OSBL3_MOUSE
ID OSBL3_MOUSE Reviewed; 855 AA.
AC Q9DBS9; E9QNI5;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Oxysterol-binding protein-related protein 3;
DE Short=ORP-3;
DE Short=OSBP-related protein 3;
GN Name=Osbpl3; Synonyms=Orp3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14593528; DOI=10.1007/s00441-003-0817-y;
RA Lehto M., Tienari J., Lehtonen S., Lehtonen E., Olkkonen V.M.;
RT "Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues:
RT the expression and intracellular localization of ORP3, ORP6, and ORP7.";
RL Cell Tissue Res. 315:39-57(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33 AND SER-272, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH OSBPL6, AND SUBCELLULAR LOCATION.
RX PubMed=30028970; DOI=10.1016/j.yexcr.2018.07.025;
RA Mochizuki S., Miki H., Zhou R., Kido Y., Nishimura W., Kikuchi M., Noda Y.;
RT "Oxysterol-binding protein-related protein (ORP) 6 localizes to the ER and
RT ER-plasma membrane contact sites and is involved in the turnover of PI4P in
RT cerebellar granule neurons.";
RL Exp. Cell Res. 370:601-612(2018).
CC -!- FUNCTION: Phosphoinositide-binding protein which associates with both
CC cell and endoplasmic reticulum (ER) membranes. Can bind to the ER
CC membrane protein VAPA and recruit VAPA to plasma membrane sites, thus
CC linking these intracellular compartments. The ORP3-VAPA complex
CC stimulates RRAS signaling which in turn attenuates integrin beta-1
CC (ITGB1) activation at the cell surface. With VAPA, may regulate ER
CC morphology. Has a role in regulation of the actin cytoskeleton, cell
CC polarity and cell adhesion. Binds to phosphoinositides with preference
CC for PI(3,4)P2 and PI(3,4,5)P3. Also binds 25-hydroxycholesterol and
CC cholesterol. {ECO:0000250|UniProtKB:Q9H4L5}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with RRAS (By
CC similarity). Interacts (phosphorylated form) with VAPA (By similarity).
CC Interacts with OSBPL6 (PubMed:30028970). {ECO:0000250|UniProtKB:Q9H4L5,
CC ECO:0000269|PubMed:30028970}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30028970}; Peripheral membrane protein
CC {ECO:0000305}. Cytoplasm, cytosol {ECO:0000269|PubMed:30028970}. Cell
CC membrane {ECO:0000269|PubMed:30028970}; Peripheral membrane protein
CC {ECO:0000305}. Cell projection, filopodium tip
CC {ECO:0000250|UniProtKB:Q9H4L5}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q9H4L5}; Peripheral membrane protein
CC {ECO:0000305}. Note=Co-localizes with OSBPL6 at contact sites between
CC the plasma membrane and the endoplasmic reticulum.
CC {ECO:0000269|PubMed:30028970}.
CC -!- TISSUE SPECIFICITY: Expressed in spinal ganglia. Expressed in a subset
CC of small lymphocytes (at protein level). {ECO:0000269|PubMed:14593528}.
CC -!- DEVELOPMENTAL STAGE: Expressed at higher levels in some regions of the
CC developing central and peripheral nervous system, including hippocampal
CC neuroepithelium, rhinencephalon, intermediate thalamus.
CC {ECO:0000269|PubMed:14593528}.
CC -!- DOMAIN: The FFAT 2 motif is required for interaction with VAPA and
CC regulation of the endoplasmic reticulum targeting of ORP3. The FFAT 1
CC motif may contribute to VAPA binding. {ECO:0000250|UniProtKB:Q9H4L5}.
CC -!- DOMAIN: The PH domain binds phosphoinositides, with a preference for
CC PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the
CC plasma membrane. {ECO:0000250|UniProtKB:Q9H4L5}.
CC -!- PTM: Phosphorylation is enhanced in vitro by phorbol-12-myristate-13-
CC acetate (PMA), forskolin and calcium ionophore A23187. Phosphorylation
CC seems to be stimulated in conditions of low cell-cell (or cell-matrix)
CC adhesion. {ECO:0000250|UniProtKB:Q9H4L5}.
CC -!- SIMILARITY: Belongs to the OSBP family. {ECO:0000305}.
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DR EMBL; AK004768; BAB23547.1; -; mRNA.
DR EMBL; AC008160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS39489.1; -.
DR RefSeq; NP_001157117.1; NM_001163645.1.
DR RefSeq; NP_082157.2; NM_027881.3.
DR RefSeq; XP_006506696.1; XM_006506633.3.
DR AlphaFoldDB; Q9DBS9; -.
DR SMR; Q9DBS9; -.
DR BioGRID; 214879; 4.
DR IntAct; Q9DBS9; 1.
DR STRING; 10090.ENSMUSP00000110112; -.
DR iPTMnet; Q9DBS9; -.
DR PhosphoSitePlus; Q9DBS9; -.
DR EPD; Q9DBS9; -.
DR jPOST; Q9DBS9; -.
DR MaxQB; Q9DBS9; -.
DR PaxDb; Q9DBS9; -.
DR PRIDE; Q9DBS9; -.
DR ProteomicsDB; 293525; -.
DR Antibodypedia; 12224; 118 antibodies from 26 providers.
DR DNASU; 71720; -.
DR Ensembl; ENSMUST00000114468; ENSMUSP00000110112; ENSMUSG00000029822.
DR GeneID; 71720; -.
DR KEGG; mmu:71720; -.
DR UCSC; uc009bwy.2; mouse.
DR CTD; 26031; -.
DR MGI; MGI:1918970; Osbpl3.
DR VEuPathDB; HostDB:ENSMUSG00000029822; -.
DR eggNOG; KOG1737; Eukaryota.
DR GeneTree; ENSGT00940000155957; -.
DR InParanoid; Q9DBS9; -.
DR TreeFam; TF320922; -.
DR Reactome; R-MMU-192105; Synthesis of bile acids and bile salts.
DR BioGRID-ORCS; 71720; 2 hits in 63 CRISPR screens.
DR ChiTaRS; Osbpl3; mouse.
DR PRO; PR:Q9DBS9; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9DBS9; protein.
DR Bgee; ENSMUSG00000029822; Expressed in urinary bladder urothelium and 176 other tissues.
DR ExpressionAtlas; Q9DBS9; baseline and differential.
DR Genevisible; Q9DBS9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032433; C:filopodium tip; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0015485; F:cholesterol binding; ISO:MGI.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0015248; F:sterol transporter activity; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037239; OSBP_sf.
DR InterPro; IPR000648; Oxysterol-bd.
DR InterPro; IPR018494; Oxysterol-bd_CS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041680; PH_8.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR10972; PTHR10972; 2.
DR Pfam; PF01237; Oxysterol_BP; 1.
DR Pfam; PF15409; PH_8; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF144000; SSF144000; 1.
DR PROSITE; PS01013; OSBP; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Endoplasmic reticulum;
KW Lipid transport; Lipid-binding; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transport.
FT CHAIN 1..855
FT /note="Oxysterol-binding protein-related protein 3"
FT /id="PRO_0000100372"
FT DOMAIN 50..145
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 161..167
FT /note="FFAT 1"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOTIF 450..454
FT /note="FFAT 2"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4L5"
FT CONFLICT 789
FT /note="N -> D (in Ref. 1; BAB23547)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 855 AA; 96966 MW; D9551D3265278DF8 CRC64;
MSDEKNLGVS QKLVSPSRST SSCSSKQGSR QDSWEVVEGL RGEMTYTQEP PVQKGFLLKK
RKWPLKGWHK RFFCLEKGIL KYAKSQADIE REKLHGCIDV GLSVMSVKKS SKCIDLDTEE
HIYHLKVKSE ELFDEWVSKL RHHRMYRQNE IAMFPRDVNH FFSGSSVTDS APGVFESVSS
RKRSSLSKQN SFPPGSNLSF SCGGDTRVPF WLQSSEDMEK CSKDMAHCHA YLLEMSQLLE
SMDVLHRTYS APAINAIQVP KPFSGPVRLH SSNPNLSTLD FGEEKSYSDG SEASSEFSKM
QEDLCHVAHK VYFALRSAFN SISVEREKLK QLMELDTSPS PSAQVVGLKH ALSSALAQNT
DLKERLRRIH AESLLLDPPA VPKPGDNLAE ENSRDEGRAL VHQLSNESRL SITDSLSEFF
DAQEVLLSPS SSENEISDDD SYVSDISDNL SLDNLSNDLD NERQTLGPVL ESSGEARSKR
RTSLPAPGPN TSSVSLWSIL RNNIGKDLSK VAMPVELNEP LNTLQRLCEE LEYSELLDKA
SRIPSPLERM VYVAAFAISA YASSYFRAGS KPFNPVLGET YECIRQDKGF QFFAEQVSHH
PPISACHAES GNFVFWQDVR WKNKFWGKSM EIVPIGTTHV TLPAFGDHFE WNKVTSCIHN
ILSGQRWIEH YGEIDIKNLN DDSCHCKVNF IKAKYWSTNA HEIEGTVFDR SGKAVHRLFG
KWHESIYCGG ASSSTCVWRA NPMPKGYEQY YGFTQFALEL NEMDPLSRSL LPPTDTRFRP
DQRLLEEGNI EEAEVQKQRI EKLQRERRRV LEENGVEHQP RFFRKSSDDA WVSNGTYLEL
RKDLGFSKLD HPVLW
