Q921I0 · ORML1_MOUSE
- ProteinORM1-like protein 1
- GeneOrmdl1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids153 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:31880535).
When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity).
When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | serine palmitoyltransferase complex | |
Biological Process | ceramide metabolic process | |
Biological Process | intracellular sphingolipid homeostasis | |
Biological Process | motor behavior | |
Biological Process | myelination | |
Biological Process | negative regulation of ceramide biosynthetic process | |
Biological Process | regulation of ceramide biosynthetic process | |
Biological Process | regulation of sphingolipid biosynthetic process | |
Biological Process | sphingolipid biosynthetic process | |
Biological Process | sphingomyelin biosynthetic process |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameORM1-like protein 1
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ921I0
- 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 | 1-21 | Cytoplasmic | ||||
Sequence: MNVGVAHSEVNPNTRVMNSRG | ||||||
Transmembrane | 22-42 | Helical | ||||
Sequence: MWLTYALGVGLLHIVLLSIPF | ||||||
Topological domain | 43-46 | Extracellular | ||||
Sequence: CSVP | ||||||
Transmembrane | 47-67 | Helical | ||||
Sequence: VAWTLTNIIHNLGMYVFLHAV | ||||||
Topological domain | 68-100 | Cytoplasmic | ||||
Sequence: KGTPFETPDQGRARLLTHWEQLDYGVQFTSSRK | ||||||
Transmembrane | 101-121 | Helical | ||||
Sequence: FFTISPIILYFLASFYTKYDP | ||||||
Topological domain | 122-123 | Extracellular | ||||
Sequence: TH | ||||||
Transmembrane | 124-140 | Helical | ||||
Sequence: FILNTASLLSVLIPKMP | ||||||
Topological domain | 141-153 | Cytoplasmic | ||||
Sequence: QLHGVRIFGINKY |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
No overt phenotype; due to the redundancy with other ORMDL proteins (PubMed:31880535).
Simultaneous knockdown of ORMDL1 and ORMDL2 do not exhibit any visible phenotype; they remain fertile and show no sign of neurodegeneration (PubMed:31880535).
Double knockdown of ORMDL1 and ORMDL3 show elevated brain levels of sphingolipids, compared with single ORMDL3 knockout and wild-type animals (PubMed:31880535).
At 8 weeks of age, both male and female ORMDL1/3 double knockout mice weigh significantly less than wild-type mice and exhibit impaired myelination and motor-function abnormalities (PubMed:31880535).
The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not viable (PubMed:31880535).
Simultaneous knockdown of ORMDL1 and ORMDL2 do not exhibit any visible phenotype; they remain fertile and show no sign of neurodegeneration (PubMed:31880535).
Double knockdown of ORMDL1 and ORMDL3 show elevated brain levels of sphingolipids, compared with single ORMDL3 knockout and wild-type animals (PubMed:31880535).
At 8 weeks of age, both male and female ORMDL1/3 double knockout mice weigh significantly less than wild-type mice and exhibit impaired myelination and motor-function abnormalities (PubMed:31880535).
The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not viable (PubMed:31880535).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 6 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000215631 | 1-153 | ORM1-like protein 1 | |||
Sequence: MNVGVAHSEVNPNTRVMNSRGMWLTYALGVGLLHIVLLSIPFCSVPVAWTLTNIIHNLGMYVFLHAVKGTPFETPDQGRARLLTHWEQLDYGVQFTSSRKFFTISPIILYFLASFYTKYDPTHFILNTASLLSVLIPKMPQLHGVRIFGINKY |
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Domain
Ceramides bind to ORMDL3 N-terminus and stabilize it in a conformation that physically restricts the accessibility of the substrates to their binding sites in the serine palmitoyltransferase (SPT) complex, hence inhibiting SPT catalytic activity. In the absence of ceramides, the N-terminus is flexible and permits substrate binding, thus liberating SPT from inhibition.
Sequence similarities
Belongs to the ORM family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length153
- Mass (Da)17,355
- Last updated2001-12-01 v1
- ChecksumA592BCA2BEB1AC6B
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 123 | in Ref. 1; BAC36865 | ||||
Sequence: H → N |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK050385 EMBL· GenBank· DDBJ | BAC34226.1 EMBL· GenBank· DDBJ | mRNA | ||
AK077562 EMBL· GenBank· DDBJ | BAC36865.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012315 EMBL· GenBank· DDBJ | AAH12315.1 EMBL· GenBank· DDBJ | mRNA | ||
BC023695 EMBL· GenBank· DDBJ | AAH23695.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025572 EMBL· GenBank· DDBJ | AAH25572.1 EMBL· GenBank· DDBJ | mRNA |