Overview
| Uniprot ID | P05164 |
|---|
| Protein Name | Myeloperoxidase |
|---|
| Gene Name | MPO |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 431 |
NRLATELKSLNPRWD |
| 474 |
LGPTAMRKYLPTYRS |
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)
Protein Sequence
10
MGVPFFSSLR
20
CMVDLGPCWA
30
GGLTAEMKLL
40
LALAGLLAIL
50
ATPQPSEGAA
60
PAVLGEVDTS
70
LVLSSMEEAK
80
QLVDKAYKER
90
RESIKQRLRS
100
GSASPMELLS
110
YFKQPVAATR
120
TAVRAADYLH
130
VALDLLERKL
140
RSLWRRPFNV
150
TDVLTPAQLN
160
VLSKSSGCAY
170
QDVGVTCPEQ
180
DKYRTITGMC
190
NNRRSPTLGA
200
SNRAFVRWLP
210
AEYEDGFSLP
220
YGWTPGVKRN
230
GFPVALARAV
240
SNEIVRFPTD
250
QLTPDQERSL
260
MFMQWGQLLD
270
HDLDFTPEPA
280
ARASFVTGVN
290
CETSCVQQPP
300
CFPLKIPPND
310
PRIKNQADCI
320
PFFRSCPACP
330
GSNITIRNQI
340
NALTSFVDAS
350
MVYGSEEPLA
360
RNLRNMSNQL
370
GLLAVNQRFQ
380
DNGRALLPFD
390
NLHDDPCLLT
400
NRSARIPCFL
410
AGDTRSSEMP
420
ELTSMHTLLL
430
REHNRLATEL
440
KSLNPRWDGE
450
RLYQEARKIV
460
GAMVQIITYR
470
DYLPLVLGPT
480
AMRKYLPTYR
490
SYNDSVDPRI
500
ANVFTNAFRY
510
GHTLIQPFMF
520
RLDNRYQPME
530
PNPRVPLSRV
540
FFASWRVVLE
550
GGIDPILRGL
560
MATPAKLNRQ
570
NQIAVDEIRE
580
RLFEQVMRIG
590
LDLPALNMQR
600
SRDHGLPGYN
610
AWRRFCGLPQ
620
PETVGQLGTV
630
LRNLKLARKL
640
MEQYGTPNNI
650
DIWMGGVSEP
660
LKRKGRVGPL
670
LACIIGTQFR
680
KLRDGDRFWW
690
ENEGVFSMQQ
700
RQALAQISLP
710
RIICDNTGIT
720
TVSKNNIFMS
730
NSYPRDFVNC
740
STLPALNLAS
WREAS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0042582 |
azurophil granule |
| Cellular Component |
GO:0035578 |
azurophil granule lumen |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0005615 |
extracellular space |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0140644 |
neutrophil extracellular trap |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0045335 |
phagocytic vesicle |
| Cellular Component |
GO:0097013 |
phagocytic vesicle lumen |
| Cellular Component |
GO:0030141 |
secretory granule |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0020037 |
heme binding |
| Molecular Function |
GO:0008201 |
heparin binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0031491 |
nucleosome binding |
| Molecular Function |
GO:0004601 |
peroxidase activity |
| Molecular Function |
GO:0140776 |
protein-containing complex destabilizing activity |
| Biological Process |
GO:0006952 |
defense response |
| Biological Process |
GO:0042742 |
defense response to bacterium |
| Biological Process |
GO:0042744 |
hydrogen peroxide catabolic process |
| Biological Process |
GO:0034374 |
low-density lipoprotein particle remodeling |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0140645 |
neutrophil extracellular trap formation |
| Biological Process |
GO:0070944 |
neutrophil-mediated killing of bacterium |
| Biological Process |
GO:0070947 |
neutrophil-mediated killing of fungus |
| Biological Process |
GO:0070943 |
neutrophil-mediated killing of symbiont cell |
| Biological Process |
GO:0006337 |
nucleosome disassembly |
| Biological Process |
GO:0032094 |
response to food |
| Biological Process |
GO:1990268 |
response to gold nanoparticle |
| Biological Process |
GO:0032496 |
response to lipopolysaccharide |
| Biological Process |
GO:0009612 |
response to mechanical stimulus |
| Biological Process |
GO:0006979 |
response to oxidative stress |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.