ID   A1M_RAT                 Reviewed;        1500 AA.
AC   Q63041; Q63332;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 135.
DE   RecName: Full=Alpha-1-macroglobulin;
DE            Short=Alpha-1-M;
DE   AltName: Full=Alpha-1-macroglobulin 165 kDa subunit;
DE   Contains:
DE     RecName: Full=Alpha-1-macroglobulin 45 kDa subunit;
DE   Flags: Precursor;
GN   Name=A1m {ECO:0000312|EMBL:AAA40723.1};
GN   Synonyms=Pzp {ECO:0000312|RGD:628643};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAA40723.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-54; 724-743; 901-930 AND
RP   1245-1269, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   STRAIN=Fischer 344 {ECO:0000312|EMBL:AAA40723.1};
RC   TISSUE=Liver {ECO:0000312|EMBL:AAA40723.1};
RX   PubMed=1725450;
RA   Eggertsen G., Hudson G., Shiels B., Reed D., Fey G.H.;
RT   "Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor
RT   from the alpha-macroglobulin-complement family.";
RL   Mol. Biol. Med. 8:287-302(1991).
RN   [2] {ECO:0000312|EMBL:AAA41591.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAA41591.1};
RC   TISSUE=Liver {ECO:0000312|EMBL:AAA41591.1};
RX   PubMed=1371696; DOI=10.1021/bi00123a020;
RA   Warmegard B., Martin N., Johansson S.;
RT   "cDNA cloning and sequencing of rat alpha 1-macroglobulin.";
RL   Biochemistry 31:2346-2352(1992).
RN   [3]
RP   PROTEIN SEQUENCE OF 1287-1294 AND 1321-1327, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA   Lubec G., Chen W.-Q.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [4] {ECO:0000312|PDB:1EDY}
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1362-1495.
RX   PubMed=11106161; DOI=10.1110/ps.9.10.1889;
RA   Xiao T., DeCamp D.L., Spran S.R.;
RT   "Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer.";
RL   Protein Sci. 9:1889-1897(2000).
CC   -!- FUNCTION: Is able to inhibit all four classes of proteinases by a
CC       unique 'trapping' mechanism. This protein has a peptide stretch, called
CC       the 'bait region' which contains specific cleavage sites for different
CC       proteinases. When a proteinase cleaves the bait region, a
CC       conformational change is induced in the protein which traps the
CC       proteinase. The entrapped enzyme remains active against low molecular
CC       weight substrates (activity against high molecular weight substrates is
CC       greatly reduced). Following cleavage in the bait region a thioester
CC       bond is hydrolyzed and mediates the covalent binding of the protein to
CC       the proteinase (By similarity). {ECO:0000250|UniProtKB:P01023}.
CC   -!- SUBUNIT: Homotetramer; disulfide-linked.
CC       {ECO:0000250|UniProtKB:P01023}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1725450}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highest level in ovary, testis,
CC       uterus and prostate. Protein found in plasma.
CC       {ECO:0000269|PubMed:1725450}.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2-
CC       macroglobulin) family. {ECO:0000255}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M77183; AAA40723.1; -; mRNA.
DR   EMBL; M84000; AAA41591.1; -; mRNA.
DR   PIR; A42210; A42210.
DR   RefSeq; NP_665722.2; NM_145779.2.
DR   PDB; 1EDY; X-ray; 2.30 A; A/B=1362-1495.
DR   PDBsum; 1EDY; -.
DR   AlphaFoldDB; Q63041; -.
DR   SMR; Q63041; -.
DR   BioGRID; 251671; 1.
DR   IntAct; Q63041; 1.
DR   STRING; 10116.ENSRNOP00000009467; -.
DR   MEROPS; I39.001; -.
DR   GlyCosmos; Q63041; 11 sites, No reported glycans.
DR   GlyGen; Q63041; 12 sites, 1 O-linked glycan (1 site).
DR   PhosphoSitePlus; Q63041; -.
DR   PaxDb; 10116-ENSRNOP00000009467; -.
DR   GeneID; 252922; -.
DR   KEGG; rno:252922; -.
DR   UCSC; RGD:628643; rat.
DR   AGR; RGD:628643; -.
DR   CTD; 5858; -.
DR   RGD; 628643; Pzp.
DR   VEuPathDB; HostDB:ENSRNOG00000006709; -.
DR   eggNOG; KOG1366; Eukaryota.
DR   HOGENOM; CLU_001634_0_1_1; -.
DR   InParanoid; Q63041; -.
DR   OrthoDB; 2970602at2759; -.
DR   PhylomeDB; Q63041; -.
DR   TreeFam; TF313285; -.
DR   EvolutionaryTrace; Q63041; -.
DR   PRO; PR:Q63041; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000006709; Expressed in liver and 15 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR   GO; GO:0048403; F:brain-derived neurotrophic factor binding; IDA:RGD.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0048406; F:nerve growth factor binding; IDA:RGD.
DR   GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   CDD; cd02897; A2M_2; 1.
DR   Gene3D; 1.50.10.20; -; 1.
DR   Gene3D; 2.20.130.20; -; 1.
DR   Gene3D; 2.60.120.1540; -; 1.
DR   Gene3D; 2.60.40.1930; -; 2.
DR   Gene3D; 2.60.40.1940; -; 1.
DR   Gene3D; 6.20.50.160; -; 1.
DR   Gene3D; 2.60.40.690; Alpha-macroglobulin, receptor-binding domain; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR   InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR   InterPro; IPR011625; A2M_N_BRD.
DR   InterPro; IPR041813; A2M_TED.
DR   InterPro; IPR047565; Alpha-macroglob_thiol-ester_cl.
DR   InterPro; IPR011626; Alpha-macroglobulin_TED.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR001599; Macroglobln_a2.
DR   InterPro; IPR019742; MacrogloblnA2_CS.
DR   InterPro; IPR002890; MG2.
DR   InterPro; IPR041555; MG3.
DR   InterPro; IPR040839; MG4.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   PANTHER; PTHR11412; MACROGLOBULIN / COMPLEMENT; 1.
DR   PANTHER; PTHR11412:SF116; PREGNANCY ZONE PROTEIN; 1.
DR   Pfam; PF00207; A2M; 1.
DR   Pfam; PF07703; A2M_BRD; 1.
DR   Pfam; PF07677; A2M_recep; 1.
DR   Pfam; PF01835; MG2; 1.
DR   Pfam; PF17791; MG3; 1.
DR   Pfam; PF17789; MG4; 1.
DR   Pfam; PF07678; TED_complement; 1.
DR   SMART; SM01360; A2M; 1.
DR   SMART; SM01359; A2M_N_2; 1.
DR   SMART; SM01361; A2M_recep; 1.
DR   SMART; SM01419; Thiol-ester_cl; 1.
DR   SUPFAM; SSF49410; Alpha-macroglobulin receptor domain; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF48239; Terpenoid cyclases/Protein prenyltransferases; 1.
DR   PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR   Genevisible; Q63041; RN.
PE   1: Evidence at protein level;
KW   3D-structure; Bait region; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW   Serine protease inhibitor; Signal; Thioester bond.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:1725450"
FT   CHAIN           25..1500
FT                   /note="Alpha-1-macroglobulin"
FT                   /id="PRO_0000271403"
FT   CHAIN           1245..1500
FT                   /note="Alpha-1-macroglobulin 45 kDa subunit"
FT                   /evidence="ECO:0000269|PubMed:1725450"
FT                   /id="PRO_0000271404"
FT   REGION          686..746
FT                   /note="Bait region"
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   REGION          1360..1500
FT                   /note="Receptor-binding domain"
FT                   /evidence="ECO:0000269|PubMed:11106161"
FT   CARBOHYD        55
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        61
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        412
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        568
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        883
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        944
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1005
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1390
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1448
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        48..86
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        249..298
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        267..286
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        277
FT                   /note="Interchain (with C-430)"
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        430
FT                   /note="Interchain (with C-277)"
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        469..562
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        594..785
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        642..689
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        835..863
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        861..897
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        935..1344
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   DISULFID        1094..1142
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   CROSSLNK        986..989
FT                   /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT                   /evidence="ECO:0000250|UniProtKB:P01023"
FT   CONFLICT        50
FT                   /note="H -> A (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        918
FT                   /note="I -> P (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        924..925
FT                   /note="IE -> AT (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          1364..1375
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   TURN            1376..1378
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1384..1393
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1395..1399
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1401..1408
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1413..1415
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   HELIX           1417..1421
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   HELIX           1422..1425
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1429..1435
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1438..1444
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1451..1461
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1469..1477
FT                   /evidence="ECO:0007829|PDB:1EDY"
FT   STRAND          1481..1487
FT                   /evidence="ECO:0007829|PDB:1EDY"
SQ   SEQUENCE   1500 AA;  167125 MW;  8ABB810985795AB2 CRC64;
     MRRNQLPIPV FLLLLLLLPR DATAATGKPR YVVLVPSELY AGVPEKVCVH LNHLNETVTL
     NVTLEYGVQY SNLLIDQAVD KDSSYCSSFT ISRPLSPSAL IAVEIKGPTH HFIKKKSMWI
     TKAESPVFVQ TDKPIYKPGQ TVKFRVVSVD ISFRPVNETF PVVYIENPKR NRIFQWQNVD
     LPGGLHQLSF PLSVEPALGI YKVVVQKDSG KKIEHSFEVK EYVLPKFEVQ VKMPKTMAFL
     EEELVVTACG LYTYGKPVPG LVTMKVCRKY TQSYSNCHGQ HSKSICEEFS KQADEKGCFR
     QVVKTKVFQP RQKGYDMKIE VEAKIKEDGT GIELTGTGSC EIANTLSKLK FTKANTFYRP
     GLPFFGQVLL VDEKGQPIPN KNLTVQVNSV RSQFTFTTDE HGLANILIDT TNFTFSFMGI
     RVIYKQNNIC FDNWWVDEYH TQADHSAARI FSPSRSYIQL ELVLGTLACG QTQEIRIHFL
     LNEDALKDAK DLTFYYLIKA RGSIFNSGSH VLPLEQGKVK GVVSFPIRVE PGMAPVAKLI
     VYTILPNEEL IADVQKFDIE KCFANTVNLS FPSAQSLPAS DTHLTVKATP LSLCALTAVD
     QSVLLLKPEA KLSPQSIYNL LPQKAEQGAY LGPLPYKGGE NCIKAEDITH NGIVYTPKQD
     LNDNDAYSVF QSIGLKIFTN TRVHKPRYCP MYQAYPPLPY VGEPQALAMS AIPGAGYRSS
     NIRTSSMMMM GASEVAQEVE VRETVRKYFP ETWIWDMVPL DLSGDGELPV KVPDTITEWK
     ASAFCLSGTT GLGLSSTISH KVFQPFFLEL TLPYSVVRGE AFILKATVLN YMPHCIRIHV
     SLEMSPDFLA VPVGSHEDSH CICGNERKTV SWAVTPKSLG EVNFTATAEA LQSPELCGNK
     VAEVPALVQK DTVVKPVIVE PEGIEKEQTY NTLLCPQDAE LQENWTLDLP ANVVEGSARA
     TQSVLGDILG SAMQNLQNLL QMPYGCGEQN MVLFVPNIYV LEYLNETQQL TEAIKSKAIS
     YLISGYQRQL NYQHSDGSYS TFGDRGMRHS QGNTWLTAFV LKAFAQAQSY IYIEKTHITN
     AFNWLSMKQR ENGCFQQSGS LLNNAMKGGV DDEVTLSAYI TIALLEMPLP VTHSVVRNAL
     FCLETAWASI SNSQESHVYT KALLAYAFAL AGNRAKRSEV LESLNKDAVN EEESVHWQRP
     KNVEENVREM RSFSYKPRAP SAEVEMTAYV LLAYLTSASS RPTRDLSSSD LTTASKIVKW
     ISKQQNSHGG FSSTQDTVVA LQALSKYGAA TFTKSNKEVS VTIESSGTVS GTLHVNNGNR
     LLLQEVRLAD LPGNYITKVS GSGCVYLQTS LKYNILPEAE GEAPFTLKVN TLPLNFDKAE
     HHRKFQIHIN VSYIGERPNS NMVIVDVKMV SGFIPVKPSV KKLQDQSNIQ RTEVNTNHVL
     IYIEKLTNQT MGFSFAVEQD IPVKNLKPAP VKVYDYYETD EFAIEEYSAP FSSDSEQGNA
//