ID MPEG1_RAT Reviewed; 714 AA. AC Q9WV57; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAR-2008, sequence version 2. DT 24-JAN-2024, entry version 77. DE RecName: Full=Macrophage-expressed gene 1 protein; DE Short=Macrophage gene 1 protein; DE Short=Mpg-1; DE AltName: Full=Perforin-2 {ECO:0000250|UniProtKB:Q2M385}; DE Short=P-2 {ECO:0000250|UniProtKB:Q2M385}; DE Contains: DE RecName: Full=Macrophage-expressed gene 1 protein, processed form {ECO:0000305}; DE Flags: Precursor; GN Name=Mpeg1; 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] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-708. RC STRAIN=Sprague-Dawley; RA Chen S., Garcia G.E., Xia Y., Wilson C.B., Ku G., Feng L.; RT "Immunoneutralization of the macrophage gene-1 product attenuates renal RT injury in experimental glomerulonephritis in WKY rats."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Pore-forming protein involved in both innate and adaptive CC immunity. Plays a central role in antigen cross-presentation in CC dendritic cells by forming a pore in antigen-containing compartments, CC thereby promoting delivery of antigens for cross-presentation. Also CC involved in innate immune response following bacterial infection; shows CC antibacterial activity against a wide spectrum of Gram-positive, Gram- CC negative and acid-fast bacteria. Reduces the viability of the CC intracytosolic pathogen L.monocytogenes by inhibiting acidification of CC the phagocytic vacuole of host cells which restricts bacterial CC translocation from the vacuole to the cytosol. Required for the CC antibacterial activity of reactive oxygen species and nitric oxide. CC {ECO:0000250|UniProtKB:A1L314}. CC -!- FUNCTION: [Macrophage-expressed gene 1 protein, processed form]: Pore- CC forming protein that plays a central role in antigen cross-presentation CC in dendritic cells by mediating delivery of antigens for cross- CC presentation. Dendritic cells bridge innate and adaptive immunity by CC capturing exogenous antigens on MHC class-I molecules and presenting CC them to naive CD8(+) T-cells. Acts by forming a pore in antigen- CC containing compartments, promoting the release of antigens into the CC cytosol, enabling generation of MHCI:peptide complexes and T-cell CC priming. {ECO:0000250|UniProtKB:A1L314}. CC -!- ACTIVITY REGULATION: Forms arc- and ring-shaped pre-pores on top of the CC membrane at neutral to slightly acidic pH conditions and converts to CC pores upon acidification. Undergoes transition from the pre-pore to the CC pore in a processive clockwise hand-over-hand process. In the pore CC state, 2 alpha-helical regions refold into transmembrane hairpins (TMH1 CC and TMH2) in each protomer that form in the ensemble complex giant CC beta-barrel transmembrane pores. {ECO:0000250|UniProtKB:A1L314}. CC -!- SUBUNIT: Homooligomer; predominantly forms a homooligomeric arc-shaped CC pore complex instead of complete rings of 16 subunits. CC {ECO:0000250|UniProtKB:A1L314}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane CC {ECO:0000250|UniProtKB:A1L314}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:A1L314}. Note=Bacterial infection induces CC translocation of the cytoplasmic vesicles to bacterium-containing CC phagocytic vesicles and fusing of the vesicles. CC {ECO:0000250|UniProtKB:A1L314}. CC -!- SUBCELLULAR LOCATION: [Macrophage-expressed gene 1 protein, processed CC form]: Cytoplasmic vesicle, phagosome membrane CC {ECO:0000250|UniProtKB:A1L314}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:A1L314}. Note=Proteolytically processed in CC lysosomes, leading to its maturation and forms pores in the membrane of CC antigen-containing phagosomes. {ECO:0000250|UniProtKB:A1L314}. CC -!- DOMAIN: The MACPF domain includes the central machinery of pore CC formation: acidification causes a significant structural rearrangement, CC leading to oligomerization and deployment of the transmembrane beta- CC strands (named TMH1 and TMH2) that enter the membrane as amphipathic CC beta-hairpins. {ECO:0000250|UniProtKB:A1L314}. CC -!- DOMAIN: The P2 region contains beta-hairpins to interact with target CC membranes. {ECO:0000250|UniProtKB:A1L314}. CC -!- PTM: Proteolytically processed in two steps to generate the Macrophage- CC expressed gene 1 protein, processed form: cleaved by trypsin in CC proximity of the helical transmembrane domain releases the ectodomain CC into the lysosomal lumen to orient the pore-forming domain toward the CC endogenous membranes, and processed by the asparagine endopeptidase CC (LGMN). Proteolytic processing in antigen-containing vesicles is pH- CC dependent. {ECO:0000250|UniProtKB:A1L314}. CC -!- PTM: Monoubiquitinated in response to bacterial infection; CC ubiquitination is required for vesicular localization and antibacterial CC activity and can be blocked by bacterial cell cycle inhibiting factor CC (cif). {ECO:0000250|UniProtKB:A1L314}. CC -!- SIMILARITY: Belongs to the MPEG1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD38417.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AABR03005343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF156540; AAD38417.1; ALT_FRAME; mRNA. DR AlphaFoldDB; Q9WV57; -. DR SMR; Q9WV57; -. DR GlyCosmos; Q9WV57; 3 sites, No reported glycans. DR GlyGen; Q9WV57; 3 sites. DR PhosphoSitePlus; Q9WV57; -. DR PaxDb; 10116-ENSRNOP00000066960; -. DR UCSC; RGD:69275; rat. DR AGR; RGD:69275; -. DR RGD; 69275; Mpeg1. DR eggNOG; ENOG502QRKR; Eukaryota. DR InParanoid; Q9WV57; -. DR PhylomeDB; Q9WV57; -. DR PRO; PR:Q9WV57; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB. DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB. DR GO; GO:0030670; C:phagocytic vesicle membrane; ISS:UniProtKB. DR GO; GO:0061474; C:phagolysosome membrane; ISS:UniProtKB. DR GO; GO:0140911; F:pore-forming activity; ISO:RGD. DR GO; GO:0022829; F:wide pore channel activity; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0140367; P:antibacterial innate immune response; ISS:UniProtKB. DR GO; GO:0002478; P:antigen processing and presentation of exogenous peptide antigen; ISS:UniProtKB. DR GO; GO:0042590; P:antigen processing and presentation of exogenous peptide antigen via MHC class I; ISS:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB. DR GO; GO:0002468; P:dendritic cell antigen processing and presentation; ISS:UniProtKB. DR CDD; cd22579; MPEG1_P2; 1. DR InterPro; IPR020864; MACPF. DR InterPro; IPR039707; MPEG1. DR PANTHER; PTHR31463; MACROPHAGE-EXPRESSED GENE 1 PROTEIN; 1. DR PANTHER; PTHR31463:SF4; MACROPHAGE-EXPRESSED GENE 1 PROTEIN; 1. DR Pfam; PF01823; MACPF; 1. DR SMART; SM00457; MACPF; 1. DR PROSITE; PS51412; MACPF_2; 1. PE 2: Evidence at transcript level; KW Adaptive immunity; Cytoplasmic vesicle; Disulfide bond; Glycoprotein; KW Immunity; Innate immunity; Membrane; Reference proteome; Signal; KW Transmembrane; Transmembrane beta strand; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..714 FT /note="Macrophage-expressed gene 1 protein" FT /id="PRO_0000324145" FT CHAIN 353..629 FT /note="Macrophage-expressed gene 1 protein, processed form" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT /id="PRO_0000459025" FT TRANSMEM 113..120 FT /note="Beta stranded" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT TRANSMEM 127..132 FT /note="Beta stranded" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT TRANSMEM 235..244 FT /note="Beta stranded" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT TRANSMEM 248..256 FT /note="Beta stranded" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT TRANSMEM 654..674 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 30..345 FT /note="MACPF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745" FT REGION 410..653 FT /note="P2" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT REGION 690..714 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 352..353 FT /note="Cleavage; by LGMN" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT SITE 357..358 FT /note="Cleavage; by LGMN" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT SITE 359..360 FT /note="Cleavage; by LGMN" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT SITE 628..629 FT /note="Cleavage; by trypsin" FT /evidence="ECO:0000250|UniProtKB:A1L314" FT CARBOHYD 185 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 269 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 375 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 34..70 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 350..369 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 385..394 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 432..446 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 436..442 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 531..569 FT /evidence="ECO:0000250|UniProtKB:A1L314" FT DISULFID 554..574 FT /evidence="ECO:0000250|UniProtKB:A1L314" SQ SEQUENCE 714 AA; 78527 MW; 3235512C40B9DF35 CRC64; MNSFMAIALI WMMIACAEAD KPLRDPGMTG FQTCKDTLKL PVLEVLPGGG WDNLRNIDMG RVIDLTYTNC KTTEDGQYII PDEVYTIPQK ESNLEMNSEI RDSWVNYQST TSFSINTELS LFSKVNGKFS TEFQRMKTLQ VKDQAVTTRV QVRNRIYTVK NSPTSELSFG FTNALMDICD QLEKNQTKMA TYLAELLVLN YGTHVITSVD AGAALVQEDH IRSSFLLDNQ NSENTVTASA GIAFLNIVNF KVETDHTSQT LLTKSYLSNR TNSRVQSFGG IPFYPGITLE TWQKGITNHL VAIDRAGLPL HFFIKPDKLP GLPGGLVKKL SKTVETAVRH YYTFNTHPGC TNVDSPNFNF QANMEDDSCD AKVTNFTFGG LYQECTELSG DALCQNLEQK NLLTGDFSCP SGYTPVHLLS QTHEEGYSRL ECKKKCTLKI FCKTVCEDVF RVAKAQFRAY WCVATGQVPD NSGLLFGGLF TDKSINPMTN AQSCPAGYIP LNLFESLKVC VSLDYELGYK FSVPFGGFFS CIMGNPLVNS DTAKDIGAPS LKKCPGGFSQ HLAVISDGCQ VSYCVKAGIF TGGSLLPVRL PPYTKPPLMS QVATNTVIVT SSETARSWIK DPQTNQWKLG EPLELHKAMT VIHGDGNGMS GGEAAGVTLG VIIALGIVIT LAIYSTRKYK KEKEYQEIEE QESLVGSFAT DASPPNGEQD PCPA //