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Protein

Alpha-2-macroglobulin

Gene

A2M

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI39.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-macroglobulin
Short name:
Alpha-2-M
Gene namesi
Name:A2M
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
Proteomesi
  • UP000001595 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000004269524 – 1474Alpha-2-macroglobulinAdd BLAST1451

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi48 ↔ 86By similarity
Glycosylationi55N-linked (GlcNAc...)By similarity1
Glycosylationi70N-linked (GlcNAc...)By similarity1
Glycosylationi247N-linked (GlcNAc...)By similarity1
Disulfide bondi251 ↔ 299By similarity
Disulfide bondi269 ↔ 287By similarity
Disulfide bondi278Interchain (with C-431)By similarity
Glycosylationi396N-linked (GlcNAc...)By similarity1
Glycosylationi410N-linked (GlcNAc...)By similarity1
Disulfide bondi431Interchain (with C-278)By similarity
Disulfide bondi470 ↔ 563By similarity
Disulfide bondi595 ↔ 771By similarity
Disulfide bondi642 ↔ 689By similarity
Cross-linki693Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)Sequence analysis
Cross-linki694Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)Sequence analysis
Disulfide bondi821 ↔ 849By similarity
Disulfide bondi847 ↔ 883By similarity
Glycosylationi869N-linked (GlcNAc...)By similarity1
Disulfide bondi921 ↔ 1321By similarity
Cross-linki972 ↔ 975Isoglutamyl cysteine thioester (Cys-Gln)By similarity
Glycosylationi991N-linked (GlcNAc...)By similarity1
Disulfide bondi1079 ↔ 1127By similarity
Disulfide bondi1352 ↔ 1467By similarity
Glycosylationi1424N-linked (GlcNAc...)By similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Thioester bond

Proteomic databases

PRIDEiQ5R4N8.

Expressioni

Tissue specificityi

Plasma.

Interactioni

Subunit structurei

Homotetramer; disulfide-linked.By similarity

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000004847.

Structurei

3D structure databases

ProteinModelPortaliQ5R4N8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni690 – 728Bait regionBy similarityAdd BLAST39
Regioni704 – 709InhibitoryBy similarity6
Regioni719 – 723InhibitoryBy similarity5
Regioni730 – 735InhibitoryBy similarity6

Sequence similaritiesi

Keywords - Domaini

Bait region, Signal

Phylogenomic databases

eggNOGiENOG410IMYI. Eukaryota.
COG2373. LUCA.
HOVERGENiHBG000039.
InParanoidiQ5R4N8.
KOiK03910.

Family and domain databases

Gene3Di1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProiIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR014756. Ig_E-set.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
IPR010916. TonB_box_CS.
[Graphical view]
PfamiPF00207. A2M. 1 hit.
PF07678. A2M_comp. 1 hit.
PF01835. A2M_N. 1 hit.
PF07703. A2M_N_2. 1 hit.
PF07677. A2M_recep. 1 hit.
PF10569. Thiol-ester_cl. 1 hit.
[Graphical view]
SMARTiSM01360. A2M. 1 hit.
SM01359. A2M_N_2. 1 hit.
SM01361. A2M_recep. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q5R4N8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TEAAEKGCVL
60 70 80 90 100
LSYLNETVTV SASLESVRGN RSLFTDLEAE NDVLHCVAFA IPKSSSNEEV
110 120 130 140 150
MFLTVQVKGP TQEFKKRTTV MVKNEDSLVF VQTDKSIYKP AQTVKFRVVS
160 170 180 190 200
MDENFHPLNE LIPLVYIQDP KGNRIAQWQS FQLEGGLKQF SFPLSSEPFQ
210 220 230 240 250
GSYKVVVQKK SGRRTEHPFT VEEFVLPKFE VQVTVPKIIT ILEEEMNVSV
260 270 280 290 300
CGLYTYGKPV PGHVTVSICR KYSDASNCHG EDSQAFCEKF SGQLNSHGCF
310 320 330 340 350
YQQVKTKVFQ LKRKEYEMKL HTKAQIQEEG TVVELTGRQS SEITRTITKL
360 370 380 390 400
SFVKADSHFR QGIPFFGQVR LVDGKGVPIP NKVIFIRGNE ANYYSNATTD
410 420 430 440 450
EHGLVQFSIN TTNVMGTSLT VRVKYKDRSP CYGYQWVSEE HEEAHHTAYL
460 470 480 490 500
VFSPSKSFVH LEPVSHELPC GQTQTVQAHY ILNGGALQGL KKLSFYYLIM
510 520 530 540 550
AKGGIVRTGT HGLLVKQEDM KGHFSISIPV KSDIAPVARL LIYAVLPTGD
560 570 580 590 600
VIGDSAKYDV ENCLANKVDL SFSPSQSLPA LHAHLRVTAA PQSLCALRAV
610 620 630 640 650
DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQGDE DCINRHNVYI
660 670 680 690 700
NGITYTPVSS TNEKDMYSFL EDMGLKAFTN SKIRKPKLCP QLQQYEMHGP
710 720 730 740 750
EGLRVGFYES DVMGRGHARL VHAEEPPTET VRKYFPETWI WDLVVVNSSG
760 770 780 790 800
VAEVGVTVPD TITEWKAGAF CLSEDAGLGI SSTASLRAFQ PFFVELTMPY
810 820 830 840 850
SVIRGEVFTL KATVLNYLPK CIRVSVQLEA SPAFLAVPVE KEQAPHCICA
860 870 880 890 900
NGRQTVSWAI TPKSLGNVNF TVSAEALESQ ELCGTEVASV PEYGKKDTVI
910 920 930 940 950
KPLLVEPEGL EKETTFNSLL CPSGGEVSEE LSLKLPPNVV EESARASVSV
960 970 980 990 1000
LGDILGSAMQ NTQNLLQMPY GCGEQNMVLF APNIYVLDYL NETQQLTPEI
1010 1020 1030 1040 1050
KSKAIGYLNT GYQRQLNYKH YDGSYSTFGE RYGRNQGNTW LTAFVLKTFA
1060 1070 1080 1090 1100
QARAYIFIDE AHITQALIWL SQRQKDNGCF RSSGSLLNNA IKGGVEDEVT
1110 1120 1130 1140 1150
LSAYITIALL EIPLTVTHPV VRNALFCLES AWKTAQEGDH GSHVYTKALL
1160 1170 1180 1190 1200
AYAFALAGNQ DKRKEVLQSL HEEAVKKDNS VHWERPQKPK APVGHFYEPQ
1210 1220 1230 1240 1250
APSAEVEMTS YALLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS
1260 1270 1280 1290 1300
TQDTVVALHA LSKYGAATFT RTGKAAQVTI QSSGTFSNKF QVDNNNRLLL
1310 1320 1330 1340 1350
QQVSLPELPG EYSMKVTGEG CVYLQTSLKY NILPEKEEFP FALGVQTLPQ
1360 1370 1380 1390 1400
TCDEPKAHTS FQISLSVSYT GSRSASNMAI VDVKMVSGFI PLKPTVKMLE
1410 1420 1430 1440 1450
RSNHVSRTEV SNNHVLIYLD KVSNQTLSLF FTVLQDVPVR DLKPAIVKVY
1460 1470
DYYETDEFAI AEYNAPCSKD LGNA
Length:1,474
Mass (Da):163,262
Last modified:December 21, 2004 - v1
Checksum:i14F19160ACBCAB6B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR861207 mRNA. Translation: CAH93278.1.
RefSeqiNP_001126929.1. NM_001133457.1.

Genome annotation databases

GeneIDi100173946.
KEGGipon:100173946.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR861207 mRNA. Translation: CAH93278.1.
RefSeqiNP_001126929.1. NM_001133457.1.

3D structure databases

ProteinModelPortaliQ5R4N8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000004847.

Protein family/group databases

MEROPSiI39.001.

Proteomic databases

PRIDEiQ5R4N8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100173946.
KEGGipon:100173946.

Organism-specific databases

CTDi2.

Phylogenomic databases

eggNOGiENOG410IMYI. Eukaryota.
COG2373. LUCA.
HOVERGENiHBG000039.
InParanoidiQ5R4N8.
KOiK03910.

Family and domain databases

Gene3Di1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProiIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR014756. Ig_E-set.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
IPR010916. TonB_box_CS.
[Graphical view]
PfamiPF00207. A2M. 1 hit.
PF07678. A2M_comp. 1 hit.
PF01835. A2M_N. 1 hit.
PF07703. A2M_N_2. 1 hit.
PF07677. A2M_recep. 1 hit.
PF10569. Thiol-ester_cl. 1 hit.
[Graphical view]
SMARTiSM01360. A2M. 1 hit.
SM01359. A2M_N_2. 1 hit.
SM01361. A2M_recep. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiA2MG_PONAB
AccessioniPrimary (citable) accession number: Q5R4N8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: December 21, 2004
Last modified: October 5, 2016
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.