Alpha-2-macroglobulin

Details

Synonyms

Alpha-2-M
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
CPAMD5

Gene Name

A2M

UniProtKB Entry

P01023Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0037100|Alpha-2-macroglobulin
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

Number of residues

1474

Molecular Weight

163289.945

Theoretical pI

6.39

GO Classification

Functions

brain-derived neurotrophic factor binding / endopeptidase inhibitor activity / identical protein binding / nerve growth factor binding / signaling receptor binding

Processes

acute inflammatory response to antigenic stimulus / acute-phase response / embryonic liver development / luteinization / response to carbon dioxide / response to glucocorticoid / response to nutrient / response to prostaglandin E

Components

collagen-containing extracellular matrix / extracellular space

General 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 bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase

Specific Function

Brain-derived neurotrophic factor binding

Pfam Domain Function

A2M (PF00207)
A2M_recep (PF07677)
MG3 (PF17791)
MG4 (PF17789)
A2M_BRD (PF07703)
MG2 (PF01835)
TED_complement (PF07678)

Signal Regions

1-23

Transmembrane Regions

Not Available

Cellular Location

Secreted

Gene sequence

>lcl|BSEQ0019028|Alpha-2-macroglobulin (A2M)
ATGGGGAAGAACAAACTCCTTCATCCAAGTCTGGTTCTTCTCCTCTTGGTCCTCCTGCCC
ACAGACGCCTCAGTCTCTGGAAAACCGCAGTATATGGTTCTGGTCCCCTCCCTGCTCCAC
ACTGAGACCACTGAGAAGGGCTGTGTCCTTCTGAGCTACCTGAATGAGACAGTGACTGTA
AGTGCTTCCTTGGAGTCTGTCAGGGGAAACAGGAGCCTCTTCACTGACCTGGAGGCGGAG
AATGACGTACTCCACTGTGTCGCCTTCGCTGTCCCAAAGTCTTCATCCAATGAGGAGGTA
ATGTTCCTCACTGTCCAAGTGAAAGGACCAACCCAAGAATTTAAGAAGCGGACCACAGTG
ATGGTTAAGAACGAGGACAGTCTGGTCTTTGTCCAGACAGACAAATCAATCTACAAACCA
GGGCAGACAGTGAAATTTCGTGTTGTCTCCATGGATGAAAACTTTCACCCCCTGAATGAG
TTGATTCCACTAGTATACATTCAGGATCCCAAAGGAAATCGCATCGCACAATGGCAGAGT
TTCCAGTTAGAGGGTGGCCTCAAGCAATTTTCTTTTCCCCTCTCATCAGAGCCCTTCCAG
GGCTCCTACAAGGTGGTGGTACAGAAGAAATCAGGTGGAAGGACAGAGCACCCTTTCACC
GTGGAGGAATTTGTTCTTCCCAAGTTTGAAGTACAAGTAACAGTGCCAAAGATAATCACC
ATCTTGGAAGAAGAGATGAATGTATCAGTGTGTGGCCTATACACATATGGGAAGCCTGTC
CCTGGACATGTGACTGTGAGCATTTGCAGAAAGTATAGTGACGCTTCCGACTGCCACGGT
GAAGATTCACAGGCTTTCTGTGAGAAATTCAGTGGACAGCTAAACAGCCATGGCTGCTTC
TATCAGCAAGTAAAAACCAAGGTCTTCCAGCTGAAGAGGAAGGAGTATGAAATGAAACTT
CACACTGAGGCCCAGATCCAAGAAGAAGGAACAGTGGTGGAATTGACTGGAAGGCAGTCC
AGTGAAATCACAAGAACCATAACCAAACTCTCATTTGTGAAAGTGGACTCACACTTTCGA
CAGGGAATTCCCTTCTTTGGGCAGGTGCGCCTAGTAGATGGGAAAGGCGTCCCTATACCA
AATAAAGTCATATTCATCAGAGGAAATGAAGCAAACTATTACTCCAATGCTACCACGGAT
GAGCATGGCCTTGTACAGTTCTCTATCAACACCACCAATGTTATGGGTACCTCTCTTACT
GTTAGGGTCAATTACAAGGATCGTAGTCCCTGTTACGGCTACCAGTGGGTGTCAGAAGAA
CACGAAGAGGCACATCACACTGCTTATCTTGTGTTCTCCCCAAGCAAGAGCTTTGTCCAC
CTTGAGCCCATGTCTCATGAACTACCCTGTGGCCATACTCAGACAGTCCAGGCACATTAT
ATTCTGAATGGAGGCACCCTGCTGGGGCTGAAGAAGCTCTCCTTCTATTATCTGATAATG
GCAAAGGGAGGCATTGTCCGAACTGGGACTCATGGACTGCTTGTGAAGCAGGAAGACATG
AAGGGCCATTTTTCCATCTCAATCCCTGTGAAGTCAGACATTGCTCCTGTCGCTCGGTTG
CTCATCTATGCTGTTTTACCTACCGGGGACGTGATTGGGGATTCTGCAAAATATGATGTT
GAAAATTGTCTGGCCAACAAGGTGGATTTGAGCTTCAGCCCATCACAAAGTCTCCCAGCC
TCACACGCCCACCTGCGAGTCACAGCGGCTCCTCAGTCCGTCTGCGCCCTCCGTGCTGTG
GACCAAAGCGTGCTGCTCATGAAGCCTGATGCTGAGCTCTCGGCGTCCTCGGTTTACAAC
CTGCTACCAGAAAAGGACCTCACTGGCTTCCCTGGGCCTTTGAATGACCAGGACGATGAA
GACTGCATCAATCGTCATAATGTCTATATTAATGGAATCACATATACTCCAGTATCAAGT
ACAAATGAAAAGGATATGTACAGCTTCCTAGAGGACATGGGCTTAAAGGCATTCACCAAC
TCAAAGATTCGTAAACCCAAAATGTGTCCACAGCTTCAACAGTATGAAATGCATGGACCT
GAAGGTCTACGTGTAGGTTTTTATGAGTCAGATGTAATGGGAAGAGGCCATGCACGCCTG
GTGCATGTTGAAGAGCCTCACACGGAGACCGTACGAAAGTACTTCCCTGAGACATGGATC
TGGGATTTGGTGGTGGTAAACTCAGCAGGTGTGGCTGAGGTAGGAGTAACAGTCCCTGAC
ACCATCACCGAGTGGAAGGCAGGGGCCTTCTGCCTGTCTGAAGATGCTGGACTTGGTATC
TCTTCCACTGCCTCTCTCCGAGCCTTCCAGCCCTTCTTTGTGGAGCTCACAATGCCTTAC
TCTGTGATTCGTGGAGAGGCCTTCACACTCAAGGCCACGGTCCTAAACTACCTTCCCAAA
TGCATCCGGGTCAGTGTGCAGCTGGAAGCCTCTCCCGCCTTCCTAGCTGTCCCAGTGGAG
AAGGAACAAGCGCCTCACTGCATCTGTGCAAACGGGCGGCAAACTGTGTCCTGGGCAGTA
ACCCCAAAGTCATTAGGAAATGTGAATTTCACTGTGAGCGCAGAGGCACTAGAGTCTCAA
GAGCTGTGTGGGACTGAGGTGCCTTCAGTTCCTGAACACGGAAGGAAAGACACAGTCATC
AAGCCTCTGTTGGTTGAACCTGAAGGACTAGAGAAGGAAACAACATTCAACTCCCTACTT
TGTCCATCAGGTGGTGAGGTTTCTGAAGAATTATCCCTGAAACTGCCACCAAATGTGGTA
GAAGAATCTGCCCGAGCTTCTGTCTCAGTTTTGGGAGACATATTAGGCTCTGCCATGCAA
AACACACAAAATCTTCTCCAGATGCCCTATGGCTGTGGAGAGCAGAATATGGTCCTCTTT
GCTCCTAACATCTATGTACTGGATTATCTAAATGAAACACAGCAGCTTACTCCAGAGATC
AAGTCCAAGGCCATTGGCTATCTCAACACTGGTTACCAGAGACAGTTGAACTACAAACAC
TATGATGGCTCCTACAGCACCTTTGGGGAGCGATATGGCAGGAACCAGGGCAACACCTGG
CTCACAGCCTTTGTTCTGAAGACTTTTGCCCAAGCTCGAGCCTACATCTTCATCGATGAA
GCACACATTACCCAAGCCCTCATATGGCTCTCCCAGAGGCAGAAGGACAATGGCTGTTTC
AGGAGCTCTGGGTCACTGCTCAACAATGCCATAAAGGGAGGAGTAGAAGATGAAGTGACC
CTCTCCGCCTATATCACCATCGCCCTTCTGGAGATTCCTCTCACAGTCACTCACCCTGTT
GTCCGCAATGCCCTGTTTTGCCTGGAGTCAGCCTGGAAGACAGCACAAGAAGGGGACCAT
GGCAGCCATGTATATACCAAAGCACTGCTGGCCTATGCTTTTGCCCTGGCAGGTAACCAG
GACAAGAGGAAGGAAGTACTCAAGTCACTTAATGAGGAAGCTGTGAAGAAAGACAACTCT
GTCCATTGGGAGCGCCCTCAGAAACCCAAGGCACCAGTGGGGCATTTTTACGAACCCCAG
GCTCCCTCTGCTGAGGTGGAGATGACATCCTATGTGCTCCTCGCTTATCTCACGGCCCAG
CCAGCCCCAACCTCGGAGGACCTGACCTCTGCAACCAACATCGTGAAGTGGATCACGAAG
CAGCAGAATGCCCAGGGCGGTTTCTCCTCCACCCAGGACACAGTGGTGGCTCTCCATGCT
CTGTCCAAATATGGAGCAGCCACATTTACCAGGACTGGGAAGGCTGCACAGGTGACTATC
CAGTCTTCAGGGACATTTTCCAGCAAATTCCAAGTGGACAACAACAACCGCCTGTTACTG
CAGCAGGTCTCATTGCCAGAGCTGCCTGGGGAATACAGCATGAAAGTGACAGGAGAAGGA
TGTGTCTACCTCCAGACATCCTTGAAATACAATATTCTCCCAGAAAAGGAAGAGTTCCCC
TTTGCTTTAGGAGTGCAGACTCTGCCTCAAACTTGTGATGAACCCAAAGCCCACACCAGC
TTCCAAATCTCCCTAAGTGTCAGTTACACAGGGAGCCGCTCTGCCTCCAACATGGCGATC
GTTGATGTGAAGATGGTCTCTGGCTTCATTCCCCTGAAGCCAACAGTGAAAATGCTTGAA
AGATCTAACCATGTGAGCCGGACAGAAGTCAGCAGCAACCATGTCTTGATTTACCTTGAT
AAGGTGTCAAATCAGACACTGAGCTTGTTCTTCACGGTTCTGCAAGATGTCCCAGTAAGA
GATCTGAAACCAGCCATAGTGAAAGTCTATGATTACTACGAGACGGATGAGTTTGCAATT
GCTGAGTACAATGCTCCTTGCAGCAAAGATCTTGGAAATGCTTGA

Chromosome Location

Locus

12p13.31

External Identifiers

Resource	Link
UniProtKB ID	P01023
UniProtKB Entry Name	A2MG_HUMAN
GenBank Protein ID	177870
GenBank Gene ID	M11313
GeneCard ID	A2M
GenAtlas ID	A2M
HGNC ID	HGNC:7
PDB ID(s)	1BV8, 2P9R, 6TAV, 7O7L, 7O7M, 7O7N, 7O7O, 7O7P, 7O7Q, 7O7R, 7O7S, 7VON, 7VOO
KEGG ID	hsa:2
NCBI Gene ID	2

General References

Kan CC, Solomon E, Belt KT, Chain AC, Hiorns LR, Fey G: Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2282-6. [Article]
Lin VK, Wang SY, Boetticher NC, Vazquez DV, Saboorian H, McConnell JD, Roehrborn CG: Alpha(2) macroglobulin, a PSA binding protein, is expressed in human prostate stroma. Prostate. 2005 May 15;63(3):299-308. [Article]
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
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Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
Matthijs G, Devriendt K, Cassiman JJ, Van den Berghe H, Marynen P: Structure of the human alpha-2 macroglobulin gene and its promotor. Biochem Biophys Res Commun. 1992 Apr 30;184(2):596-603. [Article]
Sottrup-Jensen L, Stepanik TM, Kristensen T, Wierzbicki DM, Jones CM, Lonblad PB, Magnusson S, Petersen TE: Primary structure of human alpha 2-macroglobulin. V. The complete structure. J Biol Chem. 1984 Jul 10;259(13):8318-27. [Article]
Jensen PE, Sottrup-Jensen L: Primary structure of human alpha 2-macroglobulin. Complete disulfide bridge assignment and localization of two interchain bridges in the dimeric proteinase binding unit. J Biol Chem. 1986 Dec 5;261(34):15863-9. [Article]
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Associated Data

Bio-Entities

Bio-Entity	Type
Alpha-2-macroglobulin (Humans)	protein primary

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Bacitracin	approved, vet_approved	unknown	target	inhibitor	Details
Becaplermin	approved, investigational	unknown	target		Details
Ocriplasmin	approved	no	target	ligand	Details
Copper	approved, investigational	no	carrier	binder	Details
Mangafodipir	approved, investigational, withdrawn	unknown	carrier	binder	Details
Cisplatin	approved	unknown	target		Details
Zinc	approved, investigational	unknown	target		Details
Silver	approved, investigational	unknown	target	binder	Details
Zinc acetate	approved, investigational	unknown	target		Details
Zinc chloride	approved, investigational	unknown	target	ligand	Details
Zinc sulfate, unspecified form	approved, experimental	unknown	target	ligand	Details
Anacaulase	approved, investigational	unknown	target	binder	Details