MPEG1_MOUSE
ID MPEG1_MOUSE Reviewed; 713 AA.
AC A1L314; A1L315; Q61889;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=Macrophage-expressed gene 1 protein;
DE Short=Macrophage gene 1 protein;
DE Short=Mpg-1;
DE AltName: Full=Perforin-2 {ECO:0000303|PubMed:23257510};
DE Short=P-2 {ECO:0000250|UniProtKB:Q2M385};
DE AltName: Full=Protein MPS1;
DE Flags: Precursor;
GN Name=Mpeg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-713, AND INDUCTION.
RC STRAIN=ICR;
RX PubMed=7888681;
RA Spilsbury K., O'Mara M.-A., Wu W.M., Rowe P.B., Symonds G., Takayama Y.;
RT "Isolation of a novel macrophage-specific gene by differential cDNA
RT analysis.";
RL Blood 85:1620-1629(1995).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION.
RX PubMed=23753625; DOI=10.1128/iai.00497-13;
RA Fields K.A., McCormack R., de Armas L.R., Podack E.R.;
RT "Perforin-2 restricts growth of Chlamydia trachomatis in macrophages.";
RL Infect. Immun. 81:3045-3054(2013).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=23257510; DOI=10.1159/000345249;
RA McCormack R., de Armas L.R., Shiratsuchi M., Ramos J.E., Podack E.R.;
RT "Inhibition of intracellular bacterial replication in fibroblasts is
RT dependent on the perforin-like protein (perforin-2) encoded by macrophage-
RT expressed gene 1.";
RL J. Innate Immun. 5:185-194(2013).
RN [6]
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND MUTAGENESIS OF 678-LYS--LYS-681.
RX PubMed=26418746; DOI=10.7554/elife.06505;
RA McCormack R.M., Lyapichev K., Olsson M.L., Podack E.R., Munson G.P.;
RT "Enteric pathogens deploy cell cycle inhibiting factors to block the
RT bactericidal activity of Perforin-2.";
RL Elife 4:E06505-E06505(2015).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26402460; DOI=10.7554/elife.06508;
RA McCormack R.M., de Armas L.R., Shiratsuchi M., Fiorentino D.G.,
RA Olsson M.L., Lichtenheld M.G., Morales A., Lyapichev K., Gonzalez L.E.,
RA Strbo N., Sukumar N., Stojadinovic O., Plano G.V., Munson G.P.,
RA Tomic-Canic M., Kirsner R.S., Russell D.G., Podack E.R.;
RT "Perforin-2 is essential for intracellular defense of parenchymal cells and
RT phagocytes against pathogenic bacteria.";
RL Elife 4:E06508-E06508(2015).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26831467; DOI=10.1128/iai.01434-15;
RA McCormack R., Bahnan W., Shrestha N., Boucher J., Barreto M., Barrera C.M.,
RA Dauer E.A., Freitag N.E., Khan W.N., Podack E.R., Schesser K.;
RT "Perforin-2 protects host cells and mice by restricting the vacuole to
RT cytosol transitioning of a bacterial pathogen.";
RL Infect. Immun. 84:1083-1091(2016).
RN [9]
RP FUNCTION.
RX PubMed=30249808; DOI=10.4049/jimmunol.1800365;
RA Bai F., McCormack R.M., Hower S., Plano G.V., Lichtenheld M.G.,
RA Munson G.P.;
RT "Perforin-2 breaches the envelope of phagocytosed bacteria allowing
RT antimicrobial effectors access to intracellular targets.";
RL J. Immunol. 201:2710-2720(2018).
CC -!- FUNCTION: Plays a key role in the innate immune response following
CC bacterial infection by inserting into the bacterial surface to form
CC pores (PubMed:26402460). By breaching the surface of phagocytosed
CC bacteria, allows antimicrobial effectors to enter the bacterial
CC periplasmic space and degrade bacterial proteins such as superoxide
CC dismutase sodC which contributes to bacterial virulence
CC (PubMed:30249808). Shows antibacterial activity against a wide spectrum
CC of Gram-positive, Gram-negative and acid-fast bacteria
CC (PubMed:23257510, PubMed:23753625, PubMed:26402460). Reduces the
CC viability of the intracytosolic pathogen L.monocytogenes by inhibiting
CC acidification of the phagocytic vacuole of host cells which restricts
CC bacterial translocation from the vacuole to the cytosol
CC (PubMed:26831467). Required for the antibacterial activity of reactive
CC oxygen species and nitric oxide (PubMed:26402460).
CC {ECO:0000269|PubMed:23257510, ECO:0000269|PubMed:23753625,
CC ECO:0000269|PubMed:26402460, ECO:0000269|PubMed:26831467,
CC ECO:0000269|PubMed:30249808}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:26402460, ECO:0000269|PubMed:26418746}; Single-pass
CC type I membrane protein {ECO:0000255}. Note=Bacterial infection induces
CC translocation of the cytoplasmic vesicles to bacterium-containing
CC phagocytic vesicles and fusing of the vesicles.
CC {ECO:0000269|PubMed:26402460}.
CC -!- TISSUE SPECIFICITY: Expressed constitutively in a variety of cell types
CC including macrophages, microglia, neutrophils, T cells, marginal zone B
CC cells, keratinocytes, splenocytes and intestinal epithelial cells.
CC {ECO:0000269|PubMed:26402460}.
CC -!- INDUCTION: By CSF1 in fetal liver macrophages (PubMed:7888681). By
CC interferon-alpha, by interferon-beta, by interferon-gamma and by
CC bacterial infection with E.coli and M.smegmatis in embryonic
CC fibroblasts (PubMed:23257510). {ECO:0000269|PubMed:23257510,
CC ECO:0000269|PubMed:7888681}.
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) (PubMed:26418746). {ECO:0000269|PubMed:26418746}.
CC -!- DISRUPTION PHENOTYPE: Inability of neutrophils and phagocytes to kill
CC pathogenic bacteria including M.smegmatis, M.avium and M.tuberculosis
CC (PubMed:26402460). Decreased survival following epicutaneous infection
CC with methicillin-resistant S.aureus or orogastric infection with
CC S.typhimurium in contrast to wild-type littermates which clear the
CC infections (PubMed:26402460). Rapid development of listeriosis
CC following L.monocytogenes infection with mutants showing increased
CC bacterial burden and increased serum levels of inflammatory cytokines
CC in contrast to wild-type mice which show no signs of the disease
CC (PubMed:26831467). {ECO:0000269|PubMed:26402460,
CC ECO:0000269|PubMed:26831467}.
CC -!- SIMILARITY: Belongs to the MPEG1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA73957.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC129843; AAI29844.1; -; mRNA.
DR EMBL; BC129844; AAI29845.1; -; mRNA.
DR EMBL; L20315; AAA73957.1; ALT_FRAME; mRNA.
DR PIR; I52603; I52603.
DR RefSeq; NP_034951.1; NM_010821.1.
DR PDB; 6SB1; X-ray; 2.05 A; A/B=349-631.
DR PDB; 6SB3; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=20-652.
DR PDB; 6SB4; X-ray; 3.17 A; A/B/C/D/E/F/G/H=349-631.
DR PDB; 6SB5; EM; 5.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=20-652.
DR PDBsum; 6SB1; -.
DR PDBsum; 6SB3; -.
DR PDBsum; 6SB4; -.
DR PDBsum; 6SB5; -.
DR AlphaFoldDB; A1L314; -.
DR SMR; A1L314; -.
DR BioGRID; 201477; 5.
DR STRING; 10090.ENSMUSP00000108573; -.
DR GlyGen; A1L314; 3 sites.
DR PhosphoSitePlus; A1L314; -.
DR EPD; A1L314; -.
DR MaxQB; A1L314; -.
DR PaxDb; A1L314; -.
DR PeptideAtlas; A1L314; -.
DR PRIDE; A1L314; -.
DR ProteomicsDB; 291486; -.
DR GeneID; 17476; -.
DR KEGG; mmu:17476; -.
DR CTD; 219972; -.
DR MGI; MGI:1333743; Mpeg1.
DR eggNOG; ENOG502QRKR; Eukaryota.
DR InParanoid; A1L314; -.
DR OrthoDB; 235876at2759; -.
DR PhylomeDB; A1L314; -.
DR BioGRID-ORCS; 17476; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Mpeg1; mouse.
DR PRO; PR:A1L314; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; A1L314; protein.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035915; P:pore formation in membrane of another organism; IMP:UniProtKB.
DR InterPro; IPR020864; MACPF.
DR InterPro; IPR039707; MPEG1.
DR PANTHER; PTHR31463; PTHR31463; 1.
DR Pfam; PF01823; MACPF; 1.
DR SMART; SM00457; MACPF; 1.
DR PROSITE; PS51412; MACPF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Cytoplasmic vesicle; Glycoprotein;
KW Immunity; Innate immunity; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..713
FT /note="Macrophage-expressed gene 1 protein"
FT /id="PRO_5000142312"
FT TOPO_DOM 20..653
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 675..713
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..345
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
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 MUTAGEN 678..681
FT /note="KYKK->QYQQ: Abolishes ubiquitination and
FT antibacterial activity and results in diffuse perinuclear
FT distribution."
FT /evidence="ECO:0000269|PubMed:26418746"
FT CONFLICT 414
FT /note="S -> T (in Ref. 1; AAI29845)"
FT /evidence="ECO:0000305"
FT HELIX 32..37
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 84..97
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 113..117
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 141..144
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 169..183
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 187..201
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 202..212
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 216..222
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 233..250
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 261..268
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 289..293
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:6SB3"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 324..345
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 378..393
FT /evidence="ECO:0007829|PDB:6SB1"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:6SB1"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 413..437
FT /evidence="ECO:0007829|PDB:6SB1"
FT TURN 438..440
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 441..467
FT /evidence="ECO:0007829|PDB:6SB1"
FT TURN 470..472
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 475..480
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:6SB1"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 490..493
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 499..503
FT /evidence="ECO:0007829|PDB:6SB1"
FT TURN 504..506
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 507..512
FT /evidence="ECO:0007829|PDB:6SB1"
FT HELIX 515..518
FT /evidence="ECO:0007829|PDB:6SB1"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 525..530
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 558..566
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 569..577
FT /evidence="ECO:0007829|PDB:6SB1"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 608..615
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:6SB3"
FT STRAND 622..625
FT /evidence="ECO:0007829|PDB:6SB3"
FT HELIX 631..641
FT /evidence="ECO:0007829|PDB:6SB3"
SQ SEQUENCE 713 AA; 78390 MW; E5B16F4BFFD27399 CRC64;
MNSFMALVLI WMIIACAEAD KPLGETGTTG FQICKNALKL PVLEVLPGGG WDNLRNVDMG
RVMDLTYTNC KTTEDGQYII PDEVYTIPQK ESNLEMNSEV LESWMNYQST TSLSINTELA
LFSRVNGKFS TEFQRMKTLQ VKDQAVTTRV QVRNRIYTVK TTPTSELSLG FTKALMDICD
QLEKNQTKMA TYLAELLILN YGTHVITSVD AGAALVQEDH VRSSFLLDNQ NSQNTVTASA
GIAFLNIVNF KVETDYISQT SLTKDYLSNR TNSRVQSFGG VPFYPGITLE TWQKGITNHL
VAIDRAGLPL HFFIKPDKLP GLPGPLVKKL SKTVETAVRH YYTFNTHPGC TNVDSPNFNF
QANMDDDSCD AKVTNFTFGG VYQECTELSG DVLCQNLEQK NLLTGDFSCP PGYSPVHLLS
QTHEEGYSRL ECKKKCTLKI FCKTVCEDVF RVAKAEFRAY WCVAAGQVPD NSGLLFGGVF
TDKTINPMTN AQSCPAGYIP LNLFESLKVC VSLDYELGFK FSVPFGGFFS CIMGNPLVNS
DTAKDVRAPS LKKCPGGFSQ HLAVISDGCQ VSYCVKAGIF TGGSLLPVRL PPYTKPPLMS
QVATNTVIVT NSETARSWIK DPQTNQWKLG EPLELRRAMT VIHGDSNGMS GGEAAGITLG
VTIALGIVIT LAIYGTRKYK KKEYQEIEEQ ESLVGSLATD ATVLNGEEDP SPA
