MCPT4_MOUSE
ID MCPT4_MOUSE Reviewed; 246 AA.
AC P21812; Q9EPQ9; Q9EQT2;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 25-MAY-2022, entry version 148.
DE RecName: Full=Mast cell protease 4;
DE Short=mMCP-4;
DE EC=3.4.21.-;
DE AltName: Full=MSMCP;
DE AltName: Full=Myonase;
DE AltName: Full=Serosal mast cell protease;
DE Flags: Precursor;
GN Name=Mcpt4;
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 [GENOMIC DNA / MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=1988455; DOI=10.1016/s0021-9258(18)52383-8;
RA Serafin W.E., Sullivan T.P., Conder G.A., Ebrahimi A., Marcham P.,
RA Johnson S.S., Austen K.F., Reynolds D.S.;
RT "Cloning of the cDNA and gene for mouse mast cell protease 4. Demonstration
RT of its late transcription in mast cell subclasses and analysis of its
RT homology to subclass-specific neutral proteases of the mouse and rat.";
RL J. Biol. Chem. 266:1934-1941(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=11141502; DOI=10.1016/s0002-9440(10)63967-3;
RA Ge Y., Jippo T., Lee Y.-M., Adachi S., Kitamura Y.;
RT "Independent influence of strain difference and mi transcription factor on
RT the expression of mouse mast cell chymases.";
RL Am. J. Pathol. 158:281-292(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 7-246.
RC STRAIN=Leaden X A1; TISSUE=Mastocytoma;
RX PubMed=2060576; DOI=10.1002/eji.1830210706;
RA Huang R., Blom T., Hellman L.;
RT "Cloning and structural analysis of MMCP-1, MMCP-4 and MMCP-5, three mouse
RT mast cell-specific serine proteases.";
RL Eur. J. Immunol. 21:1611-1621(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE OF 7-246, PROTEIN SEQUENCE OF 21-66; 76-84; 86-93;
RP 96-106; 126-143; 146-155; 178-180; 197-207 AND 231-238, FUNCTION, SUBUNIT,
RP TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RC TISSUE=Skeletal muscle;
RX PubMed=9538257; DOI=10.1093/oxfordjournals.jbchem.a021987;
RA Hori S., Ohtani S., Hori C., Nokihara K.;
RT "Purification and characterization of myonase from X-chromosome linked
RT muscular dystrophic mouse skeletal muscle.";
RL J. Biochem. 123:650-658(1998).
RN [5]
RP PROTEIN SEQUENCE OF 21-43.
RX PubMed=2326280; DOI=10.1073/pnas.87.8.3230;
RA Reynolds D.S., Stevens R.L., Lane W.S., Carr M.H., Austen K.F.,
RA Serafin W.E.;
RT "Different mouse mast cell populations express various combinations of at
RT least six distinct mast cell serine proteases.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3230-3234(1990).
RN [6]
RP PROTEIN SEQUENCE OF 21-40.
RX PubMed=8363563; DOI=10.1042/bj2940127;
RA Newlands G.F.J., Knox D.P., Pirie-Shepherd S.R., Miller H.R.P.;
RT "Biochemical and immunological characterization of multiple glycoforms of
RT mouse mast cell protease 1: comparison with an isolated murine serosal mast
RT cell protease (MMCP-4).";
RL Biochem. J. 294:127-135(1993).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12900518; DOI=10.1084/jem.20030671;
RA Tchougounova E., Pejler G., Abrink M.;
RT "The chymase, mouse mast cell protease 4, constitutes the major
RT chymotrypsin-like activity in peritoneum and ear tissue. A role for mouse
RT mast cell protease 4 in thrombin regulation and fibronectin turnover.";
RL J. Exp. Med. 198:423-431(2003).
CC -!- FUNCTION: Has chymotrypsin-like activity. Hydrolyzes the amide bonds of
CC synthetic substrates having Tyr and Phe residues at the P1 position.
CC Preferentially hydrolyzes the 'Tyr-4-|-Ile-5' bond of angiotensin I and
CC the 'Phe-20-|-Ala-21' bond of amyloid beta-protein, and is less active
CC towards the 'Phe-8-|-His-9' bond of angiotensin I and the 'Phe-4-|-Ala-
CC 5' and 'Tyr-10-|-Glu-11' bonds of amyloid beta-protein. Involved in
CC thrombin regulation and fibronectin processing.
CC {ECO:0000269|PubMed:12900518, ECO:0000269|PubMed:9538257}.
CC -!- ACTIVITY REGULATION: Completely inhibited by serine protease inhibitors
CC such as chymostatin, diisopropylfluorophosphate and
CC phenylmethylsulfonyl fluoride, but not by p-tosyl-L-phenylalanine
CC chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, pepstatin,
CC E-64, EDTA or o-phenanthroline. Also inhibited by lima bean trypsin
CC inhibitor, soy bean trypsin inhibitor and human plasma alpha1-
CC antichymotrypsin.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9 at high salt concentrations.;
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:9538257}.
CC -!- TISSUE SPECIFICITY: Submucosal mast cells. In femoral muscle, detected
CC in myocytes but not in mast cells. {ECO:0000269|PubMed:9538257}.
CC -!- MASS SPECTROMETRY: Mass=25187; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9538257};
CC -!- DISRUPTION PHENOTYPE: Mice display an impaired ability to inactivate
CC thrombin or degrade fibronectin in peritoneal cells.
CC {ECO:0000269|PubMed:12900518}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB18732.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M55617; AAA39989.1; -; mRNA.
DR EMBL; M55616; AAA72939.1; -; Genomic_DNA.
DR EMBL; AY007569; AAG24503.1; -; mRNA.
DR EMBL; X68804; CAA48704.1; -; mRNA.
DR EMBL; AB051900; BAB18732.1; ALT_INIT; mRNA.
DR CCDS; CCDS27140.1; -.
DR PIR; B38678; B38678.
DR PIR; JE0151; JE0151.
DR PIR; S26042; S26042.
DR RefSeq; NP_034909.2; NM_010779.2.
DR AlphaFoldDB; P21812; -.
DR SMR; P21812; -.
DR STRING; 10090.ENSMUSP00000038103; -.
DR MEROPS; S01.149; -.
DR iPTMnet; P21812; -.
DR PhosphoSitePlus; P21812; -.
DR MaxQB; P21812; -.
DR PaxDb; P21812; -.
DR PeptideAtlas; P21812; -.
DR PRIDE; P21812; -.
DR ProteomicsDB; 295713; -.
DR DNASU; 17227; -.
DR GeneID; 17227; -.
DR KEGG; mmu:17227; -.
DR CTD; 17227; -.
DR MGI; MGI:96940; Mcpt4.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; P21812; -.
DR OrthoDB; 1076876at2759; -.
DR PhylomeDB; P21812; -.
DR BRENDA; 3.4.21.39; 3474.
DR BioGRID-ORCS; 17227; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Mcpt4; mouse.
DR PRO; PR:P21812; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P21812; protein.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0002002; P:regulation of angiotensin levels in blood; IGI:MGI.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Protease;
KW Reference proteome; Serine protease; Signal; Zymogen.
FT SIGNAL 1..18
FT PROPEP 19..20
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2326280,
FT ECO:0000269|PubMed:8363563, ECO:0000269|PubMed:9538257"
FT /id="PRO_0000027453"
FT CHAIN 21..246
FT /note="Mast cell protease 4"
FT /id="PRO_0000027454"
FT DOMAIN 21..244
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 65
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 109
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 202
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT DISULFID 50..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 143..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 174..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VARIANT 61
FT /note="M -> L (in strain: C57BL/6 and Leaden X A1)"
FT VARIANT 160
FT /note="T -> I (in strain: C57BL/6 and Leaden X A1)"
FT VARIANT 246
FT /note="E -> KK (in strain: C57BL/6 and Leaden X A1)"
SQ SEQUENCE 246 AA; 27204 MW; 0887A1C71ACE2698 CRC64;
MQALLFLMAL LLPSGAGAEE IIGGVESRPH SRPYMAHLEI TTERGFTATC GGFLITRQFV
MTAAHCSGRE ITVTLGAHDV SKTESTQQKI KVEKQIVHPK YNFYSNLHDI MLLKLQKKAK
ETPSVNVIPL PRPSDFIKPG KMCRAAGWGR TGVTEPTSDT LREVKLRIMD KEACKNYWHY
DYNLQVCVGS PRKKRSAYKG DSGGPLLCAG VAHGIVSYGR GDAKPPAVFT RISSYVPWIN
RVIKGE
