Full text data of ORM1
ORM1
(AGP1)
[Confidence: low (only semi-automatic identification from reviews)]
Alpha-1-acid glycoprotein 1; AGP 1 (Orosomucoid-1; OMD 1; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Alpha-1-acid glycoprotein 1; AGP 1 (Orosomucoid-1; OMD 1; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02763
ID A1AG1_HUMAN Reviewed; 201 AA.
AC P02763; B7ZKQ5; Q5T539; Q5U067; Q8TC16;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1988, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Alpha-1-acid glycoprotein 1;
DE Short=AGP 1;
DE AltName: Full=Orosomucoid-1;
DE Short=OMD 1;
DE Flags: Precursor;
GN Name=ORM1; Synonyms=AGP1;
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 [GENOMIC DNA].
RX PubMed=2822385;
RA Dente L., Pizza M.G., Metspalu A., Cortese R.;
RT "Structure and expression of the genes coding for human alpha 1-acid
RT glycoprotein.";
RL EMBO J. 6:2289-2296(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3770479; DOI=10.1016/0378-1119(86)90051-X;
RA Board P.G., Jones I.M., Bentley A.K.;
RT "Molecular cloning and nucleotide sequence of human alpha 1 acid
RT glycoprotein cDNA.";
RL Gene 44:127-131(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2409529; DOI=10.1093/nar/13.11.3941;
RA Dente L., Ciliberto G., Cortese R.;
RT "Structure of the human alpha 1-acid glycoprotein gene: sequence
RT homology with other human acute phase protein genes.";
RL Nucleic Acids Res. 13:3941-3952(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-38.
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-38.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-38; CYS-167
RP AND MET-174.
RC TISSUE=Liver;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 19-129.
RX PubMed=4711474; DOI=10.1021/bi00738a026;
RA Schmid K., Kaufmann H., Isemura S., Bauer F., Emura J., Motoyama T.,
RA Ishiguro M., Nanno S.;
RT "Structure of alpha 1-acid glycoprotein. The complete amino acid
RT sequence, multiple amino acid substitutions, and homology with the
RT immunoglobulins.";
RL Biochemistry 12:2711-2724(1973).
RN [10]
RP PROTEIN SEQUENCE OF 129-201.
RX PubMed=4561179; DOI=10.1021/bi00770a022;
RA Ikenaka T., Ishiguro M., Emura J., Kaufmann H., Isemura S., Bauer W.,
RA Schmid K.;
RT "Isolation and partial characterization of the cyanogen bromide
RT fragments of alpha 1-acid glycoprotein and the elucidation of the
RT amino acid sequence of the carboxyl-terminal cyanogen bromide
RT fragment.";
RL Biochemistry 11:3817-3829(1972).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=4603214; DOI=10.1021/bi00710a006;
RA Schmid K., Buergi W., Collins J.H., Nanno S.;
RT "The disulfide bonds of alpha1-acid glycoprotein.";
RL Biochemistry 13:2694-2697(1974).
RN [12]
RP GLYCOSYLATION AT ASN-33; ASN-56; ASN-72; ASN-93 AND ASN-103.
RX PubMed=1567356;
RA Treuheit M.J., Costello C.E., Halsall H.B.;
RT "Analysis of the five glycosylation sites of human alpha 1-acid
RT glycoprotein.";
RL Biochem. J. 283:105-112(1992).
RN [13]
RP GLYCOSYLATION AT ASN-33.
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 [14]
RP GLYCOSYLATION AT ASN-33; ASN-72 AND ASN-93, AND MASS SPECTROMETRY.
RX PubMed=15253437; DOI=10.1021/pr034112b;
RA Hagglund P., Bunkenborg J., Elortza F., Jensen O.N., Roepstorff P.;
RT "A new strategy for identification of N-glycosylated proteins and
RT unambiguous assignment of their glycosylation sites using HILIC
RT enrichment and partial deglycosylation.";
RL J. Proteome Res. 3:556-566(2004).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33 AND ASN-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H.,
RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72; ASN-93
RP AND ASN-103, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72; ASN-93
RP AND ASN-103, 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 [18]
RP FUNCTION.
RX PubMed=17008009; DOI=10.1016/j.bbagen.2006.08.015;
RA Fitos I., Visy J., Zsila F., Mady G., Simonyi M.;
RT "Selective binding of imatinib to the genetic variants of human
RT alpha1-acid glycoprotein.";
RL Biochim. Biophys. Acta 1760:1704-1712(2006).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93, AND MASS SPECTROMETRY.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T.,
RA Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by
RT glycoprotein capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [20]
RP FUNCTION.
RX PubMed=17321687; DOI=10.1016/j.bbagen.2007.01.009;
RA Zsila F., Iwao Y.;
RT "The drug binding site of human alpha1-acid glycoprotein: insight from
RT induced circular dichroism and electronic absorption spectra.";
RL Biochim. Biophys. Acta 1770:797-809(2007).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93 AND ASN-103, AND MASS
RP 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 [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33 AND ASN-72, STRUCTURE
RP OF CARBOHYDRATES, AND MASS SPECTROMETRY.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,
RA Brinkmalm G., Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [23]
RP GLYCOSYLATION AT ASN-33, STRUCTURE OF CARBOHYDRATES, AND MASS
RP SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.M111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of
RT N-and O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 20-201, DOMAIN, AND DISULFIDE
RP BONDS.
RX PubMed=18823996; DOI=10.1016/j.jmb.2008.09.020;
RA Schonfeld D.L., Ravelli R.B., Mueller U., Skerra A.;
RT "The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid)
RT solved by UV RIP reveals the broad drug-binding activity of this human
RT plasma lipocalin.";
RL J. Mol. Biol. 384:393-405(2008).
RN [25]
RP VARIANTS ARG-38 AND MET-174.
RX PubMed=9050929; DOI=10.1007/s004390050378;
RA Yuasa I., Umetsu K., Vogt U., Nakamura H., Nanba E., Tamaki N.,
RA Irizawa Y.;
RT "Human orosomucoid polymorphism: molecular basis of the three common
RT ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S.";
RL Hum. Genet. 99:393-398(1997).
CC -!- FUNCTION: Functions as transport protein in the blood stream.
CC Binds various ligands in the interior of its beta-barrel domain.
CC Also binds synthetic drugs and influences their distribution and
CC availability in the body. Appears to function in modulating the
CC activity of the immune system during the acute-phase reaction.
CC -!- INTERACTION:
CC P05121:SERPINE1; NbExp=4; IntAct=EBI-976767, EBI-953978;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- INDUCTION: Synthesis is controlled by glucocorticoids,
CC interleukin-1 and interleukin-6, It increases 5- to 50-fold upon
CC inflammation.
CC -!- DOMAIN: Contains a beta-barrel that binds various ligands in its
CC interior.
CC -!- PTM: N-glycosylated. N-glycan heterogeneity at Asn-33: Hex5HexNAc4
CC (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor).
CC -!- POLYMORPHISM: Three common alleles of ORM1 are known. ORM1*F1 has
CC Gln-38/Val-174; ORM1*F2 has Gln-38/Met-174 and ORM1*S has Arg-
CC 38/Val-174. The sequence shown is that of allele ORM1*F1.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA29229.1; Type=Erroneous gene model prediction;
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DR EMBL; X02544; CAA26397.1; -; mRNA.
DR EMBL; M13692; AAA35515.1; -; mRNA.
DR EMBL; X05779; CAA29229.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X05780; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05781; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05782; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05783; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05784; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X06676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X06680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BT019790; AAV38593.1; -; mRNA.
DR EMBL; AK312035; BAG34972.1; -; mRNA.
DR EMBL; AL356796; CAI16859.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87416.1; -; Genomic_DNA.
DR EMBL; BC104818; AAI04819.1; -; mRNA.
DR EMBL; BC104820; AAI04821.1; -; mRNA.
DR EMBL; BC143313; AAI43314.1; -; mRNA.
DR EMBL; BC143314; AAI43315.1; -; mRNA.
DR EMBL; BC026238; AAH26238.1; -; mRNA.
DR PIR; A28346; OMHU1.
DR RefSeq; NP_000598.2; NM_000607.2.
DR UniGene; Hs.522356; -.
DR PDB; 3KQ0; X-ray; 1.80 A; A=20-201.
DR PDBsum; 3KQ0; -.
DR ProteinModelPortal; P02763; -.
DR SMR; P02763; 19-193.
DR IntAct; P02763; 7.
DR MINT; MINT-202382; -.
DR STRING; 9606.ENSP00000259396; -.
DR BindingDB; P02763; -.
DR ChEMBL; CHEMBL4285; -.
DR DrugBank; DB01418; Acenocoumarol.
DR DrugBank; DB00802; Alfentanil.
DR DrugBank; DB01429; Aprindine.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB01359; Penbutolol.
DR DrugBank; DB00946; Phenprocoumon.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00706; Tamsulosin.
DR PhosphoSite; P02763; -.
DR UniCarbKB; P02763; -.
DR DMDM; 112877; -.
DR SWISS-2DPAGE; P02763; -.
DR PaxDb; P02763; -.
DR PeptideAtlas; P02763; -.
DR PRIDE; P02763; -.
DR DNASU; 5004; -.
DR Ensembl; ENST00000259396; ENSP00000259396; ENSG00000229314.
DR GeneID; 5004; -.
DR KEGG; hsa:5004; -.
DR UCSC; uc004bik.4; human.
DR CTD; 5004; -.
DR GeneCards; GC09P117085; -.
DR HGNC; HGNC:8498; ORM1.
DR HPA; CAB006265; -.
DR HPA; HPA046438; -.
DR MIM; 138600; gene.
DR neXtProt; NX_P02763; -.
DR PharmGKB; PA260; -.
DR eggNOG; NOG41523; -.
DR HOGENOM; HOG000125170; -.
DR HOVERGEN; HBG000035; -.
DR InParanoid; P02763; -.
DR KO; K17308; -.
DR OrthoDB; EOG7B5WXT; -.
DR ChiTaRS; ORM1; human.
DR EvolutionaryTrace; P02763; -.
DR GeneWiki; ORM1; -.
DR GenomeRNAi; 5004; -.
DR NextBio; 19272; -.
DR PRO; PR:P02763; -.
DR ArrayExpress; P02763; -.
DR Bgee; P02763; -.
DR CleanEx; HS_ORM1; -.
DR Genevestigator; P02763; -.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0006953; P:acute-phase response; TAS:ProtInc.
DR GO; GO:0002682; P:regulation of immune system process; IEA:InterPro.
DR GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR001500; A1A_glycop.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR011038; Calycin-like.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR PANTHER; PTHR11967; PTHR11967; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR PIRSF; PIRSF036899; AGP; 1.
DR PRINTS; PR00708; A1AGLPROTEIN.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00213; LIPOCALIN; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Polymorphism;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal;
KW Transport.
FT SIGNAL 1 18
FT CHAIN 19 201 Alpha-1-acid glycoprotein 1.
FT /FTId=PRO_0000017860.
FT MOD_RES 19 19 Pyrrolidone carboxylic acid.
FT CARBOHYD 33 33 N-linked (GlcNAc...) (complex).
FT CARBOHYD 56 56 N-linked (GlcNAc...).
FT CARBOHYD 72 72 N-linked (GlcNAc...) (complex).
FT CARBOHYD 93 93 N-linked (GlcNAc...).
FT CARBOHYD 103 103 N-linked (GlcNAc...).
FT /FTId=CAR_000170.
FT DISULFID 23 165
FT DISULFID 90 183
FT VARIANT 38 38 Q -> R (in allele ORM1*S).
FT /FTId=VAR_013840.
FT VARIANT 167 167 R -> C (in dbSNP:rs3182034).
FT /FTId=VAR_056166.
FT VARIANT 174 174 V -> M (in allele ORM1*F2;
FT dbSNP:rs1126801).
FT /FTId=VAR_013841.
FT CONFLICT 170 170 K -> R (in Ref. 8; AAI43315).
FT CONFLICT 182 182 Missing (in Ref. 10; AA sequence).
FT CONFLICT 193 193 Missing (in Ref. 10; AA sequence).
FT HELIX 24 26
FT HELIX 33 39
FT STRAND 41 52
FT HELIX 53 59
FT STRAND 62 72
FT TURN 73 76
FT STRAND 77 86
FT STRAND 89 100
FT TURN 101 104
FT STRAND 105 110
FT STRAND 113 121
FT STRAND 127 132
FT HELIX 137 139
FT STRAND 141 149
FT TURN 153 156
FT HELIX 157 166
FT HELIX 170 172
FT HELIX 178 180
FT HELIX 184 192
SQ SEQUENCE 201 AA; 23512 MW; 63292233AD6EAD8B CRC64;
MALSWVLTVL SLLPLLEAQI PLCANLVPVP ITNATLDQIT GKWFYIASAF RNEEYNKSVQ
EIQATFFYFT PNKTEDTIFL REYQTRQDQC IYNTTYLNVQ RENGTISRYV GGQEHFAHLL
ILRDTKTYML AFDVNDEKNW GLSVYADKPE TTKEQLGEFY EALDCLRIPK SDVVYTDWKK
DKCEPLEKQH EKERKQEEGE S
//
ID A1AG1_HUMAN Reviewed; 201 AA.
AC P02763; B7ZKQ5; Q5T539; Q5U067; Q8TC16;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1988, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Alpha-1-acid glycoprotein 1;
DE Short=AGP 1;
DE AltName: Full=Orosomucoid-1;
DE Short=OMD 1;
DE Flags: Precursor;
GN Name=ORM1; Synonyms=AGP1;
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 [GENOMIC DNA].
RX PubMed=2822385;
RA Dente L., Pizza M.G., Metspalu A., Cortese R.;
RT "Structure and expression of the genes coding for human alpha 1-acid
RT glycoprotein.";
RL EMBO J. 6:2289-2296(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3770479; DOI=10.1016/0378-1119(86)90051-X;
RA Board P.G., Jones I.M., Bentley A.K.;
RT "Molecular cloning and nucleotide sequence of human alpha 1 acid
RT glycoprotein cDNA.";
RL Gene 44:127-131(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2409529; DOI=10.1093/nar/13.11.3941;
RA Dente L., Ciliberto G., Cortese R.;
RT "Structure of the human alpha 1-acid glycoprotein gene: sequence
RT homology with other human acute phase protein genes.";
RL Nucleic Acids Res. 13:3941-3952(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-38.
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-38.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-38; CYS-167
RP AND MET-174.
RC TISSUE=Liver;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 19-129.
RX PubMed=4711474; DOI=10.1021/bi00738a026;
RA Schmid K., Kaufmann H., Isemura S., Bauer F., Emura J., Motoyama T.,
RA Ishiguro M., Nanno S.;
RT "Structure of alpha 1-acid glycoprotein. The complete amino acid
RT sequence, multiple amino acid substitutions, and homology with the
RT immunoglobulins.";
RL Biochemistry 12:2711-2724(1973).
RN [10]
RP PROTEIN SEQUENCE OF 129-201.
RX PubMed=4561179; DOI=10.1021/bi00770a022;
RA Ikenaka T., Ishiguro M., Emura J., Kaufmann H., Isemura S., Bauer W.,
RA Schmid K.;
RT "Isolation and partial characterization of the cyanogen bromide
RT fragments of alpha 1-acid glycoprotein and the elucidation of the
RT amino acid sequence of the carboxyl-terminal cyanogen bromide
RT fragment.";
RL Biochemistry 11:3817-3829(1972).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=4603214; DOI=10.1021/bi00710a006;
RA Schmid K., Buergi W., Collins J.H., Nanno S.;
RT "The disulfide bonds of alpha1-acid glycoprotein.";
RL Biochemistry 13:2694-2697(1974).
RN [12]
RP GLYCOSYLATION AT ASN-33; ASN-56; ASN-72; ASN-93 AND ASN-103.
RX PubMed=1567356;
RA Treuheit M.J., Costello C.E., Halsall H.B.;
RT "Analysis of the five glycosylation sites of human alpha 1-acid
RT glycoprotein.";
RL Biochem. J. 283:105-112(1992).
RN [13]
RP GLYCOSYLATION AT ASN-33.
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 [14]
RP GLYCOSYLATION AT ASN-33; ASN-72 AND ASN-93, AND MASS SPECTROMETRY.
RX PubMed=15253437; DOI=10.1021/pr034112b;
RA Hagglund P., Bunkenborg J., Elortza F., Jensen O.N., Roepstorff P.;
RT "A new strategy for identification of N-glycosylated proteins and
RT unambiguous assignment of their glycosylation sites using HILIC
RT enrichment and partial deglycosylation.";
RL J. Proteome Res. 3:556-566(2004).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33 AND ASN-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H.,
RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72; ASN-93
RP AND ASN-103, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72; ASN-93
RP AND ASN-103, 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 [18]
RP FUNCTION.
RX PubMed=17008009; DOI=10.1016/j.bbagen.2006.08.015;
RA Fitos I., Visy J., Zsila F., Mady G., Simonyi M.;
RT "Selective binding of imatinib to the genetic variants of human
RT alpha1-acid glycoprotein.";
RL Biochim. Biophys. Acta 1760:1704-1712(2006).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93, AND MASS SPECTROMETRY.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T.,
RA Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by
RT glycoprotein capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [20]
RP FUNCTION.
RX PubMed=17321687; DOI=10.1016/j.bbagen.2007.01.009;
RA Zsila F., Iwao Y.;
RT "The drug binding site of human alpha1-acid glycoprotein: insight from
RT induced circular dichroism and electronic absorption spectra.";
RL Biochim. Biophys. Acta 1770:797-809(2007).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93 AND ASN-103, AND MASS
RP 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 [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33 AND ASN-72, STRUCTURE
RP OF CARBOHYDRATES, AND MASS SPECTROMETRY.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,
RA Brinkmalm G., Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [23]
RP GLYCOSYLATION AT ASN-33, STRUCTURE OF CARBOHYDRATES, AND MASS
RP SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.M111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of
RT N-and O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 20-201, DOMAIN, AND DISULFIDE
RP BONDS.
RX PubMed=18823996; DOI=10.1016/j.jmb.2008.09.020;
RA Schonfeld D.L., Ravelli R.B., Mueller U., Skerra A.;
RT "The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid)
RT solved by UV RIP reveals the broad drug-binding activity of this human
RT plasma lipocalin.";
RL J. Mol. Biol. 384:393-405(2008).
RN [25]
RP VARIANTS ARG-38 AND MET-174.
RX PubMed=9050929; DOI=10.1007/s004390050378;
RA Yuasa I., Umetsu K., Vogt U., Nakamura H., Nanba E., Tamaki N.,
RA Irizawa Y.;
RT "Human orosomucoid polymorphism: molecular basis of the three common
RT ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S.";
RL Hum. Genet. 99:393-398(1997).
CC -!- FUNCTION: Functions as transport protein in the blood stream.
CC Binds various ligands in the interior of its beta-barrel domain.
CC Also binds synthetic drugs and influences their distribution and
CC availability in the body. Appears to function in modulating the
CC activity of the immune system during the acute-phase reaction.
CC -!- INTERACTION:
CC P05121:SERPINE1; NbExp=4; IntAct=EBI-976767, EBI-953978;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- INDUCTION: Synthesis is controlled by glucocorticoids,
CC interleukin-1 and interleukin-6, It increases 5- to 50-fold upon
CC inflammation.
CC -!- DOMAIN: Contains a beta-barrel that binds various ligands in its
CC interior.
CC -!- PTM: N-glycosylated. N-glycan heterogeneity at Asn-33: Hex5HexNAc4
CC (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor).
CC -!- POLYMORPHISM: Three common alleles of ORM1 are known. ORM1*F1 has
CC Gln-38/Val-174; ORM1*F2 has Gln-38/Met-174 and ORM1*S has Arg-
CC 38/Val-174. The sequence shown is that of allele ORM1*F1.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA29229.1; Type=Erroneous gene model prediction;
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DR EMBL; X02544; CAA26397.1; -; mRNA.
DR EMBL; M13692; AAA35515.1; -; mRNA.
DR EMBL; X05779; CAA29229.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X05780; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05781; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05782; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05783; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X05784; CAA29229.1; JOINED; Genomic_DNA.
DR EMBL; X06676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X06680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BT019790; AAV38593.1; -; mRNA.
DR EMBL; AK312035; BAG34972.1; -; mRNA.
DR EMBL; AL356796; CAI16859.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87416.1; -; Genomic_DNA.
DR EMBL; BC104818; AAI04819.1; -; mRNA.
DR EMBL; BC104820; AAI04821.1; -; mRNA.
DR EMBL; BC143313; AAI43314.1; -; mRNA.
DR EMBL; BC143314; AAI43315.1; -; mRNA.
DR EMBL; BC026238; AAH26238.1; -; mRNA.
DR PIR; A28346; OMHU1.
DR RefSeq; NP_000598.2; NM_000607.2.
DR UniGene; Hs.522356; -.
DR PDB; 3KQ0; X-ray; 1.80 A; A=20-201.
DR PDBsum; 3KQ0; -.
DR ProteinModelPortal; P02763; -.
DR SMR; P02763; 19-193.
DR IntAct; P02763; 7.
DR MINT; MINT-202382; -.
DR STRING; 9606.ENSP00000259396; -.
DR BindingDB; P02763; -.
DR ChEMBL; CHEMBL4285; -.
DR DrugBank; DB01418; Acenocoumarol.
DR DrugBank; DB00802; Alfentanil.
DR DrugBank; DB01429; Aprindine.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB01359; Penbutolol.
DR DrugBank; DB00946; Phenprocoumon.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00706; Tamsulosin.
DR PhosphoSite; P02763; -.
DR UniCarbKB; P02763; -.
DR DMDM; 112877; -.
DR SWISS-2DPAGE; P02763; -.
DR PaxDb; P02763; -.
DR PeptideAtlas; P02763; -.
DR PRIDE; P02763; -.
DR DNASU; 5004; -.
DR Ensembl; ENST00000259396; ENSP00000259396; ENSG00000229314.
DR GeneID; 5004; -.
DR KEGG; hsa:5004; -.
DR UCSC; uc004bik.4; human.
DR CTD; 5004; -.
DR GeneCards; GC09P117085; -.
DR HGNC; HGNC:8498; ORM1.
DR HPA; CAB006265; -.
DR HPA; HPA046438; -.
DR MIM; 138600; gene.
DR neXtProt; NX_P02763; -.
DR PharmGKB; PA260; -.
DR eggNOG; NOG41523; -.
DR HOGENOM; HOG000125170; -.
DR HOVERGEN; HBG000035; -.
DR InParanoid; P02763; -.
DR KO; K17308; -.
DR OrthoDB; EOG7B5WXT; -.
DR ChiTaRS; ORM1; human.
DR EvolutionaryTrace; P02763; -.
DR GeneWiki; ORM1; -.
DR GenomeRNAi; 5004; -.
DR NextBio; 19272; -.
DR PRO; PR:P02763; -.
DR ArrayExpress; P02763; -.
DR Bgee; P02763; -.
DR CleanEx; HS_ORM1; -.
DR Genevestigator; P02763; -.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0006953; P:acute-phase response; TAS:ProtInc.
DR GO; GO:0002682; P:regulation of immune system process; IEA:InterPro.
DR GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR001500; A1A_glycop.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR011038; Calycin-like.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR PANTHER; PTHR11967; PTHR11967; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR PIRSF; PIRSF036899; AGP; 1.
DR PRINTS; PR00708; A1AGLPROTEIN.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00213; LIPOCALIN; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Polymorphism;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal;
KW Transport.
FT SIGNAL 1 18
FT CHAIN 19 201 Alpha-1-acid glycoprotein 1.
FT /FTId=PRO_0000017860.
FT MOD_RES 19 19 Pyrrolidone carboxylic acid.
FT CARBOHYD 33 33 N-linked (GlcNAc...) (complex).
FT CARBOHYD 56 56 N-linked (GlcNAc...).
FT CARBOHYD 72 72 N-linked (GlcNAc...) (complex).
FT CARBOHYD 93 93 N-linked (GlcNAc...).
FT CARBOHYD 103 103 N-linked (GlcNAc...).
FT /FTId=CAR_000170.
FT DISULFID 23 165
FT DISULFID 90 183
FT VARIANT 38 38 Q -> R (in allele ORM1*S).
FT /FTId=VAR_013840.
FT VARIANT 167 167 R -> C (in dbSNP:rs3182034).
FT /FTId=VAR_056166.
FT VARIANT 174 174 V -> M (in allele ORM1*F2;
FT dbSNP:rs1126801).
FT /FTId=VAR_013841.
FT CONFLICT 170 170 K -> R (in Ref. 8; AAI43315).
FT CONFLICT 182 182 Missing (in Ref. 10; AA sequence).
FT CONFLICT 193 193 Missing (in Ref. 10; AA sequence).
FT HELIX 24 26
FT HELIX 33 39
FT STRAND 41 52
FT HELIX 53 59
FT STRAND 62 72
FT TURN 73 76
FT STRAND 77 86
FT STRAND 89 100
FT TURN 101 104
FT STRAND 105 110
FT STRAND 113 121
FT STRAND 127 132
FT HELIX 137 139
FT STRAND 141 149
FT TURN 153 156
FT HELIX 157 166
FT HELIX 170 172
FT HELIX 178 180
FT HELIX 184 192
SQ SEQUENCE 201 AA; 23512 MW; 63292233AD6EAD8B CRC64;
MALSWVLTVL SLLPLLEAQI PLCANLVPVP ITNATLDQIT GKWFYIASAF RNEEYNKSVQ
EIQATFFYFT PNKTEDTIFL REYQTRQDQC IYNTTYLNVQ RENGTISRYV GGQEHFAHLL
ILRDTKTYML AFDVNDEKNW GLSVYADKPE TTKEQLGEFY EALDCLRIPK SDVVYTDWKK
DKCEPLEKQH EKERKQEEGE S
//
MIM
138600
*RECORD*
*FIELD* NO
138600
*FIELD* TI
*138600 OROSOMUCOID 1; ORM1
;;ORM;;
GLYCOPROTEIN, ALPHA-1-ACID, OF SERUM;;
ALPHA-1-ACID GLYCOPROTEIN;;
read moreALPHA-1-AGP; AGP1
*FIELD* TX
This serum protein, also called orosomucoid, is a monomer about 210
amino acid residues long; the amino acid sequence has been determined
through 192 amino acids. Variants have been demonstrated in the blood of
normal Caucasians and Japanese (Schmid et al., 1965). Johnson et al.
(1969) presented twin and family data supporting the view that 3
phenotypes, SS, FF and FS, are determined by 2 codominant alleles.
The structural gene for orosomucoid was assigned to the end of the long
arm of chromosome 9 by demonstration of linkage to ABO and AK1 (Eiberg
et al., 1982). The male lod score for ORM versus ABO was 5.06 at theta
0.27; for ABO versus AK, 6.27 at theta 0.13; for ORM versus AK, 1.63 at
theta 0.17. Thus, the order was judged to be ORM-AK-ABO. Cox and Francke
(1985) used hybrids of human fetal liver and rat hepatoma cells to study
the location of the genes for serum proteins. In this way they gave
direct assignment of the orosomucoid gene to chromosome 9 and the
alpha-2-HS-glycoprotein gene to chromosome 3, these having been
previously assigned by linkage to 'anchor' loci. Rocchi et al. (1986)
confirmed the assignment to chromosome 9 by Southern blot analysis of
DNA from somatic cell hybrids using a cDNA probe. On the basis of
studies in members of 3 Newfoundland kindreds with the same specific
chromosome 9 aberration, an inverted paracentric insertion, inv
ins(9)(q22.1q34.3q34.1), Allderdice et al. (1986) concluded that ORM is
located in 9q34.3-qter. Gene cloning studies by Dente et al. (1985)
suggested that there are at least 2 genes coding for alpha-1-AGP. A
conserved sequence in the 5-prime untranslated region is shared with
alpha-1-antitrypsin and with haptoglobin. Webb et al. (1988) likewise
concluded that there are at least 2 genes for alpha-1-acid glycoprotein
(alpha-1-AGP) that are in close proximity; by in situ hybridization,
they appear to be located in 9q31-q34.1. On the basis of a normal ORM1
level in a child with a deletion 9q32-qter secondary to a balanced
maternal translocation, Zuffardi et al. (1989) concluded that ORM1 may
be located in the region 9q31-q32.
Board et al. (1986) isolated a cDNA clone for ORM and presented the
complete nucleotide sequence encoding this protein. Furthermore, they
compared the derived amino acid sequence with preexisting data. Dente et
al. (1987) cloned the genomic DNA segment encoding orosomucoid and
showed that it contains 3 adjacent coding regions which they designated
AGP-A, B, and B-prime (AGP = acid-glycoprotein). The regions were
identical in exon-intron organization but had slightly different coding
potentials. These results accounted for the heterogeneity observed by
protein sequencing. Southern blot analysis indicated that the cloned
cluster contains all the orosomucoid coding sequences present in the
human genome. Most of the alpha-AGP mRNA in human liver is transcribed
from AGP-A, whose promoter and cap site have been determined, while the
level of AGP-B and B-prime mRNA in human liver is very low. Dente et al.
(1988) studied the regulation of AGP-A by transfecting cell lines and
preparing transgenic mice with constructs including the entire AGP gene.
The AGP constructs were expressed with comparable efficiency in hepatoma
and HeLa cells; however, these same constructs were expressed in
transgenic mice in a tissue-specific manner. The mRNA was found solely
in the liver. These authors found that a 6.6-kb segment consisting of
the entire coding region plus 1.2 kbs of 5-prime-flanking and 2 kbs of
3-prime-flanking DNA contained sufficient information for
tissue-specific, regulated expression of the gene. Tomei et al. (1989)
generated families of transgenic mice carrying various orosomucoid genes
and studied the ORM variants secreted into the serum of the mice.
Using a new method for ORM phenotyping, Eap et al. (1988) discovered a
rare variant tentatively assigned to the ORM2 locus and a common variant
tentatively assigned to the ORM1 locus. Umetsu et al. (1988) reported on
polymorphism of ORM1 and ORM2 in a population in the Philippines. ORM2
was nonpolymorphic, i.e., monomorphic, in that population when studied
by that method. ORM2 is polymorphic in Japan (see 138610). Luckenbach et
al. (1991) reported family studies of ORM1 subtyping.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988). Yuasa et al. (1993) reported on a total of
57 different alleles at the ORM1 and ORM2 loci, including 17 newly
identified ones. Twenty-seven were assigned to the ORM1 locus and 30 to
the ORM2 locus. They proposed a revised system of nomenclature.
Yuasa et al. (1997) noted that in plasma, ORM proteins are presented as
a mixture of ORM1 and ORM2 proteins in a molar ratio of 3:1,
respectively. Classic genetic polymorphism occurs in the more abundant
ORM1, which is controlled by the ORM1 locus. ORM1*F, the 'fast' allele,
is divided into 2 subtype alleles, ORM1*F1 and ORM1*F2. ORM1*F1 and
ORM1*S are observed worldwide and ORM1*F2 is also common in European
populations. The ORM2 locus is monomorphic in most populations. Yuasa et
al. (1997) stated that about 30 rare variant alleles had been
distinguished electrophoretically at each of the loci. The tandemly
arranged genes at the ORM1 and ORM2 loci (also designated AGP1 and AGP2,
respectively) span about 11.5 kb. Each gene consists of 6 exons and 5
introns and encodes a 183-amino acid polypeptide.
Yuasa et al. (1997) investigated the molecular basis of ORM1
polymorphism. For the detection of mutations, PCR-amplified products of
the 6 exons of the gene were screened by SSCP analysis. Sequencing of
the PCR products showed that the 3 common ORM1 alleles result from
A-to-G transitions at codons for amino acid position 20 in exon 1 and
156 in exon 5.
*FIELD* AV
.0001
OROSOMUCOID POLYMORPHISM
ORM1*F1
ORM1, GLN20, VAL156
Polymorphism of ORM proteins was first discovered after starch gel
electrophoresis of desialyzed samples by Tokita and Schmid (1963), who
proposed that the variation is controlled by 2 alleles, ORM*F and ORM*S,
for fast and slow, at a single locus. The ORM1 locus is highly
polymorphic, and ORM1*F is divided into 2 subtype alleles, ORM1*F1 and
ORM1*F2. ORM1*F1 and ORM1*S are observed worldwide and ORM1*F2 is also
common in European populations. Yuasa et al. (1997) demonstrated that
these 3 common ORM1 alleles result from A-to-G transitions at the codons
for amino acid positions 20 in exon 1 and 156 in exon 5 of the AGP1
gene: ORM1*F1 is characterized by CAG (gln) and GTG (val); ORM1*F2, by
CAG (gln) and ATG (met); and ORM1*S, by CGG (arg) and GTG (val). Yuasa
et al. (1997) discussed the phylogeny of these 3 ORM1 alleles.
.0002
OROSOMUCOID POLYMORPHISM
ORM1*F2
ORM1, GLN20, MET156
See 138600.0001 and Yuasa et al. (1997).
.0003
OROSOMUCOID POLYMORPHISM
ORM1*S
ORM1, ARG20, VAL156
See 138600.0001 and Yuasa et al. (1997).
*FIELD* SA
Dayhoff (1972); Umetsu et al. (1985); Weidinger et al. (1987)
*FIELD* RF
1. Allderdice, P. W.; Kaita, H.; Lewis, M.; McAlpine, P. J.; Wong,
P.; Anderson, J.; Giblett, E. R.: Segregation of marker loci in families
with an inherited paracentric insertion of chromosome 9. Am. J. Hum.
Genet. 39: 612-617, 1986.
2. Board, P. G.; Jones, I. M.; Bentley, A. K.: Molecular cloning
and nucleotide sequence of human alpha-1 acid glycoprotein cDNA. Gene 44:
127-131, 1986.
3. Cox, D. W.; Francke, U.: Direct assignment of orosomucoid to human
chromosome 9 and alpha-2-HS-glycoprotein to chromosome 3 using human
fetal liver x rat hepatoma hybrids. Hum. Genet. 70: 109-115, 1985.
4. Dayhoff, M. O.: Atlas of Protein Sequence and Structure. Orosomucoid.
Washington: National Biomedical Research Foundation (pub.) 5: 1972.
Pp. D310-D316.
5. Dente, L.; Ciliberto, G.; Cortese, R.: Structure of the human
alpha-1-acid glycoprotein gene: sequence homology with other human
acute phase protein genes. Nucleic Acids Res. 13: 3941-3952, 1985.
6. Dente, L.; Pizza, M. G.; Metspalu, A.; Cortese, R.: Structure
and expression of the genes coding for human alpha-1-acid glycoprotein. EMBO
J. 6: 2289-2296, 1987.
7. Dente, L.; Ruther, U.; Tripodi, M.; Wagner, E. F.; Cortese, R.
: Expression of human alpha-1-acid glycoprotein genes in cultured
cells and in transgenic mice. Genes Dev. 2: 259-266, 1988.
8. Eap, C. B.; Cuendet, C.; Baumann, P.: Orosomucoid (alpha-1 acid
glycoprotein) phenotyping by use of immobilized pH gradients with
8 M urea and immunoblotting: a new variant encountered in a population
study. Hum. Genet. 80: 183-185, 1988.
9. Eiberg, H.; Mohr, J.; Nielsen, L. S.: Linkage of orosomucoid (ORM)
to ABO and AK1. (Abstract) Cytogenet. Cell Genet. 32: 272 only,
1982.
10. Johnson, A. M.; Schmid, K.; Alper, C. A.: Inheritance of human
alpha(1)-acid glycoprotein (orosomucoid) variants. J. Clin. Invest. 48:
2293-2299, 1969.
11. Luckenbach, C.; Kompf, J.; Ritter, H.: Orosomucoid (ORM1) subtyping
and formal genetics. Hum. Genet. 87: 429-432, 1991.
12. Rocchi, M.; Roncuzzi, L.; Santamaria, R.; Archidiacono, N.; Dente,
L.; Romeo, G.: Mapping through somatic cell hybrids and cDNA probes
of protein C to chromosome 2, factor X to chromosome 13, and alpha-1-acid
glycoprotein to chromosome 9. Hum. Genet. 74: 30-33, 1986.
13. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
14. Schmid, K.; Tokita, K.; Yoshizaki, H.: The alpha-1-acid glycoprotein
variants of normal Caucasian and Japanese individuals. J. Clin. Invest. 44:
1394-1401, 1965.
15. Tokita, K.; Schmid, K.: Variants of alpha-1-acid glycoprotein. Nature 200:
266 only, 1963.
16. Tomei, L.; Eap, C. B.; Baumann, P.; Dente, L.: Use of transgenic
mice for the characterization of human alpha-1-acid glycoprotein (orosomucoid)
variants. Hum. Genet. 84: 89-91, 1989.
17. Umetsu, K.; Ikeda, N.; Kashimura, S.; Suzuki, T.: Orosomucoid
(ORM) typing by print lectinofixation: a new technique for isoelectric
focusing--two common alleles in Japan. Hum. Genet. 71: 223-224,
1985.
18. Umetsu, K.; Yuasa, I.; Nishimura, H.; Sasaki, H.; Suzuki, T.:
Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in
a Philippine population. Hum. Hered. 38: 287-290, 1988.
19. Webb, G. C.; Earle, M. E.; Merritt, C.; Board, P. G.: Localization
of human alpha-1 glycoprotein genes to 9q31-q34.1. Cytogenet. Cell
Genet. 47: 18-21, 1988.
20. Weidinger, S.; Muller, T.; Schwarzfischer, F.; Cleve, H.: Three
new orosomucoid (ORM) variants revealed by isoelectric focusing and
print immunofixation. Hum. Genet. 77: 286-288, 1987.
21. Yuasa, I.; Umetsu, K.; Vogt, U.; Nakamura, H.; Nanba, E.; Tamaki,
N.; Irizawa, Y.: Human orosomucoid polymorphism: molecular basis
of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S. Hum.
Genet. 99: 393-398, 1997.
22. Yuasa, I.; Weidinger, S.; Umetsu, K.; Suenaga, K.; Ishimoto, G.;
Eap, B. C.; Duche, J.-C.; Baumann, P.: Orosomucoid system: 17 additional
orosomucoid variants and proposal for a new nomenclature. Vox Sang. 64:
47-55, 1993.
23. Zuffardi, O.; Caiulo, A.; Maraschio, P.; Tupler, R.; Bianchi,
E.; Amisano, P.; Beluffi, G.; Moratti, R.; Liguri, G.: Regional assignment
of the loci for adenylate kinase to 9q32 and for alpha(1)-acid glycoprotein
to 9q31-q32: a locus for Goltz syndrome in region 9q32-qter? Hum.
Genet. 82: 17-19, 1989.
*FIELD* CN
Victor A. McKusick - updated: 3/4/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 04/30/1999
terry: 11/10/1997
mark: 3/4/1997
terry: 3/3/1997
mark: 6/7/1996
davew: 8/5/1994
pfoster: 2/18/1994
carol: 10/26/1993
carol: 5/12/1993
carol: 3/3/1993
supermim: 3/16/1992
*RECORD*
*FIELD* NO
138600
*FIELD* TI
*138600 OROSOMUCOID 1; ORM1
;;ORM;;
GLYCOPROTEIN, ALPHA-1-ACID, OF SERUM;;
ALPHA-1-ACID GLYCOPROTEIN;;
read moreALPHA-1-AGP; AGP1
*FIELD* TX
This serum protein, also called orosomucoid, is a monomer about 210
amino acid residues long; the amino acid sequence has been determined
through 192 amino acids. Variants have been demonstrated in the blood of
normal Caucasians and Japanese (Schmid et al., 1965). Johnson et al.
(1969) presented twin and family data supporting the view that 3
phenotypes, SS, FF and FS, are determined by 2 codominant alleles.
The structural gene for orosomucoid was assigned to the end of the long
arm of chromosome 9 by demonstration of linkage to ABO and AK1 (Eiberg
et al., 1982). The male lod score for ORM versus ABO was 5.06 at theta
0.27; for ABO versus AK, 6.27 at theta 0.13; for ORM versus AK, 1.63 at
theta 0.17. Thus, the order was judged to be ORM-AK-ABO. Cox and Francke
(1985) used hybrids of human fetal liver and rat hepatoma cells to study
the location of the genes for serum proteins. In this way they gave
direct assignment of the orosomucoid gene to chromosome 9 and the
alpha-2-HS-glycoprotein gene to chromosome 3, these having been
previously assigned by linkage to 'anchor' loci. Rocchi et al. (1986)
confirmed the assignment to chromosome 9 by Southern blot analysis of
DNA from somatic cell hybrids using a cDNA probe. On the basis of
studies in members of 3 Newfoundland kindreds with the same specific
chromosome 9 aberration, an inverted paracentric insertion, inv
ins(9)(q22.1q34.3q34.1), Allderdice et al. (1986) concluded that ORM is
located in 9q34.3-qter. Gene cloning studies by Dente et al. (1985)
suggested that there are at least 2 genes coding for alpha-1-AGP. A
conserved sequence in the 5-prime untranslated region is shared with
alpha-1-antitrypsin and with haptoglobin. Webb et al. (1988) likewise
concluded that there are at least 2 genes for alpha-1-acid glycoprotein
(alpha-1-AGP) that are in close proximity; by in situ hybridization,
they appear to be located in 9q31-q34.1. On the basis of a normal ORM1
level in a child with a deletion 9q32-qter secondary to a balanced
maternal translocation, Zuffardi et al. (1989) concluded that ORM1 may
be located in the region 9q31-q32.
Board et al. (1986) isolated a cDNA clone for ORM and presented the
complete nucleotide sequence encoding this protein. Furthermore, they
compared the derived amino acid sequence with preexisting data. Dente et
al. (1987) cloned the genomic DNA segment encoding orosomucoid and
showed that it contains 3 adjacent coding regions which they designated
AGP-A, B, and B-prime (AGP = acid-glycoprotein). The regions were
identical in exon-intron organization but had slightly different coding
potentials. These results accounted for the heterogeneity observed by
protein sequencing. Southern blot analysis indicated that the cloned
cluster contains all the orosomucoid coding sequences present in the
human genome. Most of the alpha-AGP mRNA in human liver is transcribed
from AGP-A, whose promoter and cap site have been determined, while the
level of AGP-B and B-prime mRNA in human liver is very low. Dente et al.
(1988) studied the regulation of AGP-A by transfecting cell lines and
preparing transgenic mice with constructs including the entire AGP gene.
The AGP constructs were expressed with comparable efficiency in hepatoma
and HeLa cells; however, these same constructs were expressed in
transgenic mice in a tissue-specific manner. The mRNA was found solely
in the liver. These authors found that a 6.6-kb segment consisting of
the entire coding region plus 1.2 kbs of 5-prime-flanking and 2 kbs of
3-prime-flanking DNA contained sufficient information for
tissue-specific, regulated expression of the gene. Tomei et al. (1989)
generated families of transgenic mice carrying various orosomucoid genes
and studied the ORM variants secreted into the serum of the mice.
Using a new method for ORM phenotyping, Eap et al. (1988) discovered a
rare variant tentatively assigned to the ORM2 locus and a common variant
tentatively assigned to the ORM1 locus. Umetsu et al. (1988) reported on
polymorphism of ORM1 and ORM2 in a population in the Philippines. ORM2
was nonpolymorphic, i.e., monomorphic, in that population when studied
by that method. ORM2 is polymorphic in Japan (see 138610). Luckenbach et
al. (1991) reported family studies of ORM1 subtyping.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988). Yuasa et al. (1993) reported on a total of
57 different alleles at the ORM1 and ORM2 loci, including 17 newly
identified ones. Twenty-seven were assigned to the ORM1 locus and 30 to
the ORM2 locus. They proposed a revised system of nomenclature.
Yuasa et al. (1997) noted that in plasma, ORM proteins are presented as
a mixture of ORM1 and ORM2 proteins in a molar ratio of 3:1,
respectively. Classic genetic polymorphism occurs in the more abundant
ORM1, which is controlled by the ORM1 locus. ORM1*F, the 'fast' allele,
is divided into 2 subtype alleles, ORM1*F1 and ORM1*F2. ORM1*F1 and
ORM1*S are observed worldwide and ORM1*F2 is also common in European
populations. The ORM2 locus is monomorphic in most populations. Yuasa et
al. (1997) stated that about 30 rare variant alleles had been
distinguished electrophoretically at each of the loci. The tandemly
arranged genes at the ORM1 and ORM2 loci (also designated AGP1 and AGP2,
respectively) span about 11.5 kb. Each gene consists of 6 exons and 5
introns and encodes a 183-amino acid polypeptide.
Yuasa et al. (1997) investigated the molecular basis of ORM1
polymorphism. For the detection of mutations, PCR-amplified products of
the 6 exons of the gene were screened by SSCP analysis. Sequencing of
the PCR products showed that the 3 common ORM1 alleles result from
A-to-G transitions at codons for amino acid position 20 in exon 1 and
156 in exon 5.
*FIELD* AV
.0001
OROSOMUCOID POLYMORPHISM
ORM1*F1
ORM1, GLN20, VAL156
Polymorphism of ORM proteins was first discovered after starch gel
electrophoresis of desialyzed samples by Tokita and Schmid (1963), who
proposed that the variation is controlled by 2 alleles, ORM*F and ORM*S,
for fast and slow, at a single locus. The ORM1 locus is highly
polymorphic, and ORM1*F is divided into 2 subtype alleles, ORM1*F1 and
ORM1*F2. ORM1*F1 and ORM1*S are observed worldwide and ORM1*F2 is also
common in European populations. Yuasa et al. (1997) demonstrated that
these 3 common ORM1 alleles result from A-to-G transitions at the codons
for amino acid positions 20 in exon 1 and 156 in exon 5 of the AGP1
gene: ORM1*F1 is characterized by CAG (gln) and GTG (val); ORM1*F2, by
CAG (gln) and ATG (met); and ORM1*S, by CGG (arg) and GTG (val). Yuasa
et al. (1997) discussed the phylogeny of these 3 ORM1 alleles.
.0002
OROSOMUCOID POLYMORPHISM
ORM1*F2
ORM1, GLN20, MET156
See 138600.0001 and Yuasa et al. (1997).
.0003
OROSOMUCOID POLYMORPHISM
ORM1*S
ORM1, ARG20, VAL156
See 138600.0001 and Yuasa et al. (1997).
*FIELD* SA
Dayhoff (1972); Umetsu et al. (1985); Weidinger et al. (1987)
*FIELD* RF
1. Allderdice, P. W.; Kaita, H.; Lewis, M.; McAlpine, P. J.; Wong,
P.; Anderson, J.; Giblett, E. R.: Segregation of marker loci in families
with an inherited paracentric insertion of chromosome 9. Am. J. Hum.
Genet. 39: 612-617, 1986.
2. Board, P. G.; Jones, I. M.; Bentley, A. K.: Molecular cloning
and nucleotide sequence of human alpha-1 acid glycoprotein cDNA. Gene 44:
127-131, 1986.
3. Cox, D. W.; Francke, U.: Direct assignment of orosomucoid to human
chromosome 9 and alpha-2-HS-glycoprotein to chromosome 3 using human
fetal liver x rat hepatoma hybrids. Hum. Genet. 70: 109-115, 1985.
4. Dayhoff, M. O.: Atlas of Protein Sequence and Structure. Orosomucoid.
Washington: National Biomedical Research Foundation (pub.) 5: 1972.
Pp. D310-D316.
5. Dente, L.; Ciliberto, G.; Cortese, R.: Structure of the human
alpha-1-acid glycoprotein gene: sequence homology with other human
acute phase protein genes. Nucleic Acids Res. 13: 3941-3952, 1985.
6. Dente, L.; Pizza, M. G.; Metspalu, A.; Cortese, R.: Structure
and expression of the genes coding for human alpha-1-acid glycoprotein. EMBO
J. 6: 2289-2296, 1987.
7. Dente, L.; Ruther, U.; Tripodi, M.; Wagner, E. F.; Cortese, R.
: Expression of human alpha-1-acid glycoprotein genes in cultured
cells and in transgenic mice. Genes Dev. 2: 259-266, 1988.
8. Eap, C. B.; Cuendet, C.; Baumann, P.: Orosomucoid (alpha-1 acid
glycoprotein) phenotyping by use of immobilized pH gradients with
8 M urea and immunoblotting: a new variant encountered in a population
study. Hum. Genet. 80: 183-185, 1988.
9. Eiberg, H.; Mohr, J.; Nielsen, L. S.: Linkage of orosomucoid (ORM)
to ABO and AK1. (Abstract) Cytogenet. Cell Genet. 32: 272 only,
1982.
10. Johnson, A. M.; Schmid, K.; Alper, C. A.: Inheritance of human
alpha(1)-acid glycoprotein (orosomucoid) variants. J. Clin. Invest. 48:
2293-2299, 1969.
11. Luckenbach, C.; Kompf, J.; Ritter, H.: Orosomucoid (ORM1) subtyping
and formal genetics. Hum. Genet. 87: 429-432, 1991.
12. Rocchi, M.; Roncuzzi, L.; Santamaria, R.; Archidiacono, N.; Dente,
L.; Romeo, G.: Mapping through somatic cell hybrids and cDNA probes
of protein C to chromosome 2, factor X to chromosome 13, and alpha-1-acid
glycoprotein to chromosome 9. Hum. Genet. 74: 30-33, 1986.
13. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
14. Schmid, K.; Tokita, K.; Yoshizaki, H.: The alpha-1-acid glycoprotein
variants of normal Caucasian and Japanese individuals. J. Clin. Invest. 44:
1394-1401, 1965.
15. Tokita, K.; Schmid, K.: Variants of alpha-1-acid glycoprotein. Nature 200:
266 only, 1963.
16. Tomei, L.; Eap, C. B.; Baumann, P.; Dente, L.: Use of transgenic
mice for the characterization of human alpha-1-acid glycoprotein (orosomucoid)
variants. Hum. Genet. 84: 89-91, 1989.
17. Umetsu, K.; Ikeda, N.; Kashimura, S.; Suzuki, T.: Orosomucoid
(ORM) typing by print lectinofixation: a new technique for isoelectric
focusing--two common alleles in Japan. Hum. Genet. 71: 223-224,
1985.
18. Umetsu, K.; Yuasa, I.; Nishimura, H.; Sasaki, H.; Suzuki, T.:
Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in
a Philippine population. Hum. Hered. 38: 287-290, 1988.
19. Webb, G. C.; Earle, M. E.; Merritt, C.; Board, P. G.: Localization
of human alpha-1 glycoprotein genes to 9q31-q34.1. Cytogenet. Cell
Genet. 47: 18-21, 1988.
20. Weidinger, S.; Muller, T.; Schwarzfischer, F.; Cleve, H.: Three
new orosomucoid (ORM) variants revealed by isoelectric focusing and
print immunofixation. Hum. Genet. 77: 286-288, 1987.
21. Yuasa, I.; Umetsu, K.; Vogt, U.; Nakamura, H.; Nanba, E.; Tamaki,
N.; Irizawa, Y.: Human orosomucoid polymorphism: molecular basis
of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S. Hum.
Genet. 99: 393-398, 1997.
22. Yuasa, I.; Weidinger, S.; Umetsu, K.; Suenaga, K.; Ishimoto, G.;
Eap, B. C.; Duche, J.-C.; Baumann, P.: Orosomucoid system: 17 additional
orosomucoid variants and proposal for a new nomenclature. Vox Sang. 64:
47-55, 1993.
23. Zuffardi, O.; Caiulo, A.; Maraschio, P.; Tupler, R.; Bianchi,
E.; Amisano, P.; Beluffi, G.; Moratti, R.; Liguri, G.: Regional assignment
of the loci for adenylate kinase to 9q32 and for alpha(1)-acid glycoprotein
to 9q31-q32: a locus for Goltz syndrome in region 9q32-qter? Hum.
Genet. 82: 17-19, 1989.
*FIELD* CN
Victor A. McKusick - updated: 3/4/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 04/30/1999
terry: 11/10/1997
mark: 3/4/1997
terry: 3/3/1997
mark: 6/7/1996
davew: 8/5/1994
pfoster: 2/18/1994
carol: 10/26/1993
carol: 5/12/1993
carol: 3/3/1993
supermim: 3/16/1992