Reviewed, UniProtKB/Swiss-Prot P23946 (CMA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Chymase
    EC=3.4.21.39
Alternative name(s):
    Alpha-chymase
    Mast cell protease I

Gene names

Name:	CMA1
Synonyms:	CYH, CYM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	247 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	Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.
Catalytic activity	Preferential cleavage: Phe-|-Xaa > Tyr-|-Xaa > Trp-|-Xaa > Leu-|-Xaa.
Subcellular location	Secreted. Cytoplasmic granule. Note: Mast cell granules.
Tissue specificity	Mast cells in lung, heart, skin and placenta.
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	interleukin-1 beta biosynthetic process Inferred from direct assay. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro regulation of inflammatory response Inferred by curator. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	serine-type endopeptidase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Propeptide

20 – 21

2

Activation peptide

PRO_0000027433

Chain

22 – 247

226

Chymase

PRO_0000027434

Regions

Domain

22 – 245

224

Peptidase S1

Sites

Active site

66

1

Charge relay system

Active site

110

1

Charge relay system

Active site

203

1

Charge relay system

Amino acid modifications

Glycosylation

80

1

N-linked (GlcNAc...) Ref.1

Glycosylation

103

1

N-linked (GlcNAc...)

Disulfide bond

51 ↔ 67

Disulfide bond

144 ↔ 209

Disulfide bond

175 ↔ 188

Natural variations

Natural variant

46

1

G → R: dbSNP rs5246.

VAR_011770

Natural variant

66

1

H → R: dbSNP rs5247. Ref.3

VAR_011771

Natural variant

98

1

R → H: dbSNP rs13306252.

VAR_029190

Experimental info

Sequence conflict

28

1

C → S in AAB26828. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

247

Helix Strand Turn

Details...

Beta strand

36 – 42

7

Beta strand

44 – 46

3

Beta strand

48 – 57

10

Beta strand

60 – 63

4

Helix

65 – 67

3

Beta strand

70 – 77

8

Beta strand

89 – 98

10

Turn

104 – 106

3

Beta strand

112 – 118

7

Beta strand

143 – 156

14

Beta strand

163 – 170

8

Helix

172 – 175

4

Turn

183 – 185

3

Beta strand

186 – 190

5

Beta strand

206 – 209

4

Beta strand

212 – 219

8

Beta strand

228 – 232

5

Helix

233 – 236

4

Helix

237 – 246

10

Sequences

	Sequence		Length	Mass (Da)
	P23946-1 [UniParc]. Last modified March 1, 1992. Version 1. Checksum: DC1464A049ED6B00	FASTA	247	27,325
	10 20 30 40 50 60 MLLLPLPLLL FLLCSRAEAG EIIGGTECKP HSRPYMAYLE IVTSNGPSKF CGGFLIRRNF 70 80 90 100 110 120 VLTAAHCAGR SITVTLGAHN ITEEEDTWQK LEVIKQFRHP KYNTSTLHHD IMLLKLKEKA 130 140 150 160 170 180 SLTLAVGTLP FPSQFNFVPP GRMCRVAGWG RTGVLKPGSD TLQEVKLRLM DPQACSHFRD 190 200 210 220 230 240 FDHNLQLCVG NPRKTKSAFK GDSGGPLLCA GVAQGIVSYG RSDAKPPAVF TRISHYRPWI NQILQAN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase." Caughey G.H., Zerweck E.H., Vanderslice P. J. Biol. Chem. 266:12956-12963(1991) [PubMed: 2071582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning of the gene and cDNA for human heart chymase." Urata H., Kinoshita A., Perez D.M., Misono K.S., Bumpus F.M., Graham R.M., Husain A. J. Biol. Chem. 266:17173-17179(1991) [PubMed: 1894611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Heart.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-66.
[4]	"Purification and molecular cloning of chymase from human tonsils." Sukenaga Y., Kido H., Neki A., Enomoto M., Ishida K., Takagi K., Katunuma N. FEBS Lett. 323:119-122(1993) [PubMed: 8495723] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-247.
[5]	"Angiotensin II-forming heart chymase is a mast-cell-specific enzyme." Jenne D.E., Tschopp J. Biochem. J. 276:567-568(1991) [PubMed: 2049082] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 26-60. Tissue: Placenta.
[6]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80 AND ASN-103, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A." McGrath M.E., Mirzadegan T., Schmidt B.F. Biochemistry 36:14318-14324(1997) [PubMed: 9400368] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[8]	"The 2.2-A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity." Pereira P.J.P., Wang Z.-M., Rubin H., Huber R., Bode W., Schechter N.M., Strobl S. J. Mol. Biol. 286:163-173(1999) [PubMed: 9931257] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[9]	Erratum Pereira P.J.P., Wang Z.-M., Rubin H., Huber R., Bode W., Schechter N.M., Strobl S. J. Mol. Biol. 286:817-817(1999) [PubMed: 10208809] [Abstract]
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M64269 Genomic DNA. Translation: AAA52020.1.
M69137 Genomic DNA. Translation: AAA52021.1.
M69136 mRNA. Translation: AAA52019.1.
BC069110 mRNA. Translation: AAH69110.1.
BC069370 mRNA. Translation: AAH69370.1.
BC069490 mRNA. Translation: AAH69490.1.
BC103975 mRNA. Translation: AAI03976.1.
X59072 Genomic DNA. Translation: CAA41796.1.
S61334 mRNA. Translation: AAB26828.1.

IPI

IPI00013937.

PIR

KYHUCM. A40967.

RefSeq

NP_001827.1.

UniGene

Hs.135626

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KLT	X-ray	1.90	A	22-247	[»]
1NN6	X-ray	1.75	A	20-247	[»]
1PJP	X-ray	2.20	A	22-247	[»]
1T31	X-ray	1.90	A	22-247	[»]
2HVX	X-ray	2.60	A	22-247	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.140.

PTM databases

PhosphoSite

P23946.

Proteomic databases

PRIDE

P23946.

Genome annotation databases

Ensembl

ENSG00000092009. Homo sapiens. [Contig view]

GeneID

1215.

KEGG

hsa:1215.

Organism-specific databases

GeneCards

GC14M024044.

H-InvDB

HIX0037752.

HGNC

HGNC:2097. CMA1.

HPA

CAB000363.

MIM

118938. gene.

PharmGKB

PA26623.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P23946.

OMA

P23946. RKTKSAF.

Enzyme and pathway databases

BRENDA

3.4.21.39. 247.

Gene expression databases

ArrayExpress

P23946.

Bgee

P23946.

CleanEx

HS_CMA1.

GermOnline

ENSG00000092009. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P23946.

NextBio

5003.

PMAP-CutDB

P23946.

SOURCE

Search...

Entry information

Entry name

CMA1_HUMAN

Accession

Primary (citable) accession number: P23946
Secondary accession number(s): Q16018, Q3SY36

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	June 16, 2009
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)