OSBL8_MOUSE
ID OSBL8_MOUSE Reviewed; 889 AA.
AC B9EJ86; G3X9N6; Q69ZJ4;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Oxysterol-binding protein-related protein 8;
DE Short=ORP-8;
DE Short=OSBP-related protein 8;
GN Name=Osbpl8 {ECO:0000312|MGI:MGI:2443807};
GN Synonyms=Kiaa1451 {ECO:0000303|PubMed:15368895}, Orp8;
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 461-889.
RC TISSUE=Thymus;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=17991739; DOI=10.1074/jbc.m705313200;
RA Yan D., Mayranpaa M.I., Wong J., Perttila J., Lehto M., Jauhiainen M.,
RA Kovanen P.T., Ehnholm C., Brown A.J., Olkkonen V.M.;
RT "OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol
RT efflux from macrophages.";
RL J. Biol. Chem. 283:332-340(2008).
RN [7]
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; SER-807; SER-808;
RP SER-810 AND SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=23554939; DOI=10.1371/journal.pone.0058856;
RA Beaslas O., Metso J., Nissila E., Laurila P.P., Kaiharju E., Batchu K.C.,
RA Kaipiainen L., Mayranpaa M.I., Yan D., Gylling H., Jauhiainen M.,
RA Olkkonen V.M.;
RT "Osbpl8 deficiency in mouse causes an elevation of high-density
RT lipoproteins and gender-specific alterations of lipid metabolism.";
RL PLoS ONE 8:E58856-E58856(2013).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=25347070; DOI=10.1371/journal.pone.0109024;
RA van Kampen E., Beaslas O., Hildebrand R.B., Lammers B., Van Berkel T.J.,
RA Olkkonen V.M., Van Eck M.;
RT "Orp8 deficiency in bone marrow-derived cells reduces atherosclerotic
RT lesion progression in LDL receptor knockout mice.";
RL PLoS ONE 9:E109024-E109024(2014).
CC -!- FUNCTION: Lipid transporter involved in lipid countertransport between
CC the endoplasmic reticulum and the plasma membrane: specifically
CC exchanges phosphatidylserine with phosphatidylinositol 4-phosphate
CC (PI4P), delivering phosphatidylserine to the plasma membrane in
CC exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in
CC the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a
CC mutually exclusive manner. Binds oxysterol, 25-hydroxycholesterol and
CC cholesterol. {ECO:0000250|UniProtKB:Q9BZF1}.
CC -!- SUBUNIT: Interacts with SPAG5. Interacts with NUP62.
CC {ECO:0000250|UniProtKB:Q9BZF1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9BZF1}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9BZF1}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q9BZF1}. Note=The presence of the N-terminus
CC extension contains an overall negative charge that may explain the weak
CC localization to the cortical endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q9BZF1}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in liver, spleen,
CC kidney, brain and adipose tissue. {ECO:0000269|PubMed:17991739}.
CC -!- DISRUPTION PHENOTYPE: Mice are apparently healthy and show no
CC developmental defects nor gross abnormality of glucose or lipid
CC metabolism. However, they display a significant elevation of plasma HDL
CC cholesterol and phospholipid levels. They also show a modest increase
CC of APOA1, plus a number of mild gender- or diet-specific lipid
CC metabolism phenotypes (PubMed:23554939). Deletion in bone marrow-
CC derived cells, including macrophages, reduces atherosclerotic lesion
CC progression (PubMed:25347070). {ECO:0000269|PubMed:23554939,
CC ECO:0000269|PubMed:25347070}.
CC -!- SIMILARITY: Belongs to the OSBP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDL21722.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC121871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124399; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466539; EDL21721.1; -; Genomic_DNA.
DR EMBL; CH466539; EDL21722.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC141383; AAI41384.1; -; mRNA.
DR EMBL; AK173174; BAD32452.1; -; mRNA.
DR CCDS; CCDS36056.1; -.
DR RefSeq; NP_001003717.1; NM_001003717.1.
DR RefSeq; NP_780698.2; NM_175489.3.
DR RefSeq; XP_006513702.1; XM_006513639.2.
DR AlphaFoldDB; B9EJ86; -.
DR BMRB; B9EJ86; -.
DR SMR; B9EJ86; -.
DR STRING; 10090.ENSMUSP00000100911; -.
DR iPTMnet; B9EJ86; -.
DR PhosphoSitePlus; B9EJ86; -.
DR SwissPalm; B9EJ86; -.
DR EPD; B9EJ86; -.
DR jPOST; B9EJ86; -.
DR MaxQB; B9EJ86; -.
DR PaxDb; B9EJ86; -.
DR PeptideAtlas; B9EJ86; -.
DR PRIDE; B9EJ86; -.
DR ProteomicsDB; 294115; -.
DR Antibodypedia; 680; 97 antibodies from 18 providers.
DR DNASU; 237542; -.
DR Ensembl; ENSMUST00000105275; ENSMUSP00000100911; ENSMUSG00000020189.
DR GeneID; 237542; -.
DR KEGG; mmu:237542; -.
DR UCSC; uc007gzy.1; mouse.
DR UCSC; uc007gzz.1; mouse.
DR CTD; 114882; -.
DR MGI; MGI:2443807; Osbpl8.
DR VEuPathDB; HostDB:ENSMUSG00000020189; -.
DR eggNOG; KOG2210; Eukaryota.
DR GeneTree; ENSGT00940000156622; -.
DR InParanoid; B9EJ86; -.
DR OrthoDB; 949920at2759; -.
DR PhylomeDB; B9EJ86; -.
DR TreeFam; TF312807; -.
DR Reactome; R-MMU-1482801; Acyl chain remodelling of PS.
DR BioGRID-ORCS; 237542; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Osbpl8; mouse.
DR PRO; PR:B9EJ86; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; B9EJ86; protein.
DR Bgee; ENSMUSG00000020189; Expressed in olfactory tubercle and 225 other tissues.
DR ExpressionAtlas; B9EJ86; baseline and differential.
DR Genevisible; B9EJ86; MM.
DR GO; GO:0032541; C:cortical endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IMP:MGI.
DR GO; GO:0015485; F:cholesterol binding; ISO:MGI.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
DR GO; GO:0140343; F:phosphatidylserine transfer activity; ISS: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:0032148; P:activation of protein kinase B activity; IMP:BHF-UCL.
DR GO; GO:0045444; P:fat cell differentiation; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:MGI.
DR GO; GO:0010891; P:negative regulation of sequestering of triglyceride; ISO:MGI.
DR GO; GO:0015914; P:phospholipid transport; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL.
DR GO; GO:0090204; P:protein localization to nuclear pore; IMP:MGI.
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; IPR001849; PH_domain.
DR PANTHER; PTHR10972; PTHR10972; 1.
DR Pfam; PF01237; Oxysterol_BP; 1.
DR Pfam; PF00169; PH; 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 Acetylation; Endoplasmic reticulum; Lipid transport; Lipid-binding;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..889
FT /note="Oxysterol-binding protein-related protein 8"
FT /id="PRO_0000434121"
FT TRANSMEM 871..888
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 148..265
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 321..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 772..823
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..110
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..370
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..791
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 801..815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 420..425
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 420..425
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 482..485
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 485
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 514..515
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 540
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:57262"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 706
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 710
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT BINDING 714
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol
FT 4-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58178"
FT /evidence="ECO:0000250|UniProtKB:Q02201"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZF1"
FT MOD_RES 807
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 889 AA; 101269 MW; 01565BEBAD48553C CRC64;
MEAALADGEP DRSSLLGDSK DVLGPSTVVA NSDEPQHLTP GKMSQRQGRD ANPTPTRDLP
QPSLSPASLH SQGFERGKED ISQNKDDSSL SMSKSKSESK LYNGSEKDSS TSSKLTKKES
LKVQKKNYRE EKKRATKELL STITDPSVIV MADWLKIRGT LKSWTKLWCV LKPGVLLIYK
TQKNGQWVGT VLLNACEIIE RPSKKDGFCF KLFHPLEQSI WAVKGPKGEA VGSITQPLPS
SYLIIRATSE SDGRCWMDAL ELALKCSSLL KRTMVREGKE HDLSISSDST HVTLYGLLRA
NNLHSGDNFQ LNDSEIERQH FKDQDLYSDK SDKENDPEHD ESDNEVLGKS EESDTDTSER
QDDSYIDPEP VEPLKETTYM EQSHEELGEA GEASQTETVS EENKSLIWTL LKQVRPGMDL
SRVVLPTFIL EPRSFLDKLS DYYYHADFLS EAALEENPYF RLKKVVKWYL SGFYKKPKGL
KKPYNPILGE TFRCLWIHPR TNSKTFYIAE QVSHHPPISA FYVSNRKDGF CLSGSILAKS
KFYGNSLSAI LEGEARLTFL NRGEDYVMTM PYAHCKGILY GTMTLELGGT VNITCQKTGY
SAILEFKLKP FLGSSDYVNQ ISGKLKLGKE VLATLEGHWD SEVFINDKKT DNSEIFWNPT
PDIKQWRLIR HTVKFEEQDD FESEKLWQRV TKAINAKDQT EATQEKYVLE EAQRQAARDR
KTKTQEWVCK LFELDPLTGE WHYKFSDTRP WDPLNDMIQF EKDGVIQTKV KHRTPMVSVP
KMKHKPTRQQ KKVVKGYSSP EPDIQDSSGS EAQSVKPSTR RKKGIDLGDI QSSIESIKQT
QEEIKRNIMA LRNHLLSSTP ATDYFLQQKD YFVIFLLILL QVIINFIFK
