AMBP_BOVIN
ID AMBP_BOVIN Reviewed; 352 AA.
AC P00978; P35420; Q28020; Q3SZZ4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein AMBP;
DE Contains:
DE RecName: Full=Alpha-1-microglobulin;
DE EC=1.6.2.- {ECO:0000250|UniProtKB:P02760};
DE Contains:
DE RecName: Full=Inter-alpha-trypsin inhibitor light chain;
DE Short=ITI-LC;
DE AltName: Full=BI-14;
DE AltName: Full=Bikunin;
DE AltName: Full=Cumulus extracellular matrix-stabilizing factor;
DE Short=ESF;
DE AltName: Full=HI-30;
DE Contains:
DE RecName: Full=Trypstatin;
DE Flags: Precursor;
GN Name=AMBP; Synonyms=ITIL;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8611630; DOI=10.1016/0167-4781(95)00235-9;
RA Lindqvist A., Aakerstroem B.;
RT "Bovine alpha 1-microglobulin/bikunin. Isolation and characterization of
RT liver cDNA and urinary alpha 1-microglobulin.";
RL Biochim. Biophys. Acta 1306:98-106(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 206-219.
RC TISSUE=Fetal serum;
RX PubMed=1376324; DOI=10.1016/s0021-9258(19)49851-7;
RA Chen L., Mao S.J.T., Larsen W.J.;
RT "Identification of a factor in fetal bovine serum that stabilizes the
RT cumulus extracellular matrix. A role for a member of the inter-alpha-
RT trypsin inhibitor family.";
RL J. Biol. Chem. 267:12380-12386(1992).
RN [4]
RP PROTEIN SEQUENCE OF 227-349.
RX PubMed=2408637; DOI=10.1515/bchm3.1985.366.1.473;
RA Hochstrasser K., Wachter E., Albrecht G.J., Reisinger P.;
RT "Kunitz-type proteinase inhibitors derived by limited proteolysis of the
RT inter-alpha-trypsin inhibitor, X. The amino-acid sequences of the trypsin-
RT released inhibitors from horse and pig inter-alpha-trypsin inhibitors.";
RL Biol. Chem. Hoppe-Seyler 366:473-478(1985).
RN [5]
RP PROTEIN SEQUENCE OF 227-348, AND GLYCOSYLATION AT ASN-250.
RX PubMed=6199275; DOI=10.1515/bchm2.1983.364.2.1679;
RA Hochstrasser K., Wachter E.;
RT "Kunitz-type proteinase inhibitors derived by limited proteolysis of the
RT inter-alpha-trypsin inhibitor, VII. Determination of the amino-acid
RT sequence of the trypsin-released inhibitor from bovine inter-alpha-trypsin
RT inhibitor.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1679-1687(1983).
RN [6]
RP REACTIVE SITES.
RX PubMed=6199276; DOI=10.1515/bchm2.1983.364.2.1689;
RA Hochstrasser K., Albrecht G.J., Schoenberger O.L., Wachter E.;
RT "Kunitz-type proteinase inhibitors derived by limited proteolysis of the
RT inter-alpha-trypsin inhibitor, VII. Characterization of the bovine
RT inhibitor as double-headed trypsin-elastase inhibitor.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1689-1696(1983).
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. Intravascularly, plays a regulatory role in
CC red cell homeostasis by preventing heme- and reactive oxygen species-
CC induced cell damage. Binds and degrades free heme to protect fetal and
CC adult red blood cells from hemolysis. Reduces extracellular
CC methemoglobin, a Fe3+ (ferric) form of hemoglobin that cannot bind
CC oxygen, back to the Fe2+ (ferrous) form deoxyhemoglobin, which has
CC oxygen-carrying potential. Upon acute inflammation, inhibits oxidation
CC of low-density lipoprotein particles by MPO and limits vascular damage.
CC Extravascularly, protects from oxidation products formed on
CC extracellular matrix structures and cell membranes. Catalyzes the
CC reduction of carbonyl groups on oxidized collagen fibers and preserves
CC cellular and extracellular matrix ultrastructures. Importantly,
CC counteracts the oxidative damage at blood-placenta interface,
CC preventing leakage of free fetal hemoglobin into the maternal
CC circulation. Intracellularly, has a role in maintaining mitochondrial
CC redox 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. Reduces cytochrome c from Fe3+
CC (ferric) to the Fe2+ (ferrous) state through formation of superoxide
CC anion radicals in the presence of ascorbate or NADH/NADPH electron
CC donor cofactors, ascorbate being the preferred cofactor (By
CC similarity). Has a chaperone role in facilitating the correct folding
CC of bikunin in the endoplasmic reticulum compartment (By similarity).
CC {ECO:0000250|UniProtKB:P02760, ECO:0000250|UniProtKB:Q07456}.
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 Among others, has antiprotease activity toward kallikrein, a protease
CC involved in airway inflammation; inhibits GZMK/granzyme, a granule-
CC stored serine protease involved in NK and T cell cytotoxic responses;
CC and inhibits PLG/plasmin, a protease required for activation of matrix
CC metalloproteinases. As part of I-alpha-I complex, provides for the
CC heavy chains to be transferred from I-alpha-I complex to hyaluronan in
CC the presence of TNFAIP6, in a dynamic process that releases free
CC bikunin and remodels extracellular matrix proteoglycan structures. Free
CC bikunin, but not its heavy chain-bound form, acts as potent protease
CC inhibitor in airway secretions (By similarity). Part of hyaluronan-rich
CC extracellular matrix that surrounds oocyte during cumulus oophorus
CC expansion, an indispensable process for proper ovulation (By
CC similarity). Also inhibits calcium oxalate crystallization (By
CC similarity). {ECO:0000250|UniProtKB:P02760,
CC ECO:0000250|UniProtKB:Q07456}.
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 -!- SUBUNIT: [Alpha-1-microglobulin]: Monomer. Homodimer. In plasma, it
CC occurs as a monomer or dimer and in covalently-linked complexes with
CC immunoglobulin A (IgA), ALB/albumin and F2/prothrombin. Chromophore-
CC bound alpha-1-microglobulin interacts with the constant region of
CC immunoglobulin A. Chromophore-bound alpha-1-microglobulin interacts
CC with ALB with molar ratio 2:1 and 1:1; this interaction does not
CC prevent fatty acid binding to ALB. Interacts with F2/prothrombin (via
CC N-terminus) with molar ratio 2:1 and 1:1; this interaction does not
CC prevent the activation of prothrombin to thrombin. Interacts with
CC NDUFAB1, a subunit of mitochondrial complex I (By similarity).
CC Interacts with FN1 (By similarity). {ECO:0000250|UniProtKB:P02760,
CC ECO:0000250|UniProtKB:Q64240}.
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. Interacts with TNFAIP6 (via Link domain).
CC {ECO:0000250|UniProtKB:P02760}.
CC -!- SUBUNIT: [Trypstatin]: Monomer. Also occurs as a complex with tryptase
CC in mast cells. {ECO:0000250|UniProtKB:Q64240}.
CC -!- SUBCELLULAR LOCATION: [Alpha-1-microglobulin]: Secreted
CC {ECO:0000250|UniProtKB:P02760}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P02760}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P02760}. Cell membrane
CC {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P02760}. Nucleus membrane
CC {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P02760}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P02760}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000250|UniProtKB:P02760}. 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:0000250|UniProtKB:P02760}.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- DOMAIN: [Inter-alpha-trypsin inhibitor light chain]: The Kunitz domains
CC 1 and 2 serve as protease inhibitor domains.
CC {ECO:0000250|UniProtKB:P02760}.
CC -!- PTM: The precursor is proteolytically processed into separately
CC functioning proteins. {ECO:0000250|UniProtKB:P02760}.
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:0000250|UniProtKB:P02760}.
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:0000250|UniProtKB:P02760}.
CC -!- PTM: [Inter-alpha-trypsin inhibitor light chain]: Proteolytically
CC cleaved by PRSS3 at Kunitz domain 2. {ECO:0000250|UniProtKB:P02760}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the calycin
CC superfamily. Lipocalin family. {ECO:0000305}.
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DR EMBL; U35642; AAB07599.1; -; mRNA.
DR EMBL; BC102637; AAI02638.1; -; mRNA.
DR PIR; S68149; TIBOBI.
DR RefSeq; NP_776414.1; NM_173989.3.
DR AlphaFoldDB; P00978; -.
DR SMR; P00978; -.
DR STRING; 9913.ENSBTAP00000020817; -.
DR MEROPS; I02.006; -.
DR iPTMnet; P00978; -.
DR PaxDb; P00978; -.
DR PeptideAtlas; P00978; -.
DR PRIDE; P00978; -.
DR GeneID; 280996; -.
DR KEGG; bta:280996; -.
DR CTD; 259; -.
DR eggNOG; KOG4295; Eukaryota.
DR InParanoid; P00978; -.
DR OrthoDB; 1090505at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; ISS:UniProtKB.
DR GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB.
DR GO; GO:0098633; F:collagen fibril binding; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0019862; F:IgA binding; ISS: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; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0098869; P:cellular oxidant detoxification; ISS:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:1903606; P:cytochrome c metabolic process; ISS:UniProtKB.
DR GO; GO:0020027; P:hemoglobin metabolic process; ISS:UniProtKB.
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 Cell membrane; Chromophore; Cleavage on pair of basic residues; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Extracellular matrix; Glycoprotein; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Oxidoreductase; Protease inhibitor;
KW Reference proteome; Repeat; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..203
FT /note="Alpha-1-microglobulin"
FT /id="PRO_0000017884"
FT CHAIN 206..352
FT /note="Inter-alpha-trypsin inhibitor light chain"
FT /id="PRO_0000017885"
FT CHAIN 284..344
FT /note="Trypstatin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000318925"
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 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:0000250|UniProtKB:P02760"
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:0000250|UniProtKB:P02760"
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:0000250|UniProtKB:P02760"
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:0000250|UniProtKB:P02760"
FT SITE 241..242
FT /note="Inhibitory (P1) (chymotrypsin, elastase)"
FT SITE 297..298
FT /note="Inhibitory (P1) (trypsin)"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6199275"
FT DISULFID 91..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 231..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 240..264
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 256..277
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 287..337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 296..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 312..333
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT CONFLICT 71
FT /note="I -> K (in Ref. 2; AAI02638)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="A -> T (in Ref. 2; AAI02638)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="L -> V (in Ref. 2; AAI02638)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="T -> G (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="A -> D (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="G -> L (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="E -> Q (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 298..299
FT /note="SY -> AF (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="F -> I (in Ref. 2; AAI02638)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="E -> Q (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="E -> R (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 352 AA; 39235 MW; ED31C5CA02E70B19 CRC64;
MRSLSGLLLL LTACLAVNAS SVPTLPDDIQ VQENFDLSRI YGKWFNVAVG STCPWLKRFK
EKMTMSTVVL IAGPTSKEIS VTNTHRRKGV CESISGTYEK TSADGKFLYH KAKWNITMES
YVVHTNYDEY AIFLTKKLSR RHGPTITVKL YGREPQLRES LLEEFREVAL GVGIPEDAIF
TMPDRGECVP GEQDPVPTPL SRARRAVLTQ EEEGSGAGQP VTNFSKKADS CQLDYSQGPC
LGLFKRYFYN GTSMACETFL YGGCMGNGNN FLSEKECLQT CRTVEACNLP IVQGPCRSYI
QLWAFDAVKG KCVRFSYGGC KGNGNKFYSE KECKEYCGIP GEADEELLRF SN
