Q9Y5Q0 · FADS3_HUMAN
- ProteinFatty acid desaturase 3
- GeneFADS3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids445 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mammals have different sphingoid bases that differ in their length and/or pattern of desaturation and hydroxyl groups. The predominant sphingoid base that comprises mammalian ceramides is sphing-4-enine (sphingosine or SPH) which has a trans (E) desaturation at carbon 4 (PubMed:31862735, PubMed:31916624).
FADS3 is a desaturase that introduces a cis (Z) double bond between carbon 14 and carbon 15 of the sphingoid base (also known as long chain base, LCB), producing LCBs such as sphinga-4,14-dienine (SPD, d18:2(4E,14Z)) from SPH (PubMed:31862735, PubMed:31916624, PubMed:37209771).
Prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates (PubMed:31862735, PubMed:31916624, PubMed:37209771).
Capable of metabolizing also the SPH in its free form (PubMed:31862735).
SPD ceramides occur widely in mammalian tissues and cells (PubMed:31916624).
Due to their unusual structure containing a cis double bond, SPD ceramides may have an opposite, negative role in lipid microdomain formation relative to conventional ceramides (PubMed:31916624).
Could be involved in the detoxification of 1-deoxy sphingolipids, by desaturating the cytotoxic 1-deoxysphinganine (1-deoxySA, m18:0), produced under pathological conditions, to 1-deoxysphingenine (1-deoxysphingosine, 1-deoxySO, m18:1) (Probable). Although prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates, it also exhibits activity toward dihydrosphingosine-containing CERs (N-acylsphinganines) and produces 14Z-SPH-containing sphingolipids,which can be found in patients with DEGS1 mutations (PubMed:37209771).
Its desaturase mechanism involves an electron transfer facilitated by cytochrome b5 (PubMed:37209771).
FADS3 also acts as a methyl-end fatty acyl coenzyme A (CoA) desaturase that introduces a cis double bond between the preexisting double bond and the terminal methyl group of the fatty acyl chain (By similarity).
Desaturates (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 13 to generate (11E,13Z)-octadecadienoate (also known as conjugated linoleic acid 11E,13Z-CLA) (By similarity).
FADS3 is a desaturase that introduces a cis (Z) double bond between carbon 14 and carbon 15 of the sphingoid base (also known as long chain base, LCB), producing LCBs such as sphinga-4,14-dienine (SPD, d18:2(4E,14Z)) from SPH (PubMed:31862735, PubMed:31916624, PubMed:37209771).
Prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates (PubMed:31862735, PubMed:31916624, PubMed:37209771).
Capable of metabolizing also the SPH in its free form (PubMed:31862735).
SPD ceramides occur widely in mammalian tissues and cells (PubMed:31916624).
Due to their unusual structure containing a cis double bond, SPD ceramides may have an opposite, negative role in lipid microdomain formation relative to conventional ceramides (PubMed:31916624).
Could be involved in the detoxification of 1-deoxy sphingolipids, by desaturating the cytotoxic 1-deoxysphinganine (1-deoxySA, m18:0), produced under pathological conditions, to 1-deoxysphingenine (1-deoxysphingosine, 1-deoxySO, m18:1) (Probable). Although prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates, it also exhibits activity toward dihydrosphingosine-containing CERs (N-acylsphinganines) and produces 14Z-SPH-containing sphingolipids,which can be found in patients with DEGS1 mutations (PubMed:37209771).
Its desaturase mechanism involves an electron transfer facilitated by cytochrome b5 (PubMed:37209771).
FADS3 also acts as a methyl-end fatty acyl coenzyme A (CoA) desaturase that introduces a cis double bond between the preexisting double bond and the terminal methyl group of the fatty acyl chain (By similarity).
Desaturates (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 13 to generate (11E,13Z)-octadecadienoate (also known as conjugated linoleic acid 11E,13Z-CLA) (By similarity).
Miscellaneous
A 28 kDa isoform is expressed in lung, kidney, pancreas and ovary (at protein level).
Catalytic activity
- an N-acylsphing-4-enine + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = an N-acyl-sphinga-4E,14Z-dienine + 2 Fe(III)-[cytochrome b5] + 2 H2OThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + N-(hexanoyl)sphing-4-enine + O2 = 2 Fe(III)-[cytochrome b5] + 2 H2O + N-hexanoyl-sphinga-4E,14Z-dienineThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 + sphing-4-enine = 2 Fe(III)-[cytochrome b5] + 2 H2O + sphinga-4E,14Z-dienineThis reaction proceeds in the forward direction.
- (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = (11E,13Z)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2OThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + N-acyl-1-deoxysphinganine + O2 = 2 Fe(III)-[cytochrome b5] + 2 H2O + N-acyl-1-deoxysphing-14Z-enineThis reaction proceeds in the forward direction.
- an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = an N-acylsphing-14Z-enine + 2 Fe(III)-[cytochrome b5] + 2 H2OThis reaction proceeds in the forward direction.
Pathway
Lipid metabolism; sphingolipid metabolism.
Lipid metabolism; polyunsaturated fatty acid biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Molecular Function | oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water | |
Biological Process | lipid metabolic process | |
Biological Process | sphingolipid metabolic process | |
Biological Process | unsaturated fatty acid biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameFatty acid desaturase 3
- EC number
- Short namesFADS3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y5Q0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-133 | Cytoplasmic | ||||
Sequence: MGGVGEPGPREGPAQPGAPLPTFCWEQIRAHDQPGDKWLVIERRVYDISRWAQRHPGGSRLIGHHGAEDATDAFRAFHQDLNFVRKFLQPLLIGELAPEEPSQDGPLNAQLVEDFRALHQAAEDMKLFDASPT | ||||||
Transmembrane | 134-154 | Helical | ||||
Sequence: FFAFLLGHILAMEVLAWLLIY | ||||||
Topological domain | 155-159 | Lumenal | ||||
Sequence: LLGPG | ||||||
Transmembrane | 160-180 | Helical | ||||
Sequence: WVPSALAAFILAISQAQSWCL | ||||||
Topological domain | 181-263 | Cytoplasmic | ||||
Sequence: QHDLGHASIFKKSWWNHVAQKFVMGQLKGFSAHWWNFRHFQHHAKPNIFHKDPDVTVAPVFLLGESSVEYGKKKRRYLPYNQQ | ||||||
Transmembrane | 264-284 | Helical | ||||
Sequence: HLYFFLIGPPLLTLVNFEVEN | ||||||
Topological domain | 285-306 | Lumenal | ||||
Sequence: LAYMLVCMQWADLLWAASFYAR | ||||||
Transmembrane | 307-327 | Helical | ||||
Sequence: FFLSYLPFYGVPGVLLFFVAV | ||||||
Topological domain | 328-445 | Cytoplasmic | ||||
Sequence: RVLESHWFVWITQMNHIPKEIGHEKHRDWVSSQLAATCNVEPSLFTNWFSGHLNFQIEHHLFPRMPRHNYSRVAPLVKSLCAKHGLSYEVKPFLTALVDIVRSLKKSGDIWLDAYLHQ |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_035341 | 192 | in dbSNP:rs35479241 | |||
Sequence: K → N | ||||||
Natural variant | VAR_035342 | 216 | in dbSNP:rs34511441 | |||
Sequence: N → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 419 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000307108 | 1-445 | Fatty acid desaturase 3 | |||
Sequence: MGGVGEPGPREGPAQPGAPLPTFCWEQIRAHDQPGDKWLVIERRVYDISRWAQRHPGGSRLIGHHGAEDATDAFRAFHQDLNFVRKFLQPLLIGELAPEEPSQDGPLNAQLVEDFRALHQAAEDMKLFDASPTFFAFLLGHILAMEVLAWLLIYLLGPGWVPSALAAFILAISQAQSWCLQHDLGHASIFKKSWWNHVAQKFVMGQLKGFSAHWWNFRHFQHHAKPNIFHKDPDVTVAPVFLLGESSVEYGKKKRRYLPYNQQHLYFFLIGPPLLTLVNFEVENLAYMLVCMQWADLLWAASFYARFFLSYLPFYGVPGVLLFFVAVRVLESHWFVWITQMNHIPKEIGHEKHRDWVSSQLAATCNVEPSLFTNWFSGHLNFQIEHHLFPRMPRHNYSRVAPLVKSLCAKHGLSYEVKPFLTALVDIVRSLKKSGDIWLDAYLHQ |
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in various organs and tissues including liver, kidney, brain, lung, pancreas, testis, ovary and skeletal muscle (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y5Q0 | DHRSX Q8N5I4 | 3 | EBI-17548630, EBI-3923585 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MGGVGEPGPREGPAQPGAPLP | ||||||
Domain | 20-97 | Cytochrome b5 heme-binding | ||||
Sequence: LPTFCWEQIRAHDQPGDKWLVIERRVYDISRWAQRHPGGSRLIGHHGAEDATDAFRAFHQDLNFVRKFLQPLLIGELA | ||||||
Motif | 182-186 | Histidine box-1 | ||||
Sequence: HDLGH | ||||||
Motif | 219-223 | Histidine box-2 | ||||
Sequence: HFQHH | ||||||
Motif | 383-387 | Histidine box-3 | ||||
Sequence: QIEHH |
Domain
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.
Sequence similarities
Belongs to the fatty acid desaturase type 1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length445
- Mass (Da)51,145
- Last updated1999-11-01 v1
- Checksum7840EF6BE055111D
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF084560 EMBL· GenBank· DDBJ | AAG23122.1 EMBL· GenBank· DDBJ | mRNA | ||
AF134404 EMBL· GenBank· DDBJ | AAD31282.1 EMBL· GenBank· DDBJ | mRNA | ||
AC004770 EMBL· GenBank· DDBJ | AAC23396.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AP006260 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC004901 EMBL· GenBank· DDBJ | AAH04901.1 EMBL· GenBank· DDBJ | mRNA |