CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001860
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Alpha-2-macroglobulin 
Protein Synonyms/Alias
 Alpha-2-M; C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5 
Gene Name
 A2M 
Gene Synonyms/Alias
 CPAMD5; FWP007 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
145YKPGQTVKFRVVSMDglycation[1]
382KGVPIPNKVIFIRGNglycation[1]
1003LTPEIKSKAIGYLNTglycation[1]
1162ALAGNQDKRKEVLKSacetylation[2]
1168DKRKEVLKSLNEEAVglycation[1]
Reference
 [1] Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
 Zhang Q, Tang N, Schepmoes AA, Phillips LS, Smith RD, Metz TO.
 J Proteome Res. 2008 May;7(5):2025-32. [PMID: 18396901]
 [2] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224] 
Functional Description
 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. 
Sequence Annotation
 REGION 690 728 Bait region.
 REGION 704 709 Inhibitory.
 REGION 719 723 Inhibitory.
 REGION 730 735 Inhibitory.
 CARBOHYD 55 55 N-linked (GlcNAc...).
 CARBOHYD 70 70 N-linked (GlcNAc...).
 CARBOHYD 247 247 N-linked (GlcNAc...).
 CARBOHYD 396 396 N-linked (GlcNAc...).
 CARBOHYD 410 410 N-linked (GlcNAc...).
 CARBOHYD 869 869 N-linked (GlcNAc...).
 CARBOHYD 991 991 N-linked (GlcNAc...).
 CARBOHYD 1424 1424 N-linked (GlcNAc...).
 DISULFID 48 86
 DISULFID 251 299
 DISULFID 269 287
 DISULFID 278 278 Interchain (with C-431).
 DISULFID 431 431 Interchain (with C-278).
 DISULFID 470 563
 DISULFID 595 771
 DISULFID 642 689
 DISULFID 821 849
 DISULFID 847 883
 DISULFID 921 1321
 DISULFID 1079 1127
 DISULFID 1352 1467
 CROSSLNK 693 693 Isoglutamyl lysine isopeptide (Gln-Lys)
 CROSSLNK 694 694 Isoglutamyl lysine isopeptide (Gln-Lys)
 CROSSLNK 972 975 Isoglutamyl cysteine thioester (Cys-Gln).  
Keyword
 3D-structure; Bait region; Complete proteome; Direct protein sequencing; Disulfide bond; Glycoprotein; Isopeptide bond; Polymorphism; Protease inhibitor; Reference proteome; Secreted; Serine protease inhibitor; Signal; Thioester bond. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1474 AA 
Protein Sequence
MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL LSYLNETVTV 60
SASLESVRGN RSLFTDLEAE NDVLHCVAFA VPKSSSNEEV MFLTVQVKGP TQEFKKRTTV 120
MVKNEDSLVF VQTDKSIYKP GQTVKFRVVS MDENFHPLNE LIPLVYIQDP KGNRIAQWQS 180
FQLEGGLKQF SFPLSSEPFQ GSYKVVVQKK SGGRTEHPFT VEEFVLPKFE VQVTVPKIIT 240
ILEEEMNVSV CGLYTYGKPV PGHVTVSICR KYSDASDCHG EDSQAFCEKF SGQLNSHGCF 300
YQQVKTKVFQ LKRKEYEMKL HTEAQIQEEG TVVELTGRQS SEITRTITKL SFVKVDSHFR 360
QGIPFFGQVR LVDGKGVPIP NKVIFIRGNE ANYYSNATTD EHGLVQFSIN TTNVMGTSLT 420
VRVNYKDRSP CYGYQWVSEE HEEAHHTAYL VFSPSKSFVH LEPMSHELPC GHTQTVQAHY 480
ILNGGTLLGL KKLSFYYLIM AKGGIVRTGT HGLLVKQEDM KGHFSISIPV KSDIAPVARL 540
LIYAVLPTGD VIGDSAKYDV ENCLANKVDL SFSPSQSLPA SHAHLRVTAA PQSVCALRAV 600
DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQDNE DCINRHNVYI NGITYTPVSS 660
TNEKDMYSFL EDMGLKAFTN SKIRKPKMCP QLQQYEMHGP EGLRVGFYES DVMGRGHARL 720
VHVEEPHTET VRKYFPETWI WDLVVVNSAG VAEVGVTVPD TITEWKAGAF CLSEDAGLGI 780
SSTASLRAFQ PFFVELTMPY SVIRGEAFTL KATVLNYLPK CIRVSVQLEA SPAFLAVPVE 840
KEQAPHCICA NGRQTVSWAV TPKSLGNVNF TVSAEALESQ ELCGTEVPSV PEHGRKDTVI 900
KPLLVEPEGL EKETTFNSLL CPSGGEVSEE LSLKLPPNVV EESARASVSV LGDILGSAMQ 960
NTQNLLQMPY GCGEQNMVLF APNIYVLDYL NETQQLTPEI KSKAIGYLNT GYQRQLNYKH 1020
YDGSYSTFGE RYGRNQGNTW LTAFVLKTFA QARAYIFIDE AHITQALIWL SQRQKDNGCF 1080
RSSGSLLNNA IKGGVEDEVT LSAYITIALL EIPLTVTHPV VRNALFCLES AWKTAQEGDH 1140
GSHVYTKALL AYAFALAGNQ DKRKEVLKSL NEEAVKKDNS VHWERPQKPK APVGHFYEPQ 1200
APSAEVEMTS YVLLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS TQDTVVALHA 1260
LSKYGAATFT RTGKAAQVTI QSSGTFSSKF QVDNNNRLLL QQVSLPELPG EYSMKVTGEG 1320
CVYLQTSLKY NILPEKEEFP FALGVQTLPQ TCDEPKAHTS FQISLSVSYT GSRSASNMAI 1380
VDVKMVSGFI PLKPTVKMLE RSNHVSRTEV SSNHVLIYLD KVSNQTLSLF FTVLQDVPVR 1440
DLKPAIVKVY DYYETDEFAI AEYNAPCSKD LGNA 1474 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005615; C:extracellular space; IEA:InterPro.
 GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
 GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
 GO:0019966; F:interleukin-1 binding; IDA:UniProtKB.
 GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
 GO:0043120; F:tumor necrosis factor binding; IDA:UniProtKB.
 GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome.
 GO:0001869; P:negative regulation of complement activation, lectin pathway; IDA:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0002576; P:platelet degranulation; TAS:Reactome.
 GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
 GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
 GO:0048863; P:stem cell differentiation; IEA:Compara. 
Interpro
 IPR009048; A-macroglobulin_rcpt-bd.
 IPR011626; A2M_comp.
 IPR002890; A2M_N.
 IPR011625; A2M_N_2.
 IPR001599; Macroglobln_a2.
 IPR019742; MacrogloblnA2_CS.
 IPR019565; MacrogloblnA2_thiol-ester-bond.
 IPR008930; Terpenoid_cyclase/PrenylTrfase.
 IPR010916; TonB_box_CS. 
Pfam
 PF00207; A2M
 PF07678; A2M_comp
 PF01835; A2M_N
 PF07703; A2M_N_2
 PF07677; A2M_recep
 PF10569; Thiol-ester_cl 
SMART
  
PROSITE
 PS00477; ALPHA_2_MACROGLOBULIN 
PRINTS