Protein: Protein AMBP [Cleaved into: Alpha-1-microglobulin (EC 1.6.2.-); Inter-alpha-trypsin inhibitor light chain (ITI-LC) (Bikunin) (HI-30); Trypstatin] (Q64240)
Organism: Rattus norvegicus (Rat)
Function: Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extravascular spaces and in intracellular compartments. Intravascularly, plays a regulatory role in red cell homeostasis by preventing heme- and reactive oxygen species-induced cell damage. Binds and degrades free heme to protect fetal and adult red blood cells from hemolysis. Reduces extracellular methemoglobin, a Fe3+ (ferric) form of hemoglobin that cannot bind oxygen, back to the Fe2+ (ferrous) form deoxyhemoglobin, which has oxygen-carrying potential. Upon acute inflammation, inhibits oxidation of low-density lipoprotein particles by MPO and limits vascular damage. Extravascularly, protects from oxidation products formed on extracellular matrix structures and cell membranes. Catalyzes the reduction of carbonyl groups on oxidized collagen fibers and preserves cellular and extracellular matrix ultrastructures. Importantly, counteracts the oxidative damage at blood-placenta interface, preventing leakage of free fetal hemoglobin into the maternal circulation. Intracellularly, has a role in maintaining mitochondrial redox homeostasis. Bound to complex I of the respiratory chain of mitochondria, may scavenge free radicals and preserve mitochondrial ATP synthesis. Protects renal tubule epithelial cells from heme-induced oxidative damage to mitochondria. Reduces cytochrome c from Fe3+ (ferric) to the Fe2+ (ferrous) state through formation of superoxide anion radicals in the presence of ascorbate or NADH/NADPH electron donor cofactors, ascorbate being the preferred cofactor (By similarity). Has a chaperone role in facilitating the correct folding of bikunin in the endoplasmic reticulum compartment (By similarity).
Subcellular location: [Alpha-1-microglobulin]: Secreted {ECO:0000250|UniProtKB:P02760}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P02760}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P02760}. Cell membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Nucleus membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P02760}. Note=The cellular uptake occurs via a non-endocytotic pathway and allows for localization to various membrane structures. A specific binding to plasma membrane suggests the presence of a cell receptor, yet to be identified. Directly binds collagen fibers type I. {ECO:0000250|UniProtKB:P02760}.; SUBCELLULAR LOCATION: [Inter-alpha-trypsin inhibitor light chain]: Secreted {ECO:0000250|UniProtKB:P02760}.
Sequence: MQGLGALFLLLTACLTLKADNVPTLPDIQVQENFNEARIYGKWFNLAVGSTCPWLRRIKNKMSVSTLVLQEGATEAEISVTSTQWRKGVCEEISGVYQKTDIDGKFLYHKSKWNATLESYVVHTNYDEYAIFLTKKFSHRHGPTITAKLYGREPQLRDSLLQEFREVALSVGIPENSIVFMADRGECVPGDREVESTSFARARRAVLPQENEGSGSEPLITGTLKKEDSCQLNYSEGPCLGMQQKYYYNGASMACETFQYGGCLGNGNNFASEKECLQTCRTIAACNLPIVQGPCRAFAELWAFDAAQGKCIQFIYGGCKGNGNKFYSEKECKEYCGVPGDGYEELTRS
InterPro domains: - IPR012674: Calycin (homologous_superfamily) [26-192]
- IPR000566: Lipocalin/cytosolic fatty-acid binding domain (domain) [41-184]
- IPR022272: Lipocalin family conserved site (conserved_site) [33-46]
- IPR002968: Alpha-1-microglobulin (family) [31-191]
- IPR020901: Proteinase inhibitor I2, Kunitz, conserved site (conserved_site) [258-332]
- IPR029856: Protein AMBP (family) [1-347]
- IPR036880: Pancreatic trypsin inhibitor Kunitz domain superfamily (homologous_superfamily) [221-339]
- IPR002223: Pancreatic trypsin inhibitor Kunitz domain (domain) [228-337]
Interaction partners: - Prothrombin
- Antithrombin-III
- Fibrinogen alpha chain
- Alpha-2-HS-glycoprotein
- Vitamin D-binding protein
- Hemopexin
- Albumin
- Beta-2-glycoprotein 1
- Fibrinogen beta chain
- Plasminogen
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016209 (antioxidant activity), GO:0044877 (protein-containing complex binding), GO:0016853 (isomerase activity), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0019865 (immunoglobulin binding), GO:0016860 (intramolecular oxidoreductase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0050896 (response to stimulus), GO:0006950 (response to stress), GO:0009611 (response to wounding)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031975 (envelope), GO:0016020 (membrane), GO:0019898 (extrinsic component of membrane), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0005739 (mitochondrion), GO:0031312 (extrinsic component of organelle membrane), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0005740 (mitochondrial envelope), GO:0019866 (organelle inner membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0031966 (mitochondrial membrane), GO:0005743 (mitochondrial inner membrane)