ID OSBL2_HUMAN Reviewed; 480 AA. AC Q9H1P3; A8K736; Q6IBT0; Q9BZB1; Q9Y4B8; DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Oxysterol-binding protein-related protein 2; DE Short=ORP-2; DE Short=OSBP-related protein 2; GN Name=OSBPL2; Synonyms=KIAA0772, ORP2; 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 2), AND FUNCTION. RX PubMed=11279184; DOI=10.1074/jbc.m101204200; RA Xu Y., Liu Y., Ridgway N.D., McMaster C.R.; RT "Novel members of the human oxysterol-binding protein family bind RT phospholipids and regulate vesicle transport."; RL J. Biol. Chem. 276:18407-18414(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11735225; DOI=10.1006/geno.2001.6663; RA Jaworski C.J., Moreira E., Li A., Lee R., Rodriguez I.R.; RT "A family of 12 human genes containing oxysterol-binding domains."; RL Genomics 78:185-196(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Rectum; 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 MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2). RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-116 (ISOFORM 1). RX PubMed=11483621; RA Lehto M., Laitinen S., Chinetti G., Johansson M., Ehnholm C., Staels B., RA Ikonen E., Olkkonen V.M.; RT "The OSBP-related protein family in humans."; RL J. Lipid Res. 42:1203-1213(2001). RN [10] RP FUNCTION, AND MUTAGENESIS OF MET-93; PHE-103; LYS-150; PHE-152 AND ILE-249. RX PubMed=17428193; DOI=10.1042/bj20070176; RA Suchanek M., Hynynen R., Wohlfahrt G., Lehto M., Johansson M., Saarinen H., RA Radzikowska A., Thiele C., Olkkonen V.M.; RT "The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25- RT hydroxycholesterol in an evolutionarily conserved pocket."; RL Biochem. J. 405:473-480(2007). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ILE-249. RX PubMed=19224871; DOI=10.1194/jlr.m800661-jlr200; RA Hynynen R., Suchanek M., Spandl J., Baeck N., Thiele C., Olkkonen V.M.; RT "OSBP-related protein 2 is a sterol receptor on lipid droplets that RT regulates the metabolism of neutral lipids."; RL J. Lipid Res. 50:1305-1315(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP INTERACTION WITH DIAPH1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23325789; DOI=10.1091/mbc.e12-08-0597; RA Li D., Dammer E.B., Lucki N.C., Sewer M.B.; RT "cAMP-stimulated phosphorylation of diaphanous 1 regulates protein RT stability and interaction with binding partners in adrenocortical cells."; RL Mol. Biol. Cell 24:848-857(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-20, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 49-480 IN COMPLEX WITH RP PHOSPHATIDYLINOSITOL-BISPHOSPHATE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF ILE-79; CYS-83; 87-GLU--LYS-90; TYR-110; RP 178-HIS-HIS-179; PRO-215 AND LYS-423. RX PubMed=30581148; DOI=10.1016/j.molcel.2018.11.014; RA Wang H., Ma Q., Qi Y., Dong J., Du X., Rae J., Wang J., Wu W.F., RA Brown A.J., Parton R.G., Wu J.W., Yang H.; RT "ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for RT Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2)."; RL Mol. Cell 73:458-473(2019). RN [17] RP INVOLVEMENT IN DFNA67. RX PubMed=25077649; DOI=10.1038/gim.2014.90; RA Xing G., Yao J., Wu B., Liu T., Wei Q., Liu C., Lu Y., Chen Z., Zheng H., RA Yang X., Cao X.; RT "Identification of OSBPL2 as a novel candidate gene for progressive RT nonsyndromic hearing loss by whole-exome sequencing."; RL Genet. Med. 17:210-218(2015). RN [18] RP INVOLVEMENT IN DFNA67. RX PubMed=25759012; DOI=10.1186/s13023-015-0238-5; RA Thoenes M., Zimmermann U., Ebermann I., Ptok M., Lewis M.A., Thiele H., RA Morlot S., Hess M.M., Gal A., Eisenberger T., Bergmann C., Nuernberg G., RA Nuernberg P., Steel K.P., Knipper M., Bolz H.J.; RT "OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is RT mutated in autosomal dominant hearing loss (DFNA67)."; RL Orphanet J. Rare Dis. 10:15-15(2015). RN [19] RP INVOLVEMENT IN DFNA67. RX PubMed=30894143; DOI=10.1186/s12881-019-0781-3; RA Wu N., Husile H., Yang L., Cao Y., Li X., Huo W., Bai H., Liu Y., Wu Q.; RT "A novel pathogenic variant in OSBPL2 linked to hereditary late-onset RT deafness in a Mongolian family."; RL BMC Med. Genet. 20:43-43(2019). CC -!- FUNCTION: Intracellular transport protein that binds sterols and CC phospholipids and mediates lipid transport between intracellular CC compartments. Increases plasma membrane cholesterol levels and CC decreases phosphatidylinositol-4,5-bisphosphate levels in the cell CC membrane (PubMed:30581148). Binds phosphoinositides, such as CC phosphatidylinositol-4,5-bisphosphate (PubMed:30581148). Exhibits CC strong binding to phosphatidic acid and weak binding to CC phosphatidylinositol 3-phosphate (PubMed:11279184). Binds cholesterol, CC dehydroergosterol, 22(R)-hydroxycholesterol and 25-hydroxycholesterol CC (in vitro) (PubMed:17428193, PubMed:19224871, PubMed:30581148). CC {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:19224871, CC ECO:0000269|PubMed:30581148}. CC -!- SUBUNIT: Monomer. Homotetramer; phosphatidylinositol-4,5-bisphosphate CC binding promotes formation of stable tetramers (PubMed:30581148). CC Interacts with DIAPH1. {ECO:0000269|PubMed:23325789, CC ECO:0000269|PubMed:30581148}. CC -!- INTERACTION: CC Q9H1P3; P62306: SNRPF; NbExp=3; IntAct=EBI-2828285, EBI-356900; CC Q9H1P3; Q53XM7: VAPB; NbExp=3; IntAct=EBI-2828285, EBI-10178947; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19224871, CC ECO:0000269|PubMed:30581148}. Lipid droplet CC {ECO:0000269|PubMed:19224871}. Cell membrane CC {ECO:0000269|PubMed:30581148}; Peripheral membrane protein CC {ECO:0000269|PubMed:30581148}; Cytoplasmic side CC {ECO:0000269|PubMed:30581148}. Note=Detected on the surface of CC cytosolic lipid droplets (PubMed:19224871). Recruited to the cell CC membrane by phosphatidylinositol-phosphate binding (PubMed:30581148). CC {ECO:0000269|PubMed:19224871, ECO:0000269|PubMed:30581148}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H1P3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H1P3-2; Sequence=VSP_003781; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- DISEASE: Deafness, autosomal dominant, 67 (DFNA67) [MIM:616340]: A form CC of non-syndromic sensorineural hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. {ECO:0000269|PubMed:25077649, ECO:0000269|PubMed:25759012, CC ECO:0000269|PubMed:30894143}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the OSBP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34492.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AY028168; AAK18044.1; -; mRNA. DR EMBL; AF392447; AAL40660.1; -; mRNA. DR EMBL; AB018315; BAA34492.2; ALT_INIT; mRNA. DR EMBL; AK291851; BAF84540.1; -; mRNA. DR EMBL; CR456722; CAG33003.1; -; mRNA. DR EMBL; AL354836; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW75377.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75379.1; -; Genomic_DNA. DR EMBL; BC000296; AAH00296.1; -; mRNA. DR EMBL; BC004455; AAH04455.1; -; mRNA. DR EMBL; AF331963; AAG53416.1; -; mRNA. DR CCDS; CCDS13494.1; -. [Q9H1P3-2] DR CCDS; CCDS13495.1; -. [Q9H1P3-1] DR RefSeq; NP_055650.1; NM_014835.3. [Q9H1P3-2] DR RefSeq; NP_653081.1; NM_144498.2. [Q9H1P3-1] DR RefSeq; XP_016883654.1; XM_017028165.1. DR PDB; 5ZM8; X-ray; 2.70 A; A/B=49-480. DR PDBsum; 5ZM8; -. DR AlphaFoldDB; Q9H1P3; -. DR SMR; Q9H1P3; -. DR BioGRID; 115216; 37. DR ELM; Q9H1P3; -. DR IntAct; Q9H1P3; 16. DR STRING; 9606.ENSP00000316649; -. DR SwissLipids; SLP:000001533; -. DR iPTMnet; Q9H1P3; -. DR PhosphoSitePlus; Q9H1P3; -. DR BioMuta; OSBPL2; -. DR DMDM; 20139174; -. DR EPD; Q9H1P3; -. DR jPOST; Q9H1P3; -. DR MassIVE; Q9H1P3; -. DR MaxQB; Q9H1P3; -. DR PaxDb; 9606-ENSP00000316649; -. DR PeptideAtlas; Q9H1P3; -. DR ProteomicsDB; 80434; -. [Q9H1P3-1] DR ProteomicsDB; 80435; -. [Q9H1P3-2] DR Pumba; Q9H1P3; -. DR Antibodypedia; 29467; 220 antibodies from 32 providers. DR DNASU; 9885; -. DR Ensembl; ENST00000313733.9; ENSP00000316649.3; ENSG00000130703.17. [Q9H1P3-1] DR Ensembl; ENST00000358053.3; ENSP00000350755.2; ENSG00000130703.17. [Q9H1P3-2] DR Ensembl; ENST00000643412.1; ENSP00000494549.1; ENSG00000130703.17. [Q9H1P3-1] DR Ensembl; ENST00000643981.1; ENSP00000495379.1; ENSG00000130703.17. [Q9H1P3-1] DR GeneID; 9885; -. DR KEGG; hsa:9885; -. DR MANE-Select; ENST00000313733.9; ENSP00000316649.3; NM_144498.4; NP_653081.1. DR UCSC; uc002yck.3; human. [Q9H1P3-1] DR AGR; HGNC:15761; -. DR CTD; 9885; -. DR DisGeNET; 9885; -. DR GeneCards; OSBPL2; -. DR HGNC; HGNC:15761; OSBPL2. DR HPA; ENSG00000130703; Low tissue specificity. DR MalaCards; OSBPL2; -. DR MIM; 606731; gene. DR MIM; 616340; phenotype. DR neXtProt; NX_Q9H1P3; -. DR OpenTargets; ENSG00000130703; -. DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. DR PharmGKB; PA32827; -. DR VEuPathDB; HostDB:ENSG00000130703; -. DR eggNOG; KOG2209; Eukaryota. DR GeneTree; ENSGT00940000158762; -. DR HOGENOM; CLU_007105_6_2_1; -. DR InParanoid; Q9H1P3; -. DR OMA; RTRWFYQ; -. DR OrthoDB; 960at2759; -. DR PhylomeDB; Q9H1P3; -. DR PathwayCommons; Q9H1P3; -. DR Reactome; R-HSA-192105; Synthesis of bile acids and bile salts. DR SignaLink; Q9H1P3; -. DR BioGRID-ORCS; 9885; 19 hits in 1158 CRISPR screens. DR ChiTaRS; OSBPL2; human. DR GeneWiki; OSBPL2; -. DR GenomeRNAi; 9885; -. DR Pharos; Q9H1P3; Tbio. DR PRO; PR:Q9H1P3; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9H1P3; Protein. DR Bgee; ENSG00000130703; Expressed in lateral nuclear group of thalamus and 196 other cell types or tissues. DR ExpressionAtlas; Q9H1P3; baseline and differential. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell. DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0015485; F:cholesterol binding; IDA:BHF-UCL. DR GO; GO:0120020; F:cholesterol transfer activity; IMP:UniProtKB. DR GO; GO:0008526; F:phosphatidylinositol transfer activity; IMP:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0015248; F:sterol transporter activity; IBA:GO_Central. DR GO; GO:0006699; P:bile acid biosynthetic process; TAS:Reactome. DR GO; GO:0030301; P:cholesterol transport; IMP:ARUK-UCL. DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB. DR GO; GO:0015914; P:phospholipid transport; IMP:ARUK-UCL. DR GO; GO:0007009; P:plasma membrane organization; IMP:ARUK-UCL. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR Gene3D; 2.40.160.120; -; 1. DR Gene3D; 3.30.70.3490; -; 1. DR InterPro; IPR037239; OSBP_sf. DR InterPro; IPR000648; Oxysterol-bd. DR InterPro; IPR018494; Oxysterol-bd_CS. DR PANTHER; PTHR10972; OXYSTEROL-BINDING PROTEIN-RELATED; 1. DR PANTHER; PTHR10972:SF153; OXYSTEROL-BINDING PROTEIN-RELATED PROTEIN 2; 1. DR Pfam; PF01237; Oxysterol_BP; 1. DR SUPFAM; SSF144000; Oxysterol-binding protein-like; 1. DR PROSITE; PS01013; OSBP; 1. DR Genevisible; Q9H1P3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Deafness; KW Lipid droplet; Lipid transport; Lipid-binding; Membrane; KW Non-syndromic deafness; Phosphoprotein; Reference proteome; Transport. FT CHAIN 1..480 FT /note="Oxysterol-binding protein-related protein 2" FT /id="PRO_0000100369" FT REGION 1..60 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 13..60 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 90 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000269|PubMed:30581148, FT ECO:0007744|PDB:5ZM8" FT BINDING 178..179 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000269|PubMed:30581148, FT ECO:0007744|PDB:5ZM8" FT BINDING 427..431 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000269|PubMed:30581148, FT ECO:0007744|PDB:5ZM8" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 20 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 13..24 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11279184, FT ECO:0000303|PubMed:11735225, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9872452" FT /id="VSP_003781" FT MUTAGEN 79 FT /note="I->A: No effect on phosphatidylinositide binding, FT but impaired tetramerization and decreased cholesterol FT binding, plus decreased cholesterol and FT phosphatidylinositide transport." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 83 FT /note="C->A: No effect on phosphatidylinositide binding, FT but impaired tetramerization and decreased cholesterol FT binding, plus decreased cholesterol and FT phosphatidylinositide transport." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 87..90 FT /note="Missing: Loss of the ability to promote cholesterol FT accumulation at the cell membrane. No effect on FT phosphatidylinositide levels at the cell membrane." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 93 FT /note="M->K: Mildly decreased 25-hydroxycholesterol FT binding." FT /evidence="ECO:0000269|PubMed:17428193" FT MUTAGEN 103 FT /note="F->W: Mildly decreased 25-hydroxycholesterol FT binding." FT /evidence="ECO:0000269|PubMed:17428193" FT MUTAGEN 110 FT /note="Y->A: No effect on phosphatidylinositide binding, FT but decreased cholesterol binding, plus decreased FT cholesterol and phosphatidylinositide transport." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 150 FT /note="K->A: Reduces 25-hydroxycholesterol binding." FT /evidence="ECO:0000269|PubMed:17428193" FT MUTAGEN 152 FT /note="F->D: Does not significantly impair FT 25-hydroxycholesterol binding." FT /evidence="ECO:0000269|PubMed:17428193" FT MUTAGEN 178..179 FT /note="HH->DD: Loss of increased cholesterol and decreased FT phosphatidylinositide accumulation at the cell membrane." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 215 FT /note="P->A: No effect on phosphatidylinositide binding, FT but decreased cholesterol binding, plus decreased FT cholesterol and phosphatidylinositide transport." FT /evidence="ECO:0000269|PubMed:30581148" FT MUTAGEN 249 FT /note="I->W: Reduces 25-hydroxycholesterol binding. Loss of FT 22(R)-hydroxycholesterol binding." FT /evidence="ECO:0000269|PubMed:17428193, FT ECO:0000269|PubMed:19224871" FT MUTAGEN 423 FT /note="K->A: Loss of increased cholesterol and decreased FT phosphatidylinositide accumulation at the cell membrane." FT /evidence="ECO:0000269|PubMed:30581148" FT HELIX 76..82 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 95..97 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 98..102 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 103..108 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 109..114 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 115..121 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 126..140 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 159..164 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 165..168 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 169..177 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 178..181 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 182..189 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 194..207 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 210..217 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 228..232 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 242..245 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 248..259 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 260..262 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 265..270 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 278..281 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 282..288 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 294..301 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 304..309 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 311..315 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 317..331 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 361..365 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 374..376 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 385..387 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 402..404 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 406..412 FT /evidence="ECO:0007829|PDB:5ZM8" FT HELIX 416..439 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 447..453 FT /evidence="ECO:0007829|PDB:5ZM8" FT TURN 455..457 FT /evidence="ECO:0007829|PDB:5ZM8" FT STRAND 460..464 FT /evidence="ECO:0007829|PDB:5ZM8" SQ SEQUENCE 480 AA; 55201 MW; A93D1B389D0A2740 CRC64; MNGEEEFFDA VTGFDSDNSS GEFSEANQKV TGMIDLDTSK NNRIGKTGER PSQENGIQKH RTSLPAPMFS RSDFSVWTIL KKCVGLELSK ITMPIAFNEP LSFLQRITEY MEHVYLIHRA SCQPQPLERM QSVAAFAVSA VASQWERTGK PFNPLLGETY ELIREDLGFR FISEQVSHHP PISAFHSEGL NHDFLFHGSI YPKLKFWGKS VEAEPRGTIT LELLKHNEAY TWTNPTCCVH NVIIGKLWIE QYGTVEILNH RTGHKCVLHF KPCGLFGKEL HKVEGHIQDK NKKKLFMIYG KWTECLWGID PVSYESFKKQ ERRGDHLRKA KLDEDSGKAD SDVADDVPVA QETVQVIPGS KLLWRINTRP PNSAQMYNFT SFTVSLNELE TGMEKTLPPT DCRLRPDIRG MENGNMDLAS QEKERLEEKQ REARRERAKE EAEWQTRWFY PGNNPYTGTP DWLYAGDYFE RNFSDCPDIY //