background:
This gene encodes a complex glycoprotein secreted inplasma. The precursor is proteolytically processed into distinctfunctioning proteins: alpha-1-microglobulin, which belongs to thesuperfamily of lipocalin transport proteins and may play a role inthe regulation of inflammatory processes, and bikunin, which is aurinary trypsin inhibitor belonging to the superfamily ofKunitz-type protease inhibitors and plays an important role in manyphysiological and pathological processes. This gene is located onchromosome 9 in a cluster of lipocalin genes.
Function:
Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin,and lysosomal granulocytic elastase. Inhibits calcium oxalatecrystallization.
Trypstatin is a trypsin inhibitor
Subunit:
I-alpha-I plasma protease inhibitors are assembled fromone or two heavy chains (H1, H2 or H3) and one light chain,bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 andbikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin.Alpha-1-microglobulin occurs as a monomer and also in complexeswith IgA and albumin. Alpha-1-microglobulin interacts with FN1.Trypstatin is a monomer and also occurs as a complex with tryptasein mast cells (By similarity). Alpha-1-microglobulin and bikunininteract (via SH3 domain) with HEV ORF3 protein.
Subcellular Location:
Secreted.
Tissue Specificity:
Expressed by the liver and secreted in plasma.Alpha-1-microglobulin occurs in many physiological fluids includingplasma, urine, and cerebrospinal fluid. Inter-alpha-trypsininhibitor is present in plasma and urine.
Post-translational modifications:
The precursor is proteolytically processed into separatelyfunctioning proteins.
3-hydroxykynurenine, an oxidized tryptophan metabolite thatis common in biological fluids, reacts with Cys-53, Lys-111,Lys-137, and Lys-149 to form heterogeneous polycyclic chromophoresincluding hydroxanthommatin. The reaction by alpha-1-microglobulinis autocatalytic; the human protein forms chromophore even whenexpressed in insect and bacterial cells. The chromophore can reactwith accessible cysteines forming non-reducible thioethercross-links with other molecules of alpha-1-microglobulin or withother proteins such as Ig alpha-1 chain C region 'Cys-352'.
Heavy chains are interlinked with bikunin via a chondroitin4-sulfate bridge to the their SLCterminal aspartate (By similarity).
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 theglycosaminoglycan, chondroitin sulfate, at Ser-215 allowscross-linking between the three polypeptide chains.
Similarity:
In the N-terminal section; belongs to the calycinsuperfamily. Lipocalin family.
Contains 2 BPTI/Kunitz inhibitor domains.
Database links:
UniProtKB/Swiss-Prot: P02760.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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