Biology:Alpha-1-B glycoprotein

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Alpha-1-B glycoprotein is a 54.3 kDa protein in humans that is encoded by the A1BG gene. [1] The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins. Patients who have pancreatic ductal adenocarcinoma show an overexpression of A1BG in pancreatic juice.[2]

Gene

Neighborhood

A1BG is located on the negative DNA strand of chromosome 19 from 58,858,172 – 58,864,865.[3] 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.[3]

Expression

GEO Profile of A1BG tissue expression.jpg

A1BG is expressed at high levels in the adult and fetal liver.[4] Additionally, the mammary gland shows roughly half as much expression as the liver.[4] Trace amounts of A1BG expression can be found in the blood, brain, lung, lymph node, ovary, testis, pancreas, and pancreas.[4] Liver tumors exhibit elevated levels of A1BG transcripts.[4]

mRNA

mRNA structure

The gene contains 20 distinct introns.[5] Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms.[5] There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites.[5] 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.[5]

Protein

Properties

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.[6] 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.[6]

Post-translational modifications

The NetAcet 1.0 program calculated that the first five amino acid residues serve as an N-acetylation site.[7] The NetGlycate 1.0 program predicted that the lysines located at residue 78, 114, and 227 serve as glycation points.[8] The NetNES 1.1 program predicted the leucine at residue 47 to be a nuclear export signal.[9] The NetNGlyc 1.0 program predicted four N-glycosylation sites - two of which are highly conserved internally repeated sequences.[10][11] The NetCGlyc1.0 program predicted that none of the tryptophan residues serve as C-mannosylation sites.[12]

Protein interactions

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.[13]

Sex-specific role in cardiac function

Female mice with cardiac conditional knockout of A1BG exhibit poor cardiac function, but male mice with the same knockout are unaffected.[14]

Homology

Orthologs

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.[15] Additionally, it is very likely that A1BG is further conserved throughout the mammalian clade.

Genus species Organism common name Divergence from humans (MYA) [16] NCBI protein accession number Sequence identity Protein length Common gene name
Homo sapiens[17] Human -- NP_570602 100% 495 A1BG
Pan troglodytes[18] Chimpanzee 6.2 XP_001146669 97.0% 501 PREDICTED: Alpha-1B-glycoprotein isoform 4
Pan paniscus[19] Bonobo 6.3 XP_003816677 97.0% 499 A1BG
Gorilla gorilla gorilla [20] Gorilla 8.8 XP_004061652 95.0% 275 PREDICTED: alpha-1B-glycoprotein
Pongo pygmaeus[21] Orangutan 15.7 XP_002829953 95.0% 495 alpha-1B-glycoprotein isoform 1
Macaca mulatta[22] Rhesus monkey 29.0 XM_001101821 88.0% 351 hypothetical protein EGK_11172, partial
Callithrix jacchus[23] Marmoset 42.6 XP_002762619 83.0% 500 A1BG
Mus musculus [24] Mouse 91.0 NP_001074536 44.0% 512 alpha-1B-glycoprotein precursor
Felis catus[25] Cat 94.2 XP_003997399 62.0% 481 PREDICTED: alpha-1B-glycoprotein
Equus caballus[26] Horse 97.4 XP_001495344 58.0% 568 PREDICTED: alpha-1B-glycoprotein-like
Loxodonta africana [27] African bush elephant 104.7 XP_003406722 61.0% 520 PREDICTED: alpha-1B-glycoprotein-like

Paralogs

No paralogs have been found for alpha-1B glycoprotein.[28]

Homologous domains

An initial NCBI Blast alignment of alpha-1B glycoprotein illustrates that the protein is mainly composed of three immunoglobulin domains.[29] 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.[30] Ultimately, alpha-1B glycoprotein seems to be primarily composed of four immunoglobulin domains.

Clinical significance

Steroid-resistant nephrotic syndrome

The alpha-1-glycoprotein is upregulated 11-fold in the urine of patients who have steroid resistant nephrotic syndrome.[31] A1BG was present in 7/19 patients with SRNS and was absent from all patients with steroid sensitive nephrotic syndrome.[31] 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.[31]

References

  1. ↑ "Entrez Gene: Alpha-1-B glycoprotein". https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=1. 
  2. ↑ "Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients". BMC Cancer 8: 241. 2008. doi:10.1186/1471-2407-8-241. PMID 18706098. 
  3. ↑ 3.0 3.1 "A1BG alpha-1-B glycoprotein". https://www.ncbi.nlm.nih.gov/gene/1. 
  4. ↑ 4.0 4.1 4.2 4.3 "EST Profile - Hs.529161". UniGene. National Center for Biotechnology Information, U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.529161. 
  5. ↑ 5.0 5.1 5.2 5.3 "AceView: A1BG". https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=a1bg&submit=Go. 
  6. ↑ 6.0 6.1 "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–6. March 1992. doi:10.1073/pnas.89.6.2002. PMID 1549558. Bibcode: 1992PNAS...89.2002B. 
  7. ↑ "NetAcet: prediction of N-terminal acetylation sites". Bioinformatics 21 (7): 1269–70. April 2005. doi:10.1093/bioinformatics/bti130. PMID 15539450. http://www.cbs.dtu.dk/services/NetAcet/. 
  8. ↑ "Analysis and prediction of mammalian protein glycation". Glycobiology 16 (9): 844–53. September 2006. doi:10.1093/glycob/cwl009. PMID 16762979. http://www.cbs.dtu.dk/services/NetGlycate/. 
  9. ↑ "Analysis and prediction of leucine-rich nuclear export signals". Protein Eng. Des. Sel. 17 (6): 527–36. June 2004. doi:10.1093/protein/gzh062. PMID 15314210. http://www.cbs.dtu.dk/services/NetNES/. Retrieved May 10, 2013. 
  10. ↑ Gupta, R.. "Prediction of N-glycosylation sites in human proteins". http://www.cbs.dtu.dk/services/NetNGlyc/. 
  11. ↑ "CLUSTAL V: improved software for multiple sequence alignment". Comput. Appl. Biosci. 8 (2): 189–91. April 1992. doi:10.1093/bioinformatics/8.2.189. PMID 1591615. 
  12. ↑ Julenius, Karin (2007). "NetCGlyc1.0: Prediction of mammalian C-mannosylation sites". Glycobiology 17 (8): 868–876. doi:10.1093/glycob/cwm050. PMID 17494086. http://www.cbs.dtu.dk/services/NetCGlyc/. Retrieved May 10, 2013. 
  13. ↑ "Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma". Biochemistry 43 (40): 12877–86. October 2004. doi:10.1021/bi048823e. PMID 15461460. 
  14. ↑ Shi, Wei; Sheng, Xinlei; Dorr, Kerry M.; Hutton, Josiah E.; Emerson, James I.; Davies, Haley A.; Andrade, Tia D.; Wasson, Lauren K. et al. (October 2021). "Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation" (in en). Developmental Cell 56 (21): 3019–3034.e7. doi:10.1016/j.devcel.2021.09.022. PMID 34655525. 
  15. ↑ "NCBI Blast results for A1BG protein sequence". http://blast.ncbi.nlm.nih.gov/Blast.cgi#478530307. 
  16. ↑ "Time Tree". http://www.timetree.org/. 
  17. ↑ "alpha-1-B glycoprotein [Homo sapiens"]. https://www.ncbi.nlm.nih.gov/protein/119592981?report=genbank&log$=prottop&blast_rank=2&RID=SVXAZ6UZ01R. 
  18. ↑ "PREDICTED: alpha-1B-glycoprotein isoform 4 [Pan troglodytes"]. NCBI. https://www.ncbi.nlm.nih.gov/protein/114679419?report=genbank&log$=prottop&blast_rank=6&RID=SVXAZ6UZ01R. 
  19. ↑ "PREDICTED: alpha-1B-glycoprotein [Pan paniscus"]. https://www.ncbi.nlm.nih.gov/protein/397491452?report=genbank&log$=prottop&blast_rank=7&RID=SVXAZ6UZ01R. 
  20. ↑ "PREDICTED: alpha-1B-glycoprotein". https://www.ncbi.nlm.nih.gov/protein/426390528?report=genbank&log$=prottop&blast_rank=39&RID=SVXAZ6UZ01R. 
  21. ↑ "Send to: PREDICTED: alpha-1B-glycoprotein isoform 1 [Pongo abelii"]. https://www.ncbi.nlm.nih.gov/protein/297706253?report=genbank&log$=prottop&blast_rank=8&RID=SVXAZ6UZ01R. 
  22. ↑ "hypothetical protein EGK_11172, partial [Macaca mulatta"]. https://www.ncbi.nlm.nih.gov/protein/355703999?report=genbank&log$=prottop&blast_rank=9&RID=SVXAZ6UZ01R. 
  23. ↑ "PREDICTED: alpha-1B-glycoprotein [Callithrix jacchus"]. https://www.ncbi.nlm.nih.gov/protein/390479473?report=genbank&log$=prottop&blast_rank=12&RID=SVXAZ6UZ01R. 
  24. ↑ "alpha-1B-glycoprotein precursor [Mus musculus"]. https://www.ncbi.nlm.nih.gov/protein/124486702?report=genbank&log$=prottop&blast_rank=37&RID=SVXAZ6UZ01R. 
  25. ↑ "PREDICTED: alpha-1B-glycoprotein [Felis catus"]. https://www.ncbi.nlm.nih.gov/protein/410982098?report=genbank&log$=prottop&blast_rank=24&RID=SVXAZ6UZ01R. 
  26. ↑ "PREDICTED: alpha-1B-glycoprotein-like". https://www.ncbi.nlm.nih.gov/protein/338710440?report=genbank&log$=prottop&blast_rank=33&RID=SVXAZ6UZ01R. 
  27. ↑ "PREDICTED: alpha-1B-glycoprotein-like [Loxodonta africana"]. https://www.ncbi.nlm.nih.gov/protein/344269773?report=genbank&log$=prottop&blast_rank=28&RID=SVXAZ6UZ01R. 
  28. ↑ "A1BG Gene". Weissman Institute of Science. https://www.genecards.org/cgi-bin/carddisp.pl?gene=A1BG&search=a1bg#publications. 
  29. ↑ "NCBI conserved domain search". https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?SEQUENCE=NP_570602.2&FULL. 
  30. ↑ "NCBI Blast: Protein Sequence". http://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  31. ↑ 31.0 31.1 31.2 "Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome". Proteomics: Clinical Applications 5 (5–6): 334–42. June 2011. doi:10.1002/prca.201000110. PMID 21591266. 

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