OSBL2_HUMAN
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 03-AUG-2022, entry version 165.
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};
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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; 28.
DR ELM; Q9H1P3; -.
DR IntAct; Q9H1P3; 15.
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; Q9H1P3; -.
DR PeptideAtlas; Q9H1P3; -.
DR PRIDE; Q9H1P3; -.
DR ProteomicsDB; 80434; -. [Q9H1P3-1]
DR ProteomicsDB; 80435; -. [Q9H1P3-2]
DR Antibodypedia; 29467; 195 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 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; 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; AHSAKMY; -.
DR OrthoDB; 863978at2759; -.
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; 18 hits in 1079 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 194 other tissues.
DR ExpressionAtlas; Q9H1P3; baseline and differential.
DR Genevisible; Q9H1P3; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; 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:0016020; C: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:0032934; F:sterol binding; IBA:GO_Central.
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 InterPro; IPR037239; OSBP_sf.
DR InterPro; IPR000648; Oxysterol-bd.
DR InterPro; IPR018494; Oxysterol-bd_CS.
DR PANTHER; PTHR10972; PTHR10972; 1.
DR Pfam; PF01237; Oxysterol_BP; 1.
DR SUPFAM; SSF144000; SSF144000; 1.
DR PROSITE; PS01013; OSBP; 1.
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 25-
FT 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
