P21812 (MCPT4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mast cell protease 4
Short name=mMCP-4
EC=3.4.21.-

Alternative name(s):
MSMCP
Myonase
Serosal mast cell protease

Gene names

Name:

Mcpt4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	246 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has chymotrypsin-like activity. Hydrolyzes the amide bonds of synthetic substrates having Tyr and Phe residues at the P1 position. Preferentially hydrolyzes the 'Tyr-4-|-Ile-5' bond of angiotensin I and the 'Phe-20-|-Ala-21' bond of amyloid beta-protein, and is less active towards the 'Phe-8-|-His-9' bond of angiotensin I and the 'Phe-4-|-Ala-5' and 'Tyr-10-|-Glu-11' bonds of amyloid beta-protein. Involved in thrombin regulation and fibronectin processing. Ref.4 Ref.7
Enzyme regulation	Completely inhibited by serine protease inhibitors such as chymostatin, diisopropylfluorophosphate and phenylmethylsulfonyl fluoride, but not by p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, pepstatin, E-64, EDTA or o-phenanthroline. Also inhibited by lima bean trypsin inhibitor, soy bean trypsin inhibitor and human plasma alpha1-antichymotrysin.
Subunit structure	Monomer. Ref.4
Tissue specificity	Submucosal mast cells. In femoral muscle, detected in myocytes but not in mast cells. Ref.4
Disruption phenotype	Mice display an impaired ability to inactivate thrombin or degrade fibronectin in peritoneal cells. Ref.7
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.
Biophysicochemical properties	pH dependence: Optimum pH is 9 at high salt concentrations.
Mass spectrometry	Molecular mass is 25187 Da from positions 21 - 246. Determined by MALDI. Ref.4
Sequence caution	The sequence BAB18732.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from direct assay Ref.7. Source: UniProtKB regulation of angiotensin levels in blood Inferred from genetic interaction PubMed 15173164. Source: MGI
Cellular_component	intracellular Inferred from direct assay PubMed 9360993. Source: MGI
Molecular_function	serine-type endopeptidase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18
	Propeptide	19 – 20	2	Activation peptide		PRO_0000027453
	Chain	21 – 246	226	Mast cell protease 4		PRO_0000027454
Regions
	Domain	21 – 244	224	Peptidase S1
Sites
	Active site	65	1	Charge relay system By similarity
	Active site	109	1	Charge relay system By similarity
	Active site	202	1	Charge relay system By similarity
Amino acid modifications
	Disulfide bond	50 ↔ 66		By similarity
	Disulfide bond	143 ↔ 208		By similarity
	Disulfide bond	174 ↔ 187		By similarity
Natural variations
	Natural variant	61	1	M → L in strain: C57BL/6 and Leaden X A1.
	Natural variant	160	1	T → I in strain: C57BL/6 and Leaden X A1.
	Natural variant	246	1	E → KK in strain: C57BL/6 and Leaden X A1.

Sequences

	Sequence		Length	Mass (Da)
	P21812 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 0887A1C71ACE2698	FASTA	246	27,204
	10 20 30 40 50 60 MQALLFLMAL LLPSGAGAEE IIGGVESRPH SRPYMAHLEI TTERGFTATC GGFLITRQFV 70 80 90 100 110 120 MTAAHCSGRE ITVTLGAHDV SKTESTQQKI KVEKQIVHPK YNFYSNLHDI MLLKLQKKAK 130 140 150 160 170 180 ETPSVNVIPL PRPSDFIKPG KMCRAAGWGR TGVTEPTSDT LREVKLRIMD KEACKNYWHY 190 200 210 220 230 240 DYNLQVCVGS PRKKRSAYKG DSGGPLLCAG VAHGIVSYGR GDAKPPAVFT RISSYVPWIN RVIKGE

References

[1]	"Cloning of the cDNA and gene for mouse mast cell protease 4. Demonstration of its late transcription in mast cell subclasses and analysis of its homology to subclass-specific neutral proteases of the mouse and rat." Serafin W.E., Sullivan T.P., Conder G.A., Ebrahimi A., Marcham P., Johnson S.S., Austen K.F., Reynolds D.S. J. Biol. Chem. 266:1934-1941(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Strain: BALB/c.
[2]	"Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases." Ge Y., Jippo T., Lee Y.-M., Adachi S., Kitamura Y. Am. J. Pathol. 158:281-292(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6.
[3]	"Cloning and structural analysis of MMCP-1, MMCP-4 and MMCP-5, three mouse mast cell-specific serine proteases." Huang R., Blom T., Hellman L. Eur. J. Immunol. 21:1611-1621(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 7-246. Strain: Leaden X A1. Tissue: Mastocytoma.
[4]	"Purification and characterization of myonase from X-chromosome linked muscular dystrophic mouse skeletal muscle." Hori S., Ohtani S., Hori C., Nokihara K. J. Biochem. 123:650-658(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 7-246, PROTEIN SEQUENCE OF 21-66; 76-84; 86-93; 96-106; 126-143; 146-155; 178-180; 197-207 AND 231-238, FUNCTION, SUBUNIT, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Skeletal muscle.
[5]	"Different mouse mast cell populations express various combinations of at least six distinct mast cell serine proteases." Reynolds D.S., Stevens R.L., Lane W.S., Carr M.H., Austen K.F., Serafin W.E. Proc. Natl. Acad. Sci. U.S.A. 87:3230-3234(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-43.
[6]	"Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4)." Newlands G.F.J., Knox D.P., Pirie-Shepherd S.R., Miller H.R.P. Biochem. J. 294:127-135(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-40.
[7]	"The chymase, mouse mast cell protease 4, constitutes the major chymotrypsin-like activity in peritoneum and ear tissue. A role for mouse mast cell protease 4 in thrombin regulation and fibronectin turnover." Tchougounova E., Pejler G., Abrink M. J. Exp. Med. 198:423-431(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M55617 mRNA. Translation: AAA39989.1. M55616 Genomic DNA. Translation: AAA72939.1. AY007569 mRNA. Translation: AAG24503.1. X68804 mRNA. Translation: CAA48704.1. AB051900 mRNA. Translation: BAB18732.1. Different initiation.
IPI	IPI00128498.
PIR	B38678. JE0151. S26042.
RefSeq	NP_034909.2. NM_010779.2.
UniGene	Mm.439684.
3D structure databases
ProteinModelPortal	P21812.
SMR	P21812. Positions 21-243.
ModBase	Search...
Protein family/group databases
MEROPS	S01.149.
Proteomic databases
PRIDE	P21812.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	17227.
KEGG	mmu:17227.
Organism-specific databases
CTD	17227.
MGI	MGI:96940. Mcpt4.
Phylogenomic databases
HOGENOM	HOG000251820.
HOVERGEN	HBG013304.
InParanoid	P21812.
KO	K01362.
Gene expression databases
Genevestigator	P21812.
GermOnline	ENSMUSG00000061068. Mus musculus.
Family and domain databases
InterPro	IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	291644.
SOURCE	Search...

Entry information

Entry name

MCPT4_MOUSE

Accession

Primary (citable) accession number: P21812
Secondary accession number(s): Q9EPQ9, Q9EQT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	April 3, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program