A2m alpha-2-macroglobulin [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: A2mprovided by RGD
Full Name: alpha-2-macroglobulinprovided by RGD
Primary source: RGD:2004
See related: EnsemblRapid:ENSRNOG00000028896 AllianceGenome:RGD:2004
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Mam; A2m1; A2mb; A2maa; A2MAC1
Summary: Enables endopeptidase inhibitor activity; identical protein binding activity; and neurotrophin binding activity. Involved in several processes, including acute inflammatory response; embryonic liver development; and luteinization. Located in extracellular space. Used to study hemolytic anemia and toxic shock syndrome. Biomarker of several diseases, including liver disease (multiple); membranous glomerulonephritis; osteonecrosis; peritonitis; and trypanosomiasis. Human ortholog(s) of this gene implicated in COVID-19; background diabetic retinopathy; multiple sclerosis; neurodegenerative disease (multiple); and obstructive lung disease. Orthologous to human A2M (alpha-2-macroglobulin). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Liver (RPKM 371.9), Uterus (RPKM 135.2) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4q42

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	4	NC_086022.1 (156570163..156619870)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	4	NC_051339.1 (154897770..154947787)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	4	NC_005103.4 (154309426..154359138)

Chromosome 4 - NC_086022.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Alpha-2-macroglobulin is involved in the occurrence of early-onset pre-eclampsia via its negative impact on uterine spiral artery remodeling and placental angiogenesis.
Title: Alpha-2-macroglobulin is involved in the occurrence of early-onset pre-eclampsia via its negative impact on uterine spiral artery remodeling and placental angiogenesis.
Gastric contents-induced acute lung injury elicits a liver acute phase response characterized by increased mRNA expression of alpha 2 macroglobulin and alpha1-antitrypsin.
Title: Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection.
elevated serum level correlated to glucocorticoid treatment and may represent a form of reparative response to glucocorticoid-associated damage of bone
Title: Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model.
Differentiation of protein species of alpha-2u-globulin according to database entries
Title: Differentiation of protein species of alpha-2u-globulin according to database entries: A half-theoretical approach.
Peak serum levels of alpha(2)-macroglobulin and alpha(1)-acid glycoprotein injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. No significant differences were observed for peak serum levels at 0.2 and 0.4 mL/rat.
Title: Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats.
alpha(2)M induces protein factors whose interplay underlies radioprotection
Title: Administration of rat acute-phase protein α(2)-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver.
alpha2-macroglobulin is neurotoxic by inhibiting neuroprotective activity of nerve growth factor via TrkA receptors.
Title: During glaucoma, alpha2-macroglobulin accumulates in aqueous humor and binds to nerve growth factor, neutralizing neuroprotection.
Role of cardiac isoform of alpha-2 macroglobulin in diabetic myocardium.
Title: Role of cardiac isoform of alpha-2 macroglobulin in diabetic myocardium.
Alpha2-macroglobulin is a mediator of retinal ganglion cell death in glaucoma
Title: Alpha2-macroglobulin is a mediator of retinal ganglion cell death in glaucoma.
involvement of STAT5b in alpha(2)-macroglobulin gene expression during development
Title: Nuclear localization and binding affinity of STAT5b for the alpha(2)-macroglobulin gene promoter during rat liver development and the acute-phase response.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

d4arb15 (e-PCR)
- UniSTS:121906

D4MIT20 (e-PCR)
- UniSTS:121929

D4Wox16 (e-PCR)
- UniSTS:117975

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables brain-derived neurotrophic factor binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent protein binding	ISO Inferred from Sequence Orthology more info
enables endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables growth factor binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-1 binding	ISO Inferred from Sequence Orthology more info
enables interleukin-8 binding	ISO Inferred from Sequence Orthology more info
enables nerve growth factor binding	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IBA Inferred from Biological aspect of Ancestor more info
enables protease binding	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables tumor necrosis factor binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in acute inflammatory response to antigenic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in acute-phase response	IEP Inferred from Expression Pattern more info	PubMed
involved_in embryonic liver development	IEP Inferred from Expression Pattern more info	PubMed
involved_in luteinization	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of complement activation, lectin pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in response to carbon dioxide	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to glucocorticoid	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to nutrient	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to prostaglandin E	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within stem cell differentiation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: alpha-2-macroglobulin

Names: alpha-2-M; alpha-2-macroglobulin-P

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012488.2 → NP_036620.2 alpha-2-macroglobulin precursor

See identical proteins and their annotated locations for NP_036620.2

Status: PROVISIONAL

Source sequence(s)

BC098922

UniProtKB/Swiss-Prot

P06238, Q4FZY3

UniProtKB/TrEMBL

A6ILD0

Related

ENSRNOP00000019346.5, ENSRNOT00000019346.8

Conserved Domains (6) summary

cd02897
Location:956 → 1262

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:736 → 826

A2M; Alpha-2-macroglobulin family

pfam01835
Location:132 → 224

A2M_N; MG2 domain

pfam07677
Location:1374 → 1461

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1008 → 1263

A2M_comp; A-macroglobulin complement component

pfam07703
Location:464 → 609

A2M_N_2; Alpha-2-macroglobulin family N-terminal region