ID  P02760;
PN  Trypstatin;
GN  AMBP;
OS  9606;
SL  Nucleus Position: SL-0178;
SL  Nucleus Position: SL-0182;
SL  Comments: [Alpha-1-microglobulin]: Secreted {ECO:0000269|PubMed:11877257, ECO:0000269|PubMed:32092412}. Endoplasmic reticulum {ECO:0000269|PubMed:22096585}. Cytoplasm, cytosol {ECO:0000269|PubMed:32092412}. Cell membrane {ECO:0000269|PubMed:22096585, ECO:0000269|PubMed:32092412}; Peripheral membrane protein {ECO:0000305|PubMed:22096585, ECO:0000305|PubMed:32092412}. Nucleus membrane {ECO:0000269|PubMed:22096585}; Peripheral membrane protein {ECO:0000305|PubMed:22096585}. Mitochondrion inner membrane {ECO:0000305|PubMed:23157686}; Peripheral membrane protein {ECO:0000305|PubMed:23157686}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:22096585}. 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:0000269|PubMed:22096585}.
DR  UNIPROT: P02760;
DR  UNIPROT: P00977;
DR  UNIPROT: P02759;
DR  UNIPROT: P78491;
DR  UNIPROT: Q2TU33;
DR  UNIPROT: Q5TBD7;
DR  UNIPROT: Q9UC58;
DR  UNIPROT: Q9UDI8;
DR  PDB: 1BIK;
DR  PDB: 3QKG;
DR  PDB: 4ES7;
DR  PDB: 4U30;
DR  PDB: 6EJ7;
DR  PDB: 6EJ8;
DR  PDB: 6EJ9;
DR  PDB: 6EJA;
DR  PDB: 6EJB;
DR  PDB: 6EJC;
DR  PDB: 6EJD;
DR  Pfam: PF00014;
DR  Pfam: PF00061;
DR  PROSITE: PS00280;
DR  PROSITE: PS50279;
DR  PROSITE: PS00213;
DR  OMIM: 176870;
DR  DisGeNET: 259;
DE  Function: [Alpha-1-microglobulin]: 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 (PubMed:11877257, PubMed:15683711, PubMed:22096585, PubMed:23157686, PubMed:23642167, PubMed:25698971, PubMed:32823731, PubMed:32092412). 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 (PubMed:11877257, PubMed:32092412). 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 (PubMed:15683711). Upon acute inflammation, inhibits oxidation of low- density lipoprotein particles by MPO and limits vascular damage (PubMed:25698971). 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 (PubMed:23642167, PubMed:22096585). Importantly, counteracts the oxidative damage at blood-placenta interface, preventing leakage of free fetal hemoglobin into the maternal circulation (PubMed:21356557). 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 (PubMed:23157686, PubMed:32823731). 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 (PubMed:15683711). Has a chaperone role in facilitating the correct folding of bikunin in the endoplasmic reticulum compartment (By similarity). {ECO:0000250|UniProtKB:Q07456, ECO:0000269|PubMed:11877257, ECO:0000269|PubMed:15683711, ECO:0000269|PubMed:21356557, ECO:0000269|PubMed:22096585, ECO:0000269|PubMed:23157686, ECO:0000269|PubMed:23642167, ECO:0000269|PubMed:25698971, ECO:0000269|PubMed:32092412, ECO:0000269|PubMed:32823731}. [Inter-alpha-trypsin inhibitor light chain]: Kunitz-type serine protease inhibitor and structural component of extracellular matrix with a role in extracellular space remodeling and cell adhesion (PubMed:25301953, PubMed:20463016). Among others, has antiprotease activity toward kallikrein, a protease involved in airway inflammation; inhibits GZMK/granzyme, a granule-stored serine protease involved in NK and T cell cytotoxic responses; and inhibits PLG/plasmin, a protease required for activation of matrix metalloproteinases (PubMed:16873769, PubMed:10480954, PubMed:15917224). As part of I-alpha-I complex, provides for the heavy chains to be transferred from I-alpha-I complex to hyaluronan in the presence of TNFAIP6, in a dynamic process that releases free bikunin and remodels extracellular matrix proteoglycan structures. Free bikunin, but not its heavy chain-bound form, acts as potent protease inhibitor in airway secretions (PubMed:16873769). Part of hyaluronan-rich extracellular matrix that surrounds oocyte during cumulus oophorus expansion, an indispensable process for proper ovulation (By similarity). Also inhibits calcium oxalate crystallization (PubMed:7676539). {ECO:0000250|UniProtKB:Q07456, ECO:0000269|PubMed:10480954, ECO:0000269|PubMed:15917224, ECO:0000269|PubMed:16873769, ECO:0000269|PubMed:20463016, ECO:0000269|PubMed:25301953, ECO:0000269|PubMed:7676539}. [Trypstatin]: Kunitz-type serine protease inhibitor. Has high catalytic efficiency for F10/blood coagulation factor Xa and may act as an anticoagulant by inhibiting prothrombin activation. Inhibits trypsin and mast cell CMA1/chymase and tryptase proteases. {ECO:0000250|UniProtKB:Q64240}.
DE  Reference Proteome: Yes;
DE  Interaction: P69616; IntAct: EBI-7810311; Score: 0.53
DE  Interaction: P07858; IntAct: EBI-7970369; Score: 0.60
DE  Interaction: Q92569; IntAct: EBI-2115171; Score: 0.00
DE  Interaction: P62993; IntAct: EBI-2115716; Score: 0.00
DE  Interaction: P42336; IntAct: EBI-2116612; Score: 0.00
DE  Interaction: P10176; IntAct: EBI-3904736; Score: 0.37
DE  Interaction: Q9Y4D1; IntAct: EBI-3908964; Score: 0.37
DE  Interaction: P40763; IntAct: EBI-3926609; Score: 0.37
DE  Interaction: Q99XU0; IntAct: EBI-8852714; Score: 0.35
DE  Interaction: Q13643; IntAct: EBI-10193895; Score: 0.56
DE  Interaction: P14335; IntAct: EBI-11422579; Score: 0.37
DE  Interaction: Q99IB8; IntAct: EBI-11599534; Score: 0.35
DE  Interaction: P05067; IntAct: EBI-16716791; Score: 0.40
GO  GO:0072562;
GO  GO:0009986;
GO  GO:0062023;
GO  GO:0005829;
GO  GO:0005783;
GO  GO:0070062;
GO  GO:0005576;
GO  GO:0005615;
GO  GO:0031314;
GO  GO:0005743;
GO  GO:0031965;
GO  GO:0005886;
GO  GO:0016209;
GO  GO:0019855;
GO  GO:0046904;
GO  GO:0030246;
GO  GO:0035374;
GO  GO:0098633;
GO  GO:0020037;
GO  GO:0019862;
GO  GO:0016491;
GO  GO:0016653;
GO  GO:0042803;
GO  GO:0004867;
GO  GO:0007155;
GO  GO:0098869;
GO  GO:0034614;
GO  GO:1903606;
GO  GO:0007565;
GO  GO:0042167;
GO  GO:0020027;
GO  GO:0050777;
GO  GO:0046329;
GO  GO:0030163;
TP  Membrane Topology: Peripheral; Source: UniProt - Curator Inference {ECO:0000305|PubMed:23157686};
SQ  MRSLGALLLLLSACLAVSAGPVPTPPDNIQVQENFNISRIYGKWYNLAIGSTCPWLKKIMDRMTVSTLVLGEGATEAEIS
SQ  MTSTRWRKGVCEETSGAYEKTDTDGKFLYHKSKWNITMESYVVHTNYDEYAIFLTKKFSRHHGPTITAKLYGRAPQLRET
SQ  LLQDFRVVAQGVGIPEDSIFTMADRGECVPGEQEPEPILIPRVRRAVLPQEEEGSGGGQLVTEVTKKEDSCQLGYSAGPC
SQ  MGMTSRYFYNGTSMACETFQYGGCMGNGNNFVTEKECLQTCRTVAACNLPIVRGPCRAFIQLWAFDAVKGKCVLFPYGGC
SQ  QGNGNKFYSEKECREYCGVPGDGDEELLRFSN
//