UniProt:Q14849 STARD3

chain
  • chain:1-445
checksum 8EBFBAF013CFDC7E
comment
  • 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).CATALYTIC ACTIVITY cholesterol(in) = cholesterol(out)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).INTERACTION Localizes to contact sites between the endoplasmic reticulum and late endosomes: associates with the endoplasmic reticulum membrane via interaction with VAPA, VAPB or MOSPD2.ALTERNATIVE PRODUCTS Expressed in retina.INDUCTION Not regulated by increases in total cholesterol content, or by marked alterations in cholesterol flux.DOMAIN The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2.DOMAIN 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.DOMAIN 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).PTM 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).SIMILARITY Belongs to the STARD3 family.CAUTION STARD3 was reported to function in cholesterol transport to the mitochondria or to the cell membrane (PubMed:12070139, PubMed:19965586). Other reports however showed that it mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:11053434, PubMed:28377464). Discrepancies may be due to the different cell type used and the cellular physiological state (PubMed:28377464).
crossReference
databaseName UniProt
dbId 59333
description
  • recommendedName: fullName evidence="26"StAR-related lipid transfer protein 3 alternativeName: fullName evidence="22"Metastatic lymph node gene 64 protein shortName evidence="22"MLN 64 alternativeName: fullName evidence="25"Protein CAB1 alternativeName: fullName evidence="24"START domain-containing protein 3 shortName evidence="24"StARD3
displayName UniProt:Q14849 STARD3
geneName
  • STARD3
  • CAB1
  • MLN64
identifier Q14849
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Endosome
  • Lipid transport
  • Lipid-binding
  • Membrane
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Transmembrane
  • Transmembrane helix
  • Transport
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • STARD3
otherIdentifier
  • 10948
  • 11716353_x_at
  • 11745302_a_at
  • 11758753_a_at
  • 11760262_a_at
  • 11760263_x_at
  • 16833802
  • 202991_PM_at
  • 202991_at
  • 3720344
  • 3720349
  • 3720350
  • 3720351
  • 3720352
  • 3720353
  • 3720354
  • 3720355
  • 3720356
  • 3720357
  • 3720358
  • 3720359
  • 3720360
  • 3720361
  • 3720362
  • 3720363
  • 3720364
  • 3720365
  • 3720366
  • 3720367
  • 3720368
  • 3720369
  • 3720370
  • 3720371
  • 3720372
  • 3720373
  • 3720374
  • 3720375
  • 3720376
  • 3720377
  • 3720378
  • 3720380
  • 3720382
  • 3720384
  • 37355_at
  • 68795_r_at
  • 8006877
  • 8006896
  • A_14_P121374
  • A_23_P118451
  • A_33_P3246804
  • A_33_P3356220
  • GE57186
  • GO:0005515
  • GO:0005654
  • GO:0005737
  • GO:0005739
  • GO:0005765
  • GO:0005768
  • GO:0005770
  • GO:0005789
  • GO:0005829
  • GO:0006629
  • GO:0006701
  • GO:0006839
  • GO:0006869
  • GO:0008202
  • GO:0008203
  • GO:0008289
  • GO:0015485
  • GO:0016020
  • GO:0030301
  • GO:0031902
  • GO:0042803
  • GO:0044232
  • GO:0044281
  • GO:0099044
  • GO:0120020
  • GO:0140284
  • HMNXSV003018837
  • ILMN_1657095
  • PH_hs_0004477
  • TC17002874.hg
  • TC17002875.hg
  • X80198_at
  • g5803089_3p_at
  • g5803089_3p_x_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • STAR3_HUMAN
  • A8MXA4
  • B4DUY1
  • F5H0G2
  • Q53Y53
  • Q96HM9
sequenceLength 445
species [Species:48887] Homo sapiens
stId uniprot:Q14849
url http://purl.uniprot.org/uniprot/Q14849
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