AMBP_HUMAN
ID AMBP_HUMAN Reviewed; 352 AA.
AC P02760; P00977; P02759; P78491; Q2TU33; Q5TBD7; Q9UC58; Q9UDI8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Protein AMBP {ECO:0000303|PubMed:1708673};
DE AltName: Full=Protein HC {ECO:0000303|PubMed:1714898};
DE Contains:
DE RecName: Full=Alpha-1-microglobulin {ECO:0000303|PubMed:25698971};
DE EC=1.6.2.- {ECO:0000305|PubMed:15683711};
DE AltName: Full=Alpha-1 microglycoprotein;
DE AltName: Full=Complex-forming glycoprotein heterogeneous in charge {ECO:0000303|PubMed:25698971};
DE Contains:
DE RecName: Full=Inter-alpha-trypsin inhibitor light chain;
DE Short=ITI-LC;
DE AltName: Full=Bikunin {ECO:0000303|PubMed:1708673};
DE AltName: Full=EDC1;
DE AltName: Full=HI-30;
DE AltName: Full=Uronic-acid-rich protein;
DE Contains:
DE RecName: Full=Trypstatin {ECO:0000250|UniProtKB:Q64240};
DE Flags: Precursor;
GN Name=AMBP; Synonyms=HCP, ITIL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2428011; DOI=10.1093/nar/14.15.6340;
RA Traboni C., Cortese R.;
RT "Sequence of a full length cDNA coding for human protein HC (alpha 1
RT microglobulin).";
RL Nucleic Acids Res. 14:6340-6340(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2430261; DOI=10.1093/nar/14.20.7839;
RA Kaumeyer J.F., Polazzi J.O., Kotick M.P.;
RT "The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-
RT alpha-trypsin inhibitor also encodes alpha-1-microglobulin (protein HC).";
RL Nucleic Acids Res. 14:7839-7850(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1708673; DOI=10.1515/bchm3.1990.371.2.1185;
RA Vetr H., Gebhard W.;
RT "Structure of the human alpha 1-microglobulin-bikunin gene.";
RL Biol. Chem. Hoppe-Seyler 371:1185-1196(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=1696200; DOI=10.1111/j.1432-1033.1990.tb19102.x;
RA Diarra-Mehrpour M., Bourguignon J., Sesboue R., Salier J.-P.,
RA Leveillard T., Martin J.-P.;
RT "Structural analysis of the human inter-alpha-trypsin inhibitor light-chain
RT gene.";
RL Eur. J. Biochem. 191:131-139(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell growth inhibition gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., 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., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., 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., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 20-202.
RX PubMed=6198962; DOI=10.1016/0003-9861(84)90021-3;
RA Lopez C., Grubb A.O., Mendez E.;
RT "The complete amino acid sequence of human complex-forming glycoprotein
RT heterogeneous in charge (protein HC) from one individual.";
RL Arch. Biochem. Biophys. 228:544-554(1984).
RN [11]
RP PROTEIN SEQUENCE OF 20-198.
RX PubMed=6164372; DOI=10.1016/0006-291x(81)91209-2;
RA Takagi T., Takagi K., Kawai T.;
RT "Complete amino acid sequence of human alpha 1-microglobulin.";
RL Biochem. Biophys. Res. Commun. 98:997-1001(1981).
RN [12]
RP PROTEIN SEQUENCE OF 20-198.
RA Lopez C., Grubb A.O., Mendez E.;
RT "Human protein HC displays variability in its carboxyl-terminal amino acid
RT sequence.";
RL FEBS Lett. 144:349-353(1982).
RN [13]
RP PROTEIN SEQUENCE OF 44-57, AND BINDING TO CHROMOPHORE.
RX PubMed=7506257; DOI=10.1016/s0021-9258(17)42361-1;
RA Calero M., Escribano J., Grubb A., Mendez E.;
RT "Location of a novel type of interpolypeptide chain linkage in the human
RT protein HC-IgA complex (HC-IgA) and identification of a heterogeneous
RT chromophore associated with the complex.";
RL J. Biol. Chem. 269:384-389(1994).
RN [14]
RP PROTEIN SEQUENCE OF 206-350.
RX PubMed=2408638; DOI=10.1515/bchm3.1985.366.1.479;
RA Reisinger P., Hochstrasser K., Albrecht G.J., Lempart K., Salier J.-P.;
RT "Human inter-alpha-trypsin inhibitor: localization of the Kunitz-type
RT domains in the N-terminal part of the molecule and their release by a
RT trypsin-like proteinase.";
RL Biol. Chem. Hoppe-Seyler 366:479-483(1985).
RN [15]
RP PROTEIN SEQUENCE OF 206-243 AND 275-303.
RC TISSUE=Urine;
RX PubMed=1469060; DOI=10.1002/jcb.240500303;
RA Chawla R.K., Lawson D.H., Ahmad M., Travis J.;
RT "Cancer-related urinary proteinase inhibitor, EDC1: a new method for its
RT isolation and evidence for multiple forms.";
RL J. Cell. Biochem. 50:227-236(1992).
RN [16]
RP PROTEIN SEQUENCE OF 206-223, GLYCOSYLATION AT SER-215, AND CROSS-LINK SITE
RP TO HC3.
RX PubMed=1898736; DOI=10.1016/s0021-9258(17)35235-3;
RA Enghild J.J., Salvesen G., Hefta S.A., Thoegersen I.B., Rutherfurd S.,
RA Pizzo S.V.;
RT "Chondroitin 4-sulfate covalently cross-links the chains of the human blood
RT protein pre-alpha-inhibitor.";
RL J. Biol. Chem. 266:747-751(1991).
RN [17]
RP PROTEIN SEQUENCE OF 206-223, GLYCOSYLATION AT SER-215, AND CROSS-LINK SITE
RP TO HC2.
RX PubMed=7682553; DOI=10.1016/s0021-9258(18)52933-1;
RA Enghild J.J., Salvesen G., Thoegersen I.B., Valnickova Z., Pizzo S.V.,
RA Hefta S.A.;
RT "Presence of the protein-glycosaminoglycan-protein covalent cross-link in
RT the inter-alpha-inhibitor-related proteinase inhibitor heavy chain
RT 2/bikunin.";
RL J. Biol. Chem. 268:8711-8716(1993).
RN [18]
RP PROTEIN SEQUENCE OF 206-223, AND FUNCTION.
RC TISSUE=Urine;
RX PubMed=7676539; DOI=10.1007/bf00307939;
RA Atmani F., Khan S.R.;
RT "Characterization of uronic-acid-rich inhibitor of calcium oxalate
RT crystallization isolated from rat urine.";
RL Urol. Res. 23:95-101(1995).
RN [19]
RP PROTEIN SEQUENCE OF 206-219, AND COVALENT LINKAGE WITH CHONDROITIN SULFATE.
RC TISSUE=Plasma;
RX PubMed=7513643; DOI=10.1111/j.1432-1033.1994.tb18803.x;
RA Morelle W., Capon C., Balduyck M., Sautiere P., Kouach M., Michalski C.,
RA Fournet B., Mizon J.;
RT "Chondroitin sulphate covalently cross-links the three polypeptide chains
RT of inter-alpha-trypsin inhibitor.";
RL Eur. J. Biochem. 221:881-888(1994).
RN [20]
RP GLYCOSYLATION AT SER-215 AND ASN-250, AND STRUCTURE OF CARBOHYDRATES.
RX PubMed=6171497; DOI=10.1515/bchm2.1981.362.2.1357;
RA Hochstrasser K., Schoenberger O.L., Rossmanith I., Wachter E.;
RT "Kunitz-type proteinase inhibitors derived by limited proteolysis of the
RT inter-alpha-trypsin inhibitor, V. Attachments of carbohydrates in the human
RT urinary trypsin inhibitor isolated by affinity chromatography.";
RL Hoppe-Seyler's Z. Physiol. Chem. 362:1357-1362(1981).
RN [21]
RP INHIBITORY SITE.
RX PubMed=3890890; DOI=10.1515/bchm3.1985.366.1.19;
RA Morii M., Travis J.;
RT "The reactive site of human inter-alpha-trypsin inhibitor is in the amino-
RT terminal half of the protein.";
RL Biol. Chem. Hoppe-Seyler 366:19-21(1985).
RN [22]
RP IDENTIFICATION IN INTER-ALPHA-INHIBITOR AND PRE-ALPHA-INHIBITOR COMPLEXES,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=2476436; DOI=10.1016/s0021-9258(18)71575-5;
RA Enghild J.J., Thoegersen I.B., Pizzo S.V., Salvesen G.;
RT "Analysis of inter-alpha-trypsin inhibitor and a novel trypsin inhibitor,
RT pre-alpha-trypsin inhibitor, from human plasma. Polypeptide chain
RT stoichiometry and assembly by glycan.";
RL J. Biol. Chem. 264:15975-15981(1989).
RN [23]
RP GLYCOSYLATION AT THR-24; ASN-36 AND ASN-115, AND STRUCTURE OF
RP CARBOHYDRATES.
RX PubMed=1694784; DOI=10.1016/0014-5793(90)81531-r;
RA Escribano J., Lopex-Otin C., Hjerpe A., Grubb A.O., Mendez E.;
RT "Location and characterization of the three carbohydrate prosthetic groups
RT of human protein HC.";
RL FEBS Lett. 266:167-170(1990).
RN [24]
RP BINDING OF CHROMOPHORE AT CYS-53, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Urine;
RX PubMed=1714898; DOI=10.1016/s0021-9258(18)98474-7;
RA Escribano J., Grubb A.O., Calero M., Mendez E.;
RT "The protein HC chromophore is linked to the cysteine residue at position
RT 34 of the polypeptide chain by a reduction-resistant bond and causes the
RT charge heterogeneity of protein HC.";
RL J. Biol. Chem. 266:15758-15763(1991).
RN [25]
RP BINDING TO CHROMOPHORE.
RX PubMed=7535251; DOI=10.1016/0014-5793(95)00206-o;
RA Akerstroem B., Bratt T., Enghild J.J.;
RT "Formation of the alpha 1-microglobulin chromophore in mammalian and insect
RT cells: a novel post-translational mechanism?";
RL FEBS Lett. 362:50-54(1995).
RN [26]
RP SUBUNIT, AND INTERACTION WITH F2; ALB AND IMMUNOGLOBULIN A.
RX PubMed=9183005; DOI=10.1111/j.1432-1033.1997.00676.x;
RA Berggaard T., Thelin N., Falkenberg C., Enghild J.J., Akerstroem B.;
RT "Prothrombin, albumin and immunoglobulin A form covalent complexes with
RT alpha1-microglobulin in human plasma.";
RL Eur. J. Biochem. 245:676-683(1997).
RN [27]
RP FUNCTION.
RX PubMed=10480954; DOI=10.1074/jbc.274.38.27331;
RA Wilharm E., Parry M.A., Friebel R., Tschesche H., Matschiner G.,
RA Sommerhoff C.P., Jenne D.E.;
RT "Generation of catalytically active granzyme K from Escherichia coli
RT inclusion bodies and identification of efficient granzyme K inhibitors in
RT human plasma.";
RL J. Biol. Chem. 274:27331-27337(1999).
RN [28]
RP BINDING OF CHROMOPHORE AT LYS-111; LYS-137 AND LYS-149.
RX PubMed=10631976; DOI=10.1110/ps.8.12.2611;
RA Berggaard T., Cohen A., Persson P., Lindqvist A., Cedervall T., Silow M.,
RA Thoegersen I.B., Joensson J.A., Enghild J.J., Aakerstroem B.;
RT "Alpha1-microglobulin chromophores are located to three lysine residues
RT semiburied in the lipocalin pocket and associated with a novel lipophilic
RT compound.";
RL Protein Sci. 8:2611-2620(1999).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND TISSUE
RP SPECIFICITY.
RX PubMed=11877257; DOI=10.1182/blood.v99.6.1894;
RA Allhorn M., Berggaard T., Nordberg J., Olsson M.L., Akerstroem B.;
RT "Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces
RT heme-binding and heme-degradation properties.";
RL Blood 99:1894-1901(2002).
RN [30]
RP CHROMOPHORE CHARACTERIZATION.
RX PubMed=15452109; DOI=10.1074/jbc.m408242200;
RA Sala A., Campagnoli M., Perani E., Romano A., Labo S., Monzani E.,
RA Minchiotti L., Galliano M.;
RT "Human alpha-1-microglobulin is covalently bound to kynurenine-derived
RT chromophores.";
RL J. Biol. Chem. 279:51033-51041(2004).
RN [31]
RP INTERACTION OF ALPHA-1-MICROGLOBULIN WITH HEV PROTEIN ORF3 (MICROBIAL
RP INFECTION).
RX PubMed=15037615; DOI=10.1074/jbc.m402017200;
RA Tyagi S., Surjit M., Roy A.K., Jameel S., Lal S.K.;
RT "The ORF3 protein of hepatitis E virus interacts with liver-specific
RT alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin
RT precursor (AMBP) and expedites their export from the hepatocyte.";
RL J. Biol. Chem. 279:29308-29319(2004).
RN [32]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-53; LYS-111;
RP LYS-137 AND LYS-149, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15683711; DOI=10.1016/j.freeradbiomed.2004.12.013;
RA Allhorn M., Klapyta A., Akerstroem B.;
RT "Redox properties of the lipocalin alpha1-microglobulin: reduction of
RT cytochrome c, hemoglobin, and free iron.";
RL Free Radic. Biol. Med. 38:557-567(2005).
RN [33]
RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH TNFAIP6.
RX PubMed=15917224; DOI=10.1074/jbc.m502068200;
RA Mahoney D.J., Mulloy B., Forster M.J., Blundell C.D., Fries E.,
RA Milner C.M., Day A.J.;
RT "Characterization of the interaction between tumor necrosis factor-
RT stimulated gene-6 and heparin: implications for the inhibition of plasmin
RT in extracellular matrix microenvironments.";
RL J. Biol. Chem. 280:27044-27055(2005).
RN [34]
RP INTERACTION OF BIKUNIN WITH HEV PROTEIN ORF3 (MICROBIAL INFECTION).
RX PubMed=16140784; DOI=10.1128/jvi.79.18.12081-12087.2005;
RA Tyagi S., Surjit M., Lal S.K.;
RT "The 41-amino-acid C-terminal region of the hepatitis E virus ORF3 protein
RT interacts with bikunin, a Kunitz-type serine protease inhibitor.";
RL J. Virol. 79:12081-12087(2005).
RN [35]
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, TISSUE SPECIFICITY, AND INDUCTION
RP BY TNF.
RX PubMed=16873769; DOI=10.1165/rcmb.2006-0018oc;
RA Forteza R., Casalino-Matsuda S.M., Monzon M.E., Fries E., Rugg M.S.,
RA Milner C.M., Day A.J.;
RT "TSG-6 potentiates the antitissue kallikrein activity of inter-alpha-
RT inhibitor through bikunin release.";
RL Am. J. Respir. Cell Mol. Biol. 36:20-31(2007).
RN [36]
RP FUNCTION.
RX PubMed=20463016; DOI=10.1074/jbc.m109.041046;
RA Sanggaard K.W., Scavenius C., Rasmussen A.J., Wisniewski H.G.,
RA Thoegersen I.B., Enghild J.J.;
RT "The TSG-6/HC2-mediated transfer is a dynamic process shuffling heavy
RT chains between glycosaminoglycans.";
RL J. Biol. Chem. 285:21988-21993(2010).
RN [37]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY OXIDATIVE STRESS.
RX PubMed=21356557; DOI=10.1016/j.placenta.2011.01.017;
RA May K., Rosenloef L., Olsson M.G., Centlow M., Moergelin M., Larsson I.,
RA Cederlund M., Rutardottir S., Siegmund W., Schneider H., Akerstroem B.,
RA Hansson S.R.;
RT "Perfusion of human placenta with hemoglobin introduces preeclampsia-like
RT injuries that are prevented by alpha1-microglobulin.";
RL Placenta 32:323-332(2011).
RN [38]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY OXIDATIVE STRESS, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22096585; DOI=10.1371/journal.pone.0027505;
RA Olsson M.G., Allhorn M., Larsson J., Cederlund M., Lundqvist K.,
RA Schmidtchen A., Soerensen O.E., Moergelin M., Akerstroem B.;
RT "Up-regulation of A1M/alpha1-microglobulin in skin by heme and reactive
RT oxygen species gives protection from oxidative damage.";
RL PLoS ONE 6:e27505-e27505(2011).
RN [39]
RP GLYCOSYLATION AT ASN-115 AND ASN-250, STRUCTURE OF CARBOHYDRATES, AND
RP IDENTIFICATION BY MASS 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 N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [40]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NDUFAB1.
RX PubMed=23157686; DOI=10.1089/ars.2012.4658;
RA Olsson M.G., Rosenloef L.W., Kotarsky H., Olofsson T., Leanderson T.,
RA Moergelin M., Fellman V., Aakerstroem B.;
RT "The radical-binding lipocalin A1M binds to a Complex I subunit and
RT protects mitochondrial structure and function.";
RL Antioxid. Redox Signal. 18:2017-2028(2013).
RN [41]
RP FUNCTION, INDUCTION BY OXIDATIVE STRESS, MUTAGENESIS OF CYS-53; LYS-111;
RP LYS-137 AND LYS-149, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23642167; DOI=10.3109/10715762.2013.801555;
RA Rutardottir S., Nilsson E.J., Pallon J., Gram M., Aakerstroem B.;
RT "The cysteine 34 residue of A1M/alpha1-microglobulin is essential for
RT protection of irradiated cell cultures and reduction of carbonyl groups.";
RL Free Radic. Res. 47:541-550(2013).
RN [42]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND DOMAIN.
RX PubMed=25301953; DOI=10.1074/jbc.m114.609560;
RA Pendlebury D., Wang R., Henin R.D., Hockla A., Soares A.S., Madden B.J.,
RA Kazanov M.D., Radisky E.S.;
RT "Sequence and conformational specificity in substrate recognition: several
RT human Kunitz protease inhibitor domains are specific substrates of
RT mesotrypsin.";
RL J. Biol. Chem. 289:32783-32797(2014).
RN [43]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [44]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=25698971; DOI=10.3389/fphys.2015.00011;
RA Cederlund M., Deronic A., Pallon J., Soerensen O.E., Aakerstroem B.;
RT "A1M/alpha1-microglobulin is proteolytically activated by myeloperoxidase,
RT binds its heme group and inhibits low density lipoprotein oxidation.";
RL Front. Physiol. 6:11-11(2015).
RN [45]
RP FUNCTION.
RX PubMed=32823731; DOI=10.3390/ijms21165825;
RA Kristiansson A., Davidsson S., Johansson M.E., Piel S., Elmer E.,
RA Hansson M.J., Aakerstroem B., Gram M.;
RT "alpha1-Microglobulin (A1M) Protects Human Proximal Tubule Epithelial Cells
RT from Heme-Induced Damage In Vitro.";
RL Int. J. Mol. Sci. 21:0-0(2020).
RN [46]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=32092412; DOI=10.1016/j.freeradbiomed.2020.02.018;
RA Kristiansson A., Bergwik J., Alattar A.G., Flygare J., Gram M.,
RA Hansson S.R., Olsson M.L., Storry J.R., Allhorn M., Aakerstroem B.;
RT "Human radical scavenger alpha1-microglobulin protects against hemolysis in
RT vitro and alpha1-microglobulin knockout mice exhibit a macrocytic anemia
RT phenotype.";
RL Free Radic. Biol. Med. 162:149-159(2021).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 206-352, AND DISULFIDE BOND.
RX PubMed=9566199; DOI=10.1006/jmbi.1997.1582;
RA Xu Y., Carr P.D., Guss J.M., Ollis D.L.;
RT "The crystal structure of bikunin from the inter-alpha-inhibitor complex: a
RT serine protease inhibitor with two Kunitz domains.";
RL J. Mol. Biol. 276:955-966(1998).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-202, DISULFIDE BOND, AND
RP SUBUNIT.
RX PubMed=22512701; DOI=10.1042/bj20120448;
RA Meining W., Skerra A.;
RT "The crystal structure of human alpha(1)-microglobulin reveals a potential
RT haem-binding site.";
RL Biochem. J. 445:175-182(2012).
RN [49]
RP REVIEW.
RX PubMed=11058759; DOI=10.1016/s0167-4838(00)00157-6;
RA Aakerstroem B., Loegdberg L., Berggaard T., Osmark P., Lindqvist A.;
RT "Alpha(1)-microglobulin: a yellow-brown lipocalin.";
RL Biochim. Biophys. Acta 1482:172-184(2000).
CC -!- FUNCTION: [Alpha-1-microglobulin]: Antioxidant and tissue repair
CC protein with reductase, heme-binding and radical-scavenging activities.
CC Removes and protects against harmful oxidants and repairs
CC macromolecules in intravascular and extravascular spaces and in
CC intracellular compartments (PubMed:11877257, PubMed:15683711,
CC PubMed:22096585, PubMed:23157686, PubMed:23642167, PubMed:25698971,
CC PubMed:32823731, PubMed:32092412). Intravascularly, plays a regulatory
CC role in red cell homeostasis by preventing heme- and reactive oxygen
CC species-induced cell damage. Binds and degrades free heme to protect
CC fetal and adult red blood cells from hemolysis (PubMed:11877257,
CC PubMed:32092412). Reduces extracellular methemoglobin, a Fe3+ (ferric)
CC form of hemoglobin that cannot bind oxygen, back to the Fe2+ (ferrous)
CC form deoxyhemoglobin, which has oxygen-carrying potential
CC (PubMed:15683711). Upon acute inflammation, inhibits oxidation of low-
CC density lipoprotein particles by MPO and limits vascular damage
CC (PubMed:25698971). Extravascularly, protects from oxidation products
CC formed on extracellular matrix structures and cell membranes. Catalyzes
CC the reduction of carbonyl groups on oxidized collagen fibers and
CC preserves cellular and extracellular matrix ultrastructures
CC (PubMed:23642167, PubMed:22096585). Importantly, counteracts the
CC oxidative damage at blood-placenta interface, preventing leakage of
CC free fetal hemoglobin into the maternal circulation (PubMed:21356557).
CC Intracellularly, has a role in maintaining mitochondrial redox
CC homeostasis. Bound to complex I of the respiratory chain of
CC mitochondria, may scavenge free radicals and preserve mitochondrial ATP
CC synthesis. Protects renal tubule epithelial cells from heme-induced
CC oxidative damage to mitochondria (PubMed:23157686, PubMed:32823731).
CC Reduces cytochrome c from Fe3+ (ferric) to the Fe2+ (ferrous) state
CC through formation of superoxide anion radicals in the presence of
CC ascorbate or NADH/NADPH electron donor cofactors, ascorbate being the
CC preferred cofactor (PubMed:15683711). Has a chaperone role in
CC facilitating the correct folding of bikunin in the endoplasmic
CC reticulum compartment (By similarity). {ECO:0000250|UniProtKB:Q07456,
CC ECO:0000269|PubMed:11877257, ECO:0000269|PubMed:15683711,
CC ECO:0000269|PubMed:21356557, ECO:0000269|PubMed:22096585,
CC ECO:0000269|PubMed:23157686, ECO:0000269|PubMed:23642167,
CC ECO:0000269|PubMed:25698971, ECO:0000269|PubMed:32092412,
CC ECO:0000269|PubMed:32823731}.
CC -!- FUNCTION: [Inter-alpha-trypsin inhibitor light chain]: Kunitz-type
CC serine protease inhibitor and structural component of extracellular
CC matrix with a role in extracellular space remodeling and cell adhesion
CC (PubMed:25301953, PubMed:20463016). Among others, has antiprotease
CC activity toward kallikrein, a protease involved in airway inflammation;
CC inhibits GZMK/granzyme, a granule-stored serine protease involved in NK
CC and T cell cytotoxic responses; and inhibits PLG/plasmin, a protease
CC required for activation of matrix metalloproteinases (PubMed:16873769,
CC PubMed:10480954, PubMed:15917224). As part of I-alpha-I complex,
CC provides for the heavy chains to be transferred from I-alpha-I complex
CC to hyaluronan in the presence of TNFAIP6, in a dynamic process that
CC releases free bikunin and remodels extracellular matrix proteoglycan
CC structures. Free bikunin, but not its heavy chain-bound form, acts as
CC potent protease inhibitor in airway secretions (PubMed:16873769). Part
CC of hyaluronan-rich extracellular matrix that surrounds oocyte during
CC cumulus oophorus expansion, an indispensable process for proper
CC ovulation (By similarity). Also inhibits calcium oxalate
CC crystallization (PubMed:7676539). {ECO:0000250|UniProtKB:Q07456,
CC ECO:0000269|PubMed:10480954, ECO:0000269|PubMed:15917224,
CC ECO:0000269|PubMed:16873769, ECO:0000269|PubMed:20463016,
CC ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:7676539}.
CC -!- FUNCTION: [Trypstatin]: Kunitz-type serine protease inhibitor. Has high
CC catalytic efficiency for F10/blood coagulation factor Xa and may act as
CC an anticoagulant by inhibiting prothrombin activation. Inhibits trypsin
CC and mast cell CMA1/chymase and tryptase proteases.
CC {ECO:0000250|UniProtKB:Q64240}.
CC -!- ACTIVITY REGULATION: [Inter-alpha-trypsin inhibitor light chain]: Up-
CC regulated by TNFAIP6. In a transesterification reaction, TNFAIP6
CC cleaves the ester bond between the heavy chain and the chondroitin
CC sulfate chain in I-alpha-I complex and potentiates the antiprotease
CC function of I-alpha-I complex through release of free bikunin.
CC {ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:16873769}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC The reductase activity toward cytochrome c increases at alkaline pH
CC 8-9 when compared to pH 6-7. {ECO:0000269|PubMed:15683711};
CC -!- SUBUNIT: [Alpha-1-microglobulin]: Monomer (PubMed:22512701,
CC PubMed:9183005). Homodimer (PubMed:9183005). In plasma, it occurs as a
CC monomer or dimer and in covalently-linked complexes with immunoglobulin
CC A (IgA), ALB/albumin and F2/prothrombin (PubMed:9183005). Chromophore-
CC bound alpha-1-microglobulin interacts with the constant region of
CC immunoglobulin A (PubMed:9183005). Chromophore-bound alpha-1-
CC microglobulin interacts with ALB with molar ratio 2:1 and 1:1; this
CC interaction does not prevent fatty acid binding to ALB
CC (PubMed:9183005). Interacts with F2/prothrombin (via N-terminus) with
CC molar ratio 2:1 and 1:1; this interaction does not prevent the
CC activation of prothrombin to thrombin (PubMed:9183005). Interacts with
CC NDUFAB1, a subunit of mitochondrial complex I (PubMed:23157686).
CC Interacts with FN1 (By similarity). {ECO:0000250|UniProtKB:Q64240,
CC ECO:0000269|PubMed:22512701, ECO:0000269|PubMed:23157686,
CC ECO:0000269|PubMed:9183005}.
CC -!- SUBUNIT: [Inter-alpha-trypsin inhibitor light chain]: I-alpha-I plasma
CC protease inhibitors are assembled from one or two heavy chains (HC) and
CC one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed
CC of ITIH1/HC1, ITIH2/HC2 and bikunin, and pre-alpha-inhibitor (P-alpha-
CC I) of ITIH3/HC3 and bikunin (PubMed:2476436, PubMed:16873769).
CC Interacts with TNFAIP6 (via Link domain) (PubMed:15917224).
CC {ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:16873769,
CC ECO:0000269|PubMed:2476436}.
CC -!- SUBUNIT: [Trypstatin]: Monomer. Also occurs as a complex with tryptase
CC in mast cells. {ECO:0000250|UniProtKB:Q64240}.
CC -!- SUBUNIT: [Alpha-1-microglobulin]: (Microbial infection) Interacts with
CC hepatitis E virus/HEV protein ORF3. {ECO:0000269|PubMed:15037615}.
CC -!- SUBUNIT: [Inter-alpha-trypsin inhibitor light chain]: (Microbial
CC infection) Interacts with hepatitis E virus/HEV protein ORF3.
CC {ECO:0000269|PubMed:16140784}.
CC -!- INTERACTION:
CC P02760; P07858: CTSB; NbExp=4; IntAct=EBI-2115136, EBI-715062;
CC P02760; Q13643: FHL3; NbExp=3; IntAct=EBI-2115136, EBI-741101;
CC -!- SUBCELLULAR LOCATION: [Alpha-1-microglobulin]: Secreted
CC {ECO:0000269|PubMed:11877257, ECO:0000269|PubMed:32092412}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:22096585}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:32092412}. Cell membrane
CC {ECO:0000269|PubMed:22096585, ECO:0000269|PubMed:32092412}; Peripheral
CC membrane protein {ECO:0000305|PubMed:22096585,
CC ECO:0000305|PubMed:32092412}. Nucleus membrane
CC {ECO:0000269|PubMed:22096585}; Peripheral membrane protein
CC {ECO:0000305|PubMed:22096585}. Mitochondrion inner membrane
CC {ECO:0000305|PubMed:23157686}; Peripheral membrane protein
CC {ECO:0000305|PubMed:23157686}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000269|PubMed:22096585}. Note=The cellular
CC uptake occurs via a non-endocytotic pathway and allows for localization
CC to various membrane structures. A specific binding to plasma membrane
CC suggests the presence of a cell receptor, yet to be identified.
CC Directly binds collagen fibers type I. {ECO:0000269|PubMed:22096585}.
CC -!- TISSUE SPECIFICITY: [Alpha-1-microglobulin]: Expressed by the liver and
CC secreted in plasma. Occurs in many physiological fluids including
CC plasma, urine, and cerebrospinal fluid (PubMed:11877257). Expressed in
CC epidermal keratinocytes, in dermis and epidermal-dermal junction (at
CC protein level) (PubMed:22096585). Expressed in red blood cells (at
CC protein level) (PubMed:32092412). Expressed in placenta
CC (PubMed:21356557). {ECO:0000269|PubMed:11877257,
CC ECO:0000269|PubMed:21356557, ECO:0000269|PubMed:22096585,
CC ECO:0000269|PubMed:32092412}.
CC -!- TISSUE SPECIFICITY: [Inter-alpha-trypsin inhibitor light chain]:
CC Expressed in airway epithelium and submucosal gland (at protein level).
CC Colocalizes with TNFAIP6 at the ciliary border. Present in
CC bronchoalveolar lavage fluid (at protein level).
CC {ECO:0000269|PubMed:16873769}.
CC -!- INDUCTION: [Alpha-1-microglobulin]: Up-regulated upon oxidative stress
CC (PubMed:23642167, PubMed:22096585, PubMed:21356557). Up-regulated in
CC keratinocytes upon exposure to heme and reactive oxygen species
CC (PubMed:22096585). Up-regulated in hemoglobin-perfused placenta
CC (PubMed:21356557). {ECO:0000269|PubMed:21356557,
CC ECO:0000269|PubMed:22096585, ECO:0000269|PubMed:23642167}.
CC -!- INDUCTION: [Inter-alpha-trypsin inhibitor light chain]: Up-regulated in
CC airway epithelium and submucosal gland in response to inflammatory
CC cytokine TNF. {ECO:0000269|PubMed:16873769}.
CC -!- DOMAIN: [Inter-alpha-trypsin inhibitor light chain]: The Kunitz domains
CC 1 and 2 serve as protease inhibitor domains.
CC {ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:9566199}.
CC -!- PTM: The precursor is proteolytically processed into separately
CC functioning proteins. {ECO:0000305}.
CC -!- PTM: [Alpha-1-microglobulin]: Proteolytically cleaved in the presence
CC of oxyhemoglobin or MPO (PubMed:11877257, PubMed:25698971). The cleaved
CC form t-alpha-1-microglobulin lacks the C-terminal tetrapeptide LIPR and
CC is released from IgA-alpha-1-microglobulin complex as well as from free
CC alpha-1-microglobulin when exposed to oxyhemoglobin or erythrocyte
CC membranes. The cleavage of IgA-alpha-1-microglobulin complex is
CC associated with the reduction of the covalent bond between IgA and
CC alpha-1-microglobulin, yielding an intact IgA molecule
CC (PubMed:11877257). The cleavage by MPO is associated with the transfer
CC of heme group from MPO to t-alpha-1-microglobulin (PubMed:25698971). t-
CC alpha-1-microglobulin has higher reductase activity when compared with
CC full length protein (PubMed:15683711). {ECO:0000269|PubMed:11877257,
CC ECO:0000269|PubMed:15683711, ECO:0000269|PubMed:25698971}.
CC -!- PTM: [Alpha-1-microglobulin]: 3-hydroxykynurenine, an oxidized
CC tryptophan metabolite that is common in biological fluids, reacts with
CC Cys-53, Lys-111, Lys-137, and Lys-149 to form heterogeneous polycyclic
CC chromophores including hydroxanthommatin. The reaction by alpha-1-
CC microglobulin is autocatalytic; the human protein forms chromophore
CC even when expressed in insect and bacterial cells. The chromophore can
CC react with accessible cysteines forming non-reducible thioether cross-
CC links with other molecules of alpha-1-microglobulin or with other
CC proteins such as Ig alpha-1 chain C region 'Cys-352'.
CC {ECO:0000269|PubMed:10631976, ECO:0000269|PubMed:1714898,
CC ECO:0000269|PubMed:7535251}.
CC -!- PTM: [Inter-alpha-trypsin inhibitor light chain]: Heavy chains are
CC interlinked with bikunin via a chondroitin 4-sulfate bridge to the C-
CC terminal aspartate. {ECO:0000269|PubMed:1898736,
CC ECO:0000269|PubMed:6171497, ECO:0000269|PubMed:7682553}.
CC -!- PTM: [Inter-alpha-trypsin inhibitor light chain]: Proteolytically
CC cleaved by PRSS3 at Kunitz domain 2. {ECO:0000269|PubMed:25301953}.
CC -!- PTM: N- and O-glycosylated. N-glycan heterogeneity at Asn-115:
CC Hex5HexNAc4 (major), Hex6HexNAc5 (minor) and dHex1Hex6HexNAc5 (minor).
CC N-glycan at Asn-250: Hex5HexNAc4. O-linkage of the glycosaminoglycan,
CC chondroitin sulfate, at Ser-215 allows cross-linking between the three
CC polypeptide chains. {ECO:0000269|PubMed:1694784,
CC ECO:0000269|PubMed:1898736, ECO:0000269|PubMed:22171320,
CC ECO:0000269|PubMed:6171497, ECO:0000269|PubMed:7682553}.
CC -!- MISCELLANEOUS: In vitro, the first twelve residues of the amino end of
CC the inhibitor appear to have a reactive site capable of inhibiting the
CC activity of a number of enzymes. Its in vivo function is not known.
CC -!- SIMILARITY: In the N-terminal section; belongs to the calycin
CC superfamily. Lipocalin family. {ECO:0000305}.
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DR EMBL; X04225; CAA27803.1; -; mRNA.
DR EMBL; X04494; CAA28182.1; -; mRNA.
DR EMBL; X54816; CAA38585.1; -; Genomic_DNA.
DR EMBL; X54817; CAA38585.1; JOINED; Genomic_DNA.
DR EMBL; X54818; CAA38585.1; JOINED; Genomic_DNA.
DR EMBL; X54817; CAA38586.1; -; Genomic_DNA.
DR EMBL; X54818; CAA38587.1; -; Genomic_DNA.
DR EMBL; M88249; AAA59196.1; -; Genomic_DNA.
DR EMBL; M88165; AAA59196.1; JOINED; Genomic_DNA.
DR EMBL; M88243; AAA59196.1; JOINED; Genomic_DNA.
DR EMBL; M88244; AAA59196.1; JOINED; Genomic_DNA.
DR EMBL; M88246; AAA59196.1; JOINED; Genomic_DNA.
DR EMBL; M88247; AAA59196.1; JOINED; Genomic_DNA.
DR EMBL; AY544123; AAT11154.1; -; mRNA.
DR EMBL; AK290837; BAF83526.1; -; mRNA.
DR EMBL; AL137850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87404.1; -; Genomic_DNA.
DR EMBL; BC041593; AAH41593.1; -; mRNA.
DR CCDS; CCDS6800.1; -.
DR PIR; S13433; HCHU.
DR RefSeq; NP_001624.1; NM_001633.3.
DR PDB; 1BIK; X-ray; 2.50 A; A=206-352.
DR PDB; 3QKG; X-ray; 2.30 A; A=20-202.
DR PDB; 4ES7; X-ray; 2.00 A; A=27-193.
DR PDB; 4U30; X-ray; 2.50 A; W/X/Y/Z=283-340.
DR PDB; 6EJ7; X-ray; 2.00 A; B=210-221.
DR PDB; 6EJ8; X-ray; 2.09 A; B=210-221.
DR PDB; 6EJ9; X-ray; 2.02 A; B=210-220.
DR PDB; 6EJA; X-ray; 1.94 A; B=210-221.
DR PDB; 6EJB; X-ray; 2.56 A; B=210-221.
DR PDB; 6EJC; X-ray; 2.06 A; B=210-221.
DR PDB; 6EJD; X-ray; 2.68 A; B=210-221.
DR PDBsum; 1BIK; -.
DR PDBsum; 3QKG; -.
DR PDBsum; 4ES7; -.
DR PDBsum; 4U30; -.
DR PDBsum; 6EJ7; -.
DR PDBsum; 6EJ8; -.
DR PDBsum; 6EJ9; -.
DR PDBsum; 6EJA; -.
DR PDBsum; 6EJB; -.
DR PDBsum; 6EJC; -.
DR PDBsum; 6EJD; -.
DR AlphaFoldDB; P02760; -.
DR SMR; P02760; -.
DR BioGRID; 106757; 17.
DR IntAct; P02760; 12.
DR MINT; P02760; -.
DR STRING; 9606.ENSP00000265132; -.
DR MEROPS; I02.005; -.
DR MEROPS; I02.006; -.
DR CarbonylDB; P02760; -.
DR GlyConnect; 21; 31 N-Linked glycans (2 sites), 7 O-Linked glycans (3 sites).
DR GlyGen; P02760; 7 sites, 32 N-linked glycans (2 sites), 8 O-linked glycans (3 sites).
DR iPTMnet; P02760; -.
DR PhosphoSitePlus; P02760; -.
DR BioMuta; AMBP; -.
DR DMDM; 122801; -.
DR SWISS-2DPAGE; P02760; -.
DR CPTAC; non-CPTAC-1152; -.
DR CPTAC; non-CPTAC-1153; -.
DR jPOST; P02760; -.
DR MassIVE; P02760; -.
DR MaxQB; P02760; -.
DR PaxDb; P02760; -.
DR PeptideAtlas; P02760; -.
DR PRIDE; P02760; -.
DR ProteomicsDB; 51583; -.
DR Antibodypedia; 876; 561 antibodies from 36 providers.
DR DNASU; 259; -.
DR Ensembl; ENST00000265132.8; ENSP00000265132.3; ENSG00000106927.12.
DR GeneID; 259; -.
DR KEGG; hsa:259; -.
DR MANE-Select; ENST00000265132.8; ENSP00000265132.3; NM_001633.4; NP_001624.1.
DR UCSC; uc004bie.5; human.
DR CTD; 259; -.
DR DisGeNET; 259; -.
DR GeneCards; AMBP; -.
DR HGNC; HGNC:453; AMBP.
DR HPA; ENSG00000106927; Tissue enriched (liver).
DR MIM; 176870; gene.
DR neXtProt; NX_P02760; -.
DR OpenTargets; ENSG00000106927; -.
DR PharmGKB; PA24759; -.
DR VEuPathDB; HostDB:ENSG00000106927; -.
DR eggNOG; KOG4295; Eukaryota.
DR GeneTree; ENSGT00940000160109; -.
DR HOGENOM; CLU_067584_0_0_1; -.
DR InParanoid; P02760; -.
DR OrthoDB; 1090505at2759; -.
DR PhylomeDB; P02760; -.
DR TreeFam; TF351222; -.
DR PathwayCommons; P02760; -.
DR Reactome; R-HSA-2168880; Scavenging of heme from plasma.
DR SignaLink; P02760; -.
DR BioGRID-ORCS; 259; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; AMBP; human.
DR EvolutionaryTrace; P02760; -.
DR GeneWiki; Alpha-1-microglobulin/bikunin_precursor; -.
DR GenomeRNAi; 259; -.
DR Pharos; P02760; Tbio.
DR PRO; PR:P02760; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P02760; protein.
DR Bgee; ENSG00000106927; Expressed in right lobe of liver and 105 other tissues.
DR ExpressionAtlas; P02760; baseline and differential.
DR Genevisible; P02760; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0019855; F:calcium channel inhibitor activity; NAS:UniProtKB.
DR GO; GO:0046904; F:calcium oxalate binding; NAS:UniProtKB.
DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB.
DR GO; GO:0098633; F:collagen fibril binding; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0019862; F:IgA binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016653; F:oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB.
DR GO; GO:0098869; P:cellular oxidant detoxification; IDA:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:UniProtKB.
DR GO; GO:1903606; P:cytochrome c metabolic process; IDA:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; NAS:UniProtKB.
DR GO; GO:0042167; P:heme catabolic process; NAS:UniProtKB.
DR GO; GO:0020027; P:hemoglobin metabolic process; IDA:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; NAS:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; TAS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR CDD; cd00109; KU; 2.
DR Gene3D; 2.40.128.20; -; 1.
DR Gene3D; 4.10.410.10; -; 2.
DR InterPro; IPR002968; A1-microglobln.
DR InterPro; IPR029856; AMBP.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR022272; Lipocalin_CS.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR PANTHER; PTHR46676; PTHR46676; 1.
DR Pfam; PF00014; Kunitz_BPTI; 2.
DR Pfam; PF00061; Lipocalin; 1.
DR PRINTS; PR01215; A1MCGLOBULIN.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00131; KU; 2.
DR SUPFAM; SSF50814; SSF50814; 1.
DR SUPFAM; SSF57362; SSF57362; 2.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 2.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 2.
DR PROSITE; PS00213; LIPOCALIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Chromophore;
KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Glycoprotein;
KW Host-virus interaction; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Oxidoreductase; Protease inhibitor;
KW Proteoglycan; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:6164372,
FT ECO:0000269|PubMed:6198962, ECO:0000269|Ref.12"
FT CHAIN 20..203
FT /note="Alpha-1-microglobulin"
FT /id="PRO_0000017886"
FT CHAIN 206..352
FT /note="Inter-alpha-trypsin inhibitor light chain"
FT /id="PRO_0000017887"
FT CHAIN 284..344
FT /note="Trypstatin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000318926"
FT DOMAIN 231..281
FT /note="BPTI/Kunitz inhibitor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 287..337
FT /note="BPTI/Kunitz inhibitor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT REGION 206..226
FT /note="Glycopeptide (secretory piece)"
FT BINDING 53
FT /ligand="3-hydroxy-L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:58125"
FT /ligand_note="multimeric 3-hydroxykynurenine chromophore"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:1714898"
FT BINDING 111
FT /ligand="3-hydroxy-L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:58125"
FT /ligand_note="multimeric 3-hydroxykynurenine chromophore"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:10631976"
FT BINDING 137
FT /ligand="3-hydroxy-L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:58125"
FT /ligand_note="multimeric 3-hydroxykynurenine chromophore"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:10631976"
FT BINDING 149
FT /ligand="3-hydroxy-L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:58125"
FT /ligand_note="multimeric 3-hydroxykynurenine chromophore"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:10631976"
FT SITE 199
FT /note="Cleavage; in the presence of oxyhemoglobin or MPO"
FT /evidence="ECO:0000269|PubMed:11877257"
FT SITE 241..242
FT /note="Inhibitory (P1) (chymotrypsin, elastase)"
FT /evidence="ECO:0000250"
FT SITE 297..298
FT /note="Inhibitory (P1) (trypsin)"
FT /evidence="ECO:0000250"
FT CARBOHYD 24
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:1694784"
FT /id="CAR_000172"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:1694784"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:1694784,
FT ECO:0000269|PubMed:22171320"
FT CARBOHYD 215
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000269|PubMed:1898736,
FT ECO:0000269|PubMed:6171497, ECO:0000269|PubMed:7682553"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:22171320,
FT ECO:0000269|PubMed:6171497"
FT DISULFID 91..188
FT /evidence="ECO:0000269|PubMed:22512701"
FT DISULFID 231..281
FT /evidence="ECO:0000269|PubMed:9566199"
FT DISULFID 240..264
FT /evidence="ECO:0000269|PubMed:9566199"
FT DISULFID 256..277
FT /evidence="ECO:0000269|PubMed:9566199"
FT DISULFID 287..337
FT /evidence="ECO:0000269|PubMed:9566199"
FT DISULFID 296..320
FT /evidence="ECO:0000269|PubMed:9566199"
FT DISULFID 312..333
FT /evidence="ECO:0000269|PubMed:9566199"
FT MUTAGEN 53
FT /note="C->S: Impairs the reductase activity toward
FT cytochrome c independently of the electron donnor.
FT Decreases the reductase activity toward methemoglobin.
FT Decreases the reductase activity toward oxidized collagen."
FT /evidence="ECO:0000269|PubMed:15683711,
FT ECO:0000269|PubMed:23642167"
FT MUTAGEN 111
FT /note="K->T: Impairs the reductase activity toward
FT cytochrome c in the presence of NADPH; when associated with
FT T-137 and T-149. Impairs the reductase activity toward
FT oxidized collagen; when associated with T-137 and T-149."
FT /evidence="ECO:0000269|PubMed:15683711,
FT ECO:0000269|PubMed:23642167"
FT MUTAGEN 137
FT /note="K->T: Impairs the reductase activity toward
FT cytochrome c in the presence of NADPH; when associated with
FT T-111 and T-149. Impairs the reductase activity toward
FT oxidized collagen; when associated with T-111 and T-149."
FT /evidence="ECO:0000269|PubMed:15683711,
FT ECO:0000269|PubMed:23642167"
FT MUTAGEN 149
FT /note="K->T: Impairs the reductase activity toward
FT cytochrome c in the presence of NADPH; when associated with
FT T-111 and T-137. Impairs the reductase activity toward
FT oxidized collagen; when associated with T-111 and T-137."
FT /evidence="ECO:0000269|PubMed:15683711,
FT ECO:0000269|PubMed:23642167"
FT CONFLICT 48..57
FT /note="Missing (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="Missing (in Ref. 10; AA sequence and 12; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="Missing (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="H -> T (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="Missing (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="E -> Q (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="S -> T (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="G -> T (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 291..292
FT /note="IV -> VI (in Ref. 14; AA sequence and 15; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="Missing (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="G -> E (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 42..51
FT /evidence="ECO:0007829|PDB:4ES7"
FT HELIX 54..59
FT /evidence="ECO:0007829|PDB:4ES7"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 78..87
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 90..100
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:4ES7"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 116..125
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 127..142
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 145..155
FT /evidence="ECO:0007829|PDB:4ES7"
FT HELIX 159..170
FT /evidence="ECO:0007829|PDB:4ES7"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:4ES7"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:4ES7"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:6EJC"
FT STRAND 244..250
FT /evidence="ECO:0007829|PDB:1BIK"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:1BIK"
FT HELIX 274..281
FT /evidence="ECO:0007829|PDB:1BIK"
FT HELIX 284..288
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 300..306
FT /evidence="ECO:0007829|PDB:1BIK"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:1BIK"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:1BIK"
FT HELIX 330..337
FT /evidence="ECO:0007829|PDB:1BIK"
SQ SEQUENCE 352 AA; 38999 MW; BC001780094CBD06 CRC64;
MRSLGALLLL LSACLAVSAG PVPTPPDNIQ VQENFNISRI YGKWYNLAIG STCPWLKKIM
DRMTVSTLVL GEGATEAEIS MTSTRWRKGV CEETSGAYEK TDTDGKFLYH KSKWNITMES
YVVHTNYDEY AIFLTKKFSR HHGPTITAKL YGRAPQLRET LLQDFRVVAQ GVGIPEDSIF
TMADRGECVP GEQEPEPILI PRVRRAVLPQ EEEGSGGGQL VTEVTKKEDS CQLGYSAGPC
MGMTSRYFYN GTSMACETFQ YGGCMGNGNN FVTEKECLQT CRTVAACNLP IVRGPCRAFI
QLWAFDAVKG KCVLFPYGGC QGNGNKFYSE KECREYCGVP GDGDEELLRF SN
