A2m alpha-2-macroglobulin [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: A2mprovided by MGI
Official Full Name: alpha-2-macroglobulinprovided by MGI
Primary source: MGI:MGI:2449119
See related: Ensembl:ENSMUSG00000030111 AllianceGenome:MGI:2449119
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: A2mp
Summary: Predicted to enable several functions, including cytokine binding activity; growth factor binding activity; and serine-type endopeptidase inhibitor activity. Acts upstream of or within stem cell differentiation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Is expressed in several structures, including brain; embryo mesenchyme; liver; meninges; and retina. 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, Apr 2022]
Expression: Biased expression in liver E18 (RPKM 215.0), placenta adult (RPKM 27.2) and 1 other tissue See more
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Genomic context

Location:: 6 F1; 6 57.49 cM

Exon count:: 37

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (121612920..121656197)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (121636165..121679238)

Chromosome 6 - NC_000072.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

To investigate the pharmacokinetics (PKs) and pharmacodynamics (PDs) for ION-353382, an antisense oligonucleotide (ASO) targeting scavenger receptor class B type I (SRB1) mRNA, using alpha-2-macroglobulin (A2M), murinoglobulin double-knockout (DKO), and wild-type mice
Title: Pharmacokinetic and Pharmacodynamic Investigations of ION-353382, a Model Antisense Oligonucleotide: Using Alpha-2-Macroglobulin and Murinoglobulin Double-Knockout Mice.
A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated alpha2M, hepcidin remains labile and available to down-regulate Fpn1.
Title: Hepcidin bound to α2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels.
Data show that MAA-A2M adduct formation abrogated the binding of A2M bait region with TGF-beta1, trypsin, and elastase.
Title: Modification of mouse A2M B (620-792) and A2M N (168-230) by malondialdehyde and acetaldehyde attenuates the proteinase and TGF-β1 binding ability of A2MB.
MMP9 production promoted by the alpha(2)M*/LRP1 interaction required the activation of both MAPK-ERK1/2 and NF-kappaB signaling pathways.
Title: Activated α(2) macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-κB activation in macrophage-derived cell lines.
Prion protein paralog doppel protein interacts with alpha-2-macroglobulin
Title: Prion protein paralog doppel protein interacts with alpha-2-macroglobulin: a plausible mechanism for doppel-mediated neurodegeneration.
the inhibition of proteases on the surface of microorganisms by an ancestral alpha2M-like thiol ester protein may generate "arrays" of oligomannose glycans to which MBL or other lectins can bind
Title: Interaction of mannan binding lectin with alpha2 macroglobulin via exposed oligomannose glycans: a conserved feature of the thiol ester protein family?
Data describe the role of the PI3-kinase/PDK/Akt/p70s6k signaling cascade in alpha 2-macroglobulin-induced cellular proliferation and the role of CREB in these events.
Title: Activation of Akt/PDK signaling in macrophages upon binding of receptor-recognized forms of alpha2-macroglobulin to its cellular receptor: effect of silencing the CREB gene.
review the A2M gene families of mice and humans, the predicted structural relationships between A2M and its pregnancy induced forms and the postulated roles for this gene family in normal pregnancy.
Title: Functions of alpha 2 macroglobulins in pregnancy.
IL-11 signals through the Jak2/Stat3 pathway in decidual cells to stimulate the expression of alpha(2)-MG, a protease inhibitor essential for normal placentation in pregnancy.
Title: The role of interleukin-11 in pregnancy involves up-regulation of alpha2-macroglobulin gene through janus kinase 2-signal transducer and activator of transcription 3 pathway in the decidua.
the 4622-base pair cDNA encodes a protein of 1473 AA with >70% sequence identity and all typical domains of other A2M-family members in humans and rodents
Title: Characterization of a murine alpha 2 macroglobulin gene expressed in reproductive and cardiovascular tissue.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A2m (e-PCR), detects polymorphism
- UniSTS:545844

D4Arb40 (e-PCR), detects polymorphism
- UniSTS:227699

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables brain-derived neurotrophic factor binding	ISO Inferred from Sequence Orthology more info
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	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	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
enables peptidase inhibitor activity	TAS Traceable Author Statement 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 protein binding	IPI Inferred from Physical Interaction more info	PubMed
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
acts_upstream_of_or_within female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of complement activation, lectin pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within stem cell differentiation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor 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-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_175628.3 → NP_783327.2 alpha-2-macroglobulin-P precursor

See identical proteins and their annotated locations for NP_783327.2

Status: VALIDATED

Source sequence(s)

AI850558, BC072642, BY785372, CN701262

Consensus CDS

CCDS39617.1

UniProtKB/Swiss-Prot

E9QMQ7, Q6GQT1, Q811S0

Related

ENSMUSP00000032203.8, ENSMUST00000032203.9

Conserved Domains (6) summary

cd02897
Location:958 → 1264

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:738 → 828

A2M; Alpha-2-macroglobulin family

pfam01835
Location:135 → 227

A2M_N; MG2 domain

pfam07677
Location:1376 → 1463

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1010 → 1266

A2M_comp; A-macroglobulin complement component

pfam07703
Location:473 → 612

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

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000072.7 Reference GRCm39 C57BL/6J

Range

121612920..121656197

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011241322.3 → XP_011239624.1 alpha-2-macroglobulin-P isoform X1

Conserved Domains (5) summary

pfam00207
Location:738 → 828

A2M; Alpha-2-macroglobulin family

pfam17789
Location:356 → 451

MG4; Macroglobulin domain MG4

pfam17791
Location:229 → 316

MG3; Macroglobulin domain MG3

pfam01835
Location:135 → 227

A2M_N; MG2 domain

pfam07703
Location:465 → 612

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