MPO
entrez
4353
canonical
uniprot
P05164
canonical
ensembl
ENSG00000005381
resolver
ensp
ENSP00000225275
resolver
genesymbol
MPO
resolver
hgnc
HGNC:7218
resolver
uniprot
A1L4B8
resolver
uniprot
Q14862
resolver
uniprot
Q4PJH5
resolver
uniprot
Q9UCL7
resolver
uniprot_entry
PERM_HUMAN
resolver
uniprot_sec
A1L4B8
resolver
uniprot_sec
Q14862
resolver
uniprot_sec
Q4PJH5
resolver
uniprot_sec
Q9UCL7
resolver
activity_regulation
ACTIVITY REGULATION: The peroxidase activity is inhibited by CP (ceruloplasmin) (By similarity). The peroxidase activity is inhibited by 2-thioxanthines which form a covalent attachment with the heme group (PubMed:21880720). Inhibited by 3-(2-ethoxypropyl)- 2-thioxo-2,3-dihydro-1H-purin-6(9H)-one, a derivative of 2-thioxanthine that couples with the heme group (PubMed:22352991). Specifically inhibited by aromatic hydroxamates, such as trifluoromethyl-substituted aromatic hydroxamate HX1 (PubMed:24194519). {ECO:0000250|UniProtKB:P11247, ECO:0000269|PubMed:21880720, ECO:0000269|PubMed:22352991, ECO:0000269|PubMed:24194519}.
uniprot
proteins
amino_acid_sequence
MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTSLVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLHVALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMCNNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTDQLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPNDPRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQLGLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLLREHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYRSYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLEGGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYNAWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPLLACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMSNSYPRDFVNCSTLPALNLASWREAS
uniprot
proteins
disease_involvement
DISEASE: Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:4978299, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.11.2.2
uniprot
proteins
function
FUNCTION: Peroxidase that plays a central role in the host defense system of polymorphonuclear leukocytes by mediating both (1) formation of neutrophil extracellular trap (NETs) and (2) microbicidal activity (PubMed:16125131, PubMed:17438335, PubMed:20974672, PubMed:20974816, PubMed:22131345, PubMed:25066128, PubMed:28574339, PubMed:40963017, PubMed:4978299, PubMed:6295491). Promotes NET formation by mediating chromatin disassembly: translocates to the nucleus and specifically binds to nucleosomes, both as monomer and homodimer, leading to nucleosome unstacking and initial chromatin decondensation (PubMed:40963017). Homodimers clash with one end of the nucleosomal DNA, leading to DNA unwrapping, initiating complete disassembly of nucleosomes and chromatin transformation into NETs in an ATP-independent manner (PubMed:40963017). NETs, which are mainly composed of DNA fibers and globular proteins, are then extruded into the extracellular space by neutrophils to trap pathogens and release antimicrobial proteins to destroy them (PubMed:40963017). Participates to the microbicidal activity against a wide range of organisms by acting as a peroxidase that catalyzes the formation of oxidants in presence of hydrogen peroxide (PubMed:16125131, PubMed:17074761, PubMed:17438335, PubMed:21880720, PubMed:22131345, PubMed:22352991, PubMed:22902565, PubMed:24194519, PubMed:33273015, PubMed:9359420, PubMed:9922160). Mediates the formation of hypohalous acids, mainly hypochlorous acid (HOCl) in physiologic situations, that greatly enhance polymorphonuclear leukocyte microbicidal activity (PubMed:16125131, PubMed:17074761, PubMed:17438335, PubMed:19608745, PubMed:21880720, PubMed:22902565, PubMed:24194519, PubMed:9359420, PubMed:9922160). In addition to hypochlorous acid, catalyzes formation of hypobromous acid (HOBr), hypoiodous acid (HOI) and hypothiocyanous acid (HOSCN) (PubMed:1318692, PubMed:16125131, PubMed:17438335, PubMed:19608745, PubMed:6295491, PubMed:9359420). Also catalyzes oxidation of nitrite into the highly reactive nitrogen dioxide radical (PubMed:10777476, PubMed:8385644, PubMed:9450756). Formation of oxidants are widely believed to be responsible for much of the anti-bactericidal activity of neutrophils (PubMed:8385644, PubMed:9450756). Oxidants, such as hypochlorous acid or nitrogen dioxide radical, can also oxidize amino acid residues on proteins and generate chlorination and nitration post-translational modifications, respectively (PubMed:15314690, PubMed:15326314, PubMed:15498770, PubMed:15574409, PubMed:16091367, PubMed:7622459). Chlorination and nitration of the lipid-free form of APOA1 impairs cholesterol transport (PubMed:15326314, PubMed:15498770, PubMed:15574409). Superoxides generated by MPO can also promote dioxygenation of tryptophan residues on proteins (PubMed:16091367, PubMed:40081572). Also able to oxidize melatonin into N1-acetyl-N2-formyl-5-methoxykynuramine either in presence of hydrogen peroxide or superoxide (PubMed:15636586, PubMed:16148002). Oxidizes urate into 5-hydroxyisourate (PubMed:21266577). Functions as a nitric oxide (NO) oxidase during inflammation, by catalytically consuming NO, impairing NO's ability to maintain vascular tone and function (PubMed:12089442). May also mediate the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low-density lipoprotein particles and limits vascular damage (PubMed:25698971). {ECO:0000269|PubMed:10777476, ECO:0000269|PubMed:12089442, ECO:0000269|PubMed:1318692, ECO:0000269|PubMed:15314690, ECO:0000269|PubMed:15326314, ECO:0000269|PubMed:15498770, ECO:0000269|PubMed:15574409, ECO:0000269|PubMed:15636586, ECO:0000269|PubMed:16091367, ECO:0000269|PubMed:16125131, ECO:0000269|PubMed:16148002, ECO:0000269|PubMed:17074761, ECO:0000269|PubMed:17438335, ECO:0000269|PubMed:19608745, ECO:0000269|PubMed:20974672, ECO:0000269|PubMed:20974816, ECO:0000269|PubMed:21266577, ECO:0000269|PubMed:21880720, ECO:0000269|PubMed:22131345, ECO:0000269|PubMed:22352991, ECO:0000269|PubMed:22902565, ECO:0000269|PubMed:24194519, ECO:0000269|PubMed:25066128, ECO:0000269|PubMed:25698971, ECO:0000269|PubMed:28574339, ECO:0000269|PubMed:33273015, ECO:0000269|PubMed:40081572, ECO:0000269|PubMed:40963017, ECO:0000269|PubMed:4978299, ECO:0000269|PubMed:6295491, ECO:0000269|PubMed:7622459, ECO:0000269|PubMed:8385644, ECO:0000269|PubMed:9359420, ECO:0000269|PubMed:9450756, ECO:0000269|PubMed:9922160}.; FUNCTION: [Myeloperoxidase light chain]: Light chain of the mature myeloperoxidase. {ECO:0000305}.; FUNCTION: [Myeloperoxidase heavy chain]: Heavy chain of the mature myeloperoxidase. {ECO:0000305}.; FUNCTION: (Microbial infection) The peroxidase activity is inhibited by S.aureus peroxidase inhibitor SPIN that blocks substrate access to the catalytic heme. {ECO:0000269|PubMed:28808028, ECO:0000269|PubMed:29306874, ECO:0000269|PubMed:36150500}.
uniprot
proteins
mass_dalton
83869
uniprot
proteins
mutagenesis
MUTAGEN 129..136; /note="KLRSLWRR->ALASLWAA: Prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase."; /evidence="ECO:0000269|PubMed:22902565"; MUTAGEN 129; /note="K->A: Prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. Decreased peroxidase activity."; /evidence="ECO:0000269|PubMed:22902565"; MUTAGEN 131; /note="R->A: Prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. Does not affect the peroxidase activity."; /evidence="ECO:0000269|PubMed:22902565"; MUTAGEN 135; /note="R->A: Prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. Does not affect the peroxidase activity."; /evidence="ECO:0000269|PubMed:22902565"; MUTAGEN 136; /note="R->A: Prevents cleavage by subtilisin-like protases and maturation of myeloperoxidase. Does not affect the peroxidase activity."; /evidence="ECO:0000269|PubMed:22902565"; MUTAGEN 260; /note="D->V,N: Impaired binding to heme b, leading to decreased peroxidase activity."; /evidence="ECO:0000269|PubMed:17438335"; MUTAGEN 587; /note="N->D: Abolished interaction with H-502, leading to abolished peroxidase activity."; /evidence="ECO:0000269|PubMed:19608745
uniprot
proteins
post_translational_modification
PTM: Mature myeloperoxidase is a homodimer linked by disulfide bond, with each monomer composed of a heavy and light chain (PubMed:2154223, PubMed:22902565, PubMed:2820530, PubMed:28348079, PubMed:6095812). Myeloperoxidase encompasses a series of critical proteolytic processing steps during maturation: after cotranslational cleavage of the signal peptide and N-linked glycosylation followed by limited deglucosylation, myeloperoxidase acquires heme in the endoplasmic reticulum (ER) to form the 84 kDa myeloperoxidase (also named promyeloperoxidase) (PubMed:22902565, PubMed:2820530, PubMed:28348079, PubMed:6096138). A proconvertase then eliminates the propeptide region (49-164) in a post-ER compartment producing an intermediate species that is subsequently processed by cysteine proteases to the light chain and heavy chain followed by homodimerization (PubMed:22902565, PubMed:28348079). {ECO:0000269|PubMed:2154223, ECO:0000269|PubMed:22902565, ECO:0000269|PubMed:2820530, ECO:0000269|PubMed:28348079, ECO:0000269|PubMed:6095812, ECO:0000269|PubMed:6096138}.; PTM: Myeloperoxidase monomers are linked by an interchain disulfide bond at Cys-319 (PubMed:10766826, PubMed:28348079). During maturation, the 84 kDa myeloperoxidase (also named promyeloperoxidase) precursor contains a disulfide bond between Cys-158 and Cys-319 that prevents homodimerization (PubMed:28348079). {ECO:0000269|PubMed:10766826, ECO:0000269|PubMed:28348079}.; PTM: N-glycosylated; all sites contain a fraction of paucimannose-type glycans (PubMed:31719144). Asn-323 contains phosphorylated (probably mannose-6-phosphate) and paucimannose-type N-glycans (PubMed:31719144, PubMed:6096138). Asn-355 and Asn-391 primarily show high-mannose or paucimannose glycan-types without core-fucosylation, but are partially deglucosylated during maturation of the protein (PubMed:2820530, PubMed:31719144). Truncation of N-glycans leads to increased myeloperoxidase activity (PubMed:33273015). Asn-483 contains paucimannose-type glycans, with abundant signals of sialylated complex glycans (PubMed:31719144). Asn-729 only contains paucimannose-type glycans (PubMed:31719144). {ECO:0000269|PubMed:2820530, ECO:0000269|PubMed:31719144, ECO:0000269|PubMed:33273015, ECO:0000269|PubMed:6096138}.
uniprot
proteins
protein_family
Peroxidase family
uniprot
proteins
protein_family
XPO subfamily
uniprot
proteins
pubmed
10766826
uniprot
proteins
pubmed
10777476
uniprot
proteins
pubmed
11705390
uniprot
proteins
pubmed
12089442
uniprot
proteins
pubmed
1318692
uniprot
proteins
pubmed
1334087
uniprot
proteins
pubmed
15314690
uniprot
proteins
pubmed
15326314
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498770
uniprot
proteins
pubmed
15574409
uniprot
proteins
pubmed
15636586
uniprot
proteins
pubmed
16091367
uniprot
proteins
pubmed
16125131
uniprot
proteins
pubmed
16148002
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16740002
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17074761
uniprot
proteins
pubmed
17438335
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19608745
uniprot
proteins
pubmed
20332087
uniprot
proteins
pubmed
20974672
uniprot
proteins
pubmed
20974816
uniprot
proteins
pubmed
21266577
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
2154223
uniprot
proteins
pubmed
21880720
uniprot
proteins
pubmed
22131345
uniprot
proteins
pubmed
22352991
uniprot
proteins
pubmed
22902565
uniprot
proteins
pubmed
23843990
uniprot
proteins
pubmed
24194519
uniprot
proteins
pubmed
2444596
uniprot
proteins
pubmed
25066128
uniprot
proteins
pubmed
2552418
uniprot
proteins
pubmed
25698971
uniprot
proteins
pubmed
2820530
uniprot
proteins
pubmed
2829220
uniprot
proteins
pubmed
28348079
uniprot
proteins
pubmed
28574339
uniprot
proteins
pubmed
28808028
uniprot
proteins
pubmed
2884926
uniprot
proteins
pubmed
2903767
uniprot
proteins
pubmed
29306874
uniprot
proteins
pubmed
2981589
uniprot
proteins
pubmed
3029127
uniprot
proteins
pubmed
3031585
uniprot
proteins
pubmed
31719144
uniprot
proteins
pubmed
32434865
uniprot
proteins
pubmed
33273015
uniprot
proteins
pubmed
36150500
uniprot
proteins
pubmed
3654979
uniprot
proteins
pubmed
37198333
uniprot
proteins
pubmed
40081572
uniprot
proteins
pubmed
40963017
uniprot
proteins
pubmed
4978299
uniprot
proteins
pubmed
6095812
uniprot
proteins
pubmed
6096138
uniprot
proteins
pubmed
6192815
uniprot
proteins
pubmed
6295491
uniprot
proteins
pubmed
7622459
uniprot
proteins
pubmed
7840679
uniprot
proteins
pubmed
7904599
uniprot
proteins
pubmed
8142659
uniprot
proteins
pubmed
8383257
uniprot
proteins
pubmed
8385644
uniprot
proteins
pubmed
8390465
uniprot
proteins
pubmed
8621627
uniprot
proteins
pubmed
9354683
uniprot
proteins
pubmed
9359420
uniprot
proteins
pubmed
9450756
uniprot
proteins
pubmed
9637725
uniprot
proteins
pubmed
9922160
uniprot
proteins
sequence_length
745
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:25066128, ECO:0000269|PubMed:2981589, ECO:0000269|PubMed:6095812, ECO:0000269|PubMed:6192815}. Cytolytic granule {ECO:0000269|PubMed:25066128, ECO:0000269|PubMed:2981589, ECO:0000269|PubMed:6095812, ECO:0000269|PubMed:6192815}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:17074761}. Secreted {ECO:0000269|PubMed:22131345, ECO:0000269|PubMed:40963017, ECO:0000269|PubMed:6095812}. Nucleus {ECO:0000269|PubMed:25066128, ECO:0000269|PubMed:2829220, ECO:0000269|PubMed:40963017}. Chromosome {ECO:0000269|PubMed:2829220, ECO:0000269|PubMed:40963017}. Note=Localizes to azurophil granules, a type of primary lysosome found in neutrophils and monocytes that contains antimicrobial proteins (PubMed:25066128, PubMed:2981589, PubMed:6095812, PubMed:6192815). A substantial fraction is also constitutively secreted by normal bone marrow granulocyte precursors (PubMed:6095812). During formation of neutrophil extracellular traps (NETs), translocates into the nucleus and associates to chromatin, leading to chromatin dislocation and its transformation into NETs (PubMed:25066128, PubMed:40963017). Core component of NETs (PubMed:22131345, PubMed:32434865, PubMed:40963017). {ECO:0000269|PubMed:22131345, ECO:0000269|PubMed:25066128, ECO:0000269|PubMed:2981589, ECO:0000269|PubMed:32434865, ECO:0000269|PubMed:40963017, ECO:0000269|PubMed:6095812, ECO:0000269|PubMed:6192815}.
uniprot
proteins