Alpha-1-B glycoprotein

A1BG is located on the negative DNA strand of chromosome 19 from 58,858,172 – 58,864,865.[7] Additionally, A1BG is located directly adjacent to the ZSCAN22 gene (58,838,385-58,853,712) on the positive DNA strand, as well as the ZNF837 (58,878,990 - 58,892,389, complement) and ZNF497 (58865723 - 58,874,214, complement) genes on the negative strand.[7]

A1BG is expressed at high levels in the adult and fetal liver.[8] Additionally, the mammary gland shows roughly half as much expression as the liver.[8] Trace amounts of A1BG expression can be found in the blood, brain, lung, lymph node, ovary, testis, pancreas, and pancreas.[8] Liver tumors exhibit elevated levels of A1BG transcripts.[8]

The gene contains 20 distinct introns.[9] Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms.[9] There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites.[9] The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 4 cassette exons, overlapping exons with different boundaries, splicing versus retention of 3 introns.[9]

The San Diego Super Computer's Statistical Analysis of Protein (SAPS) program determined that alpha-1B glycoprotein has 495 amino acids residues, an isoelectric point of 5.47, and a molecular mass of 54.3 kDa. Additionally, it suggested that no transmembrane domains exist in alpha-1B glycoprotein.[10] According to NCBI, the amino acid sequence MLVVFLLLWGVTWGPVTEA is a signal peptide on the N-terminus of the protein that might function as an endoplasmic reticulum import signal.[10]

The NetAcet 1.0 program calculated that the first five amino acid residues serve as an N-acetylation site.[11] The NetGlycate 1.0 program predicted that the lysines located at residue 78, 114, and 227 serve as glycation points.[12] The NetNES 1.1 program predicted the leucine at residue 47 to be a nuclear export signal.[13] The NetNGlyc 1.0 program predicted four N-glycosylation sites - two of which are highly conserved internally repeated sequences.[14][15] The NetCGlyc1.0 program predicted that none of the tryptophan residues serve as C-mannosylation sites.[16]

A study by Udby et al. showed that Cysteine-rich secretory protein 3 is a ligand of alpha-1B glycoprotein in human plasma and they suggest that the A1BG-CRISP-3 complex displays a similar function in protecting the circulation from a potentially harmful effect of free CRISP-3.[17]

Female mice with cardiac conditional knockout of A1BG exhibit poor cardiac function, but male mice with the same knockout are unaffected.[18]

In addition to the table below, alpha-1B glycoprotein is also conserved in the white-cheeked crested gibbon, baboon, bolivian squirrel monkey, sheep, dog, wild boar, Chinese tree shrew, Chinese hamster, black flying fox, rabbit, guinea pig, giant panda, cow, rat, and the naked mole-rat.[19] Additionally, it is very likely that A1BG is further conserved throughout the mammalian clade.

No paralogs have been found for alpha-1B glycoprotein.[32]

An initial NCBI Blast alignment of alpha-1B glycoprotein illustrates that the protein is mainly composed of three immunoglobulin domains.[33] There is a large segment of amino acids from position 297 to 400 that is not shown to be an immunoglobulin domain. However, a NCBI BLAST alignment of just the amino acids from 297 to 400 does illustrate that the latter sequence is indeed a fourth immunoglobulin domain.[34] Ultimately, alpha-1B glycoprotein seems to be primarily composed of four immunoglobulin domains.

The alpha-1-glycoprotein is upregulated 11-fold in the urine of patients who have steroid resistant nephrotic syndrome.[35] A1BG was present in 7/19 patients with SRNS and was absent from all patients with steroid sensitive nephrotic syndrome.[35] The 13.8 kDa A1BG fragment had a high discriminatory power for steroid resistance in pediatric nephrotic syndrome, but is only present in a subset of patients.[35]