A2M alpha-2-macroglobulin [Homo sapiens (human)] - Gene

Summary

Official Symbol: A2Mprovided by HGNC
Official Full Name: alpha-2-macroglobulinprovided by HGNC
Primary source: HGNC:HGNC:7
See related: Ensembl:ENSG00000175899 MIM:103950; AllianceGenome:HGNC:7
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: A2MD; CPAMD5; FWP007; S863-7
Summary: The protein encoded by this gene is a protease inhibitor and cytokine transporter. It uses a bait-and-trap mechanism to inhibit a broad spectrum of proteases, including trypsin, thrombin and collagenase. It can also inhibit inflammatory cytokines, and it thus disrupts inflammatory cascades. Mutations in this gene are a cause of alpha-2-macroglobulin deficiency. This gene is implicated in Alzheimer's disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. A related pseudogene, which is also located on the p arm of chromosome 12, has been identified. [provided by RefSeq, Nov 2016]
Expression: Broad expression in lung (RPKM 732.0), urinary bladder (RPKM 374.7) and 21 other tissues See more
Orthologs: all
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Genomic context

Location:: 12p13.31

Exon count:: 37

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (9067708..9116229, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (9049893..9098416, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (9220304..9268825, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Alpha-2-Macroglobulin Is a Novel Anticancer Agent.
Title: Alpha-2-Macroglobulin Is a Novel Anticancer Agent.
CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in lower extremity arteriosclerosis obliterans.
Title: CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in lower extremity arteriosclerosis obliterans.
Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
Title: Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
[Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy].
Title: [Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy].
Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.
Title: Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.
Alpha-2-macroglobulin prevents platelet aggregation induced by brain-derived neurotrophic factor.
Title: Alpha-2-macroglobulin prevents platelet aggregation induced by brain-derived neurotrophic factor.
Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.
Title: Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.
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.
LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter.
Title: LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter.
A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1beta/NF-kappaB pathway.
Title: A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1β/NF-κB pathway.

Submit: New GeneRIF Correction See all GeneRIFs (129)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of alpha-2-macroglobulin (A2M) in peptide-treated PBMCs	PubMed
Tat	tat	Binding of HIV-1 Tat to LRP inhibits neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor and amyloid beta-protein	PubMed
retropepsin	gag-pol	The cleavage site of alpha 2-Macroglobulin by HIV-1 protease is the Phe684-Tyr685 bond	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11157 (e-PCR)
- UniSTS:46849

SGC33440 (e-PCR)
- UniSTS:54816

G59851 (e-PCR)
- UniSTS:137000

SGC31674 (e-PCR)
- UniSTS:40245

D12S1395E (e-PCR)
- UniSTS:147540

GDB:181517 (e-PCR)
- UniSTS:155252

RH46356 (e-PCR)
- UniSTS:75646

D12S1160E (e-PCR)
- UniSTS:151442

G44356 (e-PCR)
- UniSTS:95143

RH1601 (e-PCR)
- UniSTS:25036

RH70338 (e-PCR)
- UniSTS:31955

PMC311069P4 (e-PCR)
- UniSTS:272885

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in acute inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in embryonic liver development	IEA Inferred from Electronic Annotation more info
involved_in luteinization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of complement activation, lectin pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in response to carbon dioxide	IEA Inferred from Electronic Annotation more info
involved_in response to glucocorticoid	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to prostaglandin E	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: alpha-2-macroglobulin

Names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5; alpha-2-M

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.

Genomic

NG_011717.2 RefSeqGene

Range

5044..53255

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_591

mRNA and Protein(s)

NM_000014.6 → NP_000005.3 alpha-2-macroglobulin isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a). Both variants 1 and 2 encode isoform a.

Source sequence(s)

AC007436

Consensus CDS

CCDS44827.1

UniProtKB/Swiss-Prot

P01023, Q13677, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97

Related

ENSP00000323929.8, ENST00000318602.12

Conserved Domains (7) 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:129 → 221

A2M_N; MG2 domain

pfam07677
Location:1376 → 1463

A2M_recep; A-macroglobulin receptor

pfam07703
Location:459 → 607

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

pfam17789
Location:350 → 445

MG4; Macroglobulin domain MG4

pfam17791
Location:223 → 313

MG3; Macroglobulin domain MG3
NM_001347423.2 → NP_001334352.2 alpha-2-macroglobulin isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) splices out a region of the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same isoform (a).

Source sequence(s)

AC007436

Consensus CDS

CCDS44827.1

UniProtKB/Swiss-Prot

P01023, Q13677, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97

Conserved Domains (7) 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:129 → 221

A2M_N; MG2 domain

pfam07677
Location:1376 → 1463

A2M_recep; A-macroglobulin receptor

pfam07703
Location:459 → 607

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

pfam17789
Location:350 → 445

MG4; Macroglobulin domain MG4

pfam17791
Location:223 → 313

MG3; Macroglobulin domain MG3
NM_001347424.2 → NP_001334353.2 alpha-2-macroglobulin isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate splice site in the 5' region, and it thus differs in its 5' UTR and initiates translation from a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AC007436

Conserved Domains (7) summary

cd02897
Location:858 → 1164

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:638 → 728

A2M; Alpha-2-macroglobulin family

pfam07677
Location:1276 → 1363

A2M_recep; A-macroglobulin receptor

pfam17789
Location:250 → 345

MG4; Macroglobulin domain MG4

pfam17791
Location:123 → 210

MG3; Macroglobulin domain MG3

pfam01835
Location:29 → 121

A2M_N; MG2 domain

pfam07703
Location:359 → 507

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
NM_001347425.2 → NP_001334354.2 alpha-2-macroglobulin isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an exon in the 5' region, and it thus differs in its 5' UTR and initiates translation from a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AC007436

Conserved Domains (7) summary

cd02897
Location:808 → 1114

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:588 → 678

A2M; Alpha-2-macroglobulin family

pfam07677
Location:1226 → 1313

A2M_recep; A-macroglobulin receptor

pfam17789
Location:200 → 295

MG4; Macroglobulin domain MG4

pfam17791
Location:73 → 160

MG3; Macroglobulin domain MG3

pfam01835
Location:1 → 71

A2M_N; MG2 domain

pfam07703
Location:309 → 457

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

9067708..9116229 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006719056.4 → XP_006719119.1 alpha-2-macroglobulin isoform X1

Conserved Domains (7) summary

COG2373
Location:124 → 1071

YfaS; Uncharacterized conserved protein YfaS, alpha-2-macroglobulin family [General function prediction only]

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:129 → 221

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:461 → 606

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