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Identification
HMDB Protein ID HMDBP02061
Secondary Accession Numbers
  • 7540
Name Alpha-2-macroglobulin
Synonyms
  1. Alpha-2-M
  2. C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
Gene Name A2M
Protein Type Enzyme
Biological Properties
General Function Involved in protein binding
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region part
extracellular space
extracellular region
Function
binding
peptidase inhibitor activity
endopeptidase inhibitor activity
enzyme regulator activity
enzyme inhibitor activity
protein binding
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location Chromosome:1
Locus 12p13.3-p12.3
SNPs A2M
Gene Sequence
>4425 bp
ATGGGGAAGAACAAACTCCTTCATCCAAGTCTGGTTCTTCTCCTCTTGGTCCTCCTGCCC
ACAGACGCCTCAGTCTCTGGAAAACCGCAGTATATGGTTCTGGTCCCCTCCCTGCTCCAC
ACTGAGACCACTGAGAAGGGCTGTGTCCTTCTGAGCTACCTGAATGAGACAGTGACTGTA
AGTGCTTCCTTGGAGTCTGTCAGGGGAAACAGGAGCCTCTTCACTGACCTGGAGGCGGAG
AATGACGTACTCCACTGTGTCGCCTTCGCTGTCCCAAAGTCTTCATCCAATGAGGAGGTA
ATGTTCCTCACTGTCCAAGTGAAAGGACCAACCCAAGAATTTAAGAAGCGGACCACAGTG
ATGGTTAAGAACGAGGACAGTCTGGTCTTTGTCCAGACAGACAAATCAATCTACAAACCA
GGGCAGACAGTGAAATTTCGTGTTGTCTCCATGGATGAAAACTTTCACCCCCTGAATGAG
TTGATTCCACTAGTATACATTCAGGATCCCAAAGGAAATCGCATCGCACAATGGCAGAGT
TTCCAGTTAGAGGGTGGCCTCAAGCAATTTTCTTTTCCCCTCTCATCAGAGCCCTTCCAG
GGCTCCTACAAGGTGGTGGTACAGAAGAAATCAGGTGGAAGGACAGAGCACCCTTTCACC
GTGGAGGAATTTGTTCTTCCCAAGTTTGAAGTACAAGTAACAGTGCCAAAGATAATCACC
ATCTTGGAAGAAGAGATGAATGTATCAGTGTGTGGCCTATACACATATGGGAAGCCTGTC
CCTGGACATGTGACTGTGAGCATTTGCAGAAAGTATAGTGACGCTTCCGACTGCCACGGT
GAAGATTCACAGGCTTTCTGTGAGAAATTCAGTGGACAGCTAAACAGCCATGGCTGCTTC
TATCAGCAAGTAAAAACCAAGGTCTTCCAGCTGAAGAGGAAGGAGTATGAAATGAAACTT
CACACTGAGGCCCAGATCCAAGAAGAAGGAACAGTGGTGGAATTGACTGGAAGGCAGTCC
AGTGAAATCACAAGAACCATAACCAAACTCTCATTTGTGAAAGTGGACTCACACTTTCGA
CAGGGAATTCCCTTCTTTGGGCAGGTGCGCCTAGTAGATGGGAAAGGCGTCCCTATACCA
AATAAAGTCATATTCATCAGAGGAAATGAAGCAAACTATTACTCCAATGCTACCACGGAT
GAGCATGGCCTTGTACAGTTCTCTATCAACACCACCAACGTTATGGGTACCTCTCTTACT
GTTAGGGTCAATTACAAGGATCGTAGTCCCTGTTACGGCTACCAGTGGGTGTCAGAAGAA
CACGAAGAGGCACATCACACTGCTTATCTTGTGTTCTCCCCAAGCAAGAGCTTTGTCCAC
CTTGAGCCCATGTCTCATGAACTACCCTGTGGCCATACTCAGACAGTCCAGGCACATTAT
ATTCTGAATGGAGGCACCCTGCTGGGGCTGAAGAAGCTCTCCTTTTATTATCTGATAATG
GCAAAGGGAGGCATTGTCCGAACTGGGACTCATGGACTGCTTGTGAAGCAGGAAGACATG
AAGGGCCATTTTTCCATCTCAATCCCTGTGAAGTCAGACATTGCTCCTGTCGCTCGGTTG
CTCATCTATGCTGTTTTACCTACCGGGGACGTGATTGGGGATTCTGCAAAATATGATGTT
GAAAATTGTCTGGCCAACAAGGTGGATTTGAGCTTCAGCCCATCACAAAGTCTCCCAGCC
TCACACGCCCACCTGCGAGTCACAGCGGCTCCTCAGTCCGTCTGCGCCCTCCGTGCTGTG
GACCAAAGCGTGCTGCTCATGAAGCCTGATGCTGAGCTCTCGGCGTCCTCGGTTTACAAC
CTGCTACCAGAAAAGGACCTCACTGGCTTCCCTGGGCCTTTGAATGACCAGGACGATGAA
GACTGCATCAATCGTCATAATGTCTATATTAATGGAATCACATATACTCCAGTATCAAGT
ACAAATGAAAAGGATATGTACAGCTTCCTAGAGGACATGGGCTTAAAGGCATTCACCAAC
TCAAAGATTCGTAAACCCAAAATGTGTCCACAGCTTCAACAGTATGAAATGCATGGACCT
GAAGGTCTACGTGTAGGTTTTTATGAGTCAGATGTAATGGGAAGAGGCCATGCACGCCTG
GTGCATGTTGAAGAGCCTCACACGGAGACCGTACGAAAGTACTTCCCTGAGACATGGATC
TGGGATTTGGTGGTGGTAAACTCAGCAGGGGTGGCTGAGGTAGGAGTAACAGTCCCTGAC
ACCATCACCGAGTGGAAGGCAGGGGCCTTCTGCCTGTCTGAAGATGCTGGACTTGGTATC
TCTTCCACTGCCTCTCTCCGAGCCTTCCAGCCCTTCTTTGTGGAGCTTACAATGCCTTAC
TCTGTGATTCGTGGAGAGGCCTTCACACTCAAGGCCACGGTCCTAAACTACCTTCCCAAA
TGCATCCGGGTCAGTGTGCAGCTGGAAGCCTCTCCCGCCTTCCTTGCTGTCCCAGTGGAG
AAGGAACAAGCGCCTCACTGCATCTGTGCAAACGGGCGGCAAACTGTGTCCTGGGCAGTA
ACCCCAAAGTCATTAGGAAATGTGAATTTCACTGTGAGCGCAGAGGCACTAGAGTCTCAA
GAGCTGTGTGGGACTGAGGTGCCTTCAGTTCCTGAACACGGAAGGAAAGACACAGTCATC
AAGCCTCTGTTGGTTGAACCTGAAGGACTAGAGAAGGAAACAACATTCAACTCCCTACTT
TGTCCATCAGGTGGTGAGGTTTCTGAAGAATTATCCCTGAAACTGCCACCAAATGTGGTA
GAAGAATCTGCCCGAGCTTCTGTCTCAGTTTTGGGAGACATATTAGGCTCTGCCATGCAA
AACACACAAAATCTTCTCCAGATGCCCTATGGCTGTGGAGAGCAGAATATGGTCCTCTTT
GCTCCTAACATCTATGTACTGGATTATCTAAATGAAACACAGCAGCTTACTCCAGAGGTC
AAGTCCAAGGCCATTGGCTATCTCAACACTGGTTACCAGAGACAGTTGAACTACAAACAC
TATGATGGCTCCTACAGCACCTTTGGGGAGCGATATGGCAGGAACCAGGGCAACACCTGG
CTCACAGCCTTTGTTCTGAAGACTTTTGCCCAAGCTCGAGCCTACATCTTCATCGATGAA
GCACACATTACCCAAGCCCTCATATGGCTCTCCCAGAGGCAGAAGGACAATGGCTGTTTC
AGGAGCTCTGGGTCACTGCTCAACAATGCCATAAAGGGAGGAGTAGAAGATGAAGTGACC
CTCTCCGCCTATATCACCATCGCCCTTCTGGAGATTCCTCTCACAGTCACTCACCCTGTT
GTCCGCAATGCCCTGTTTTGCCTGGAGTCAGCCTGGAAGACAGCACAAGAAGGGGACCAT
GGCAGCCATGTATATACCAAAGCACTGCTGGCCTATGCTTTTGCCCTGGCAGGTAACCAG
GACAAGAGGAAGGAAGTACTCAAGTCACTTAATGAGGAAGCTGTGAAGAAAGACAACTCT
GTCCATTGGGAGCGCCCTCAGAAACCCAAGGCACCAGTGGGGCATTTTTACGAACCCCAG
GCTCCCTCTGCTGAGGTGGAGATGACATCCTATGTGCTCCTCGCTTATCTCACGGCCCAG
CCAGCCCCAACCTCGGAGGACCTGACCTCTGCAACCAACATCGTGAAGTGGATCACGAAG
CAGCAGAATGCCCAGGGCGGTTTCTCCTCCACCCAGGACACAGTGGTGGCTCTCCATGCT
CTGTCCAAATATGGAGCCGCCACATTTACCAGGACTGGGAAGGCTGCACAGGTGACTATC
CAGTCTTCAGGGACATTTTCCAGCAAATTCCAAGTGGACAACAACAATCGCCTGTTACTG
CAGCAGGTCTCATTGCCAGAGCTGCCTGGGGAATACAGCATGAAAGTGACAGGAGAAGGA
TGTGTCTACCTCCAGACCTCCTTGAAATACAATATTCTCCCAGAAAAGGAAGAGTTCCCC
TTTGCTTTAGGAGTGCAGACTCTGCCTCAAACTTGTGATGAACCCAAAGCCCACACCAGC
TTCCAAATCTCCCTAAGTGTCAGTTACACAGGGAGCCGCTCTGCCTCCAACATGGCGATC
GTTGATGTGAAGATGGTCTCTGGCTTCATTCCCCTGAAGCCAACAGTGAAAATGCTTGAA
AGATCTAACCATGTGAGCCGGACAGAAGTCAGCAGCAACCATGTCTTGATTTACCTTGAT
AAGGTGTCAAATCAGACACTGAGCTTGTTCTTCACGGTTCTGCAAGATGTCCCAGTAAGA
GATCTCAAACCAGCCATAGTGAAAGTCTATGATTACTACGAGACGGATGAGTTTGCAATC
GCTGAGTACAATGCTCCTTGCAGCAAAGATCTTGGAAATGCTTGA
Protein Properties
Number of Residues 1474
Molecular Weight 163289.9
Theoretical pI 6.43
Pfam Domain Function
Signals
  • 1-23
Transmembrane Regions
  • None
Protein Sequence
>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
GenBank ID Protein 177870
UniProtKB/Swiss-Prot ID P01023
UniProtKB/Swiss-Prot Entry Name A2MG_HUMAN
PDB IDs
GenBank Gene ID M11313
GeneCard ID A2M
GenAtlas ID A2M
HGNC ID HGNC:7
References
General References
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  4. 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. [PubMed:17974005 ]
  5. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952 ]
  6. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. [PubMed:14760718 ]
  7. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519 ]
  8. 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. [PubMed:2581245 ]
  9. 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. [PubMed:15611997 ]
  10. 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. [PubMed:1374237 ]
  11. 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. [PubMed:6203908 ]
  12. 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. [PubMed:2430963 ]
  13. Marynen P, Devriendt K, Van den Berghe H, Cassiman JJ: A genetic polymorphism in a functional domain of human pregnancy zone protein: the bait region. Genomic structure of the bait domains of human pregnancy zone protein and alpha 2 macroglobulin. FEBS Lett. 1990 Mar 26;262(2):349-52. [PubMed:1692292 ]
  14. Poller W, Faber JP, Klobeck G, Olek K: Cloning of the human alpha 2-macroglobulin gene and detection of mutations in two functional domains: the bait region and the thiolester site. Hum Genet. 1992 Jan;88(3):313-9. [PubMed:1370808 ]
  15. Bell GI, Rall LB, Sanchez-Pescador R, Merryweather JP, Scott J, Eddy RL, Shows TB: Human alpha 2-macroglobulin gene is located on chromosome 12. Somat Cell Mol Genet. 1985 May;11(3):285-9. [PubMed:2408344 ]
  16. Hall PK, Nelles LP, Travis J, Roberts RC: Proteolytic cleavage sites on alpha 2-macroglobulin resulting in proteinase binding are different for trypsin and Staphylococcus aureus V-8 proteinase. Biochem Biophys Res Commun. 1981 May 15;100(1):8-16. [PubMed:6167263 ]
  17. Sottrup-Jensen L, Lonblad PB, Stepanik TM, Petersen TE, Magnusson S, Jornvall H: Primary structure of the 'bait' region for proteinases in alpha 2-macroglobulin. Nature of the complex. FEBS Lett. 1981 May 18;127(2):167-73. [PubMed:6165619 ]
  18. Mortensen SB, Sottrup-Jensen L, Hansen HF, Petersen TE, Magnusson S: Primary and secondary cleavage sites in the bait region of alpha 2-macroglobulin. FEBS Lett. 1981 Dec 7;135(2):295-300. [PubMed:6172288 ]
  19. Virca GD, Salvesen GS, Travis J: Human neutrophil elastase and cathepsin G cleavage sites in the bait region of alpha 2-macroglobulin. Proposed structural limits of the bait region. Hoppe Seylers Z Physiol Chem. 1983 Sep;364(9):1297-302. [PubMed:6195065 ]
  20. Huang W, Dolmer K, Liao X, Gettins PG: Localization of basic residues required for receptor binding to the single alpha-helix of the receptor binding domain of human alpha2-macroglobulin. Protein Sci. 1998 Dec;7(12):2602-12. [PubMed:9865955 ]
  21. Doan N, Gettins PG: Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. Biochem J. 2007 Oct 1;407(1):23-30. [PubMed:17608619 ]
  22. Poller W, Faber JP, Olek K: Sequence polymorphism in the human alpha-2-macroglobulin (A2M) gene. Nucleic Acids Res. 1991 Jan 11;19(1):198. [PubMed:1707161 ]