A1M_RAT
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 03-AUG-2022, entry version 128.
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}.
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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 GlyGen; Q63041; 11 sites.
DR PaxDb; Q63041; -.
DR PRIDE; Q63041; -.
DR GeneID; 252922; -.
DR KEGG; rno:252922; -.
DR UCSC; RGD:628643; rat.
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 OMA; EMFPVVY; -.
DR OrthoDB; 354230at2759; -.
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 tissues.
DR Genevisible; Q63041; RN.
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 GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR CDD; cd02897; A2M_2; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
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; 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 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 SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
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
