Q9Y619 (ORNT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial ornithine transporter 1

Alternative name(s):
Solute carrier family 25 member 15

Gene names

Name:	SLC25A15
Synonyms:	ORNT1
ORF Names:	SP1855

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	301 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ornithine transport across inner mitochondrial membrane, from the cytoplasm to the matrix.
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Involvement in disease	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) [MIM:238970]: Autosomal recessive disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. It causes a functional impairment of the urea cycle. Note: The disease is caused by mutations affecting the gene represented in this entry.
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
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular amino acid metabolic process Traceable author statement Ref.1. Source: ProtInc mitochondrial ornithine transport Traceable author statement Ref.1. Source: ProtInc urea cycle Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Traceable author statement Ref.1. Source: ProtInc mitochondrial inner membrane Traceable author statement. Source: Reactome
Molecular_function	L-ornithine transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 301	301	Mitochondrial ornithine transporter 1		PRO_0000090650
Regions
	Transmembrane	5 – 25	21	Helical; Name=1; Potential
	Transmembrane	68 – 88	21	Helical; Name=2; Potential
	Transmembrane	110 – 130	21	Helical; Name=3; Potential
	Transmembrane	168 – 188	21	Helical; Name=4; Potential
	Transmembrane	207 – 227	21	Helical; Name=5; Potential
	Transmembrane	237 – 257	21	Helical; Name=6; Potential
	Repeat	7 – 91	85	Solcar 1
	Repeat	104 – 197	94	Solcar 2
	Repeat	207 – 293	87	Solcar 3
Natural variations
	Natural variant	27	1	G → E in HHH syndrome. Ref.7		VAR_012757
	Natural variant	27	1	G → R in HHH syndrome; incapable of catalyzing homo-exchanges of ornithine, arginine, lysine and citrulline. Ref.2 Ref.8 Ref.9 Ref.12		VAR_012758
	Natural variant	37	1	M → R in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.12		VAR_058948
	Natural variant	70	1	A → L in HHH syndrome; requires 2 nucleotide substitutions; uncertain pathogenicity. Ref.12		VAR_058949
	Natural variant	71	1	L → Q in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.12		VAR_058950
	Natural variant	113	1	G → C in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.11 Ref.12		VAR_058951
	Natural variant	126	1	P → R in HHH syndrome. Ref.10		VAR_012759
	Natural variant	180	1	E → K in HHH syndrome. Ref.1		VAR_012760
	Natural variant	188	1	F → L in HHH syndrome; maintains a residual transport activity of 10%. Ref.12		VAR_058952
	Natural variant	188	1	Missing in HHH syndrome. Ref.1 Ref.2 Ref.8 Ref.9		VAR_012761
	Natural variant	190	1	G → D in HHH syndrome; maintains a residual transport activity of 35%. Ref.2 Ref.8 Ref.9		VAR_012762
	Natural variant	216	1	G → S in HHH syndrome. Ref.12		VAR_058953
	Natural variant	254	1	I → L. Corresponds to variant rs17849654 [ dbSNP | Ensembl ].		VAR_012763
	Natural variant	272	1	T → I in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.12		VAR_058954
	Natural variant	273	1	M → K in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.11 Ref.12		VAR_058955
	Natural variant	275	1	R → Q in HHH syndrome. Ref.2 Ref.8 Ref.9		VAR_012764
	Natural variant	283	1	L → F in HHH syndrome; exhibits very low transport activity despite normal insertion in the liposomal membrane. Ref.12		VAR_058956

Sequences

	Sequence		Length	Mass (Da)
	Q9Y619 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 34436A15B105DC53	FASTA	301	32,736
	10 20 30 40 50 60 MKSNPAIQAA IDLTAGAAGG TACVLTGQPF DTMKVKMQTF PDLYRGLTDC CLKTYSQVGF 70 80 90 100 110 120 RGFYKGTSPA LIANIAENSV LFMCYGFCQQ VVRKVAGLDK QAKLSDLQNA AAGSFASAFA 130 140 150 160 170 180 ALVLCPTELV KCRLQTMYEM ETSGKIAKSQ NTVWSVIKSI LRKDGPLGFY HGLSSTLLRE 190 200 210 220 230 240 VPGYFFFFGG YELSRSFFAS GRSKDELGPV PLMLSGGVGG ICLWLAVYPV DCIKSRIQVL 250 260 270 280 290 300 SMSGKQAGFI RTFINVVKNE GITALYSGLK PTMIRAFPAN GALFLAYEYS RKLMMNQLEA Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter." Camacho J.A., Obie C., Biery B., Goodman B.K., Hu A., Almashanu S., Steel G., Casey R., Lombard M., Mitchell G.A., Valle D. Nat. Genet. 22:151-158(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HHH SYNDROME LYS-180 AND PHE-188 DEL.
[2]	"The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms." Fiermonte G., Dolce V., David L., Santorelli F.M., Dionisi-Vici C., Palmieri F., Walker J.E. J. Biol. Chem. 278:32778-32783(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION OF VARIANTS HHH SYNDROME ARG-27; PHE-188 DEL; ASP-190 AND GLN-275.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Skin.
[7]	"Three novel mutations (G27E, insAAC, R179X) in the ORNT1 gene of Japanese patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome." Tsujino S., Kanazawa N., Ohashi T., Eto Y., Saito T., Kira J., Yamada T. Ann. Neurol. 47:625-631(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHH SYNDROME GLU-27.
[8]	"Seven novel mutations in the ORNT1 gene (SLC25A15) in patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome." Salvi S., Dionisi-Vici C., Bertini E., Verardo M., Santorelli F.M. Hum. Mutat. 18:460-460(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHH SYNDROME ARG-27; PHE-188 DEL; ASP-190 AND GLN-275.
[9]	"Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome." Salvi S., Santorelli F.M., Bertini E., Boldrini R., Meli C., Donati A., Burlina A.B., Rizzo C., Di Capua M., Fariello G., Dionisi-Vici C. Neurology 57:911-914(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHH SYNDROME ARG-27; PHE-188 DEL; ASP-190 AND GLN-275.
[10]	"A novel mutation, P126R, in a Japanese patient with HHH syndrome." Miyamoto T., Kanazawa N., Hayakawa C., Tsujino S. Pediatr. Neurol. 26:65-67(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHH SYNDROME ARG-126.
[11]	"HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation." Fecarotta S., Parenti G., Vajro P., Zuppaldi A., Della Casa R., Carbone M.T., Correra A., Torre G., Riva S., Dionisi-Vici C., Santorelli F.M., Andria G. J. Inherit. Metab. Dis. 29:186-189(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHH SYNDROME CYS-113 AND LYS-273.
[12]	"Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study." Tessa A., Fiermonte G., Dionisi-Vici C., Paradies E., Baumgartner M.R., Chien Y.-H., Loguercio C., de Baulny H.O., Nassogne M.-C., Schiff M., Deodato F., Parenti G., Rutledge S.L., Vilaseca M.A., Melone M.A.B., Scarano G., Aldamiz-Echevarria L., Besley G. , Walter J., Martinez-Hernandez E., Hernandez J.M., Pierri C.L., Palmieri F., Santorelli F.M. Hum. Mutat. 30:741-748(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHH SYNDROME ARG-27; ARG-37; LEU-70; GLN-71; LEU-188; SER-216; ILE-272 AND PHE-283, CHARACTERIZATION OF VARIANTS HHH SYNDROME ARG-37; GLN-71; CYS-113; ILE-272; LYS-273 AND PHE-283.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF112968 mRNA. Translation: AAD45238.1. AJ309943 Genomic DNA. Translation: CAC83972.1. AF177333 mRNA. Translation: AAG17977.1. AL161614 Genomic DNA. Translation: CAH72774.1. CH471075 Genomic DNA. Translation: EAX08630.1. BC002702 mRNA. Translation: AAH02702.1.
IPI	IPI00003389.
RefSeq	NP_055067.1. NM_014252.3.
UniGene	Hs.646645.
3D structure databases
ProteinModelPortal	Q9Y619.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000342267.
Protein family/group databases
TCDB	2.A.29.19.2. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	Q9Y619.
Polymorphism databases
DMDM	20139303.
Proteomic databases
PaxDb	Q9Y619.
PRIDE	Q9Y619.
Protocols and materials databases
DNASU	10166.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338625; ENSP00000342267; ENSG00000102743. ENST00000426521; ENSP00000431313; ENSG00000102743.
GeneID	10166.
KEGG	hsa:10166.
UCSC	uc001uxn.3. human.
Organism-specific databases
CTD	10166.
GeneCards	GC13P041363.
H-InvDB	HIX0011260.
HGNC	HGNC:10985. SLC25A15.
HPA	HPA042146.
MIM	238970. phenotype. 603861. gene.
neXtProt	NX_Q9Y619.
Orphanet	415. Hyperornithinemia-hyperammonemia-homocitrullinuria.
PharmGKB	PA35861.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245037.
HOGENOM	HOG000168307.
HOVERGEN	HBG062630.
InParanoid	Q9Y619.
KO	K15101.
OMA	SRKLMMN.
OrthoDB	EOG44TP8N.
PhylomeDB	Q9Y619.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q9Y619.
Gene expression databases
ArrayExpress	Q9Y619.
Bgee	Q9Y619.
CleanEx	HS_SLC25A15.
Genevestigator	Q9Y619.
GermOnline	ENSG00000102743. Homo sapiens.
Family and domain databases
Gene3D	1.50.40.10. 1 hit.
InterPro	IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC25A15. human.
DrugBank	DB00129. L-Ornithine.
GenomeRNAi	10166.
NextBio	38490.
SOURCE	Search...

Entry information

Entry name

ORNT1_HUMAN

Accession

Primary (citable) accession number: Q9Y619
Secondary accession number(s): Q5VZD8, Q9HC45

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 11, 2002
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 115 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.