Full text data of HYOU1
HYOU1
(GRP170, ORP150)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein; ORP-150; 170 kDa glucose-regulated protein; GRP-170; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein; ORP-150; 170 kDa glucose-regulated protein; GRP-170; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y4L1
ID HYOU1_HUMAN Reviewed; 999 AA.
AC Q9Y4L1; A8C1Z0; Q2I204; Q53H25;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Hypoxia up-regulated protein 1;
DE AltName: Full=150 kDa oxygen-regulated protein;
DE Short=ORP-150;
DE AltName: Full=170 kDa glucose-regulated protein;
DE Short=GRP-170;
DE Flags: Precursor;
GN Name=HYOU1; Synonyms=GRP170, ORP150;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Astrocytoma;
RX PubMed=9020069; DOI=10.1006/bbrc.1996.5890;
RA Ikeda J., Kaneda S., Kuwabara K., Ogawa S., Kobayashi T.,
RA Matsumoto M., Yura T., Yanagi H.;
RT "Cloning and expression of cDNA encoding the human 150 kDa oxygen-
RT regulated protein, ORP150.";
RL Biochem. Biophys. Res. Commun. 230:94-99(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10965054;
RA Kaneda S., Yura T., Yanagi H.;
RT "Production of three distinct mRNAs of 150 kDa oxygen-regulated
RT protein (ORP150) by alternative promoters: preferential induction of
RT one species under stress conditions.";
RL J. Biochem. 128:529-538(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=17131193; DOI=10.1007/s10930-006-9038-z;
RA Takeuchi S.;
RT "Molecular cloning, sequence, function and structural basis of human
RT heart 150 kDa oxygen-regulated protein, an ER chaperone.";
RL Protein J. 25:517-528(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 241-256; 541-555; 577-594 AND 754-768, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP FUNCTION.
RX PubMed=10037731; DOI=10.1074/jbc.274.10.6397;
RA Ozawa K., Kuwabara K., Tamatani M., Takatsuji K., Tsukamoto Y.,
RA Kaneda S., Yanagi H., Stern D.M., Eguchi Y., Tsujimoto Y., Ogawa S.,
RA Tohyama M.;
RT "150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced
RT apoptotic cell death.";
RL J. Biol. Chem. 274:6397-6404(1999).
RN [9]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.E02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein
RT complexes in endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [10]
RP GLYCOSYLATION AT ASN-155; ASN-515; ASN-596; ASN-830; ASN-862 AND
RP ASN-931.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515; ASN-830; ASN-869 AND
RP ASN-931, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515; ASN-596; ASN-830;
RP ASN-862 AND ASN-931, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [15]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Has a pivotal role in cytoprotective cellular mechanisms
CC triggered by oxygen deprivation. May play a role as a molecular
CC chaperone and participate in protein folding.
CC -!- SUBUNIT: Part of a large chaperone multiprotein complex comprising
CC DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1,
CC UGT1A1 and very small amounts of ERP29, but not, or at very low
CC levels, CALR nor CANX.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC -!- TISSUE SPECIFICITY: Highly expressed in tissues that contain well-
CC developed endoplasmic reticulum and synthesize large amounts of
CC secretory proteins. Highly expressed in liver and pancreas and
CC lower expression in brain and kidney. Also expressed in
CC macrophages within aortic atherosclerotic plaques, and in breast
CC cancers.
CC -!- INDUCTION: By hypoxia and also by 2-deoxyglucose or tunicamycin.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
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DR EMBL; U65785; AAC50947.1; -; mRNA.
DR EMBL; AB009979; BAF80348.1; -; Genomic_DNA.
DR EMBL; DQ350134; ABC75106.1; -; mRNA.
DR EMBL; DQ372932; ABD14370.1; -; mRNA.
DR EMBL; AK314178; BAG36860.1; -; mRNA.
DR EMBL; AK222756; BAD96476.1; -; mRNA.
DR EMBL; EF444986; ACA06002.1; -; Genomic_DNA.
DR PIR; JC5278; JC5278.
DR RefSeq; NP_001124463.1; NM_001130991.1.
DR RefSeq; NP_006380.1; NM_006389.3.
DR UniGene; Hs.277704; -.
DR ProteinModelPortal; Q9Y4L1; -.
DR SMR; Q9Y4L1; 35-613, 711-817.
DR IntAct; Q9Y4L1; 7.
DR MINT; MINT-4105974; -.
DR STRING; 9606.ENSP00000278752; -.
DR ChEMBL; CHEMBL2216741; -.
DR PhosphoSite; Q9Y4L1; -.
DR DMDM; 10720185; -.
DR REPRODUCTION-2DPAGE; IPI00000877; -.
DR PaxDb; Q9Y4L1; -.
DR PeptideAtlas; Q9Y4L1; -.
DR PRIDE; Q9Y4L1; -.
DR Ensembl; ENST00000404233; ENSP00000384144; ENSG00000149428.
DR Ensembl; ENST00000571646; ENSP00000458419; ENSG00000262812.
DR GeneID; 10525; -.
DR KEGG; hsa:10525; -.
DR UCSC; uc001put.2; human.
DR CTD; 10525; -.
DR GeneCards; GC11M118914; -.
DR HGNC; HGNC:16931; HYOU1.
DR HPA; HPA049296; -.
DR MIM; 601746; gene.
DR neXtProt; NX_Q9Y4L1; -.
DR PharmGKB; PA38427; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000007865; -.
DR HOVERGEN; HBG106402; -.
DR InParanoid; Q9Y4L1; -.
DR KO; K09486; -.
DR OMA; KAKFTKP; -.
DR PhylomeDB; Q9Y4L1; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HYOU1; human.
DR GeneWiki; HYOU1; -.
DR GenomeRNAi; 10525; -.
DR NextBio; 39930; -.
DR PMAP-CutDB; Q9Y4L1; -.
DR PRO; PR:Q9Y4L1; -.
DR ArrayExpress; Q9Y4L1; -.
DR Bgee; Q9Y4L1; -.
DR CleanEx; HS_HYOU1; -.
DR Genevestigator; Q9Y4L1; -.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR PROSITE; PS00297; HSP70_1; FALSE_NEG.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chaperone; Complete proteome; Direct protein sequencing;
KW Endoplasmic reticulum; Glycoprotein; Nucleotide-binding;
KW Reference proteome; Signal; Stress response.
FT SIGNAL 1 32 By similarity.
FT CHAIN 33 999 Hypoxia up-regulated protein 1.
FT /FTId=PRO_0000013538.
FT MOTIF 996 999 Prevents secretion from ER (Potential).
FT COMPBIAS 603 606 Poly-Glu.
FT COMPBIAS 636 641 Poly-Pro.
FT CARBOHYD 155 155 N-linked (GlcNAc...).
FT CARBOHYD 222 222 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 515 515 N-linked (GlcNAc...).
FT CARBOHYD 596 596 N-linked (GlcNAc...).
FT CARBOHYD 830 830 N-linked (GlcNAc...).
FT CARBOHYD 862 862 N-linked (GlcNAc...).
FT CARBOHYD 869 869 N-linked (GlcNAc...).
FT CARBOHYD 922 922 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 931 931 N-linked (GlcNAc...).
FT CONFLICT 75 75 K -> E (in Ref. 5; BAD96476).
FT CONFLICT 92 92 N -> D (in Ref. 5; BAD96476).
FT CONFLICT 255 255 M -> T (in Ref. 5; BAD96476).
FT CONFLICT 442 442 V -> A (in Ref. 5; BAD96476).
SQ SEQUENCE 999 AA; 111335 MW; FCE0F292466AFAB9 CRC64;
MADKVRRQRP RRRVCWALVA VLLADLLALS DTLAVMSVDL GSESMKVAIV KPGVPMEIVL
NKESRRKTPV IVTLKENERF FGDSAASMAI KNPKATLRYF QHLLGKQADN PHVALYQARF
PEHELTFDPQ RQTVHFQISS QLQFSPEEVL GMVLNYSRSL AEDFAEQPIK DAVITVPVFF
NQAERRAVLQ AARMAGLKVL QLINDNTATA LSYGVFRRKD INTTAQNIMF YDMGSGSTVC
TIVTYQMVKT KEAGMQPQLQ IRGVGFDRTL GGLEMELRLR ERLAGLFNEQ RKGQRAKDVR
ENPRAMAKLL REANRLKTVL SANADHMAQI EGLMDDVDFK AKVTRVEFEE LCADLFERVP
GPVQQALQSA EMSLDEIEQV ILVGGATRVP RVQEVLLKAV GKEELGKNIN ADEAAAMGAV
YQAAALSKAF KVKPFVVRDA VVYPILVEFT REVEEEPGIH SLKHNKRVLF SRMGPYPQRK
VITFNRYSHD FNFHINYGDL GFLGPEDLRV FGSQNLTTVK LKGVGDSFKK YPDYESKGIK
AHFNLDESGV LSLDRVESVF ETLVEDSAEE ESTLTKLGNT ISSLFGGGTT PDAKENGTDT
VQEEEESPAE GSKDEPGEQV ELKEEAEAPV EDGSQPPPPE PKGDATPEGE KATEKENGDK
SEAQKPSEKA EAGPEGVAPA PEGEKKQKPA RKRRMVEEIG VELVVLDLPD LPEDKLAQSV
QKLQDLTLRD LEKQEREKAA NSLEAFIFET QDKLYQPEYQ EVSTEEQREE ISGKLSAAST
WLEDEGVGAT TVMLKEKLAE LRKLCQGLFF RVEERKKWPE RLSALDNLLN HSSMFLKGAR
LIPEMDQIFT EVEMTTLEKV INETWAWKNA TLAEQAKLPA TEKPVLLSKD IEAKMMALDR
EVQYLLNKAK FTKPRPRPKD KNGTRAEPPL NASASDQGEK VIPPAGQTED AEPISEPEKV
ETGSEPGDTE PLELGGPGAE PEQKEQSTGQ KRPLKNDEL
//
ID HYOU1_HUMAN Reviewed; 999 AA.
AC Q9Y4L1; A8C1Z0; Q2I204; Q53H25;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Hypoxia up-regulated protein 1;
DE AltName: Full=150 kDa oxygen-regulated protein;
DE Short=ORP-150;
DE AltName: Full=170 kDa glucose-regulated protein;
DE Short=GRP-170;
DE Flags: Precursor;
GN Name=HYOU1; Synonyms=GRP170, ORP150;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Astrocytoma;
RX PubMed=9020069; DOI=10.1006/bbrc.1996.5890;
RA Ikeda J., Kaneda S., Kuwabara K., Ogawa S., Kobayashi T.,
RA Matsumoto M., Yura T., Yanagi H.;
RT "Cloning and expression of cDNA encoding the human 150 kDa oxygen-
RT regulated protein, ORP150.";
RL Biochem. Biophys. Res. Commun. 230:94-99(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10965054;
RA Kaneda S., Yura T., Yanagi H.;
RT "Production of three distinct mRNAs of 150 kDa oxygen-regulated
RT protein (ORP150) by alternative promoters: preferential induction of
RT one species under stress conditions.";
RL J. Biochem. 128:529-538(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=17131193; DOI=10.1007/s10930-006-9038-z;
RA Takeuchi S.;
RT "Molecular cloning, sequence, function and structural basis of human
RT heart 150 kDa oxygen-regulated protein, an ER chaperone.";
RL Protein J. 25:517-528(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 241-256; 541-555; 577-594 AND 754-768, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP FUNCTION.
RX PubMed=10037731; DOI=10.1074/jbc.274.10.6397;
RA Ozawa K., Kuwabara K., Tamatani M., Takatsuji K., Tsukamoto Y.,
RA Kaneda S., Yanagi H., Stern D.M., Eguchi Y., Tsujimoto Y., Ogawa S.,
RA Tohyama M.;
RT "150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced
RT apoptotic cell death.";
RL J. Biol. Chem. 274:6397-6404(1999).
RN [9]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.E02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein
RT complexes in endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [10]
RP GLYCOSYLATION AT ASN-155; ASN-515; ASN-596; ASN-830; ASN-862 AND
RP ASN-931.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515; ASN-830; ASN-869 AND
RP ASN-931, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515; ASN-596; ASN-830;
RP ASN-862 AND ASN-931, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-515, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [15]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Has a pivotal role in cytoprotective cellular mechanisms
CC triggered by oxygen deprivation. May play a role as a molecular
CC chaperone and participate in protein folding.
CC -!- SUBUNIT: Part of a large chaperone multiprotein complex comprising
CC DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1,
CC UGT1A1 and very small amounts of ERP29, but not, or at very low
CC levels, CALR nor CANX.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC -!- TISSUE SPECIFICITY: Highly expressed in tissues that contain well-
CC developed endoplasmic reticulum and synthesize large amounts of
CC secretory proteins. Highly expressed in liver and pancreas and
CC lower expression in brain and kidney. Also expressed in
CC macrophages within aortic atherosclerotic plaques, and in breast
CC cancers.
CC -!- INDUCTION: By hypoxia and also by 2-deoxyglucose or tunicamycin.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; U65785; AAC50947.1; -; mRNA.
DR EMBL; AB009979; BAF80348.1; -; Genomic_DNA.
DR EMBL; DQ350134; ABC75106.1; -; mRNA.
DR EMBL; DQ372932; ABD14370.1; -; mRNA.
DR EMBL; AK314178; BAG36860.1; -; mRNA.
DR EMBL; AK222756; BAD96476.1; -; mRNA.
DR EMBL; EF444986; ACA06002.1; -; Genomic_DNA.
DR PIR; JC5278; JC5278.
DR RefSeq; NP_001124463.1; NM_001130991.1.
DR RefSeq; NP_006380.1; NM_006389.3.
DR UniGene; Hs.277704; -.
DR ProteinModelPortal; Q9Y4L1; -.
DR SMR; Q9Y4L1; 35-613, 711-817.
DR IntAct; Q9Y4L1; 7.
DR MINT; MINT-4105974; -.
DR STRING; 9606.ENSP00000278752; -.
DR ChEMBL; CHEMBL2216741; -.
DR PhosphoSite; Q9Y4L1; -.
DR DMDM; 10720185; -.
DR REPRODUCTION-2DPAGE; IPI00000877; -.
DR PaxDb; Q9Y4L1; -.
DR PeptideAtlas; Q9Y4L1; -.
DR PRIDE; Q9Y4L1; -.
DR Ensembl; ENST00000404233; ENSP00000384144; ENSG00000149428.
DR Ensembl; ENST00000571646; ENSP00000458419; ENSG00000262812.
DR GeneID; 10525; -.
DR KEGG; hsa:10525; -.
DR UCSC; uc001put.2; human.
DR CTD; 10525; -.
DR GeneCards; GC11M118914; -.
DR HGNC; HGNC:16931; HYOU1.
DR HPA; HPA049296; -.
DR MIM; 601746; gene.
DR neXtProt; NX_Q9Y4L1; -.
DR PharmGKB; PA38427; -.
DR eggNOG; COG0443; -.
DR HOGENOM; HOG000007865; -.
DR HOVERGEN; HBG106402; -.
DR InParanoid; Q9Y4L1; -.
DR KO; K09486; -.
DR OMA; KAKFTKP; -.
DR PhylomeDB; Q9Y4L1; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HYOU1; human.
DR GeneWiki; HYOU1; -.
DR GenomeRNAi; 10525; -.
DR NextBio; 39930; -.
DR PMAP-CutDB; Q9Y4L1; -.
DR PRO; PR:Q9Y4L1; -.
DR ArrayExpress; Q9Y4L1; -.
DR Bgee; Q9Y4L1; -.
DR CleanEx; HS_HYOU1; -.
DR Genevestigator; Q9Y4L1; -.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR PROSITE; PS00297; HSP70_1; FALSE_NEG.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chaperone; Complete proteome; Direct protein sequencing;
KW Endoplasmic reticulum; Glycoprotein; Nucleotide-binding;
KW Reference proteome; Signal; Stress response.
FT SIGNAL 1 32 By similarity.
FT CHAIN 33 999 Hypoxia up-regulated protein 1.
FT /FTId=PRO_0000013538.
FT MOTIF 996 999 Prevents secretion from ER (Potential).
FT COMPBIAS 603 606 Poly-Glu.
FT COMPBIAS 636 641 Poly-Pro.
FT CARBOHYD 155 155 N-linked (GlcNAc...).
FT CARBOHYD 222 222 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 515 515 N-linked (GlcNAc...).
FT CARBOHYD 596 596 N-linked (GlcNAc...).
FT CARBOHYD 830 830 N-linked (GlcNAc...).
FT CARBOHYD 862 862 N-linked (GlcNAc...).
FT CARBOHYD 869 869 N-linked (GlcNAc...).
FT CARBOHYD 922 922 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 931 931 N-linked (GlcNAc...).
FT CONFLICT 75 75 K -> E (in Ref. 5; BAD96476).
FT CONFLICT 92 92 N -> D (in Ref. 5; BAD96476).
FT CONFLICT 255 255 M -> T (in Ref. 5; BAD96476).
FT CONFLICT 442 442 V -> A (in Ref. 5; BAD96476).
SQ SEQUENCE 999 AA; 111335 MW; FCE0F292466AFAB9 CRC64;
MADKVRRQRP RRRVCWALVA VLLADLLALS DTLAVMSVDL GSESMKVAIV KPGVPMEIVL
NKESRRKTPV IVTLKENERF FGDSAASMAI KNPKATLRYF QHLLGKQADN PHVALYQARF
PEHELTFDPQ RQTVHFQISS QLQFSPEEVL GMVLNYSRSL AEDFAEQPIK DAVITVPVFF
NQAERRAVLQ AARMAGLKVL QLINDNTATA LSYGVFRRKD INTTAQNIMF YDMGSGSTVC
TIVTYQMVKT KEAGMQPQLQ IRGVGFDRTL GGLEMELRLR ERLAGLFNEQ RKGQRAKDVR
ENPRAMAKLL REANRLKTVL SANADHMAQI EGLMDDVDFK AKVTRVEFEE LCADLFERVP
GPVQQALQSA EMSLDEIEQV ILVGGATRVP RVQEVLLKAV GKEELGKNIN ADEAAAMGAV
YQAAALSKAF KVKPFVVRDA VVYPILVEFT REVEEEPGIH SLKHNKRVLF SRMGPYPQRK
VITFNRYSHD FNFHINYGDL GFLGPEDLRV FGSQNLTTVK LKGVGDSFKK YPDYESKGIK
AHFNLDESGV LSLDRVESVF ETLVEDSAEE ESTLTKLGNT ISSLFGGGTT PDAKENGTDT
VQEEEESPAE GSKDEPGEQV ELKEEAEAPV EDGSQPPPPE PKGDATPEGE KATEKENGDK
SEAQKPSEKA EAGPEGVAPA PEGEKKQKPA RKRRMVEEIG VELVVLDLPD LPEDKLAQSV
QKLQDLTLRD LEKQEREKAA NSLEAFIFET QDKLYQPEYQ EVSTEEQREE ISGKLSAAST
WLEDEGVGAT TVMLKEKLAE LRKLCQGLFF RVEERKKWPE RLSALDNLLN HSSMFLKGAR
LIPEMDQIFT EVEMTTLEKV INETWAWKNA TLAEQAKLPA TEKPVLLSKD IEAKMMALDR
EVQYLLNKAK FTKPRPRPKD KNGTRAEPPL NASASDQGEK VIPPAGQTED AEPISEPEKV
ETGSEPGDTE PLELGGPGAE PEQKEQSTGQ KRPLKNDEL
//
MIM
601746
*RECORD*
*FIELD* NO
601746
*FIELD* TI
*601746 HYPOXIA UP-REGULATED 1; HYOU1
;;OXYGEN-REGULATED PROTEIN, 150-KD; ORP150
*FIELD* TX
read more
CLONING
Astrocytes retain cell viability, even in extreme ischemia, and
proliferate in damaged brain (Petito et al., 1990; Janeczko, 1991). Rat
astrocytes exposed to hypoxia followed by reoxygenation were reported to
release increased amounts of interleukin-6 (147620) that could promote
neuronal survival in ischemic brain (Maeda et al., 1994). Kuwabara et
al. (1996) observed a 150-kD protein, called oxygen-regulated protein
(ORP150) by them, in the endoplasmic reticulum (ER) of cultured
astrocytes that was induced specifically by hypoxia and not by other
stimuli.
Ikeda et al. (1997) reported the cloning of human and rat ORP150 cDNAs
from hypoxia-treated human astrocytoma U373 cells and rat astrocytes,
respectively. The full-length 4,503-bp human cDNA contains a 2,997-bp
open reading frame predicted to encode a polypeptide of 999 amino acids
with a calculated molecular mass of 111,330 Da. The deduced amino acid
sequences of human and rat ORP150 exhibit high similarity (over 90%
identity) to each other. The first 32 residues represent the signal
peptide necessary for secretion. The C-terminal KNDEL sequence resembles
KDEL, a motif found in ER-resident proteins, suggesting that ORP150
resides in the ER. The N-terminal half of ORP150 has a modest similarity
to the ATPase domain of numerous HSP70 family sequences (see 140550).
Northern blot analysis revealed a marked similarity of expression
between ORP150 and GRP78 (138120) in U373 cells during hypoxia stress.
(The GRP78 protein is produced in cultured rat astrocytes exposed to
hypoxia or hypoxia/reoxygenation.) They also found that ORP150 mRNA was
highly expressed in the liver and pancreas, whereas little expression
was observed in the kidney and brain, similarly to the expression
pattern of GRP78. Ikeda et al. (1997) proposed that ORP150 plays an
important role in protein folding and secretion in the ER, perhaps as a
molecular chaperone in concert with other GRPs, to cope with
environmental stress.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HYOU1
gene to chromosome 11 (TMAP stSG31085).
GENE FUNCTION
Tamatani et al. (2001) found that although ORP150 was sparingly
upregulated in neurons from human brain undergoing ischemic stress,
there was robust induction in astrocytes. Cultured neurons
overexpressing ORP150 were resistant to hypoxemic stress, whereas
astrocytes with inhibited ORP150 expression were more vulnerable. Mice
with targeted neuronal overexpression of ORP150 had smaller strokes
compared with controls. Neurons with increased ORP150 demonstrated
suppressed caspase-3-like activity and enhanced brain-derived
neurotrophic factor (BDNF) (113505) under hypoxia signaling. Tamatani et
al. (2001) concluded that ORP150 is an integral participant in ischemic
cytoprotective pathways.
Ozawa et al. (2001) demonstrated coexpression, colocalization, and
coimmunoprecipitation of ORP150 and vascular endothelial growth factor
(VEGF; 192240) in the ER of macrophages within the neovasculature of
human wound granulation tissue. In vitro, inhibition of ORP150 resulted
in retention of VEGF within the ER, whereas overexpression of ORP150
promoted the secretion of VEGF into hypoxic culture supernatants,
indicating that ORP150 may participate in VEGF transport to the
cytoplasm. In wounds of diabetic mice, overexpression of ORP150 resulted
in accelerated repair and closure; suppression of ORP150 delayed repair.
Ozawa et al. (2001) concluded that ORP150 plays a role in the promotion
of angiogenesis, and more generally acts as a molecular chaperone under
hypoxic conditions to facilitate protein transport and processing in the
ER.
Two members of the HSP70 family are required for protein biogenesis in
the yeast endoplasmic reticulum: Lhs1 (homologous to HYOU1) and Kar2
(homologous to HSPA5, or BiP; 138120). Steel et al. (2004) found that
Lhs1 and Kar2 specifically interacted to couple, and coordinately
regulate, their respective activities. Lhs1 stimulated Kar2 by providing
a specific nucleotide exchange activity, whereas Kar2 reciprocally
activated the Lhs1 ATPase. In yeast, the 2 ATPase activities are
coupled, and their coordinated regulation is essential for normal
function in vivo.
Zhao et al. (2010) showed that overexpression of Hyou1 prevented ER
stress and rescued neurodegeneration of Purkinje cells in Sil1 (608005)
-/- mice, whereas decreasing expression of Hyou1 exacerbated these
phenotypes. Purkinje cells from the caudal lobules of the cerebellum
from Sil1 -/- mice typically do not show signs of ER stress; however,
decreased expression of Hyou1 in these cells resulted in signs of ER
stress, ubiquitin-positive inclusions, and death. Zhao et al. (2010)
suggested that HYOU1 and SIL1 have partially redundant functions as BiP
nucleotide exchange factors in Purkinje cells.
*FIELD* RF
1. Ikeda, J.; Kaneda, S.; Kuwabara, K.; Ogawa, S.; Kobayashi, T.;
Matsumoto, M.; Yura, T.; Yanagi, H.: Cloning and expression of cDNA
encoding the human 150 kDa oxygen-regulated protein, ORP150. Biochem.
Biophys. Res. Commun. 230: 94-99, 1997.
2. Janeczko, K.: The proliferative response of S-100 protein-positive
glial cells to injury in the neonatal rat brain. Brain Res. 564:
86-90, 1991.
3. Kuwabara, K.; Matsumoto, M.; Ikeda, J.; Hori, O.; Ogawa, S.; Maeda,
Y.; Kitagawa, K.; Imuta, N.; Kinoshita, T.; Stern, D. M.; Yanagi,
H.; Kamada, T.: Purification and characterization of a novel stress
protein, the 150-kDa oxygen-regulated protein (ORP150), from cultured
rat astrocytes and its expression in ischemic mouse brain. J. Biol.
Chem. 271: 5025-5032, 1996.
4. Maeda, Y.; Matsumoto, M.; Hori, O.; Kuwabara, K.; Ogawa, S.; Yan,
S. D.; Ohtsuki, T.; Kinoshita, T.; Kamada, T.; Stern, D. M.: Hypoxia/reoxygenation-mediated
induction of astrocyte interleukin 6: a paracrine mechanism potentially
enhancing neuron survival. J. Exp. Med. 180: 2297-2308, 1994.
5. Ozawa, K.; Kondo, T.; Hori, O.; Kitao, Y.; Stern, D. M.; Eisenmenger,
W.; Ogawa, S.; Ohshima, T.: Expression of the oxygen-regulated protein
ORP150 accelerates wound healing by modulating intracellular VEGF
transport. J. Clin. Invest. 108: 41-50, 2001.
6. Petito, C. K.; Morgello, S.; Felix, J. C.; Lesser, M. L.: The
two patterns of reactive astrocytosis in post ischemic rat brain. J.
Cereb. Blood Flow Metab. l0: 850-859, 1990.
7. Steel, G. J.; Fullerton, D. M.; Tyson, J. R.; Stirling, C. J.:
Coordinated activation of Hsp70 chaperones. Science 303: 98-101,
2004.
8. Tamatani, M.; Matsuyama, T.; Yamaguchi, A.; Mitsuda, N.; Tsukamoto,
Y.; Taniguchi, M.; Che, Y. H.; Ozawa, K.; Hori, O.; Nishimura, H.;
Yamashita, A.; Okabe, M.; Yanagi, H.; Stern, D. M.; Ogawa, S.; Tohyama,
M.: ORP150 protects against hypoxia/ischemia-induced neuronal death. Nature
Med. 7: 317-323, 2001.
9. Zhao, L.; Rosales, C.; Seburn, K.; Ron, D.; Ackerman, S. L.: Alteration
of the unfolded protein response modifies neurodegeneration in a mouse
model of Marinesco-Sjogren syndrome. Hum. Molec. Genet. 19: 25-35,
2010.
*FIELD* CN
George E. Tiller - updated: 11/12/2010
Cassandra L. Kniffin - updated: 9/30/2004
Ada Hamosh - updated: 1/8/2004
Joanna S. Amberger - updated: 7/15/2002
Ada Hamosh - updated: 4/4/2001
*FIELD* CD
Wilson H. Y. Lo: 2/26/1997
*FIELD* ED
wwang: 11/18/2010
terry: 11/12/2010
tkritzer: 11/16/2004
ckniffin: 9/30/2004
tkritzer: 1/20/2004
terry: 1/8/2004
joanna: 7/15/2002
alopez: 4/5/2001
terry: 4/4/2001
dkim: 7/30/1998
alopez: 6/25/1997
jenny: 5/30/1997
jenny: 5/29/1997
jenny: 5/28/1997
mark: 4/10/1997
*RECORD*
*FIELD* NO
601746
*FIELD* TI
*601746 HYPOXIA UP-REGULATED 1; HYOU1
;;OXYGEN-REGULATED PROTEIN, 150-KD; ORP150
*FIELD* TX
read more
CLONING
Astrocytes retain cell viability, even in extreme ischemia, and
proliferate in damaged brain (Petito et al., 1990; Janeczko, 1991). Rat
astrocytes exposed to hypoxia followed by reoxygenation were reported to
release increased amounts of interleukin-6 (147620) that could promote
neuronal survival in ischemic brain (Maeda et al., 1994). Kuwabara et
al. (1996) observed a 150-kD protein, called oxygen-regulated protein
(ORP150) by them, in the endoplasmic reticulum (ER) of cultured
astrocytes that was induced specifically by hypoxia and not by other
stimuli.
Ikeda et al. (1997) reported the cloning of human and rat ORP150 cDNAs
from hypoxia-treated human astrocytoma U373 cells and rat astrocytes,
respectively. The full-length 4,503-bp human cDNA contains a 2,997-bp
open reading frame predicted to encode a polypeptide of 999 amino acids
with a calculated molecular mass of 111,330 Da. The deduced amino acid
sequences of human and rat ORP150 exhibit high similarity (over 90%
identity) to each other. The first 32 residues represent the signal
peptide necessary for secretion. The C-terminal KNDEL sequence resembles
KDEL, a motif found in ER-resident proteins, suggesting that ORP150
resides in the ER. The N-terminal half of ORP150 has a modest similarity
to the ATPase domain of numerous HSP70 family sequences (see 140550).
Northern blot analysis revealed a marked similarity of expression
between ORP150 and GRP78 (138120) in U373 cells during hypoxia stress.
(The GRP78 protein is produced in cultured rat astrocytes exposed to
hypoxia or hypoxia/reoxygenation.) They also found that ORP150 mRNA was
highly expressed in the liver and pancreas, whereas little expression
was observed in the kidney and brain, similarly to the expression
pattern of GRP78. Ikeda et al. (1997) proposed that ORP150 plays an
important role in protein folding and secretion in the ER, perhaps as a
molecular chaperone in concert with other GRPs, to cope with
environmental stress.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HYOU1
gene to chromosome 11 (TMAP stSG31085).
GENE FUNCTION
Tamatani et al. (2001) found that although ORP150 was sparingly
upregulated in neurons from human brain undergoing ischemic stress,
there was robust induction in astrocytes. Cultured neurons
overexpressing ORP150 were resistant to hypoxemic stress, whereas
astrocytes with inhibited ORP150 expression were more vulnerable. Mice
with targeted neuronal overexpression of ORP150 had smaller strokes
compared with controls. Neurons with increased ORP150 demonstrated
suppressed caspase-3-like activity and enhanced brain-derived
neurotrophic factor (BDNF) (113505) under hypoxia signaling. Tamatani et
al. (2001) concluded that ORP150 is an integral participant in ischemic
cytoprotective pathways.
Ozawa et al. (2001) demonstrated coexpression, colocalization, and
coimmunoprecipitation of ORP150 and vascular endothelial growth factor
(VEGF; 192240) in the ER of macrophages within the neovasculature of
human wound granulation tissue. In vitro, inhibition of ORP150 resulted
in retention of VEGF within the ER, whereas overexpression of ORP150
promoted the secretion of VEGF into hypoxic culture supernatants,
indicating that ORP150 may participate in VEGF transport to the
cytoplasm. In wounds of diabetic mice, overexpression of ORP150 resulted
in accelerated repair and closure; suppression of ORP150 delayed repair.
Ozawa et al. (2001) concluded that ORP150 plays a role in the promotion
of angiogenesis, and more generally acts as a molecular chaperone under
hypoxic conditions to facilitate protein transport and processing in the
ER.
Two members of the HSP70 family are required for protein biogenesis in
the yeast endoplasmic reticulum: Lhs1 (homologous to HYOU1) and Kar2
(homologous to HSPA5, or BiP; 138120). Steel et al. (2004) found that
Lhs1 and Kar2 specifically interacted to couple, and coordinately
regulate, their respective activities. Lhs1 stimulated Kar2 by providing
a specific nucleotide exchange activity, whereas Kar2 reciprocally
activated the Lhs1 ATPase. In yeast, the 2 ATPase activities are
coupled, and their coordinated regulation is essential for normal
function in vivo.
Zhao et al. (2010) showed that overexpression of Hyou1 prevented ER
stress and rescued neurodegeneration of Purkinje cells in Sil1 (608005)
-/- mice, whereas decreasing expression of Hyou1 exacerbated these
phenotypes. Purkinje cells from the caudal lobules of the cerebellum
from Sil1 -/- mice typically do not show signs of ER stress; however,
decreased expression of Hyou1 in these cells resulted in signs of ER
stress, ubiquitin-positive inclusions, and death. Zhao et al. (2010)
suggested that HYOU1 and SIL1 have partially redundant functions as BiP
nucleotide exchange factors in Purkinje cells.
*FIELD* RF
1. Ikeda, J.; Kaneda, S.; Kuwabara, K.; Ogawa, S.; Kobayashi, T.;
Matsumoto, M.; Yura, T.; Yanagi, H.: Cloning and expression of cDNA
encoding the human 150 kDa oxygen-regulated protein, ORP150. Biochem.
Biophys. Res. Commun. 230: 94-99, 1997.
2. Janeczko, K.: The proliferative response of S-100 protein-positive
glial cells to injury in the neonatal rat brain. Brain Res. 564:
86-90, 1991.
3. Kuwabara, K.; Matsumoto, M.; Ikeda, J.; Hori, O.; Ogawa, S.; Maeda,
Y.; Kitagawa, K.; Imuta, N.; Kinoshita, T.; Stern, D. M.; Yanagi,
H.; Kamada, T.: Purification and characterization of a novel stress
protein, the 150-kDa oxygen-regulated protein (ORP150), from cultured
rat astrocytes and its expression in ischemic mouse brain. J. Biol.
Chem. 271: 5025-5032, 1996.
4. Maeda, Y.; Matsumoto, M.; Hori, O.; Kuwabara, K.; Ogawa, S.; Yan,
S. D.; Ohtsuki, T.; Kinoshita, T.; Kamada, T.; Stern, D. M.: Hypoxia/reoxygenation-mediated
induction of astrocyte interleukin 6: a paracrine mechanism potentially
enhancing neuron survival. J. Exp. Med. 180: 2297-2308, 1994.
5. Ozawa, K.; Kondo, T.; Hori, O.; Kitao, Y.; Stern, D. M.; Eisenmenger,
W.; Ogawa, S.; Ohshima, T.: Expression of the oxygen-regulated protein
ORP150 accelerates wound healing by modulating intracellular VEGF
transport. J. Clin. Invest. 108: 41-50, 2001.
6. Petito, C. K.; Morgello, S.; Felix, J. C.; Lesser, M. L.: The
two patterns of reactive astrocytosis in post ischemic rat brain. J.
Cereb. Blood Flow Metab. l0: 850-859, 1990.
7. Steel, G. J.; Fullerton, D. M.; Tyson, J. R.; Stirling, C. J.:
Coordinated activation of Hsp70 chaperones. Science 303: 98-101,
2004.
8. Tamatani, M.; Matsuyama, T.; Yamaguchi, A.; Mitsuda, N.; Tsukamoto,
Y.; Taniguchi, M.; Che, Y. H.; Ozawa, K.; Hori, O.; Nishimura, H.;
Yamashita, A.; Okabe, M.; Yanagi, H.; Stern, D. M.; Ogawa, S.; Tohyama,
M.: ORP150 protects against hypoxia/ischemia-induced neuronal death. Nature
Med. 7: 317-323, 2001.
9. Zhao, L.; Rosales, C.; Seburn, K.; Ron, D.; Ackerman, S. L.: Alteration
of the unfolded protein response modifies neurodegeneration in a mouse
model of Marinesco-Sjogren syndrome. Hum. Molec. Genet. 19: 25-35,
2010.
*FIELD* CN
George E. Tiller - updated: 11/12/2010
Cassandra L. Kniffin - updated: 9/30/2004
Ada Hamosh - updated: 1/8/2004
Joanna S. Amberger - updated: 7/15/2002
Ada Hamosh - updated: 4/4/2001
*FIELD* CD
Wilson H. Y. Lo: 2/26/1997
*FIELD* ED
wwang: 11/18/2010
terry: 11/12/2010
tkritzer: 11/16/2004
ckniffin: 9/30/2004
tkritzer: 1/20/2004
terry: 1/8/2004
joanna: 7/15/2002
alopez: 4/5/2001
terry: 4/4/2001
dkim: 7/30/1998
alopez: 6/25/1997
jenny: 5/30/1997
jenny: 5/29/1997
jenny: 5/28/1997
mark: 4/10/1997