Q9Y619 · ORNT1_HUMAN
- ProteinMitochondrial ornithine transporter 1
- GeneSLC25A15
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids301 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mitochondrial ornithine-citrulline antiporter (Probable) (PubMed:12807890, PubMed:22262851).
Catalyzes the exchange between cytosolic ornithine and mitochondrial citrulline plus an H+, the proton compensates the positive charge of ornithine thus leading to an electroneutral transport. Plays a crucial role in the urea cycle, by connecting the cytosolic and the intramitochondrial reactions of the urea cycle (Probable) (PubMed:12807890, PubMed:22262851).
Lysine and arginine are also transported by the antiport mechanism (Probable) (PubMed:12807890).
In addition, catalyzes an electroneutral exchange of ornithine or lysine for H+, a reaction driven by the pH gradient across the inner membrane (By similarity).
Catalyzes the exchange between cytosolic ornithine and mitochondrial citrulline plus an H+, the proton compensates the positive charge of ornithine thus leading to an electroneutral transport. Plays a crucial role in the urea cycle, by connecting the cytosolic and the intramitochondrial reactions of the urea cycle (Probable) (PubMed:12807890, PubMed:22262851).
Lysine and arginine are also transported by the antiport mechanism (Probable) (PubMed:12807890).
In addition, catalyzes an electroneutral exchange of ornithine or lysine for H+, a reaction driven by the pH gradient across the inner membrane (By similarity).
Catalytic activity
- H+(in) + L-citrulline(in) + L-ornithine(out) = H+(out) + L-citrulline(out) + L-ornithine(in)H+ (in)CHEBI:15378
+ L-citrulline (in)CHEBI:57743+ L-ornithine (out)CHEBI:46911= H+ (out)CHEBI:15378+ L-citrulline (out)CHEBI:57743+ L-ornithine (in)CHEBI:46911 - L-arginine(out) + L-ornithine(in) = L-arginine(in) + L-ornithine(out)
- L-lysine(in) + L-ornithine(out) = L-lysine(out) + L-ornithine(in)
- H+(in) + L-lysine(out) = H+(out) + L-lysine(in)
- H+(in) + L-ornithine(out) = H+(out) + L-ornithine(in)
Activity regulation
Inhibited by pyridoxal 5'-phosphate as well as by mercurials (mersalyl, p-chloromercuribenzene sulfonate, and mercuric chloride), N-ethylmaleimide and spermine.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.52 mM | citruline | |||||
1.58 mM | arginine | |||||
0.8 mM | lysine | |||||
0.22 mM | ornithine |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
3 mmol/min/g | with arginine as substrate | ||||
3 mmol/min/g | with citruline as substrate | ||||
3 mmol/min/g | with lysine as substrate | ||||
3 mmol/min/g | with ornithine as substrate |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrion | |
Molecular Function | antiporter activity | |
Molecular Function | L-arginine transmembrane transporter activity | |
Molecular Function | L-lysine transmembrane transporter activity | |
Molecular Function | L-ornithine transmembrane transporter activity | |
Biological Process | L-arginine transmembrane transport | |
Biological Process | L-lysine transmembrane transport | |
Biological Process | mitochondrial L-ornithine transmembrane transport | |
Biological Process | urea cycle |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMitochondrial ornithine transporter 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y619
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
Mitochondrion membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 5-25 | Helical; Name=1 | ||||
Sequence: PAIQAAIDLTAGAAGGTACVL | ||||||
Transmembrane | 68-88 | Helical; Name=2 | ||||
Sequence: SPALIANIAENSVLFMCYGFC | ||||||
Transmembrane | 110-130 | Helical; Name=3 | ||||
Sequence: AAAGSFASAFAALVLCPTELV | ||||||
Transmembrane | 168-188 | Helical; Name=4 | ||||
Sequence: GFYHGLSSTLLREVPGYFFFF | ||||||
Transmembrane | 207-227 | Helical; Name=5 | ||||
Sequence: LGPVPLMLSGGVGGICLWLAV | ||||||
Transmembrane | 237-257 | Helical; Name=6 | ||||
Sequence: IQVLSMSGKQAGFIRTFINVV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS)
- Note
- DescriptionAn autosomal recessive disorder of the urea cycle characterized by onset in early life. The acute phase of the disease is characterized by vomiting, ataxia, lethargy, confusion, and coma. Chronic clinical manifestations include hypotonia, developmental delay, progressive encephalopathy with mental regression, and spastic paraparesis with pyramidal signs.
- See alsoMIM:238970
Natural variants in HHHS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087078 | 15 | A>V | in HHHS; abolishes ornithine/ornithine exchange; dbSNP:rs202247806 | |
VAR_012757 | 27 | G>E | in HHHS; dbSNP:rs1208994024 | |
VAR_012758 | 27 | G>R | in HHHS; incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline; dbSNP:rs104894430 | |
VAR_058948 | 37 | M>R | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908533 | |
VAR_058949 | 70 | A>L | in HHHS; uncertain significance; requires 2 nucleotide substitutions; dbSNP:rs1064793683 | |
VAR_058950 | 71 | L>Q | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908534 | |
VAR_058951 | 113 | G>C | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs199894905 | |
VAR_012759 | 126 | P>R | in HHHS | |
VAR_012760 | 180 | E>K | in HHHS; does not affect mitochondrial localization; dbSNP:rs104894424 | |
VAR_058952 | 188 | F>L | in HHHS; dbSNP:rs141028076 | |
VAR_012761 | 188 | missing | in HHHS; maintains a residual transport activity of 10%. Not detected at mitochondrion membrane; dbSNP:rs202247803 | |
VAR_012762 | 190 | G>D | in HHHS; maintains a residual transport activity of 35%; dbSNP:rs202247804 | |
VAR_058953 | 216 | G>S | in HHHS; dbSNP:rs1417167600 | |
VAR_058954 | 272 | T>I | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908535 | |
VAR_058955 | 273 | M>K | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs202247808 | |
VAR_012764 | 275 | R>Q | in HHHS; incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline; dbSNP:rs104894431 | |
VAR_058956 | 283 | L>F | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs202247809 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087078 | 15 | in HHHS; abolishes ornithine/ornithine exchange; dbSNP:rs202247806 | |||
Sequence: A → V | ||||||
Natural variant | VAR_012757 | 27 | in HHHS; dbSNP:rs1208994024 | |||
Sequence: G → E | ||||||
Natural variant | VAR_012758 | 27 | in HHHS; incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline; dbSNP:rs104894430 | |||
Sequence: G → R | ||||||
Natural variant | VAR_058948 | 37 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908533 | |||
Sequence: M → R | ||||||
Natural variant | VAR_058949 | 70 | in HHHS; uncertain significance; requires 2 nucleotide substitutions; dbSNP:rs1064793683 | |||
Sequence: A → L | ||||||
Natural variant | VAR_058950 | 71 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908534 | |||
Sequence: L → Q | ||||||
Mutagenesis | 74 | Does not affect ornithine-ornithine exchange. Does not affect substrate specificity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 81 | Reduced ornithine-ornithine exchange. Does not affect substrate specificity. | ||||
Sequence: L → A | ||||||
Natural variant | VAR_058951 | 113 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs199894905 | |||
Sequence: G → C | ||||||
Natural variant | VAR_012759 | 126 | in HHHS | |||
Sequence: P → R | ||||||
Mutagenesis | 179 | Reduced uptake rate for ornithine transport. Favors the transport of L-arginine and L-lysine with respect to that of L-ornithine. | ||||
Sequence: R → K | ||||||
Mutagenesis | 179 | Substrate specificities are markedly altered. Vmax value is 14-fold lower for ornithine as substrate. | ||||
Sequence: R → Q | ||||||
Mutagenesis | 179-301 | Incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_012760 | 180 | in HHHS; does not affect mitochondrial localization; dbSNP:rs104894424 | |||
Sequence: E → K | ||||||
Mutagenesis | 180 | Substrate specificities are markedly altered. Vmax value is 14-fold lower for ornithine as substrate. Decreased strongly L-ornithine transport but not L-arginine and L-lysine transport. | ||||
Sequence: E → D | ||||||
Natural variant | VAR_058952 | 188 | in HHHS; dbSNP:rs141028076 | |||
Sequence: F → L | ||||||
Natural variant | VAR_012761 | 188 | in HHHS; maintains a residual transport activity of 10%. Not detected at mitochondrion membrane; dbSNP:rs202247803 | |||
Sequence: Missing | ||||||
Natural variant | VAR_012762 | 190 | in HHHS; maintains a residual transport activity of 35%; dbSNP:rs202247804 | |||
Sequence: G → D | ||||||
Natural variant | VAR_058953 | 216 | in HHHS; dbSNP:rs1417167600 | |||
Sequence: G → S | ||||||
Mutagenesis | 224 | Exhibits an altered substrate specificity. Favors the transport of L-arginine and L-lysine with respect to that of L-ornithine. | ||||
Sequence: W → A | ||||||
Natural variant | VAR_012763 | 254 | in dbSNP:rs17849654 | |||
Sequence: I → L | ||||||
Natural variant | VAR_058954 | 272 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs121908535 | |||
Sequence: T → I | ||||||
Natural variant | VAR_058955 | 273 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs202247808 | |||
Sequence: M → K | ||||||
Natural variant | VAR_012764 | 275 | in HHHS; incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline; dbSNP:rs104894431 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_058956 | 283 | in HHHS; exhibits very low transport activity despite normal insertion in the liposomal membrane; dbSNP:rs202247809 | |||
Sequence: L → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 338 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000090650 | 1-301 | Mitochondrial ornithine transporter 1 | |||
Sequence: MKSNPAIQAAIDLTAGAAGGTACVLTGQPFDTMKVKMQTFPDLYRGLTDCCLKTYSQVGFRGFYKGTSPALIANIAENSVLFMCYGFCQQVVRKVAGLDKQAKLSDLQNAAAGSFASAFAALVLCPTELVKCRLQTMYEMETSGKIAKSQNTVWSVIKSILRKDGPLGFYHGLSSTLLREVPGYFFFFGGYELSRSFFASGRSKDELGPVPLMLSGGVGGICLWLAVYPVDCIKSRIQVLSMSGKQAGFIRTFINVVKNEGITALYSGLKPTMIRAFPANGALFLAYEYSRKLMMNQLEAY |
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in liver, pancreas, testis, lung and small intestine. Lower levels are detected in spleen, kidney, brain and heart.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 7-91 | Solcar 1 | ||||
Sequence: IQAAIDLTAGAAGGTACVLTGQPFDTMKVKMQTFPDLYRGLTDCCLKTYSQVGFRGFYKGTSPALIANIAENSVLFMCYGFCQQV | ||||||
Repeat | 104-197 | Solcar 2 | ||||
Sequence: LSDLQNAAAGSFASAFAALVLCPTELVKCRLQTMYEMETSGKIAKSQNTVWSVIKSILRKDGPLGFYHGLSSTLLREVPGYFFFFGGYELSRSF | ||||||
Repeat | 207-293 | Solcar 3 | ||||
Sequence: LGPVPLMLSGGVGGICLWLAVYPVDCIKSRIQVLSMSGKQAGFIRTFINVVKNEGITALYSGLKPTMIRAFPANGALFLAYEYSRKL |
Sequence similarities
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length301
- Mass (Da)32,736
- Last updated1999-11-01 v1
- Checksum34436A15B105DC53
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF112968 EMBL· GenBank· DDBJ | AAD45238.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ309943 EMBL· GenBank· DDBJ | CAC83972.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF177333 EMBL· GenBank· DDBJ | AAG17977.1 EMBL· GenBank· DDBJ | mRNA | ||
AL161614 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471075 EMBL· GenBank· DDBJ | EAX08630.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002702 EMBL· GenBank· DDBJ | AAH02702.1 EMBL· GenBank· DDBJ | mRNA |