ID MPEG1_HUMAN Reviewed; 716 AA. AC Q2M385; Q2M1T6; Q8TEF8; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2006, sequence version 1. DT 13-NOV-2019, entry version 102. 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:23753625}; DE Short=P-2 {ECO:0000303|PubMed:23753625}; DE Flags: Precursor; GN Name=MPEG1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-552. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP TISSUE SPECIFICITY. RX PubMed=7888681; RA Spilsbury K., O'Mara M.-A., Wu W.M., Rowe P.B., Symonds G., RA Takayama Y.; RT "Isolation of a novel macrophage-specific gene by differential cDNA RT analysis."; RL Blood 85:1620-1629(1995). RN [5] 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 RT macrophages."; RL Infect. Immun. 81:3045-3054(2013). RN [6] RP FUNCTION, AND TISSUE SPECIFICITY. 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., RA Gonzalez L.E., Strbo N., Sukumar N., Stojadinovic O., Plano G.V., RA Munson G.P., Tomic-Canic M., Kirsner R.S., Russell D.G., Podack E.R.; RT "Perforin-2 is essential for intracellular defense of parenchymal RT cells and phagocytes against pathogenic bacteria."; RL Elife 4:E06508-E06508(2015). RN [7] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, AND RP INDUCTION. RX PubMed=28705375; DOI=10.1016/j.cellimm.2017.07.001; RA Xiong P., Shiratsuchi M., Matsushima T., Liao J., Tanaka E., RA Nakashima Y., Takayanagi R., Ogawa Y.; RT "Regulation of expression and trafficking of perforin-2 by LPS and RT TNF-alpha."; RL Cell. Immunol. 320:1-10(2017). RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=30609079; DOI=10.1111/exd.13870; RA Strbo N., Pastar I., Romero L., Chen V., Vujanac M., Sawaya A.P., RA Jozic I., Ferreira A.D.F., Wong L.L., Head C., Stojadinovic O., RA Garcia D., O'Neill K., Drakulich S., Taller S., Kirsner R.S., RA Tomic-Canic M.; RT "Single cell analyses reveal specific distribution of anti-bacterial RT molecule Perforin-2 in human skin and its modulation by wounding and RT Staphylococcus aureus infection."; RL Exp. Dermatol. 28:225-232(2019). CC -!- FUNCTION: Plays a key role in the innate immune response following CC bacterial infection by inserting into the bacterial surface to CC form pores (By similarity). By breaching the surface of CC phagocytosed bacteria, allows antimicrobial effectors to enter the CC bacterial periplasmic space and degrade bacterial proteins such as CC superoxide dismutase sodC which contributes to bacterial virulence CC (By similarity). Shows antibacterial activity against a wide CC spectrum of Gram-positive, Gram-negative and acid-fast bacteria CC (PubMed:23753625, PubMed:26402460, PubMed:30609079). Reduces the CC viability of the intracytosolic pathogen L.monocytogenes by CC inhibiting acidification of the phagocytic vacuole of host cells CC which restricts bacterial translocation from the vacuole to the CC cytosol (By similarity). Required for the antibacterial activity CC of reactive oxygen species and nitric oxide (By similarity). CC {ECO:0000250|UniProtKB:A1L314, ECO:0000269|PubMed:23753625, CC ECO:0000269|PubMed:26402460, ECO:0000269|PubMed:30609079}. CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:28705375}; Single-pass type I membrane protein CC {ECO:0000255}. Note=Bacterial infection induces translocation of CC the cytoplasmic vesicles to bacterium-containing phagocytic CC vesicles and fusing of the vesicles. CC {ECO:0000269|PubMed:28705375}. CC -!- SUBCELLULAR LOCATION: Isoform 2: Secreted CC {ECO:0000269|PubMed:28705375}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=PRF2a {ECO:0000303|PubMed:28705375}; CC IsoId=Q2M385-1; Sequence=Displayed; CC Name=2; Synonyms=PRF2b {ECO:0000303|PubMed:28705375}; CC IsoId=Q2M385-2; Sequence=Not described; CC Note=Lacks the C-terminal transmembrane domain. CC {ECO:0000269|PubMed:28705375}; CC -!- TISSUE SPECIFICITY: Expressed constitutively in a variety of cell CC types including macrophages, natural killer cells, neutrophils, CC keratinocytes and monocytes (PubMed:26402460, PubMed:28705375, CC PubMed:7888681). In skin, expressed in both hematopoietic and non- CC hematopoietic cells with expression detected in a variety of cell CC types including keratinocytes, fibroblasts and endothelial cells CC (PubMed:30609079). {ECO:0000269|PubMed:26402460, CC ECO:0000269|PubMed:28705375, ECO:0000269|PubMed:30609079, CC ECO:0000269|PubMed:7888681}. CC -!- INDUCTION: By wounding; increased levels are observed in CC hematopoietic cells 48 hours after wounding (PubMed:30609079). CC Following wounding, repressed by infection with S.aureus CC (PubMed:30609079). Isoform 1: By lipopolysaccharide and TNF CC (PubMed:28705375). Isoform 2: By lipopolysaccharide and TNF CC (PubMed:28705375). {ECO:0000269|PubMed:28705375, CC ECO:0000269|PubMed:30609079}. CC -!- PTM: Monoubiquitinated in response to bacterial infection; CC ubiquitination is required for vesicular localization and CC antibacterial activity and can be blocked by bacterial cell cycle CC inhibiting factor (cif) (By similarity). CC {ECO:0000250|UniProtKB:A1L314}. CC -!- SIMILARITY: Belongs to the MPEG1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB84992.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AK074166; BAB84992.1; ALT_INIT; mRNA. DR EMBL; CH471076; EAW73839.1; -; Genomic_DNA. DR EMBL; BC104997; AAI04998.1; -; mRNA. DR EMBL; BC112230; AAI12231.1; -; mRNA. DR CCDS; CCDS41650.1; -. [Q2M385-1] DR RefSeq; NP_001034485.1; NM_001039396.1. [Q2M385-1] DR PDB; 6U23; EM; 3.49 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=18-653. DR PDB; 6U2J; EM; 2.37 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=18-653. DR PDB; 6U2K; EM; 2.93 A; B=18-653. DR PDB; 6U2L; EM; 2.83 A; A/AA/B/BB/C/CC/D/DD/E/EE/F/FF/G/GG/H/HH/I/II/J/JJ/K/KK/L/LL/M/MM/N/NN/O/OO=18-653. DR PDB; 6U2W; EM; 3.63 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=18-653. DR PDBsum; 6U23; -. DR PDBsum; 6U2J; -. DR PDBsum; 6U2K; -. DR PDBsum; 6U2L; -. DR PDBsum; 6U2W; -. DR SMR; Q2M385; -. DR BioGrid; 128608; 2. DR IntAct; Q2M385; 3. DR STRING; 9606.ENSP00000354335; -. DR BindingDB; Q2M385; -. DR ChEMBL; CHEMBL3414409; -. DR TCDB; 1.C.39.14.1; the membrane attack complex/perforin (macpf) family. DR iPTMnet; Q2M385; -. DR PhosphoSitePlus; Q2M385; -. DR BioMuta; MPEG1; -. DR DMDM; 121941470; -. DR jPOST; Q2M385; -. DR MassIVE; Q2M385; -. DR MaxQB; Q2M385; -. DR PaxDb; Q2M385; -. DR PeptideAtlas; Q2M385; -. DR PRIDE; Q2M385; -. DR ProteomicsDB; 61365; -. DR Ensembl; ENST00000361050; ENSP00000354335; ENSG00000197629. [Q2M385-1] DR GeneID; 219972; -. DR KEGG; hsa:219972; -. DR UCSC; uc001nnu.5; human. [Q2M385-1] DR CTD; 219972; -. DR DisGeNET; 219972; -. DR GeneCards; MPEG1; -. DR HGNC; HGNC:29619; MPEG1. DR HPA; HPA046801; -. DR MIM; 610390; gene. DR neXtProt; NX_Q2M385; -. DR OpenTargets; ENSG00000197629; -. DR PharmGKB; PA164723088; -. DR eggNOG; ENOG410IER6; Eukaryota. DR eggNOG; ENOG410ZMVS; LUCA. DR GeneTree; ENSGT00390000008048; -. DR HOGENOM; HOG000024828; -. DR InParanoid; Q2M385; -. DR OMA; RPPLMSQ; -. DR OrthoDB; 235876at2759; -. DR PhylomeDB; Q2M385; -. DR TreeFam; TF331165; -. DR GenomeRNAi; 219972; -. DR Pharos; Q2M385; -. DR PRO; PR:Q2M385; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000197629; Expressed in 172 organ(s), highest expression level in leukocyte. DR Genevisible; Q2M385; HS. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0045335; C:phagocytic vesicle; ISS: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; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0035915; P:pore formation in membrane of other organism; ISS: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; Alternative splicing; Antibiotic; Antimicrobial; KW Complete proteome; Cytoplasmic vesicle; Glycoprotein; Immunity; KW Innate immunity; Membrane; Polymorphism; Reference proteome; Secreted; KW Signal; Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 716 Macrophage-expressed gene 1 protein. FT {ECO:0000255}. FT /FTId=PRO_0000324143. FT TOPO_DOM 18 655 Lumenal. {ECO:0000255}. FT TRANSMEM 656 676 Helical. {ECO:0000255}. FT TOPO_DOM 677 716 Cytoplasmic. {ECO:0000255}. FT DOMAIN 30 345 MACPF. {ECO:0000255|PROSITE- FT ProRule:PRU00745}. FT CARBOHYD 185 185 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 255 255 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 269 269 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 375 375 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VARIANT 467 467 A -> T (in dbSNP:rs544864). FT /FTId=VAR_051200. FT VARIANT 552 552 P -> L (in dbSNP:rs7926933). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_051201. FT VARIANT 694 694 Q -> R (in dbSNP:rs17153442). FT /FTId=VAR_051202. SQ SEQUENCE 716 AA; 78587 MW; C863E3AF2029A0AA CRC64; MNNFRATILF WAAAAWAKSG KPSGEMDEVG VQKCKNALKL PVLEVLPGGG WDNLRNVDMG RVMELTYSNC RTTEDGQYII PDEIFTIPQK QSNLEMNSEI LESWANYQSS TSYSINTELS LFSKVNGKFS TEFQRMKTLQ VKDQAITTRV QVRNLVYTVK INPTLELSSG FRKELLDISD RLENNQTRMA TYLAELLVLN YGTHVTTSVD AGAALIQEDH LRASFLQDSQ SSRSAVTASA GLAFQNTVNF KFEENYTSQN VLTKSYLSNR TNSRVQSIGG VPFYPGITLQ AWQQGITNHL VAIDRSGLPL HFFINPNMLP DLPGPLVKKV SKTVETAVKR YYTFNTYPGC TDLNSPNFNF QANTDDGSCE GKMTNFSFGG VYQECTQLSG NRDVLLCQKL EQKNPLTGDF SCPSGYSPVH LLSQIHEEGY NHLECHRKCT LLVFCKTVCE DVFQVAKAEF RAFWCVASSQ VPENSGLLFG GLFSSKSINP MTNAQSCPAG YFPLRLFENL KVCVSQDYEL GSRFAVPFGG FFSCTVGNPL VDPAISRDLG APSLKKCPGG FSQHPALISD GCQVSYCVKS GLFTGGSLPP ARLPPFTRPP LMSQAATNTV IVTNSENARS WIKDSQTHQW RLGEPIELRR AMNVIHGDGG GLSGGAAAGV TVGVTTILAV VITLAIYGTR KFKKKAYQAI EERQSLVPGT AATGDTTYQE QGQSPA //