ID STAR3_HUMAN Reviewed; 445 AA. AC Q14849; A8MXA4; B4DUY1; F5H0G2; Q53Y53; Q96HM9; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 208. DE RecName: Full=StAR-related lipid transfer protein 3 {ECO:0000305}; DE AltName: Full=Metastatic lymph node gene 64 protein {ECO:0000303|PubMed:11053434}; DE Short=MLN 64 {ECO:0000303|PubMed:11053434}; DE AltName: Full=Protein CAB1 {ECO:0000303|PubMed:9270027}; DE AltName: Full=START domain-containing protein 3 {ECO:0000303|PubMed:21322544}; DE Short=StARD3 {ECO:0000303|PubMed:21322544}; GN Name=STARD3 {ECO:0000312|HGNC:HGNC:17579}; GN Synonyms=CAB1 {ECO:0000303|PubMed:9270027}, MLN64 GN {ECO:0000303|PubMed:11053434}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-117. RC TISSUE=Mammary carcinoma; RX PubMed=7490069; DOI=10.1006/geno.1995.1163; RA Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G., Chenard M.-P., RA Lidereau R., Basset P., Rio M.-C.; RT "Identification of four novel human genes amplified and overexpressed in RT breast carcinoma and localized to the q11-q21.3 region of chromosome 17."; RL Genomics 28:367-376(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-117. RC TISSUE=Esophageal carcinoma; RX PubMed=9270027; RA Akiyama N., Sasaki H., Ishizuka T., Kishi T., Sakamoto H., Onda M., RA Hirai H., Yazaki Y., Sugimura T., Terada M.; RT "Isolation of a candidate gene, CAB1, for cholesterol transport to RT mitochondria from the c-ERBB-2 amplicon by a modified cDNA selection RT method."; RL Cancer Res. 57:3548-3553(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-117. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT RP GLN-117. RC TISSUE=Placenta, and Small intestine; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLN-117 RP AND ALA-216. RC TISSUE=Lung, Skin, and Spleen; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, AND MUTAGENESIS OF RP 66-LEU-LEU-67; TYR-89; TYR-113; ASN-219 AND ASN-311. RX PubMed=11053434; DOI=10.1074/jbc.m006279200; RA Alpy F., Stoeckel M.-E., Dierich A., Escola J.-M., Wendling C., RA Chenard M.-P., Vanier M.T., Gruenberg J., Tomasetto C., Rio M.-C.; RT "The steroidogenic acute regulatory protein homolog MLN64, a late endosomal RT cholesterol-binding protein."; RL J. Biol. Chem. 276:4261-4269(2001). RN [8] RP FUNCTION. RX PubMed=12070139; DOI=10.1074/jbc.m200003200; RA Zhang M., Liu P., Dwyer N.K., Christenson L.K., Fujimoto T., Martinez F., RA Comly M., Hanover J.A., Blanchette-Mackie E.J., Strauss J.F. III; RT "MLN64 mediates mobilization of lysosomal cholesterol to steroidogenic RT mitochondria."; RL J. Biol. Chem. 277:33300-33310(2002). RN [9] RP SUBUNIT, INTERACTION WITH STARD3NL, AND DOMAIN. RX PubMed=15718238; DOI=10.1074/jbc.m500723200; RA Alpy F., Latchumanan V.K., Kedinger V., Janoshazi A., Thiele C., RA Wendling C., Rio M.C., Tomasetto C.; RT "Functional characterization of the MENTAL domain."; RL J. Biol. Chem. 280:17945-17952(2005). RN [10] RP FUNCTION. RX PubMed=15930133; DOI=10.1091/mbc.e04-12-1105; RA Hoelttae-Vuori M., Alpy F., Tanhuanpaeae K., Jokitalo E., Mutka A.L., RA Ikonen E.; RT "MLN64 is involved in actin-mediated dynamics of late endocytic RT organelles."; RL Mol. Biol. Cell 16:3873-3886(2005). RN [11] RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH STARD3NL, AND DOMAIN. RX PubMed=16709157; DOI=10.1042/bst0340343; RA Alpy F., Tomasetto C.; RT "MLN64 and MENTHO, two mediators of endosomal cholesterol transport."; RL Biochem. Soc. Trans. 34:343-345(2006). RN [12] RP 3D-STRUCTURE MODELING. RX PubMed=16990645; DOI=10.1194/jlr.m600232-jlr200; RA Murcia M., Faraldo-Gomez J.D., Maxfield F.R., Roux B.; RT "Modeling the structure of the StART domains of MLN64 and StAR proteins in RT complex with cholesterol."; RL J. Lipid Res. 47:2614-2630(2006). RN [13] RP FUNCTION. RX PubMed=19965586; DOI=10.1194/jlr.m002345; RA Charman M., Kennedy B.E., Osborne N., Karten B.; RT "MLN64 mediates egress of cholesterol from endosomes to mitochondria in the RT absence of functional Niemann-Pick Type C1 protein."; RL J. Lipid Res. 51:1023-1034(2010). RN [14] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=21322544; DOI=10.1021/bi101906y; RA Li B., Vachali P., Frederick J.M., Bernstein P.S.; RT "Identification of StARD3 as a lutein-binding protein in the macula of the RT primate retina."; RL Biochemistry 50:2541-2549(2011). RN [15] RP FUNCTION. RX PubMed=22514632; DOI=10.1371/journal.pone.0034424; RA Liapis A., Chen F.W., Davies J.P., Wang R., Ioannou Y.A.; RT "MLN64 transport to the late endosome is regulated by binding to 14-3-3 via RT a non-canonical binding site."; RL PLoS ONE 7:E34424-E34424(2012). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VAPA AND VAPB, MUTAGENESIS RP OF 206-GLN--GLU-211, FFAT MOTIF, AND DOMAIN. RX PubMed=24105263; DOI=10.1242/jcs.139295; RA Alpy F., Rousseau A., Schwab Y., Legueux F., Stoll I., Wendling C., RA Spiegelhalter C., Kessler P., Mathelin C., Rio M.C., Levine T.P., RA Tomasetto C.; RT "STARD3 or STARD3NL and VAP form a novel molecular tether between late RT endosomes and the ER."; RL J. Cell Sci. 126:5500-5512(2013). RN [17] RP INDUCTION. RX PubMed=27679500; DOI=10.1007/s13238-016-0315-0; RA Pinto J.B., Graham A.; RT "The role of endosomal cholesterol trafficking protein, StAR-related lipid RT transfer domain 3 (StarD3/MLN64), in BRIN-BD11 insulinoma cells."; RL Protein Cell 7:833-838(2016). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VAPA AND VAPB, RP LIPID-BINDING, AND MUTAGENESIS OF 207-PHE-TYR-208 AND 307-MET--ASN-311. RX PubMed=28377464; DOI=10.15252/embj.201695917; RA Wilhelm L.P., Wendling C., Vedie B., Kobayashi T., Chenard M.P., RA Tomasetto C., Drin G., Alpy F.; RT "STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at RT membrane contact sites."; RL EMBO J. 36:1412-1433(2017). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH MOSPD2, SUBCELLULAR RP LOCATION, DOMAIN, AND MUTAGENESIS OF 207-PHE-TYR-208. RX PubMed=29858488; DOI=10.15252/embr.201745453; RA Di Mattia T., Wilhelm L.P., Ikhlef S., Wendling C., Spehner D., Nomine Y., RA Giordano F., Mathelin C., Drin G., Tomasetto C., Alpy F.; RT "Identification of MOSPD2, a novel scaffold for endoplasmic reticulum RT membrane contact sites."; RL EMBO Rep. 19:0-0(2018). RN [20] {ECO:0007744|PDB:1EM2} RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 216-445. RX PubMed=10802740; DOI=10.1038/75192; RA Tsujishita Y., Hurley J.H.; RT "Structure and lipid transport mechanism of a StAR-related domain."; RL Nat. Struct. Biol. 7:408-414(2000). RN [21] {ECO:0007744|PDB:5I9J} RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 216-444. RX PubMed=27487925; DOI=10.1107/s2053230x16010694; RA Horvath M.P., George E.W., Tran Q.T., Baumgardner K., Zharov G., Lee S., RA Sharifzadeh H., Shihab S., Mattinson T., Li B., Bernstein P.S.; RT "Structure of the lutein-binding domain of human StARD3 at 1.74A resolution RT and model of a complex with lutein."; RL Acta Crystallogr. F 72:609-618(2016). RN [22] {ECO:0007744|PDB:6TQR, ECO:0007744|PDB:6TQU} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 200-216 IN COMPLEX WITH THE MSP RP DOMAIN OF VAPA AND MOSPD2, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, RP PHOSPHORYLATION AT SER-209, INTERACTION WITH VAPA; VAPB AND MOSPD2, RP MUTAGENESIS OF SER-209 AND PRO-210, AND FFAT MOTIF. RX PubMed=33124732; DOI=10.15252/embj.2019104369; RA Di Mattia T., Martinet A., Ikhlef S., McEwen A.G., Nomine Y., Wendling C., RA Poussin-Courmontagne P., Voilquin L., Eberling P., Ruffenach F., RA Cavarelli J., Slee J., Levine T.P., Drin G., Tomasetto C., Alpy F.; RT "FFAT motif phosphorylation controls formation and lipid transfer function RT of inter-organelle contacts."; RL EMBO J. 39:e104369-e104369(2020). CC -!- FUNCTION: Sterol-binding protein that mediates cholesterol transport CC from the endoplasmic reticulum to endosomes (PubMed:11053434, CC PubMed:15930133, PubMed:22514632, PubMed:28377464, PubMed:33124732). CC The sterol transport mechanism is triggered by phosphorylation of FFAT CC motif that leads to membrane tethering between the endoplasmic CC reticulum and late endosomes via interaction with VAPA and VAPB CC (PubMed:24105263, PubMed:28377464, PubMed:33124732). Acts as a lipid CC transfer protein that redirects sterol to the endosome at the expense CC of the cell membrane and favors membrane formation inside endosomes CC (PubMed:28377464). May also mediate cholesterol transport between other CC membranes, such as mitochondria membrane or cell membrane CC (PubMed:12070139, PubMed:19965586). However, such results need CC additional experimental evidences; probably mainly mediates cholesterol CC transport from the endoplasmic reticulum to endosomes CC (PubMed:28377464). Does not activate transcriptional cholesterol CC sensing (PubMed:28377464). Able to bind other lipids, such as lutein, a CC xanthophyll carotenoids that form the macular pigment of the retina CC (PubMed:21322544). {ECO:0000269|PubMed:11053434, CC ECO:0000269|PubMed:12070139, ECO:0000269|PubMed:15930133, CC ECO:0000269|PubMed:19965586, ECO:0000269|PubMed:21322544, CC ECO:0000269|PubMed:22514632, ECO:0000269|PubMed:24105263, CC ECO:0000269|PubMed:28377464, ECO:0000269|PubMed:33124732}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747, CC ChEBI:CHEBI:16113; Evidence={ECO:0000269|PubMed:11053434, CC ECO:0000269|PubMed:15930133, ECO:0000269|PubMed:22514632, CC ECO:0000269|PubMed:28377464, ECO:0000269|PubMed:33124732}; CC -!- SUBUNIT: Homodimer (PubMed:15718238, PubMed:16709157). Interacts (via CC the MENTAL domain) with STARD3NL (PubMed:15718238, PubMed:16709157). CC Interacts (via phosphorylated FFAT motif) with VAPA (via MSP domain) CC (PubMed:24105263, PubMed:28377464, PubMed:33124732). Interacts (via CC phosphorylated FFAT motif) with VAPB (via MSP domain) (PubMed:24105263, CC PubMed:28377464, PubMed:33124732). Interacts (via phosphorylated FFAT CC motif) with MOSPD2 (via MSP domain); this interaction allows enrichment CC of MOSPD2 around endosomes (PubMed:29858488, PubMed:33124732). CC {ECO:0000269|PubMed:15718238, ECO:0000269|PubMed:16709157, CC ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:28377464, CC ECO:0000269|PubMed:29858488, ECO:0000269|PubMed:33124732}. CC -!- INTERACTION: CC Q14849; Q13520: AQP6; NbExp=3; IntAct=EBI-9819324, EBI-13059134; CC Q14849; Q9HD26: GOPC; NbExp=3; IntAct=EBI-9819324, EBI-349832; CC Q14849; Q8NHP6: MOSPD2; NbExp=6; IntAct=EBI-9819324, EBI-2812848; CC Q14849; Q96K19-5: RNF170; NbExp=3; IntAct=EBI-9819324, EBI-12055631; CC Q14849-1; Q9P0L0: VAPA; NbExp=4; IntAct=EBI-9819369, EBI-1059156; CC -!- SUBCELLULAR LOCATION: Late endosome membrane CC {ECO:0000269|PubMed:11053434, ECO:0000269|PubMed:16709157, CC ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:28377464, CC ECO:0000269|PubMed:29858488}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localizes to contact sites between the endoplasmic CC reticulum and late endosomes: associates with the endoplasmic reticulum CC membrane via interaction with VAPA, VAPB or MOSPD2. CC {ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:29858488}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q14849-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14849-2; Sequence=VSP_042710; CC Name=3; CC IsoId=Q14849-3; Sequence=VSP_045361; CC -!- TISSUE SPECIFICITY: Expressed in retina. {ECO:0000269|PubMed:21322544}. CC -!- INDUCTION: Not regulated by increases in total cholesterol content, or CC by marked alterations in cholesterol flux. CC {ECO:0000269|PubMed:27679500}. CC -!- DOMAIN: The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2. CC {ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:29858488}. CC -!- DOMAIN: The START domain mediates lipid-transfer between membranes. It CC contains a hydrophobic cavity able to accommodate one lipid molecule, CC thereby serving as a 'hydrophobic bridge' across the aqueous gap CC between donor and acceptor organelle membranes. CC {ECO:0000305|PubMed:28377464}. CC -!- DOMAIN: The MENTAL domain anchors the protein in endosome membranes and CC exposes the START domain in the cytosol (PubMed:11053434). It binds CC cholesterol and mediates homotypic as well as heterotypic interactions CC between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157). CC {ECO:0000269|PubMed:11053434, ECO:0000269|PubMed:15718238, CC ECO:0000269|PubMed:16709157}. CC -!- PTM: Phosphorylation at Ser-209 is necessary and sufficient for the CC direct interaction of the phosphorylated FFAT motif with the MSP domain CC of MOSPD2, VAPA and VAPB and allows the tethering of two membranes that CC participates in the formation of ER-endosome contacts CC (PubMed:33124732). Phosphorylation of the FFAT motif leads to CC conformation changes (PubMed:33124732). Additional phosphorylations CC around the core FFAT motif (QFYSPPE) are not essential but strengthen CC the interaction with MOSPD2, VAPA and VAPB (PubMed:33124732). CC Phosphorylation at Ser-209 of FFAT motif drives membrane tethering CC between the endoplasmic reticulum and late endosomes via interaction CC with VAPA and VAPB that in turn allows the efficient transport of CC sterol mediated by the START domain (PubMed:33124732). CC {ECO:0000269|PubMed:33124732}. CC -!- SIMILARITY: Belongs to the STARD3 family. {ECO:0000305}. CC -!- CAUTION: STARD3 was reported to function in cholesterol transport to CC the mitochondria or to the cell membrane (PubMed:12070139, CC PubMed:19965586). Other reports however showed that it mediates CC cholesterol transport from the endoplasmic reticulum to endosomes CC (PubMed:11053434, PubMed:28377464). Discrepancies may be due to the CC different cell type used and the cellular physiological state CC (PubMed:28377464). {ECO:0000269|PubMed:11053434, CC ECO:0000269|PubMed:12070139, ECO:0000269|PubMed:19965586, CC ECO:0000269|PubMed:28377464}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/202/MLN64"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X80198; CAA56489.1; -; mRNA. DR EMBL; D38255; BAA22525.1; -; mRNA. DR EMBL; BT006964; AAP35610.1; -; mRNA. DR EMBL; AK300176; BAG61955.1; -; mRNA. DR EMBL; AK300842; BAG62493.1; -; mRNA. DR EMBL; AC087491; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008356; AAH08356.1; -; mRNA. DR EMBL; BC008747; AAH08747.1; -; mRNA. DR EMBL; BC025679; AAH25679.1; -; mRNA. DR CCDS; CCDS11341.1; -. [Q14849-1] DR CCDS; CCDS54117.1; -. [Q14849-3] DR CCDS; CCDS54118.1; -. [Q14849-2] DR PIR; I38027; I38027. DR RefSeq; NP_001159409.1; NM_001165937.1. [Q14849-3] DR RefSeq; NP_001159410.1; NM_001165938.1. [Q14849-2] DR RefSeq; NP_006795.3; NM_006804.3. [Q14849-1] DR RefSeq; XP_016879530.1; XM_017024041.1. [Q14849-1] DR PDB; 1EM2; X-ray; 2.20 A; A=216-444. DR PDB; 5I9J; X-ray; 1.74 A; A=216-444. DR PDB; 6TQR; X-ray; 1.85 A; E/F=200-216. DR PDB; 6TQU; X-ray; 2.40 A; C/D=196-216. DR PDBsum; 1EM2; -. DR PDBsum; 5I9J; -. DR PDBsum; 6TQR; -. DR PDBsum; 6TQU; -. DR AlphaFoldDB; Q14849; -. DR SMR; Q14849; -. DR BioGRID; 116148; 96. DR IntAct; Q14849; 20. DR STRING; 9606.ENSP00000337446; -. DR BindingDB; Q14849; -. DR ChEMBL; CHEMBL4523297; -. DR SwissLipids; SLP:000000712; -. DR TCDB; 9.B.64.1.1; the putative cholesterol transporter (start1) family. DR iPTMnet; Q14849; -. DR MetOSite; Q14849; -. DR PhosphoSitePlus; Q14849; -. DR BioMuta; STARD3; -. DR DMDM; 116242802; -. DR EPD; Q14849; -. DR jPOST; Q14849; -. DR MassIVE; Q14849; -. DR MaxQB; Q14849; -. DR PaxDb; 9606-ENSP00000337446; -. DR PeptideAtlas; Q14849; -. DR ProteomicsDB; 25332; -. DR ProteomicsDB; 60208; -. [Q14849-1] DR ProteomicsDB; 60209; -. [Q14849-2] DR Pumba; Q14849; -. DR Antibodypedia; 28306; 100 antibodies from 22 providers. DR DNASU; 10948; -. DR Ensembl; ENST00000336308.10; ENSP00000337446.5; ENSG00000131748.16. [Q14849-1] DR Ensembl; ENST00000394250.8; ENSP00000377794.4; ENSG00000131748.16. [Q14849-2] DR Ensembl; ENST00000544210.6; ENSP00000439869.2; ENSG00000131748.16. [Q14849-3] DR GeneID; 10948; -. DR KEGG; hsa:10948; -. DR MANE-Select; ENST00000336308.10; ENSP00000337446.5; NM_006804.4; NP_006795.3. DR UCSC; uc002hsd.4; human. [Q14849-1] DR AGR; HGNC:17579; -. DR CTD; 10948; -. DR DisGeNET; 10948; -. DR GeneCards; STARD3; -. DR HGNC; HGNC:17579; STARD3. DR HPA; ENSG00000131748; Low tissue specificity. DR MIM; 607048; gene. DR neXtProt; NX_Q14849; -. DR OpenTargets; ENSG00000131748; -. DR PharmGKB; PA134981867; -. DR VEuPathDB; HostDB:ENSG00000131748; -. DR eggNOG; KOG3845; Eukaryota. DR GeneTree; ENSGT00940000159051; -. DR HOGENOM; CLU_033480_0_0_1; -. DR InParanoid; Q14849; -. DR OMA; AWVETWF; -. DR OrthoDB; 3740290at2759; -. DR PhylomeDB; Q14849; -. DR TreeFam; TF313869; -. DR PathwayCommons; Q14849; -. DR Reactome; R-HSA-196108; Pregnenolone biosynthesis. DR SignaLink; Q14849; -. DR BioGRID-ORCS; 10948; 20 hits in 1150 CRISPR screens. DR ChiTaRS; STARD3; human. DR EvolutionaryTrace; Q14849; -. DR GenomeRNAi; 10948; -. DR Pharos; Q14849; Tbio. DR PRO; PR:Q14849; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q14849; Protein. DR Bgee; ENSG00000131748; Expressed in right lung and 174 other cell types or tissues. DR ExpressionAtlas; Q14849; baseline and differential. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0140284; C:endoplasmic reticulum-endosome membrane contact site; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB. DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB. DR GO; GO:0120020; F:cholesterol transfer activity; IEA:InterPro. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008203; P:cholesterol metabolic process; TAS:ProtInc. DR GO; GO:0030301; P:cholesterol transport; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. DR GO; GO:0006839; P:mitochondrial transport; TAS:ProtInc. DR GO; GO:0006701; P:progesterone biosynthetic process; IEA:Ensembl. DR GO; GO:0008202; P:steroid metabolic process; TAS:ProtInc. DR GO; GO:0099044; P:vesicle tethering to endoplasmic reticulum; IDA:UniProtKB. DR CDD; cd08906; START_STARD3-like; 1. DR DisProt; DP02835; -. DR Gene3D; 3.30.530.20; -; 1. DR InterPro; IPR019498; MENTAL. DR InterPro; IPR000799; StAR-like. DR InterPro; IPR029867; STARD3_MLN64_C. DR InterPro; IPR023393; START-like_dom_sf. DR InterPro; IPR002913; START_lipid-bd_dom. DR PANTHER; PTHR46121:SF2; STAR-RELATED LIPID TRANSFER PROTEIN 3; 1. DR PANTHER; PTHR46121; STEROIDOGENIC ACUTE REGULATORY PROTEIN-LIKE; 1. DR Pfam; PF10457; MENTAL; 1. DR Pfam; PF01852; START; 1. DR PRINTS; PR00978; STARPROTEIN. DR SMART; SM00234; START; 1. DR SUPFAM; SSF55961; Bet v1-like; 1. DR PROSITE; PS51439; MENTAL; 1. DR PROSITE; PS50848; START; 1. DR Genevisible; Q14849; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Endosome; Lipid transport; KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..445 FT /note="StAR-related lipid transfer protein 3" FT /id="PRO_0000220653" FT TOPO_DOM 1..51 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:11053434" FT TRANSMEM 52..72 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00770" FT TOPO_DOM 73..94 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 95..115 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00770" FT TOPO_DOM 116..120 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 121..141 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00770" FT TOPO_DOM 142..148 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 149..169 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00770" FT TOPO_DOM 170..445 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:11053434" FT DOMAIN 46..217 FT /note="MENTAL" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00770" FT DOMAIN 230..443 FT /note="START" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197" FT MOTIF 206..212 FT /note="FFAT" FT /evidence="ECO:0000269|PubMed:24105263, FT ECO:0000269|PubMed:33124732" FT MOD_RES 209 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:33124732" FT VAR_SEQ 122..183 FT /note="WVIAVTTLVSSAFLIVKVILSELLSKGAFGYLLPIVSFVLAWLETWFLDFKV FT LPQEAEEERW -> SRRWCPVHSSLSRSSSLSCSAKGHLATCSPSSLLSSPGWRPGSLT FT SKSYPRKLKRSDSAPPG (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045361" FT VAR_SEQ 126..143 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042710" FT VARIANT 117 FT /note="R -> Q (in dbSNP:rs1877031)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7490069, FT ECO:0000269|PubMed:9270027, ECO:0000269|Ref.3" FT /id="VAR_027877" FT VARIANT 216 FT /note="G -> A (in dbSNP:rs11556624)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027878" FT MUTAGEN 66..67 FT /note="LL->AS: Abolishes localization to late endosomes and FT leads to mislocalization to the endoplasmic reticulum." FT /evidence="ECO:0000269|PubMed:11053434" FT MUTAGEN 89 FT /note="Y->V: Abolishes localization to late endosomes and FT leads to mislocalization to the endoplasmic reticulum." FT /evidence="ECO:0000269|PubMed:11053434" FT MUTAGEN 113 FT /note="Y->A: Does not affect localization to late FT endosomes." FT /evidence="ECO:0000269|PubMed:11053434" FT MUTAGEN 206..212 FT /note="Missing: Abolishes interaction with VAPA and VAPB, FT thereby preventing contact with the endoplasmic reticulum FT membrane." FT /evidence="ECO:0000269|PubMed:24105263" FT MUTAGEN 207..208 FT /note="FY->AA: Abolishes interaction with VAPA, VAPB and FT MOSPD2, thereby preventing contact with the endoplasmic FT reticulum membrane. Abolishes cholesterol accumulation in FT endosomes." FT /evidence="ECO:0000269|PubMed:28377464, FT ECO:0000269|PubMed:29858488" FT MUTAGEN 209 FT /note="S->A: Impairs VAPA and VAPB interaction. Does not FT affect endoplasmic reticulum membrane location of VAPA, FT VAPB and MOSPD2. Is unable to make ER-endosome contacts. FT Does not accumulate cholesterol in late endosomes (LEs). FT Does not interact with MOSPD2." FT /evidence="ECO:0000269|PubMed:33124732" FT MUTAGEN 209 FT /note="S->D: Does not affect VAPA and VAPB interactions; FT when associated with A-210. Does not interact with VAPA and FT VAPB. Recruits VAPA and VAPB around the endosome; when FT associated with A-210. Restores cholesterol accumulation in FT late endosomes; when associated with A-210. Moderately FT interacts with MOSPD2. Almost impairs interaction with FT MOSPD2; when associated with A-210." FT /evidence="ECO:0000269|PubMed:33124732" FT MUTAGEN 210 FT /note="P->A: Does not affect VAPA and VAPB interactions; FT when associated with D-209. Improve VAPA interaction. Does FT not interact with VAPA and VAPB. Recruits VAPA and VAPB FT around the endosome; when associated with D-209.Restores FT cholesterol accumulation in late endosomes; when associated FT with A-209. Almost impairs interaction with MOSPD2; when FT associated with A-209." FT /evidence="ECO:0000269|PubMed:33124732" FT MUTAGEN 219 FT /note="N->A: Does not affect localization to late FT endosomes." FT /evidence="ECO:0000269|PubMed:11053434" FT MUTAGEN 307..311 FT /note="MVLWN->NVLWD: Abolishes ability to transfer FT cholesterol between membranes." FT /evidence="ECO:0000269|PubMed:28377464" FT MUTAGEN 311 FT /note="N->A: Does not affect localization to late FT endosomes." FT /evidence="ECO:0000269|PubMed:11053434" FT HELIX 233..254 FT /evidence="ECO:0007829|PDB:5I9J" FT HELIX 255..258 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 260..264 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 270..276 FT /evidence="ECO:0007829|PDB:5I9J" FT TURN 277..279 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 280..291 FT /evidence="ECO:0007829|PDB:5I9J" FT HELIX 293..300 FT /evidence="ECO:0007829|PDB:5I9J" FT HELIX 304..310 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 314..323 FT /evidence="ECO:0007829|PDB:5I9J" FT TURN 324..326 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 327..334 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 345..355 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 357..366 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 385..392 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 400..406 FT /evidence="ECO:0007829|PDB:5I9J" FT STRAND 412..414 FT /evidence="ECO:0007829|PDB:5I9J" FT HELIX 416..443 FT /evidence="ECO:0007829|PDB:5I9J" SQ SEQUENCE 445 AA; 50502 MW; 8EBFBAF013CFDC7E CRC64; MSKLPRELTR DLERSLPAVA SLGSSLSHSQ SLSSHLLPPP EKRRAISDVR RTFCLFVTFD LLFISLLWII ELNTNTGIRK NLEQEIIQYN FKTSFFDIFV LAFFRFSGLL LGYAVLRLRH WWVIAVTTLV SSAFLIVKVI LSELLSKGAF GYLLPIVSFV LAWLETWFLD FKVLPQEAEE ERWYLAAQVA VARGPLLFSG ALSEGQFYSP PESFAGSDNE SDEEVAGKKS FSAQEREYIR QGKEATAVVD QILAQEENWK FEKNNEYGDT VYTIEVPFHG KTFILKTFLP CPAELVYQEV ILQPERMVLW NKTVTACQIL QRVEDNTLIS YDVSAGAAGG VVSPRDFVNV RRIERRRDRY LSSGIATSHS AKPPTHKYVR GENGPGGFIV LKSASNPRVC TFVWILNTDL KGRLPRYLIH QSLAATMFEF AFHLRQRISE LGARA //