P23946 (CMA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. Expressed in both normal skin and in urticaria pigmentosa lesions. Ref.3
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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	interleukin-1 beta biosynthetic process Inferred from direct assay. Source: BHF-UCL proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of inflammatory response Inferred by curator. Source: BHF-UCL
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	serine-type endopeptidase activity Non-traceable author statement Ref.3. 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 Ref.9

Glycosylation

103

1

N-linked (GlcNAc...) Ref.9

Disulfide bond

51 ↔ 67

Disulfide bond

144 ↔ 209

Disulfide bond

175 ↔ 188

Natural variations

Natural variant

46

1

G → R.
Corresponds to variant rs5246 [ dbSNP | Ensembl ].

VAR_011770

Natural variant

66

1

H → R. Ref.6
Corresponds to variant rs5247 [ dbSNP | Ensembl ].

VAR_011771

Natural variant

98

1

R → H.
Corresponds to variant rs13306252 [ dbSNP | Ensembl ].

VAR_029190

Experimental info

Sequence conflict

28

1

C → S in AAB26828. Ref.7

Sequence conflict

131 – 132

2

FP → AV AA sequence Ref.3

Secondary structure

1

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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 [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]	"Determination of the primary structures of human skin chymase and cathepsin G from cutaneous mast cells of urticaria pigmentosa lesions." Schechter N.M., Wang Z.M., Blacher R.W., Lessin S.R., Lazarus G.S., Rubin H. J. Immunol. 152:4062-4069(1994) [PubMed: 8144971] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-56; 123-132; 136-148; 167-194 AND 197-247, TISSUE SPECIFICITY. Tissue: Skin.
[4]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	"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.
[8]	"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 [GENOMIC DNA] OF 26-60. Tissue: Placenta.
[9]	"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.
[10]	"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).
[11]	"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).
[12]	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

EMBL
GenBank
DDBJ

M64269 Genomic DNA. Translation: AAA52020.1.
M69137 Genomic DNA. Translation: AAA52021.1.
M69136 mRNA. Translation: AAA52019.1.
AB451464 mRNA. Translation: BAG70278.1.
CH471078 Genomic DNA. Translation: EAW66007.1.
BC069110 mRNA. Translation: AAH69110.1.
BC069370 mRNA. Translation: AAH69370.1.
BC069490 mRNA. Translation: AAH69490.1.
BC103975 mRNA. Translation: AAI03976.1.
S61334 mRNA. Translation: AAB26828.1.
X59072 Genomic DNA. Translation: CAA41796.1.

IPI

IPI00013937.

PIR

KYHUCM. A40967.

RefSeq

NP_001827.1. NM_001836.2.

UniGene

Hs.135626.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3N7O	X-ray	1.80	A	22-247	[»]
3S0N	X-ray	1.95	A	22-247	[»]

ProteinModelPortal

P23946.

SMR

P23946. Positions 24-247.

ModBase

Search...

Protein-protein interaction databases

STRING

P23946.

Protein family/group databases

MEROPS

S01.140.

PTM databases

PhosphoSite

P23946.

Polymorphism databases

DMDM

126825.

Proteomic databases

PRIDE

P23946.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000206446; ENSP00000206446; ENSG00000092009.
ENST00000250378; ENSP00000250378; ENSG00000092009.

GeneID

1215.

KEGG

hsa:1215.

UCSC

uc001wpp.1. human.

Organism-specific databases

CTD

1215.

GeneCards

GC14M024974.

H-InvDB

HIX0202104.

HGNC

HGNC:2097. CMA1.

HPA

CAB000363.

MIM

118938. gene.

neXtProt

NX_P23946.

PharmGKB

PA26623.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07867.

GeneTree

ENSGT00580000081281.

HOGENOM

HBG755338.

HOVERGEN

HBG013304.

InParanoid

P23946.

OMA

HHDIMLL.

OrthoDB

EOG4R23VK.

PhylomeDB

P23946.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P23946.

Bgee

P23946.

CleanEx

HS_CMA1.

Genevestigator

P23946.

GermOnline

ENSG00000092009. Homo sapiens.

Family and domain databases

InterPro

IPR009003. Pept_cys/ser_Trypsin-like.
IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

KO

K01329.

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

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): B5BUM8 , Q16018, Q3SY36, Q9UDH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	January 25, 2012
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.