A2M (alpha-2-macroglobulin)

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Gene miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases Related genes Diseases linked via similar genes

Gene

• Entrez ID: 2
• Gene name: Alpha-2-macroglobulin
• Gene symbol: A2M
• Synonyms (NCBI Gene): A2MD, CPAMD5, FWP007, S863-7
• Chromosome: 12
• Chromosome location: 12p13.31
• 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021948	hsa-miR-128-3p	Microarray	17612493
MIRT023224	hsa-miR-122-5p	Microarray	17612493
MIRT027430	hsa-miR-98-5p	Microarray	19088304
MIRT736703	hsa-miR-146b-5p	Luciferase reporter assay, Western blotting, qRT-PCR, ELISA	31422941

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Unknown	11466367
STAT3	Unknown	11466367
TFCP2	Unknown	10455131

Gene ontology (GO) Show/Hide all (28)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001869	Process	Negative regulation of complement activation, lectin pathway	IDA	12538697
GO:0002020	Function	Protease binding	IBA
GO:0002020	Function	Protease binding	IPI	7679575, 18485748
GO:0004866	Function	Endopeptidase inhibitor activity	IBA
GO:0004866	Function	Endopeptidase inhibitor activity	IDA	7679575
GO:0004866	Function	Endopeptidase inhibitor activity	IEA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	12538697
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0005102	Function	Signaling receptor binding	IMP	15226301
GO:0005515	Function	Protein binding	IPI	6698368, 14687906, 32814053
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0019838	Function	Growth factor binding	IDA	9398211
GO:0019899	Function	Enzyme binding	IPI	11435418
GO:0019959	Function	Interleukin-8 binding	IPI	10880251
GO:0019966	Function	Interleukin-1 binding	IDA	9714181
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0031012	Component	Extracellular matrix	HDA	28327460
GO:0031012	Component	Extracellular matrix	HDA	25037231, 28675934
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0043120	Function	Tumor necrosis factor binding	IDA	9714181
GO:0048306	Function	Calcium-dependent protein binding	IPI	15226301
GO:0048863	Process	Stem cell differentiation	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337, 21362503, 23533145
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 103950
• HGNC: 7
• e!Ensembl: ENSG00000175899

Protein

• UniProt ID: P01023
• Protein name: Alpha-2-macroglobulin (Alpha-2-M) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5)
• Protein function: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bai
• PDB: 1BV8 , 2P9R , 6TAV , 7O7L , 7O7M , 7O7N , 7O7O , 7O7P , 7O7Q , 7O7R , 7O7S , 7VON , 7VOO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00207	A2M	738 → 828	Alpha-2-macroglobulin family	Family
  PF01835	MG2	128 → 221	MG2 domain	Domain
  PF07677	A2M_recep	1376 → 1463	A-macroglobulin receptor binding domain	Domain
  PF07678	TED_complement	948 → 1264	A-macroglobulin TED domain	Domain
  PF07703	A2M_BRD	459 → 607	Alpha-2-macroglobulin bait region domain	Domain
  PF17789	MG4	350 → 445	Macroglobulin domain MG4	Domain
  PF17791	MG3	223 → 313	Macroglobulin domain MG3	Domain

• Tissue specificity: TISSUE SPECIFICITY: Secreted in plasma. {ECO:0000269|PubMed:6203908}.
• Sequence:

  MGKNKLLHPSLVLLLLVLLPTDASVSGKPQYMVLVPSLLHTETTEKGCVLLSYLNETVTV
  SASLESVRGNRSLFTDLEAENDVLHCVAFAVPKSSSNEEVMFLTVQVKGPTQEFKKRTTV
  MVKNEDSLVFVQTDKSIYKPGQTVKFRVVSMDENFHPLNELIPLVYIQDPKGNRIAQWQS
  FQLEGGLKQFSFPLSSEPFQGSYKVVVQKKSGGRTEHPFTVEEFVLPKFEVQVTVPKIIT
  ILEEEMNVSVCGLYTYGKPVPGHVTVSICRKYSDASDCHGEDSQAFCEKFSGQLNSHGCF
  YQQVKTKVFQLKRKEYEMKLHTEAQIQEEGTVVELTGRQSSEITRTITKLSFVKVDSHFR
  QGIPFFGQVRLVDGKGVPIPNKVIFIRGNEANYYSNATTDEHGLVQFSINTTNVMGTSLT
  VRVNYKDRSPCYGYQWVSEEHEEAHHTAYLVFSPSKSFVHLEPMSHELPCGHTQTVQAHY
  ILNGGTLLGLKKLSFYYLIMAKGGIVRTGTHGLLVKQEDMKGHFSISIPVKSDIAPVARL
  LIYAVLPTGDVIGDSAKYDVENCLANKVDLSFSPSQSLPASHAHLRVTAAPQSVCALRAV
  DQSVLLMKPDAELSASSVYNLLPEKDLTGFPGPLNDQDNEDCINRHNVYINGITYTPVSS
  TNEKDMYSFLEDMGLKAFTNSKIRKPKMCPQLQQYEMHGPEGLRVGFYESDVMGRGHARL
  VHVEEPHTETVRKYFPETWIWDLVVVNSAGVAEVGVTVPDTITEWKAGAFCLSEDAGLGI
  SSTASLRAFQPFFVELTMPYSVIRGEAFTLKATVLNYLPKCIRVSVQLEASPAFLAVPVE
  KEQAPHCICANGRQTVSWAVTPKSLGNVNFTVSAEALESQELCGTEVPSVPEHGRKDTVI
  KPLLVEPEGLEKETTFNSLLCPSGGEVSEELSLKLPPNVVEESARASVSVLGDILGSAMQ
  NTQNLLQMPYGCGEQNMVLFAPNIYVLDYLNETQQLTPEIKSKAIGYLNTGYQRQLNYKH
  YDGSYSTFGERYGRNQGNTWLTAFVLKTFAQARAYIFIDEAHITQALIWLSQRQKDNGCF
  RSSGSLLNNAIKGGVEDEVTLSAYITIALLEIPLTVTHPVVRNALFCLESAWKTAQEGDH
  GSHVYTKALLAYAFALAGNQDKRKEVLKSLNEEAVKKDNSVHWERPQKPKAPVGHFYEPQ
  APSAEVEMTSYVLLAYLTAQPAPTSEDLTSATNIVKWITKQQNAQGGFSSTQDTVVALHA
  LSKYGAATFTRTGKAAQVTIQSSGTFSSKFQVDNNNRLLLQQVSLPELPGEYSMKVTGEG
  CVYLQTSLKYNILPEKEEFPFALGVQTLPQTCDEPKAHTSFQISLSVSYTGSRSASNMAI
  VDVKMVSGFIPLKPTVKMLERSNHVSRTEVSSNHVLIYLDKVSNQTLSLFFTVLQDVPVR
  DLKPAIVKVYDYYETDEFAIAEYNAPCSKDLGNA

• Sequence length: 1474

Pathways

KEGG Pathway	Reactome Pathway
Complement and coagulation cascades	Platelet degranulation
	Intrinsic Pathway of Fibrin Clot Formation
	Degradation of the extracellular matrix
	Rho GTPase cycle
	HDL assembly

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations Show/Hide Unknown Diseases (32)
Phenotype Name	Clinical Significance	Source	Reference	Evidence Score
A2M POLYMORPHISM	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
A2M-related disorder	Likely benign; Benign; Uncertain significance	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Acute myeloid leukemia	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALPHA-2-MACROGLOBULIN POLYMORPHISM	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE, FAMILIAL, 1	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMERS DISEASE	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	15509519	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLONIC NEOPLASMS	—	CTD	15059925	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATOLENTICULAR DEGENERATION	—	CTD, Disgenet CTD, Disgenet	23519153	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE, ACUTE	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS	—	CTD, Disgenet CTD, Disgenet	26396155	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign; Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG DISEASES	—	CTD, Disgenet CTD, Disgenet	2475424	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG DISEASES, OBSTRUCTIVE	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG NEOPLASMS	—	CTD	17902193, 19180532	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL DEPRESSION	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEPHROTIC SYNDROME	—	CTD, Disgenet CTD, Disgenet	11304663	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	Disgenet	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign; Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	30019117	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance; Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining Show/Hide Text Mining Associations (150)
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Confusional Senile Dementia	Senile Dementia	CTD_human_DG	15023809, 9697696, 9811940		★☆☆☆☆ Found in Text Mining only
Acute Kidney Insufficiency	Acute Kidney Insufficiency	CTD_human_DG	23052191		★☆☆☆☆ Found in Text Mining only
alpha 1-Antitrypsin Deficiency	Alpha 1-Antitrypsin Deficiency	BEFREE	6169740, 6189643		★☆☆☆☆ Found in Text Mining only
alpha-2-Macroglobulin Deficiency	Alpha-2-Macroglobulin Deficiency	BEFREE	2475424		★☆☆☆☆ Found in Text Mining only
alpha-2-Macroglobulin Deficiency	Alpha-2-Macroglobulin Deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	10688047, 11058432, 11106172, 18842138, 19105203, 29154276, 34958020, 35387811, 9837937	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	27872486, 35456941	Stimulate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Early Onset	Alzheimer disease	CTD_human_DG	15023809, 9697696, 9811940		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	10477119, 10505652, 10527839, 11166925, 11290389, 15211070, 20493925		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	CTD_human_DG	15023809, 9697696, 9811940		★☆☆☆☆ Found in Text Mining only

Related Genes

Sort by: Blended Diseases Pathways Evidence source

IGFBP1 3 shared diseasesLiver cirrhosis, Colonic neoplasms, Kidney failure 4 shared evidence sourcesCTD (Colonic neoplasms), Disgenet (Kidney failure), CTD (Liver cirrhosis), Disgenet (Liver cirrhosis) Related via 3 shared diseases including Liver cirrhosis, Colonic neoplasms — evidence mostly CTD. GUCA2B 2 shared diseasesNephrotic syndrome, Kidney failure 3 shared evidence sourcesDisgenet (Nephrotic syndrome), Disgenet (Kidney failure), CTD (Nephrotic syndrome) Related via 2 shared diseases including Nephrotic syndrome, Kidney failure — evidence mostly Disgenet. SERPING1 2 shared diseasesLiver cirrhosis, Lung neoplasms 3 shared pathwaysComplement and coagulation cascades, Platelet degranulation , Intrinsic Pathway of Fibrin Clot Formation 3 shared evidence sourcesCTD (Liver cirrhosis), Disgenet (Liver cirrhosis), CTD (Lung neoplasms) Related via 3 shared pathways including Complement and coagulation cascades, Platelet degranulation — evidence mostly CTD. CXCL14 2 shared diseasesLiver cirrhosis, Lung neoplasms 3 shared evidence sourcesCTD (Liver cirrhosis), Disgenet (Liver cirrhosis), CTD (Lung neoplasms) Related via 2 shared diseases including Liver cirrhosis, Lung neoplasms — evidence mostly CTD. HSD11B2 2 shared diseasesLiver cirrhosis, Nephrotic syndrome 4 shared evidence sourcesDisgenet (Nephrotic syndrome), CTD (Liver cirrhosis), Disgenet (Liver cirrhosis), CTD (Nephrotic syndrome) Related via 2 shared diseases including Liver cirrhosis, Nephrotic syndrome — evidence mostly Disgenet.

Related Gene	Shared Diseases	Shared Disease Names	Shared Pathways	Shared Pathway Names	Shared Evidence Sources	Shared Evidence Names
IGFBP1	3	["Liver cirrhosis","Colonic neoplasms","Kidney failure"]	0	[]	4	["CTD (Colonic neoplasms)","Disgenet (Kidney failure)","CTD (Liver cirrhosis)","Disgenet (Liver cirrhosis)"]
GUCA2B	2	["Nephrotic syndrome","Kidney failure"]	0	[]	3	["Disgenet (Nephrotic syndrome)","Disgenet (Kidney failure)","CTD (Nephrotic syndrome)"]
SERPING1	2	["Liver cirrhosis","Lung neoplasms"]	3	["Complement and coagulation cascades","Platelet degranulation ","Intrinsic Pathway of Fibrin Clot Formation"]	3	["CTD (Liver cirrhosis)","Disgenet (Liver cirrhosis)","CTD (Lung neoplasms)"]
CXCL14	2	["Liver cirrhosis","Lung neoplasms"]	0	[]	3	["CTD (Liver cirrhosis)","Disgenet (Liver cirrhosis)","CTD (Lung neoplasms)"]
HSD11B2	2	["Liver cirrhosis","Nephrotic syndrome"]	0	[]	4	["Disgenet (Nephrotic syndrome)","CTD (Liver cirrhosis)","Disgenet (Liver cirrhosis)","CTD (Nephrotic syndrome)"]

Diseases Linked via Similar Genes

Endometriosis Linked via 2 of 5 related genesIGFBP1, CXCL14 Myocardial infarction Linked via 2 of 5 related genesIGFBP1, HSD11B2 Obesity Linked via 2 of 5 related genesSERPING1, HSD11B2 Asthma Linked via 2 of 5 related genesCXCL14, HSD11B2 Biliary cirrhosis Linked via 1 of 5 related genesIGFBP1

Disease	Linked Via (Gene Count)	Linked Via (Gene Names)
Endometriosis	2	["IGFBP1","CXCL14"]
Myocardial infarction	2	["IGFBP1","HSD11B2"]
Obesity	2	["SERPING1","HSD11B2"]
Asthma	2	["CXCL14","HSD11B2"]
Biliary cirrhosis	1	["IGFBP1"]