OSBP1_RABIT
ID OSBP1_RABIT Reviewed; 809 AA.
AC P16258;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Oxysterol-binding protein 1;
GN Name=OSBP;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2777807; DOI=10.1016/s0021-9258(19)84776-2;
RA Dawson P.A., Ridgway N.D., Slaughter C.A., Brown M.S., Goldstein J.L.;
RT "cDNA cloning and expression of oxysterol-binding protein, an oligomer with
RT a potential leucine zipper.";
RL J. Biol. Chem. 264:16798-16803(1989).
RN [2]
RP FUNCTION, STEROL-BINDING, DOMAIN, AND MUTAGENESIS OF TYR-298 AND TYR-458.
RX PubMed=18165705; DOI=10.1074/jbc.m707631200;
RA Wang P.-Y., Weng J., Lee S., Anderson R.G.W.;
RT "The N-terminus controls sterol binding while the C-terminus regulates the
RT scaffolding function of OSBP.";
RL J. Biol. Chem. 283:8034-8045(2008).
CC -!- FUNCTION: Lipid transporter involved in lipid countertransport between
CC the Golgi complex and membranes of the endoplasmic reticulum:
CC specifically exchanges sterol with phosphatidylinositol 4-phosphate
CC (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is
CC degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum
CC (By similarity). Binds cholesterol and a range of oxysterols including
CC 25-hydroxycholesterol (PubMed:18165705). Cholesterol binding promotes
CC the formation of a complex with PP2A and a tyrosine phosphatase which
CC dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its
CC disassembly (By similarity). Regulates cholesterol efflux by decreasing
CC ABCA1 stability (By similarity). {ECO:0000250|UniProtKB:P22059,
CC ECO:0000269|PubMed:18165705}.
CC -!- SUBUNIT: Homodimer or homotrimer. Interacts (via FFAT motif) with VAPA.
CC Interacts (via C-terminus) with RELCH (via the third HEAT repeat) (By
CC similarity). Found in a complex composed of RELCH, OSBP1 and RAB11A (By
CC similarity). {ECO:0000250|UniProtKB:P22059,
CC ECO:0000250|UniProtKB:Q3B7Z2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P22059}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P22059}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P22059}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P22059}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P22059}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P22059}. Note=Predominantly cytosolic.
CC {ECO:0000250|UniProtKB:P22059}.
CC -!- DOMAIN: The PH and the Ala/Gly-rich domains control cholesterol binding
CC without affecting 25-hydroxycholesterol binding.
CC {ECO:0000269|PubMed:18165705}.
CC -!- DOMAIN: The second coiled-coil domain is required for interaction with
CC the tyrosine phosphatase. {ECO:0000269|PubMed:18165705}.
CC -!- DOMAIN: The FFAT motif is required for interaction with VATA and proper
CC localization of the protein. {ECO:0000250|UniProtKB:P22059}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the OSBP family. {ECO:0000305}.
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DR EMBL; J05056; AAA31427.1; -; mRNA.
DR PIR; A34404; A34404.
DR RefSeq; NP_001075702.1; NM_001082233.1.
DR AlphaFoldDB; P16258; -.
DR BMRB; P16258; -.
DR SMR; P16258; -.
DR STRING; 9986.ENSOCUP00000001854; -.
DR iPTMnet; P16258; -.
DR PRIDE; P16258; -.
DR GeneID; 100009048; -.
DR KEGG; ocu:100009048; -.
DR CTD; 5007; -.
DR eggNOG; KOG1737; Eukaryota.
DR InParanoid; P16258; -.
DR OrthoDB; 542090at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; IDA:BHF-UCL.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0120015; F:sterol transfer activity; ISS:UniProtKB.
DR GO; GO:0032367; P:intracellular cholesterol transport; ISS:UniProtKB.
DR GO; GO:0015918; P:sterol transport; ISS:UniProtKB.
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; Coiled coil; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; Golgi apparatus; Lipid transport; Lipid-binding;
KW Membrane; Phosphoprotein; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT CHAIN 2..809
FT /note="Oxysterol-binding protein 1"
FT /id="PRO_0000100365"
FT DOMAIN 90..183
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 17..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 729..761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 293..328
FT /evidence="ECO:0000255"
FT COILED 732..762
FT /evidence="ECO:0000255"
FT MOTIF 360..366
FT /note="FFAT"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT COMPBIAS 729..760
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 119..124
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:P35844"
FT BINDING 316
FT /ligand="20-hydroxycholesterol"
FT /ligand_id="ChEBI:CHEBI:1296"
FT /evidence="ECO:0000250|UniProtKB:P35844"
FT BINDING 316
FT /ligand="25-hydroxycholesterol"
FT /ligand_id="ChEBI:CHEBI:42977"
FT /evidence="ECO:0000250|UniProtKB:P35844"
FT BINDING 316
FT /ligand="7beta-hydroxycholesterol"
FT /ligand_id="ChEBI:CHEBI:42989"
FT /evidence="ECO:0000250|UniProtKB:P35844"
FT BINDING 316
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:P35844"
FT BINDING 316
FT /ligand="ergosterol"
FT /ligand_id="ChEBI:CHEBI:16933"
FT /evidence="ECO:0000250|UniProtKB:P35844"
FT BINDING 495..498
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:P35844"
FT BINDING 524..525
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:P35844"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3B7Z2"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 379
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22059"
FT MUTAGEN 298
FT /note="Y->S: No effect on cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:18165705"
FT MUTAGEN 458
FT /note="Y->S: Abolishes cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:18165705"
SQ SEQUENCE 809 AA; 89478 MW; 55C6CAE1B985B1E0 CRC64;
MAATELRGVV GPGPAAIAAP GGGGAGPPVV GGGGGGRGDA GPGSGAASGT VAAAAAGGQG
PGAGGVAAAA GPAPTPPAGG SGSSGTGGSG SAREGWLFKW TNYIKGYQRR WFVLSNGLLS
YYRSKAEMRH TCRGTINLAT ANITVEDSCN FIISNGGAQT YHLKASSEVE RQRWVTALEL
AKAKAVKMLA ESDESGDEES VSQTDKTELQ NTLRTLSSKV EDLSTCNDLI AKHGTALQRS
LSELESLKLP AESNEKIKQV NERATLFRIT SNAMINACRD FLVLAQTHSK KWQKSLQYER
DQRIRLEETL EQLAKQHNHL ERAFRGATVL PAHTSGSAGS GKDQCCSGKG DMSDEDDENE
FFDAPEIITM PENLGHKRTG SNISGASSDI SLDEQYKHQL EETKKEKRTR IPYKPNYSLN
LWSIMKNCIG KELSKIPMPV NFNEPLSMLQ RLTEDLEYHE LLDRAAKCEN SLEQLCYVAA
FTVSSYSTTV FRTSKPFNPL LGETFELDRL EENGYRSLCE QVSHHPPAAA HHAESKNGWT
LRQEIKITSK FRGKYLSIMP LGTIHCIFHA TGHHYTWKKV TTTVHNIIVG KLWIDQSGEI
DIVNHKTGDK CNLKFVPYSY FSRDVARKVT GEVTDPSGKV HFALLGTWDE KMDCFKVQPV
SGENGGDARQ RGHEAEESRV MLWKRNPLPK NAENMYYFSE LALTLNAWEG GTAPTDSRLR
PDQRLMENGR WDEANAEKQR LEEKQRLSRK KREAEAMKAT EDGTPYDPYK ALWFERKKDP
VTKELTHIYR GEYWECKEKQ DWNSCPDIF
