O75907 · DGAT1_HUMAN
- ProteinDiacylglycerol O-acyltransferase 1
- GeneDGAT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids488 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates (PubMed:16214399, PubMed:18768481, PubMed:28420705, PubMed:32433610, PubMed:32433611, PubMed:9756920).
Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats (PubMed:18768481).
In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage (PubMed:16214399).
Also present in female mammary glands, where it produces fat in the milk (By similarity).
May be involved in VLDL (very low density lipoprotein) assembly (PubMed:18768481).
In contrast to DGAT2 it is not essential for survival (By similarity).
Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders (PubMed:16214399).
Exhibits additional acyltransferase activities, includin acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases (By similarity).
Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705).
Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats (PubMed:18768481).
In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage (PubMed:16214399).
Also present in female mammary glands, where it produces fat in the milk (By similarity).
May be involved in VLDL (very low density lipoprotein) assembly (PubMed:18768481).
In contrast to DGAT2 it is not essential for survival (By similarity).
Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders (PubMed:16214399).
Exhibits additional acyltransferase activities, includin acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases (By similarity).
Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705).
Catalytic activity
- a 1,2-diacyl-sn-glycerol + an acyl-CoA = a triacyl-sn-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 2-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1,2-di-(9Z-octadecenoyl)-sn-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoAThis reaction proceeds in the forward direction.
- all-trans-retinol + hexadecanoyl-CoA = all-trans-retinyl hexadecanoate + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecenyl)-glycerol = 1-O-(9Z-octadecyl)-3-(9Z-octadecenoyl)-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecyl)-3-(9Z-octadecenoyl)-glycerol = 1-O-(9Z-octadecenyl)-2,3-di-(9Z-octadecenoyl)glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H+ = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2OThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-3-(9Z)-octadecenoyl-sn-glycerol + CoAThis reaction proceeds in the forward direction.
- hexadecane-1,2-diol + 2 hexadecanoyl-CoA = 1,2-O,O-dihexadecanoyl-1,2-hexadecanediol + 2 CoAThis reaction proceeds in the forward direction.
- hexadecane-1,2-diol + hexadecanoyl-CoA = 2-hydroxyhexadecyl hexadecanoate + CoAThis reaction proceeds in the forward direction.
- 2-(9Z-octadecenoyl)-glycerol + hexadecanoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + CoAThis reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycerol + hexadecanoyl-CoA = 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + CoAThis reaction proceeds in the forward direction.
- hexadecan-1-ol + hexadecanoyl-CoA = CoA + hexadecanyl hexadecanoateThis reaction proceeds in the forward direction.
- 13-cis-retinol + hexadecanoyl-CoA = 13-cis-retinyl hexadecanoate + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1,3-di-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 2,3-di-(9Z)-octadecenoyl-sn-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoAThis reaction proceeds in the forward direction.
Activity regulation
XP620 is a selective DGAT1 inhibitor.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
25.9 μM | retinol | |||||
13.9 μM | palmitoyl coenzyme A | |||||
14.6 μM | (9Z)-octadecenoyl-CoA | |||||
8.6 μM | octadecanoyl-CoA | |||||
6.4 μM | hexadecanoyl-coA | |||||
6.2 μM | (9Z)-hexadecenoyl-CoA | |||||
597.1 μM | 1,2-di-(9Z-octadecenoyl)-sn-glycerol (with DGAT1 as homodimer) | |||||
497.5 μM | 1,2-di-(9Z-octadecenoyl)-sn-glycerol (with DGAT1 as homotetramer) |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
956.6 pmol/min/ug | with (9Z)-octadecenoyl-CoA as substrate | ||||
839.4 pmol/min/ug | with octadecanoyl-CoA as substrate | ||||
767.8 pmol/min/ug | with hexadecanoyl-coA as substrate | ||||
838.6 pmol/min/ug | with (9Z)-hexadecenoyl-CoA as substrate | ||||
3310 pmol/min/ug | with 1,2-di-(9Z-octadecenoyl)-sn-glycerol (with DGAT1 as homodimer) as substrate | ||||
3628 pmol/min/ug | with 1,2-di-(9Z-octadecenoyl)-sn-glycerol (with DGAT1 as homotetramer) as substrate |
Pathway
Lipid metabolism; glycerolipid metabolism.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 374-382 | an acyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: WQNWNIPVH | ||||||
Binding site | 390 | an acyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 404 | an acyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Active site | 415 | |||||
Sequence: H | ||||||
Site | 416 | Important for catalytic activity | ||||
Sequence: E | ||||||
Binding site | 477 | an acyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Cellular Component | specific granule membrane | |
Molecular Function | 2-acylglycerol O-acyltransferase activity | |
Molecular Function | acyltransferase activity | |
Molecular Function | diacylglycerol O-acyltransferase activity | |
Molecular Function | identical protein binding | |
Molecular Function | retinol O-fatty-acyltransferase activity | |
Biological Process | diacylglycerol metabolic process | |
Biological Process | fatty acid homeostasis | |
Biological Process | lipid storage | |
Biological Process | long-chain fatty-acyl-CoA metabolic process | |
Biological Process | monoacylglycerol biosynthetic process | |
Biological Process | triglyceride biosynthetic process | |
Biological Process | triglyceride metabolic process | |
Biological Process | very-low-density lipoprotein particle assembly |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameDiacylglycerol O-acyltransferase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75907
- 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 | 1-83 | Cytoplasmic | ||||
Sequence: MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDAGVGSGHWELRCHRLQDSLFSSDSGFS | ||||||
Transmembrane | 84-118 | Helical; Name=1 | ||||
Sequence: NYRGILNWCVVMLILSNARLFLENLIKYGILVDPI | ||||||
Topological domain | 119-130 | Lumenal | ||||
Sequence: QVVSLFLKDPYS | ||||||
Transmembrane | 131-156 | Helical; Name=2 | ||||
Sequence: WPAPCLVIAANVFAVAAFQVEKRLAV | ||||||
Topological domain | 157-161 | Cytoplasmic | ||||
Sequence: GALTE | ||||||
Transmembrane | 162-184 | Helical; Name=3 | ||||
Sequence: QAGLLLHVANLATILCFPAAVVL | ||||||
Topological domain | 185-191 | Lumenal | ||||
Sequence: LVESITP | ||||||
Transmembrane | 192-223 | Helical; Name=4 | ||||
Sequence: VGSLLALMAHTILFLKLFSYRDVNSWCRRARA | ||||||
Topological domain | 224-273 | Cytoplasmic | ||||
Sequence: KAASAGKKASSAAAPHTVSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRI | ||||||
Transmembrane | 274-308 | Helical; Name=5 | ||||
Sequence: RKRFLLRRILEMLFFTQLQVGLIQQWMVPTIQNSM | ||||||
Topological domain | 309-315 | Lumenal | ||||
Sequence: KPFKDMD | ||||||
Transmembrane | 316-353 | Helical; Name=6 | ||||
Sequence: YSRIIERLLKLAVPNHLIWLIFFYWLFHSCLNAVAELM | ||||||
Topological domain | 354-399 | Cytoplasmic | ||||
Sequence: QFGDREFYRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSS | ||||||
Transmembrane | 400-420 | Helical; Name=7 | ||||
Sequence: KWMARTGVFLASAFFHEYLVS | ||||||
Topological domain | 421-428 | Lumenal | ||||
Sequence: VPLRMFRL | ||||||
Transmembrane | 429-447 | Helical; Name=8 | ||||
Sequence: WAFTGMMAQIPLAWFVGRF | ||||||
Topological domain | 448-449 | Cytoplasmic | ||||
Sequence: FQ | ||||||
Transmembrane | 450-481 | Helical; Name=9 | ||||
Sequence: GNYGNAAVWLSLIIGQPIAVLMYVHDYYVLNY | ||||||
Topological domain | 482-488 | Lumenal | ||||
Sequence: EAPAAEA |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Diarrhea 7, protein-losing enteropathy type (DIAR7)
- Note
- DescriptionA life-threatening disease characterized by severe, intractable, watery diarrhea.
- See alsoMIM:615863
Natural variants in DIAR7
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_082141 | 458-488 | missing | in DIAR7; uncertain significance |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 346 | Strongly reduced diacylglycerol O-acyltransferase activity. | ||||
Sequence: L → W | ||||||
Mutagenesis | 371 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 375 | Slightly decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 377 | Abolished diacylglycerol O-acyltransferase activity. | ||||
Sequence: W → F | ||||||
Mutagenesis | 378 | Abolished diacylglycerol O-acyltransferase activity. | ||||
Sequence: N → A or L | ||||||
Mutagenesis | 381 | Does not affect diacylglycerol O-acyltransferase activity. | ||||
Sequence: V → A | ||||||
Mutagenesis | 381 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: V → W | ||||||
Mutagenesis | 382 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 385 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: C → W | ||||||
Mutagenesis | 386 | Slightly decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: I → A | ||||||
Mutagenesis | 390 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 391 | Slightly decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 400 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: K → L | ||||||
Mutagenesis | 404 | Does not affect diacylglycerol O-acyltransferase activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 404 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: R → L | ||||||
Mutagenesis | 407 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: V → F | ||||||
Mutagenesis | 411 | Abolished diacylglycerol O-acyltransferase activity. | ||||
Sequence: S → A or W | ||||||
Mutagenesis | 411 | Decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: S → I | ||||||
Mutagenesis | 415 | Abolished diacylglycerol O-acyltransferase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 416 | Abolished diacylglycerol O-acyltransferase activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 434 | Reduced diacylglycerol O-acyltransferase activity. | ||||
Sequence: M → A or I | ||||||
Mutagenesis | 437 | Reduced diacylglycerol O-acyltransferase activity. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_082141 | 458-488 | in DIAR7; uncertain significance | |||
Sequence: Missing | ||||||
Mutagenesis | 465 | Reduced diacylglycerol O-acyltransferase activity. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 469 | Slightly decreased diacylglycerol O-acyltransferase activity. | ||||
Sequence: V → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,055 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, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000207654 | 1-488 | UniProt | Diacylglycerol O-acyltransferase 1 | |||
Sequence: MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDAGVGSGHWELRCHRLQDSLFSSDSGFSNYRGILNWCVVMLILSNARLFLENLIKYGILVDPIQVVSLFLKDPYSWPAPCLVIAANVFAVAAFQVEKRLAVGALTEQAGLLLHVANLATILCFPAAVVLLVESITPVGSLLALMAHTILFLKLFSYRDVNSWCRRARAKAASAGKKASSAAAPHTVSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRIRKRFLLRRILEMLFFTQLQVGLIQQWMVPTIQNSMKPFKDMDYSRIIERLLKLAVPNHLIWLIFFYWLFHSCLNAVAELMQFGDREFYRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSSKWMARTGVFLASAFFHEYLVSVPLRMFRLWAFTGMMAQIPLAWFVGRFFQGNYGNAAVWLSLIIGQPIAVLMYVHDYYVLNYEAPAAEA | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 17 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 18 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 18 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer or homotetramer; both forms have similar enzymatic activities.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75907 | DGAT1 O75907 | 4 | EBI-3906527, EBI-3906527 | |
XENO | O75907 | PRO_0000045602 Q99IB8 | 2 | EBI-3906527, EBI-6927873 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-57 | Disordered | ||||
Sequence: MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDA | ||||||
Region | 1-91 | Involved in homomerization | ||||
Sequence: MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDAGVGSGHWELRCHRLQDSLFSSDSGFSNYRGILNW | ||||||
Region | 119-130 | Extracellular loop 1 (EL1) | ||||
Sequence: QVVSLFLKDPYS | ||||||
Region | 131-488 | MBOAT fold | ||||
Sequence: WPAPCLVIAANVFAVAAFQVEKRLAVGALTEQAGLLLHVANLATILCFPAAVVLLVESITPVGSLLALMAHTILFLKLFSYRDVNSWCRRARAKAASAGKKASSAAAPHTVSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRIRKRFLLRRILEMLFFTQLQVGLIQQWMVPTIQNSMKPFKDMDYSRIIERLLKLAVPNHLIWLIFFYWLFHSCLNAVAELMQFGDREFYRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSSKWMARTGVFLASAFFHEYLVSVPLRMFRLWAFTGMMAQIPLAWFVGRFFQGNYGNAAVWLSLIIGQPIAVLMYVHDYYVLNYEAPAAEA | ||||||
Region | 224-276 | Intracellular loop 1 (IL1) | ||||
Sequence: KAASAGKKASSAAAPHTVSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRIRKR | ||||||
Region | 354-399 | Intracellular loop 2 (IL2) | ||||
Sequence: QFGDREFYRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSS | ||||||
Motif | 360-366 | FYXDWWN motif | ||||
Sequence: FYRDWWN | ||||||
Region | 380-394 | Amphipathic helix (AH) | ||||
Sequence: PVHKWCIRHFYKPML |
Domain
The disordered N-terminal region is required for the diacylglycerol O-acyltransferase activity and may regulate enzymatic function via its interaction with the MBOAT fold.
The MBOAT fold forms a reaction chamber in the endoplasmic reticulum membrane that encloses the active sites (PubMed:32433610, PubMed:32433611).
The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule (PubMed:32433610).
The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol (PubMed:32433610).
The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule (PubMed:32433610).
The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol (PubMed:32433610).
Sequence similarities
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length488
- Mass (Da)55,278
- Last updated2003-07-25 v2
- Checksum6574D5DBF15D6171
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A0MR74 | A0A0A0MR74_HUMAN | DGAT1 | 315 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 129 | in Ref. 1; AAC63997 | ||||
Sequence: Y → H |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF059202 EMBL· GenBank· DDBJ | AAC63997.1 EMBL· GenBank· DDBJ | mRNA | ||
AB057815 EMBL· GenBank· DDBJ | BAC66170.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471162 EMBL· GenBank· DDBJ | EAW82127.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471162 EMBL· GenBank· DDBJ | EAW82129.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC015762 EMBL· GenBank· DDBJ | AAH15762.1 EMBL· GenBank· DDBJ | mRNA | ||
BC023565 EMBL· GenBank· DDBJ | AAH23565.1 EMBL· GenBank· DDBJ | mRNA | ||
BC150649 EMBL· GenBank· DDBJ | AAI50650.1 EMBL· GenBank· DDBJ | mRNA |