Alpha-1-B glycoprotein
Alpha-1-B glycoprotein is a 54.3 kDa protein in humans that is encoded by the A1BG gene.
  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.

# Gene

## Neighborhood
A1BG is located on the negative DNA strand of chromosome 19 from 58,858,172  58,864,865.  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.

## Transcriptions
According to one source, A1BG is transcribed from the direction of ZNF497: 3' - 58864890: CGAGCCACCCCACCGCCCTCCCTTGG+1GGCCTCATTGCTGCAGACGCTCACCCCAGACACTCACTGCACCGGAGTGAGCGCGACCATCATG : 58866601-5', where the second 'G' at left of four Gs in a row is the TSS. Transcription was triggered in cell cultures and the transcription start site was found using reverse transcriptase. But, the mechanism for transcription is unknown.
Controlling the transcription of A1BG may have significant immune function against snake envenomation. A1BG forms a complex that is similar to those formed between toxins from snake venom and A1BG-like plasma proteins which inhibits the toxic effect of snake venom metalloproteinases or myotoxins and protects the animal from envenomation.

## Expression
A1BG is expressed at high levels in the adult and fetal liver.  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.

# mRNA

## mRNA structure
The gene contains 20 distinct introns.  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.

# Protein
"Alpha-1B-glycoprotein (A1BG) is an acute phase protein, its concentration in serum increases in response to inflammatory processes. It has been detected in the urine of children with  SRNS, and it has been shown that A1BG can be used to differentiate SRNS from  SSNS , , ."
The acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating neutrophils and their precursors.

## 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.  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.

## Post-translational modifications
The NetAcet 1.0 program calculated that the first five amino acid residues serve as an N-acetylation site.  The NetGlycate 1.0 program predicted that the lysines located at residue 78, 114, and 227 serve as glycation points.  The NetNES 1.1 program predicted the leucine at residue 47 to be a nuclear export signal. The NetNGlyc 1.0 program predicted four N-glycosylation sites - two of which are highly conserved internally repeated sequences. The NetCGlyc1.0 program predicted that none of the tryptophan residues serve as C-mannosylation sites.
"The monosialylated glycan (Hexose5HexNAc4Neu5Ac1)  attached at ASN363 on A1BG."

## 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.

## Protein enrichments
Alpha-1B-glycoprotein, an extracellular matrix protein, showed an enrichment in human atrial appendages.

# 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.  Additionally, it is very likely that A1BG is further conserved throughout the mammalian clade.

## Paralogs
No paralogs have been found for alpha-1B glycoprotein.

## Homologous domains
An initial NCBI Blast alignment of alpha-1B glycoprotein illustrates that the protein is mainly composed of three immunoglobulin domains.  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 297-400 does illustrate that the latter sequence is indeed a fourth immunoglobulin domain.   Ultimately, alpha-1B glycoprotein seems to be primarily composed of four immunoglobulin domains.

# Clinical significance

## Bladder cancers
"Urinary serotransferrin and haptoglobin were associated with the presence of bladder cancer, but most discriminatory was -1B-glycoprotein (A1BG-human). This protein was detected in all Con A-captured fractions of bladder cancer patients samples but, more importantly, was never found to occur in non-tumor-bearing patients urine."
"No specific function has been ascribed to A1BG to date, but an indication of a function comes from the characterization of the opossum A1BG homologue, oprin.33 Oprin is a metalloproteinase inhibitor, which in some properties, but not in sequence, resembles the tissue inhibitor of metalloproteinases (TIMPs), a family of proteins with complex roles in tumor progression and angiogenesis.34 An association of A1BG expression with cancer has been described in one previous study. In a study that utilized expressed sequence tag (EST) profiling of cDNA libraries, Yoon et al. identified A1BG as 1 of 14 genes confirmed to be highly expressed in human hepatocellular carcinoma (HCC) cell lines and liver tumor tissue specimens.35"

## Breast cancers
"Alpha-1B-glycoprotein is a secreted glycoprotein with some similarity to the immunoglobulin family and basically very few known functions70.  has been described in proteomic studies of several cancer types like breast cancer71, oral squamous carcinoma72, in the serum of non-small cell lung cancer73, and in pancreatic ductal adenocarcinoma74. Here we describe for the first time a negative correlation of alpha-1B-glycoprotein tissue expression to melanoma survival."

## Cervical adenocarcinoma
"The expression of high-abundance serum proteins in newly diagnosed patients with endometrial adenocarcinoma (EACa), squamous cell cervical carcinoma (SCCa) and cervical adenocarcinoma (ACCa), relative to control female subjects, was analyzed by subjecting serum samples to 2-DE followed by image analysis of the silver-stained protein profiles. The three cohorts of cancer patients demonstrated different altered expression of serum high-abundance proteins compared to negative control women. The expression of 1-antitrypsin, 1-B glycoprotein , cleaved high-molecular-weight kininogen (light chain) and antithrombin III were consistently altered in all the patients."
"The upregulated expression of ABG  consistently observed in all the patients ."

## Cervical intraepithelial neoplasia
"A1BG  expression was elevated in several cancers including cervical intraepithelial neoplasia (28), which suggested it may be play a role in carcinogenesis."
"Cervical cancer develops due to persistent infection with the oncogenic Human Papilloma Virus (HPV), which progresses into an intraepithelial lesion, then into invasive cervical cancer."
"The eight highest score spots that were found to be overexpressed in the  CIN III sera group were identified as -1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with  in the control group."

## Chronic bronchitis
"Transforming growth factor beta-1 precursor and interferon beta precursor were up-regulated in CB, while interleukin 6, tumor necrosis factor (TNF) and a variant TNF receptor 13B were down-regulated in CB. Additionally, glycoprotein- and apolipoprotein-associated proteins including apolipoprotein A-IV and -1-B-glycoprotein were up-regulated in CB, indicating an involvement in the pathogenesis of CB but not silicosis. By contrast, HLA-DRB1, medullasin and the proto-oncogene c-Fos were up-regulated in CB."

## Endometrial adenocarcinoma
"The upregulated expression of ABG  consistently observed in all the patients ."

## Hepatocellular carcinoma
"10 commonly down-regulated genes  from the  HCC pool  ALB, HP, AMBP, FGG, GC, FGB, A1BG, VTN, SERPINC1, and FGA".
"Among the down-regulated genes, AMBP, GC, SERPINC1 and A1BG might be also candidates for the diagnosis and treatment of liver cancer because they are known to be immune-related proteins or plasma proteins."

## Non-small cell lung cancers
"Clinically, the treatment of non-small cell lung cancer (NSCLC) can be improved by the early detection and risk screening among population."
"To the best of our knowledge, our study here is the first report that links the A1BG blood/tissue expression with lung cancer diseases, and we validated this linkage in a cohort of about 100 patients, which is much larger than the sample sets in above previous studies."

## Normal pressure hydrocephalus
The "expressed differences in cerebrospinal fluid (CSF) protein patterns  of normal pressure hydrocephalus (NPH)  over-expression of 2HS glycoprotein, 1 antichimotrypsin and 1beta glycoprotein and the under-expression of glial fibrillary acidic protein, apolipoproteins (AIV, J and E), complement C3c, anti-thrombin, 2 antiplasmin and albumin".

## Oral squamous carcinomas

## Pancreatic ductal adenocarcinoma
Patients who have pancreatic ductal adenocarcinoma show an overexpression of MMP-9, DJ-1 and A1BG in pancreatic juice.

## Papillary thyroid carcinoma
Group A consists of "papillary thyroid carcinoma patients with non-131I-avid lung metastases and  131I-avid lung metastases."
"Of the 11 identified proteins, six were downregulated  and five were upregulated  in group A."
"A1BG and afamin,  are carcinogenesis-related proteins".
The "protein levels of A1BG did not differ significantly between the two groups."

## Rheumatoid arthritis
A1BG has been proposed as an autoantigen in rheumatoid arthritis.
Rheumatoid arthritis "RA patients revealed an increase in the expression of  and A1BG in the plasma as compared to osteoarthritis patients."
"Presence of autoantibodies against GFAP and A1BG in the plasma samples of RA patients were confirmed by Western blot analysis after separating the recombinant pure GFAP and A1BG proteins on SDS-PAGE."
Reactivity "of A1BG in RA plasma was 5 fold higher than OA plasma and 6 fold  than healthy control .
"GFAP and A1BG autoantigens are shown to be associated with RA and autoantibodies against GFAP and A1BG were isolated in RA plasma."

## Squamous cell cervical carcinoma
Plasma "samples from six healthy females  compared with six females with squamous cell carcinoma (SCC) and  A1BG and C3 were  overexpressed using 2D-GE analysis."
"The upregulated expression of ABG  consistently observed in all the patients ."

## Steroid-resistant nephrotic syndrome
"Focal segmental glomerulosclerosis (FSGS) is a glomerular scarring disease characterized by increased extracellular matrix within the glomerular tuft . The sclerotic lesions occur focally and in only some segments of glomeruli, and are typically not associated with immune complex deposition . It is believed that the loss of foot process of podocytes is also one of the most important characteristics of FSGS . FSGS is a major cause of steroid resistant nephrotic syndrome, which could lead to end-stage renal failure ."
"A1BG (Alpha-1B-glycoprotein) is a plasma glycoprotein with homology to the immunoglobulin supergene family . Implication of this protein in responsiveness to steroid drugs reported by Pyaphanee et al.] and Huang et al. ]. Underrepresentation of this protein in steroid sensitive patients in our data set is thus consistent with previous findings."
The alpha-1-glycoprotein is upregulated 11-fold in the urine of patients who have steroid resistant nephrotic syndrome.  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.