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MGP000135

UniProt Annotations

Entry Information

Gene Name	alpha-1-microglobulin/bikunin precursor
Protein Entry	AMBP_HUMAN
UniProt ID	P02760
Species	Human

Comments

Comment type	Description
Function	Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin, and lysosomal granulocytic elastase. Inhibits calcium oxalate crystallization. {ECO:0000269\|PubMed:7676539}.
Function	Trypstatin is a trypsin inhibitor. {ECO:0000250}.
Interaction	P07858:CTSB; NbExp=4; IntAct=EBI-2115136, EBI-715062;
Miscellaneous	In vitro, the first twelve residues of the amino end of the inhibitor appear to have a reactive site capable of inhibiting the activity of a number of enzymes. Its in vivo function is not known.
Ptm	3-hydroxykynurenine, an oxidized tryptophan metabolite that is common in biological fluids, reacts with Cys-53, Lys-111, Lys- 137, and Lys-149 to form heterogeneous polycyclic chromophores including hydroxanthommatin. The reaction by alpha-1-microglobulin is autocatalytic; the human protein forms chromophore even when expressed in insect and bacterial cells. The chromophore can react with accessible cysteines forming non-reducible thioether cross- links with other molecules of alpha-1-microglobulin or with other proteins such as Ig alpha-1 chain C region 'Cys-352'.
Ptm	Heavy chains are interlinked with bikunin via a chondroitin 4-sulfate bridge to the their C-terminal aspartate. {ECO:0000250}.
Ptm	N- and O-glycosylated. N-glycan heterogeneity at Asn-115: Hex5HexNAc4 (major), Hex6HexNAc5 (minor) and dHex1Hex6HexNAc5 (minor). N-glycan at Asn-250: Hex5HexNAc4. O-linkage of the glycosaminoglycan, chondroitin sulfate, at Ser-215 allows cross- linking between the three polypeptide chains. {ECO:0000269\|PubMed:1694784, ECO:0000269\|PubMed:1898736, ECO:0000269\|PubMed:22171320, ECO:0000269\|PubMed:6171497, ECO:0000269\|PubMed:7682553}.
Ptm	The precursor is proteolytically processed into separately functioning proteins.
Similarity	Contains 2 BPTI/Kunitz inhibitor domains. {ECO:0000255\|PROSITE-ProRule:PRU00031}.
Similarity	In the N-terminal section; belongs to the calycin superfamily. Lipocalin family. {ECO:0000305}.
Subcellular Location	Secreted.
Subunit	I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (H1, H2 or H3) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2 and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin. Alpha-1-microglobulin occurs as a monomer and also in complexes with IgA and albumin. Alpha-1-microglobulin interacts with FN1. Trypstatin is a monomer and also occurs as a complex with tryptase in mast cells (By similarity). Alpha-1-microglobulin and bikunin interact (via SH3 domain) with HEV ORF3 protein. {ECO:0000250, ECO:0000269\|PubMed:15037615, ECO:0000269\|PubMed:16140784}.
Tissue Specificity	Expressed by the liver and secreted in plasma. Alpha-1-microglobulin occurs in many physiological fluids including plasma, urine, and cerebrospinal fluid. Inter-alpha- trypsin inhibitor is present in plasma and urine.