Q14849 · STAR3_HUMAN
- ProteinStAR-related lipid transfer protein 3
- GeneSTARD3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids445 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:11053434, PubMed:15930133, PubMed:22514632, PubMed:28377464, PubMed:33124732).
The sterol transport mechanism is triggered by phosphorylation of FFAT motif that leads to membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes (PubMed:28377464).
May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane (PubMed:12070139, PubMed:19965586).
However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:28377464).
Does not activate transcriptional cholesterol sensing (PubMed:28377464).
Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina (PubMed:21322544).
The sterol transport mechanism is triggered by phosphorylation of FFAT motif that leads to membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes (PubMed:28377464).
May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane (PubMed:12070139, PubMed:19965586).
However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:28377464).
Does not activate transcriptional cholesterol sensing (PubMed:28377464).
Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina (PubMed:21322544).
Catalytic activity
- cholesterol(in) = cholesterol(out)
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum-endosome membrane contact site | |
Cellular Component | endosome | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | late endosome membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | mitochondrion | |
Cellular Component | nucleoplasm | |
Cellular Component | organelle membrane contact site | |
Molecular Function | cholesterol binding | |
Molecular Function | cholesterol transfer activity | |
Molecular Function | protein homodimerization activity | |
Biological Process | cholesterol metabolic process | |
Biological Process | cholesterol transport | |
Biological Process | lipid metabolic process | |
Biological Process | mitochondrial transport | |
Biological Process | progesterone biosynthetic process | |
Biological Process | steroid metabolic process | |
Biological Process | vesicle tethering to endoplasmic reticulum |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameStAR-related lipid transfer protein 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ14849
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Late endosome membrane ; Multi-pass membrane protein
Note: Localizes to contact sites between the endoplasmic reticulum and late endosomes: associates with the endoplasmic reticulum membrane via interaction with VAPA, VAPB or MOSPD2.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-51 | Cytoplasmic | ||||
Sequence: MSKLPRELTRDLERSLPAVASLGSSLSHSQSLSSHLLPPPEKRRAISDVRR | ||||||
Transmembrane | 52-72 | Helical | ||||
Sequence: TFCLFVTFDLLFISLLWIIEL | ||||||
Topological domain | 73-94 | Extracellular | ||||
Sequence: NTNTGIRKNLEQEIIQYNFKTS | ||||||
Transmembrane | 95-115 | Helical | ||||
Sequence: FFDIFVLAFFRFSGLLLGYAV | ||||||
Topological domain | 116-120 | Cytoplasmic | ||||
Sequence: LRLRH | ||||||
Transmembrane | 121-141 | Helical | ||||
Sequence: WWVIAVTTLVSSAFLIVKVIL | ||||||
Topological domain | 142-148 | Extracellular | ||||
Sequence: SELLSKG | ||||||
Transmembrane | 149-169 | Helical | ||||
Sequence: AFGYLLPIVSFVLAWLETWFL | ||||||
Topological domain | 170-445 | Cytoplasmic | ||||
Sequence: DFKVLPQEAEEERWYLAAQVAVARGPLLFSGALSEGQFYSPPESFAGSDNESDEEVAGKKSFSAQEREYIRQGKEATAVVDQILAQEENWKFEKNNEYGDTVYTIEVPFHGKTFILKTFLPCPAELVYQEVILQPERMVLWNKTVTACQILQRVEDNTLISYDVSAGAAGGVVSPRDFVNVRRIERRRDRYLSSGIATSHSAKPPTHKYVRGENGPGGFIVLKSASNPRVCTFVWILNTDLKGRLPRYLIHQSLAATMFEFAFHLRQRISELGARA |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 66-67 | Abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum. | ||||
Sequence: LL → AS | ||||||
Mutagenesis | 89 | Abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum. | ||||
Sequence: Y → V | ||||||
Mutagenesis | 113 | Does not affect localization to late endosomes. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_027877 | 117 | in dbSNP:rs1877031 | |||
Sequence: R → Q | ||||||
Mutagenesis | 206-212 | Abolishes interaction with VAPA and VAPB, thereby preventing contact with the endoplasmic reticulum membrane. | ||||
Sequence: Missing | ||||||
Mutagenesis | 207-208 | Abolishes interaction with VAPA, VAPB and MOSPD2, thereby preventing contact with the endoplasmic reticulum membrane. Abolishes cholesterol accumulation in endosomes. | ||||
Sequence: FY → AA | ||||||
Mutagenesis | 209 | Impairs VAPA and VAPB interaction. Does not affect endoplasmic reticulum membrane location of VAPA, VAPB and MOSPD2. Is unable to make ER-endosome contacts. Does not accumulate cholesterol in late endosomes (LEs). Does not interact with MOSPD2. | ||||
Sequence: S → A | ||||||
Mutagenesis | 209 | Does not affect VAPA and VAPB interactions; when associated with A-210. Does not interact with VAPA and VAPB. Recruits VAPA and VAPB around the endosome; when associated with A-210. Restores cholesterol accumulation in late endosomes; when associated with A-210. Moderately interacts with MOSPD2. Almost impairs interaction with MOSPD2; when associated with A-210. | ||||
Sequence: S → D | ||||||
Mutagenesis | 210 | Does not affect VAPA and VAPB interactions; when associated with D-209. Improve VAPA interaction. Does not interact with VAPA and VAPB. Recruits VAPA and VAPB around the endosome; when associated with D-209.Restores cholesterol accumulation in late endosomes; when associated with A-209. Almost impairs interaction with MOSPD2; when associated with A-209. | ||||
Sequence: P → A | ||||||
Natural variant | VAR_027878 | 216 | in dbSNP:rs11556624 | |||
Sequence: G → A | ||||||
Mutagenesis | 219 | Does not affect localization to late endosomes. | ||||
Sequence: N → A | ||||||
Mutagenesis | 307-311 | Abolishes ability to transfer cholesterol between membranes. | ||||
Sequence: MVLWN → NVLWD | ||||||
Mutagenesis | 311 | Does not affect localization to late endosomes. | ||||
Sequence: N → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 518 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000220653 | 1-445 | UniProt | StAR-related lipid transfer protein 3 | |||
Sequence: MSKLPRELTRDLERSLPAVASLGSSLSHSQSLSSHLLPPPEKRRAISDVRRTFCLFVTFDLLFISLLWIIELNTNTGIRKNLEQEIIQYNFKTSFFDIFVLAFFRFSGLLLGYAVLRLRHWWVIAVTTLVSSAFLIVKVILSELLSKGAFGYLLPIVSFVLAWLETWFLDFKVLPQEAEEERWYLAAQVAVARGPLLFSGALSEGQFYSPPESFAGSDNESDEEVAGKKSFSAQEREYIRQGKEATAVVDQILAQEENWKFEKNNEYGDTVYTIEVPFHGKTFILKTFLPCPAELVYQEVILQPERMVLWNKTVTACQILQRVEDNTLISYDVSAGAAGGVVSPRDFVNVRRIERRRDRYLSSGIATSHSAKPPTHKYVRGENGPGGFIVLKSASNPRVCTFVWILNTDLKGRLPRYLIHQSLAATMFEFAFHLRQRISELGARA | |||||||
Modified residue | 209 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 209 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 217 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 221 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Ser-209 is necessary and sufficient for the direct interaction of the phosphorylated FFAT motif with the MSP domain of MOSPD2, VAPA and VAPB and allows the tethering of two membranes that participates in the formation of ER-endosome contacts (PubMed:33124732).
Phosphorylation of the FFAT motif leads to conformation changes (PubMed:33124732).
Additional phosphorylations around the core FFAT motif (QFYSPPE) are not essential but strengthen the interaction with MOSPD2, VAPA and VAPB (PubMed:33124732).
Phosphorylation at Ser-209 of FFAT motif drives membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB that in turn allows the efficient transport of sterol mediated by the START domain (PubMed:33124732).
Phosphorylation of the FFAT motif leads to conformation changes (PubMed:33124732).
Additional phosphorylations around the core FFAT motif (QFYSPPE) are not essential but strengthen the interaction with MOSPD2, VAPA and VAPB (PubMed:33124732).
Phosphorylation at Ser-209 of FFAT motif drives membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB that in turn allows the efficient transport of sterol mediated by the START domain (PubMed:33124732).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in retina.
Induction
Not regulated by increases in total cholesterol content, or by marked alterations in cholesterol flux.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:15718238, PubMed:16709157).
Interacts (via the MENTAL domain) with STARD3NL (PubMed:15718238, PubMed:16709157).
Interacts (via phosphorylated FFAT motif) with VAPA (via MSP domain) (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Interacts (via phosphorylated FFAT motif) with VAPB (via MSP domain) (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Interacts (via phosphorylated FFAT motif) with MOSPD2 (via MSP domain); this interaction allows enrichment of MOSPD2 around endosomes (PubMed:29858488, PubMed:33124732).
Interacts (via the MENTAL domain) with STARD3NL (PubMed:15718238, PubMed:16709157).
Interacts (via phosphorylated FFAT motif) with VAPA (via MSP domain) (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Interacts (via phosphorylated FFAT motif) with VAPB (via MSP domain) (PubMed:24105263, PubMed:28377464, PubMed:33124732).
Interacts (via phosphorylated FFAT motif) with MOSPD2 (via MSP domain); this interaction allows enrichment of MOSPD2 around endosomes (PubMed:29858488, PubMed:33124732).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q14849 | AQP6 Q13520 | 3 | EBI-9819324, EBI-13059134 | |
BINARY | Q14849 | CBARP Q8N350 | 2 | EBI-9819324, EBI-9355611 | |
BINARY | Q14849 | GOPC Q9HD26 | 3 | EBI-9819324, EBI-349832 | |
BINARY | Q14849 | MOSPD2 Q8NHP6 | 6 | EBI-9819324, EBI-2812848 | |
BINARY | Q14849 | RNF170 Q96K19-5 | 3 | EBI-9819324, EBI-12055631 | |
BINARY | Q14849-1 | VAPA Q9P0L0 | 4 | EBI-9819369, EBI-1059156 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 46-217 | MENTAL | ||||
Sequence: ISDVRRTFCLFVTFDLLFISLLWIIELNTNTGIRKNLEQEIIQYNFKTSFFDIFVLAFFRFSGLLLGYAVLRLRHWWVIAVTTLVSSAFLIVKVILSELLSKGAFGYLLPIVSFVLAWLETWFLDFKVLPQEAEEERWYLAAQVAVARGPLLFSGALSEGQFYSPPESFAGS | ||||||
Motif | 206-212 | FFAT | ||||
Sequence: QFYSPPE | ||||||
Domain | 230-443 | START | ||||
Sequence: SFSAQEREYIRQGKEATAVVDQILAQEENWKFEKNNEYGDTVYTIEVPFHGKTFILKTFLPCPAELVYQEVILQPERMVLWNKTVTACQILQRVEDNTLISYDVSAGAAGGVVSPRDFVNVRRIERRRDRYLSSGIATSHSAKPPTHKYVRGENGPGGFIVLKSASNPRVCTFVWILNTDLKGRLPRYLIHQSLAATMFEFAFHLRQRISELGA |
Domain
The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2.
The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a 'hydrophobic bridge' across the aqueous gap between donor and acceptor organelle membranes.
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (PubMed:11053434).
It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157).
It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157).
Sequence similarities
Belongs to the STARD3 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q14849-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length445
- Mass (Da)50,502
- Last updated2006-10-17 v2
- Checksum8EBFBAF013CFDC7E
Q14849-2
- Name2
- Differences from canonical
- 126-143: Missing
Q14849-3
- Name3
- Differences from canonical
- 122-183: WVIAVTTLVSSAFLIVKVILSELLSKGAFGYLLPIVSFVLAWLETWFLDFKVLPQEAEEERW → SRRWCPVHSSLSRSSSLSCSAKGHLATCSPSSLLSSPGWRPGSLTSKSYPRKLKRSDSAPPG
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X80198 EMBL· GenBank· DDBJ | CAA56489.1 EMBL· GenBank· DDBJ | mRNA | ||
D38255 EMBL· GenBank· DDBJ | BAA22525.1 EMBL· GenBank· DDBJ | mRNA | ||
BT006964 EMBL· GenBank· DDBJ | AAP35610.1 EMBL· GenBank· DDBJ | mRNA | ||
AK300176 EMBL· GenBank· DDBJ | BAG61955.1 EMBL· GenBank· DDBJ | mRNA | ||
AK300842 EMBL· GenBank· DDBJ | BAG62493.1 EMBL· GenBank· DDBJ | mRNA | ||
AC087491 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC008356 EMBL· GenBank· DDBJ | AAH08356.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008747 EMBL· GenBank· DDBJ | AAH08747.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025679 EMBL· GenBank· DDBJ | AAH25679.1 EMBL· GenBank· DDBJ | mRNA |