Alpha-1-B glycoprotein

A1BG is located on the negative DNA strand of chromosome 19 from 58,858,172 – 58,864,865.{{cite web|title=A1BG alpha-1-B glycoprotein|url=https://www.ncbi.nlm.nih.gov/gene/1|access-date=May 10, 2013}} 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.

File:GEO Profile of A1BG tissue expression.jpg#filelinks

A1BG is expressed at high levels in the adult and fetal liver.{{cite web | url = https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.529161 | title = EST Profile - Hs.529161 | work = UniGene | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine | access-date = 2013-05-11 }} Additionally, the mammary gland shows roughly half as much expression as the liver. Trace amounts of A1BG expression can be found in the blood, brain, lung, lymph node, ovary, testis, pancreas, and pancreas. Liver tumors exhibit elevated levels of A1BG transcripts.

The gene contains 20 distinct introns.{{cite web|title=AceView: A1BG|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=a1bg&submit=Go|access-date=May 11, 2013}} Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms. There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites. 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.

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.{{cite journal |vauthors=Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S | title = Methods and algorithms for statistical analysis of protein sequences | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 6 | pages = 2002–6 |date=March 1992 | pmid = 1549558 | pmc = 48584 | doi = 10.1073/pnas.89.6.2002| bibcode = 1992PNAS...89.2002B | doi-access = free }} 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.

The NetAcet 1.0 program calculated that the first five amino acid residues serve as an N-acetylation site.{{cite journal |vauthors=Kiemer L, Bendtsen JD, Blom N | title = NetAcet: prediction of N-terminal acetylation sites | journal = Bioinformatics | volume = 21 | issue = 7 | pages = 1269–70 |date=April 2005 | pmid = 15539450 | doi = 10.1093/bioinformatics/bti130 | url = http://www.cbs.dtu.dk/services/NetAcet/ | doi-access = free }} The NetGlycate 1.0 program predicted that the lysines located at residue 78, 114, and 227 serve as glycation points.{{cite journal |vauthors=Johansen MB, Kiemer L, Brunak S | title = Analysis and prediction of mammalian protein glycation | journal = Glycobiology | volume = 16 | issue = 9 | pages = 844–53 |date=September 2006 | pmid = 16762979 | doi = 10.1093/glycob/cwl009 | url = http://www.cbs.dtu.dk/services/NetGlycate/ | citeseerx = 10.1.1.128.831 }} The NetNES 1.1 program predicted the leucine at residue 47 to be a nuclear export signal.{{cite journal |vauthors=la Cour T, Kiemer L, Mølgaard A, Gupta R, Skriver K, Brunak S | title = Analysis and prediction of leucine-rich nuclear export signals | journal = Protein Eng. Des. Sel. | volume = 17 | issue = 6 | pages = 527–36 |date=June 2004 | pmid = 15314210 | doi = 10.1093/protein/gzh062 | url = http://www.cbs.dtu.dk/services/NetNES/|access-date=May 10, 2013 | doi-access = free }} The NetNGlyc 1.0 program predicted four N-glycosylation sites - two of which are highly conserved internally repeated sequences.{{cite web|last=Gupta|first=R.|title=Prediction of N-glycosylation sites in human proteins|url=http://www.cbs.dtu.dk/services/NetNGlyc/|access-date=May 10, 2013}}{{cite journal |vauthors=Higgins DG, Bleasby AJ, Fuchs R | title = CLUSTAL V: improved software for multiple sequence alignment | journal = Comput. Appl. Biosci. | volume = 8 | issue = 2 | pages = 189–91 |date=April 1992 | pmid = 1591615 | doi = 10.1093/bioinformatics/8.2.189}} The NetCGlyc1.0 program predicted that none of the tryptophan residues serve as C-mannosylation sites.{{cite journal|last=Julenius|first=Karin|title=NetCGlyc1.0: Prediction of mammalian C-mannosylation sites|journal=Glycobiology|year=2007|volume=17|issue=8|pages=868–876|url=http://www.cbs.dtu.dk/services/NetCGlyc/|access-date=May 10, 2013|doi=10.1093/glycob/cwm050|pmid=17494086|doi-access=free}}

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.{{cite journal |vauthors=Udby L, Sørensen OE, Pass J, Johnsen AH, Behrendt N, Borregaard N, Kjeldsen L | title = Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma | journal = Biochemistry | volume = 43 | issue = 40 | pages = 12877–86 |date=October 2004 | pmid = 15461460 | doi = 10.1021/bi048823e }}

Female mice with cardiac conditional knockout of A1BG exhibit poor cardiac function, but male mice with the same knockout are unaffected.{{Cite journal|last1=Shi|first1=Wei|last2=Sheng|first2=Xinlei|last3=Dorr|first3=Kerry M.|last4=Hutton|first4=Josiah E.|last5=Emerson|first5=James I.|last6=Davies|first6=Haley A.|last7=Andrade|first7=Tia D.|last8=Wasson|first8=Lauren K.|last9=Greco|first9=Todd M.|last10=Hashimoto|first10=Yutaka|last11=Federspiel|first11=Joel D.|date=October 2021|title=Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation|journal=Developmental Cell|volume=56 |issue=21 |language=en|pages=3019–3034.e7|doi=10.1016/j.devcel.2021.09.022|pmid=34655525 |pmc=9290207 }}

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.{{cite web|title=NCBI Blast results for A1BG protein sequence|url=http://blast.ncbi.nlm.nih.gov/Blast.cgi#478530307|access-date=May 11, 2013}} Additionally, it is very likely that A1BG is further conserved throughout the mammalian clade.

No paralogs have been found for alpha-1B glycoprotein.{{cite web|title=A1BG Gene|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=A1BG&search=a1bg#publications|publisher=Weissman Institute of Science|access-date=May 10, 2013}}

An initial NCBI Blast alignment of alpha-1B glycoprotein illustrates that the protein is mainly composed of three immunoglobulin domains.{{cite web|title=NCBI conserved domain search|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?SEQUENCE=NP_570602.2&FULL|access-date=May 10, 2013}} 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.{{cite web|title=NCBI Blast: Protein Sequence|url=http://blast.ncbi.nlm.nih.gov/Blast.cgi|access-date=May 10, 2013}} 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.{{cite journal |vauthors=Piyaphanee N, Ma Q, Kremen O, Czech K, Greis K, Mitsnefes M, Devarajan P, Bennett MR | title = Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome | journal = Proteomics: Clinical Applications | volume = 5 | issue = 5–6 | pages = 334–42 |date=June 2011 | pmid = 21591266 | doi = 10.1002/prca.201000110 | pmc = 7039306 }} A1BG was present in 7/19 patients with SRNS and was absent from all patients with steroid sensitive nephrotic syndrome. 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.

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• {{UCSC gene info|A1BG}}