD4; affects function as shown by complementation studies in yeast. Ref.9
VAR_065125
Natural variant1771G → A in MCPHA. Ref.8
VAR_014103

Experimental info

Sequence conflict1861F → L in AAQ54327. Ref.3

Sequences

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

Last modified March 1, 2001. Version 1.
Checksum: 57CE0F01D538B1BE

FASTA32035,511
        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 

« Hide

Isoform 2 [UniParc].

Checksum: C8AB0D60A989456C
Show »

FASTA26329,217

References

« Hide '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] (ISOFORM 1), 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]Li H., Yu R., Zhou G., Ke R., Shen C., Lin L., Yang S.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[6]"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.
[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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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.
[9]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ251857 mRNA. Translation: CAC27560.1.
AJ301616 Genomic DNA. Translation: CAC37793.1.
AF182404 mRNA. Translation: AAG16903.1.
AY346372 mRNA. Translation: AAQ54327.1.
AC022211 Genomic DNA. No translation available.
BC001075 mRNA. Translation: AAH01075.1.
BC005120 mRNA. Translation: AAH05120.1.
CCDSCCDS11720.1.
RefSeqNP_001119593.1. NM_001126121.1. [Q9HC21-1]
NP_001119594.1. NM_001126122.1. [Q9HC21-1]
NP_068380.3. NM_021734.4. [Q9HC21-1]
XP_005257616.1. XM_005257559.1. [Q9HC21-1]
XP_005257617.1. XM_005257560.1. [Q9HC21-1]
XP_005257618.1. XM_005257561.1. [Q9HC21-1]
XP_005257619.1. XM_005257562.1. [Q9HC21-1]
XP_006722070.1. XM_006722007.1. [Q9HC21-1]
UniGeneHs.514470.

3D structure databases

ProteinModelPortalQ9HC21.
SMRQ9HC21. Positions 20-305.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121903. 1 interaction.
IntActQ9HC21. 2 interactions.
STRING9606.ENSP00000319574.

Protein family/group databases

TCDB2.A.29.16.1. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteQ9HC21.

Polymorphism databases

DMDM20137652.

Proteomic databases

MaxQBQ9HC21.
PaxDbQ9HC21.
PRIDEQ9HC21.

Protocols and materials databases

DNASU60386.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000320362; ENSP00000319574; ENSG00000125454.
ENST00000375261; ENSP00000364410; ENSG00000125454.
ENST00000402418; ENSP00000385312; ENSG00000125454.
ENST00000416858; ENSP00000397818; ENSG00000125454.
ENST00000442286; ENSP00000402202; ENSG00000125454.
ENST00000580994; ENSP00000463795; ENSG00000125454.
GeneID60386.
KEGGhsa:60386.
UCSCuc002jns.4. human. [Q9HC21-1]

Organism-specific databases

CTD60386.
GeneCardsGC17M073266.
GeneReviewsSLC25A19.
HGNCHGNC:14409. SLC25A19.
MIM606521. gene.
607196. phenotype.
613710. phenotype.
neXtProtNX_Q9HC21.
Orphanet99742. Amish lethal microcephaly.
217396. Progressive demyelinating neuropathy with bilateral striatal necrosis.
PharmGKBPA37879.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310116.
HOGENOMHOG000165726.
HOVERGENHBG105731.
InParanoidQ9HC21.
KOK15108.
OMAMFFWYEF.
PhylomeDBQ9HC21.
TreeFamTF313047.

Gene expression databases

ArrayExpressQ9HC21.
BgeeQ9HC21.
CleanExHS_SLC25A19.
GenevestigatorQ9HC21.

Family and domain databases

Gene3D1.50.40.10. 1 hit.
InterProIPR002067. Mit_carrier.
IPR018108. Mitochondrial_sb/sol_carrier.
IPR023395. Mt_carrier_dom.
[Graphical view]
PfamPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSPR00926. MITOCARRIER.
SUPFAMSSF103506. SSF103506. 1 hit.
PROSITEPS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC25A19.
GenomeRNAi60386.
NextBio35501809.
PROQ9HC21.
SOURCESearch...

Entry information

Entry nameTPC_HUMAN
AccessionPrimary (citable) accession number: Q9HC21
Secondary accession number(s): E9PF74, Q6V9R7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 126 of the entry and version 1 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 17

Human chromosome 17: entries, gene names and cross-references to MIM