UniProt functional annotation for P22307



	UniProt functional annotation for P22307

UniProt code: P22307.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: [Isoform SCPx]: Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids (PubMed:10706581). Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA) (PubMed:10706581). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro (By similarity). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl- branched fatty acyl-CoAs (By similarity). {ECO:0000250|UniProtKB:P11915, ECO:0000250|UniProtKB:P32020, ECO:0000269|PubMed:10706581}.

Function: [Isoform SCP2]: Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis (PubMed:17157249, PubMed:8300590, PubMed:7642518). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol (By similarity). Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity). {ECO:0000250|UniProtKB:P11915, ECO:0000250|UniProtKB:P32020, ECO:0000269|PubMed:17157249, ECO:0000269|PubMed:7642518, ECO:0000269|PubMed:8300590}.

Catalytic activity: [Isoform SCPx]: Reaction=choloyl-CoA + propanoyl-CoA = 3alpha,7alpha,12alpha- trihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA + CoA; Xref=Rhea:RHEA:16865, ChEBI:CHEBI:57287, ChEBI:CHEBI:57373, ChEBI:CHEBI:57392, ChEBI:CHEBI:58507; EC=2.3.1.176; Evidence={ECO:0000305|PubMed:10706581}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16867; Evidence={ECO:0000305|PubMed:10706581};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA; Xref=Rhea:RHEA:21564, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:58342, ChEBI:CHEBI:90726; EC=2.3.1.16; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + hexanoyl-CoA = 3-oxooctanoyl-CoA + CoA; Xref=Rhea:RHEA:31203, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:62619, ChEBI:CHEBI:62620; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31205; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CoA; Xref=Rhea:RHEA:18161, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57349, ChEBI:CHEBI:57385; EC=2.3.1.155; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18163; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=3-oxohexadecanedioyl-CoA + CoA = acetyl-CoA + tetradecanedioyl-CoA; Xref=Rhea:RHEA:40343, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:77081, ChEBI:CHEBI:77084; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40344; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=propanoyl-CoA + tetradecanoyl-CoA = 3-oxo-2- methylhexadecanoyl-CoA + CoA; Xref=Rhea:RHEA:46344, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57392, ChEBI:CHEBI:86042; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:46346; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + butanoyl-CoA = 3-oxohexanoyl-CoA + CoA; Xref=Rhea:RHEA:31111, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57371, ChEBI:CHEBI:62418; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31113; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + octanoyl-CoA = 3-oxodecanoyl-CoA + CoA; Xref=Rhea:RHEA:31087, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57386, ChEBI:CHEBI:62548; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31089; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + decanoyl-CoA = 3-oxododecanoyl-CoA + CoA; Xref=Rhea:RHEA:31183, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61430, ChEBI:CHEBI:62615; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31185; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + dodecanoyl-CoA = 3-oxotetradecanoyl-CoA + CoA; Xref=Rhea:RHEA:31091, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57375, ChEBI:CHEBI:62543; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31093; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=acetyl-CoA + hexadecanoyl-CoA = 3-oxooctadecanoyl-CoA + CoA; Xref=Rhea:RHEA:35279, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57379, ChEBI:CHEBI:71407; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:35281; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=3-oxo-(9Z-octadecenoyl)-CoA + CoA = (7Z)-hexadecenoyl-CoA + acetyl-CoA; Xref=Rhea:RHEA:47400, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:87695, ChEBI:CHEBI:87698; Evidence={ECO:0000250|UniProtKB:P11915}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47401; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCPx]: Reaction=cholesta-5,7-dien-3beta-ol(in) = cholesta-5,7-dien-3beta- ol(out); Xref=Rhea:RHEA:62960, ChEBI:CHEBI:17759; Evidence={ECO:0000250|UniProtKB:P11915};

Catalytic activity: [Isoform SCP2]: Reaction=cholesta-5,7-dien-3beta-ol(in) = cholesta-5,7-dien-3beta- ol(out); Xref=Rhea:RHEA:62960, ChEBI:CHEBI:17759; Evidence={ECO:0000269|PubMed:7642518};

Subunit: [Isoform SCP2]: Interacts with PEX5; the interaction is essential for peroxisomal import. {ECO:0000269|PubMed:17157249}.

Subcellular location: [Isoform SCP2]: Peroxisome {ECO:0000250|UniProtKB:P32020}. Cytoplasm {ECO:0000269|PubMed:10706581, ECO:0000269|PubMed:17157249}. Mitochondrion {ECO:0000269|PubMed:17157249}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P32020}. Mitochondrion {ECO:0000250|UniProtKB:P32020}.

Subcellular location: [Isoform SCPx]: Peroxisome {ECO:0000250|UniProtKB:P11915}.

Tissue specificity: Liver, fibroblasts, and placenta.

Induction: Up-regulated by 4-hydroxy-tamoxifen. {ECO:0000269|PubMed:14563822}.

Ptm: [Isoform SCP2]: preSCP2, a protein with a molecular mass of about 15 kDa, is processed into its mature form (SCP2) by proteolytic cleavage of a 20 residue leader sequence after translocation into peroxisomes. {ECO:0000250|UniProtKB:O62742}.

Disease: Leukoencephalopathy with dystonia and motor neuropathy (LKDMN) [MIM:613724]: A syndrome characterized by leukoencephalopathy, dystonic head tremor, spasmodic torticollis and reduced tendon reflexes in lower extremities. Additional features include hyposmia, pathologic saccadic eye movements, a slight hypoacusis, accumulation of branched-chain pristanic acid in plasma, and the presence of abnormal bile alcohol glucuronides in urine. {ECO:0000269|PubMed:16685654}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=Expression at protein level is almost abolished in Zellweger syndrome. Cholesterol transfer from the endoplasmic reticulum to the plasma membrane was reduced in patient fibroblasts compared to controls. {ECO:0000269|PubMed:7642518}.

Miscellaneous: [Isoform SCP2]: Contains a putative mitochondrial transit peptide at positions 1-20. {ECO:0000305|PubMed:17157249}.

Miscellaneous: [Isoform 4]: Produced by alternative splicing. {ECO:0000305}.

Miscellaneous: [Isoform 7]: Produced by alternative splicing. {ECO:0000305}.

Miscellaneous: [Isoform 8]: Produced by alternative splicing. {ECO:0000305}.

Similarity: In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family. {ECO:0000305}.

Sequence caution: Sequence=AAA03558.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		[Isoform SCPx]: Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids (PubMed:10706581). Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA) (PubMed:10706581). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro (By similarity). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl- branched fatty acyl-CoAs (By similarity). {ECO:0000250\|UniProtKB:P11915, ECO:0000250\|UniProtKB:P32020, ECO:0000269\|PubMed:10706581}.



Function:		[Isoform SCP2]: Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis (PubMed:17157249, PubMed:8300590, PubMed:7642518). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol (By similarity). Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity). {ECO:0000250\|UniProtKB:P11915, ECO:0000250\|UniProtKB:P32020, ECO:0000269\|PubMed:17157249, ECO:0000269\|PubMed:7642518, ECO:0000269\|PubMed:8300590}.


Catalytic activity:		[Isoform SCPx]: Reaction=choloyl-CoA + propanoyl-CoA = 3alpha,7alpha,12alpha- trihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA + CoA; Xref=Rhea:RHEA:16865, ChEBI:CHEBI:57287, ChEBI:CHEBI:57373, ChEBI:CHEBI:57392, ChEBI:CHEBI:58507; EC=2.3.1.176; Evidence={ECO:0000305\|PubMed:10706581}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16867; Evidence={ECO:0000305\|PubMed:10706581};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA; Xref=Rhea:RHEA:21564, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:58342, ChEBI:CHEBI:90726; EC=2.3.1.16; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + hexanoyl-CoA = 3-oxooctanoyl-CoA + CoA; Xref=Rhea:RHEA:31203, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:62619, ChEBI:CHEBI:62620; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31205; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CoA; Xref=Rhea:RHEA:18161, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57349, ChEBI:CHEBI:57385; EC=2.3.1.155; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18163; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=3-oxohexadecanedioyl-CoA + CoA = acetyl-CoA + tetradecanedioyl-CoA; Xref=Rhea:RHEA:40343, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:77081, ChEBI:CHEBI:77084; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40344; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=propanoyl-CoA + tetradecanoyl-CoA = 3-oxo-2- methylhexadecanoyl-CoA + CoA; Xref=Rhea:RHEA:46344, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:57392, ChEBI:CHEBI:86042; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:46346; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + butanoyl-CoA = 3-oxohexanoyl-CoA + CoA; Xref=Rhea:RHEA:31111, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57371, ChEBI:CHEBI:62418; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31113; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + octanoyl-CoA = 3-oxodecanoyl-CoA + CoA; Xref=Rhea:RHEA:31087, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57386, ChEBI:CHEBI:62548; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31089; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + decanoyl-CoA = 3-oxododecanoyl-CoA + CoA; Xref=Rhea:RHEA:31183, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61430, ChEBI:CHEBI:62615; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31185; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + dodecanoyl-CoA = 3-oxotetradecanoyl-CoA + CoA; Xref=Rhea:RHEA:31091, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57375, ChEBI:CHEBI:62543; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31093; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=acetyl-CoA + hexadecanoyl-CoA = 3-oxooctadecanoyl-CoA + CoA; Xref=Rhea:RHEA:35279, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57379, ChEBI:CHEBI:71407; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:35281; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=3-oxo-(9Z-octadecenoyl)-CoA + CoA = (7Z)-hexadecenoyl-CoA + acetyl-CoA; Xref=Rhea:RHEA:47400, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:87695, ChEBI:CHEBI:87698; Evidence={ECO:0000250\|UniProtKB:P11915}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47401; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCPx]: Reaction=cholesta-5,7-dien-3beta-ol(in) = cholesta-5,7-dien-3beta- ol(out); Xref=Rhea:RHEA:62960, ChEBI:CHEBI:17759; Evidence={ECO:0000250\|UniProtKB:P11915};
Catalytic activity:		[Isoform SCP2]: Reaction=cholesta-5,7-dien-3beta-ol(in) = cholesta-5,7-dien-3beta- ol(out); Xref=Rhea:RHEA:62960, ChEBI:CHEBI:17759; Evidence={ECO:0000269\|PubMed:7642518};
Subunit:		[Isoform SCP2]: Interacts with PEX5; the interaction is essential for peroxisomal import. {ECO:0000269\|PubMed:17157249}.
Subcellular location:		[Isoform SCP2]: Peroxisome {ECO:0000250\|UniProtKB:P32020}. Cytoplasm {ECO:0000269\|PubMed:10706581, ECO:0000269\|PubMed:17157249}. Mitochondrion {ECO:0000269\|PubMed:17157249}. Endoplasmic reticulum {ECO:0000250\|UniProtKB:P32020}. Mitochondrion {ECO:0000250\|UniProtKB:P32020}.
Subcellular location:		[Isoform SCPx]: Peroxisome {ECO:0000250\|UniProtKB:P11915}.
Tissue specificity:		Liver, fibroblasts, and placenta.
Induction:		Up-regulated by 4-hydroxy-tamoxifen. {ECO:0000269\|PubMed:14563822}.
Ptm:		[Isoform SCP2]: preSCP2, a protein with a molecular mass of about 15 kDa, is processed into its mature form (SCP2) by proteolytic cleavage of a 20 residue leader sequence after translocation into peroxisomes. {ECO:0000250\|UniProtKB:O62742}.
Disease:		Leukoencephalopathy with dystonia and motor neuropathy (LKDMN) [MIM:613724]: A syndrome characterized by leukoencephalopathy, dystonic head tremor, spasmodic torticollis and reduced tendon reflexes in lower extremities. Additional features include hyposmia, pathologic saccadic eye movements, a slight hypoacusis, accumulation of branched-chain pristanic acid in plasma, and the presence of abnormal bile alcohol glucuronides in urine. {ECO:0000269\|PubMed:16685654}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=Expression at protein level is almost abolished in Zellweger syndrome. Cholesterol transfer from the endoplasmic reticulum to the plasma membrane was reduced in patient fibroblasts compared to controls. {ECO:0000269\|PubMed:7642518}.
Miscellaneous:		[Isoform SCP2]: Contains a putative mitochondrial transit peptide at positions 1-20. {ECO:0000305\|PubMed:17157249}.
Miscellaneous:		[Isoform 4]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous:		[Isoform 7]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous:		[Isoform 8]: Produced by alternative splicing. {ECO:0000305}.
Similarity:		In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family. {ECO:0000305}.
Sequence caution:		Sequence=AAA03558.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};