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P23946 (CMA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chymase

EC=3.4.21.39
Alternative name(s):
Alpha-chymase
Mast cell protease I
Gene names
Name:CMA1
Synonyms:CYH, CYM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length247 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiotensin maturation

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

interleukin-1 beta biosynthetic process

Inferred from direct assay PubMed 1919436. Source: BHF-UCL

midbrain development

Inferred from electronic annotation. Source: Ensembl

peptide metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of inflammatory response

Inferred by curator PubMed 1919436. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

secretory granule

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionpeptide binding

Inferred from electronic annotation. Source: Ensembl

serine-type endopeptidase activity

Non-traceable author statement Ref.3. Source: UniProtKB

serine-type peptidase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Propeptide20 – 212Activation peptide
PRO_0000027433
Chain22 – 247226Chymase
PRO_0000027434

Regions

Domain22 – 245224Peptidase S1

Sites

Active site661Charge relay system
Active site1101Charge relay system
Active site2031Charge relay system

Amino acid modifications

Glycosylation801N-linked (GlcNAc...) Ref.1 Ref.9
Glycosylation1031N-linked (GlcNAc...) Ref.9
Disulfide bond51 ↔ 67
Disulfide bond144 ↔ 209
Disulfide bond175 ↔ 188

Natural variations

Natural variant461G → R.
Corresponds to variant rs5246 [ dbSNP | Ensembl ].
VAR_011770
Natural variant661H → R. Ref.6
Corresponds to variant rs5247 [ dbSNP | Ensembl ].
VAR_011771
Natural variant981R → H.
Corresponds to variant rs13306252 [ dbSNP | Ensembl ].
VAR_029190

Experimental info

Sequence conflict281C → S in AAB26828. Ref.7
Sequence conflict131 – 1322FP → AV AA sequence Ref.3

Secondary structure

......................................... 247
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23946 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: DC1464A049ED6B00

FASTA24727,325
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80 AND ASN-103.
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
CCDSCCDS9630.1.
PIRKYHUCM. A40967.
RefSeqNP_001827.1. NM_001836.3.
UniGeneHs.135626.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KLTX-ray1.90A22-247[»]
1NN6X-ray1.75A20-247[»]
1PJPX-ray2.20A22-247[»]
1T31X-ray1.90A22-247[»]
2HVXX-ray2.60A22-247[»]
3N7OX-ray1.80A22-247[»]
3S0NX-ray1.95A22-247[»]
4AFQX-ray1.51A/B22-247[»]
4AFSX-ray1.90A22-247[»]
4AFUX-ray1.82A/B22-247[»]
4AFZX-ray2.25A/B22-247[»]
4AG1X-ray1.40A22-247[»]
4AG2X-ray1.80A/B22-247[»]
4K2YX-ray2.30A22-247[»]
4K5ZX-ray1.80A22-247[»]
4K60X-ray1.50A22-247[»]
4K69X-ray1.50A22-247[»]
4KP0X-ray2.80A22-247[»]
ProteinModelPortalP23946.
SMRP23946. Positions 22-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107624. 2 interactions.
STRING9606.ENSP00000250378.

Chemistry

BindingDBP23946.
ChEMBLCHEMBL4068.
GuidetoPHARMACOLOGY2340.

Protein family/group databases

MEROPSS01.140.

PTM databases

PhosphoSiteP23946.

Polymorphism databases

DMDM126825.

Proteomic databases

PaxDbP23946.
PRIDEP23946.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250378; ENSP00000250378; ENSG00000092009.
GeneID1215.
KEGGhsa:1215.
UCSCuc001wpp.1. human.

Organism-specific databases

CTD1215.
GeneCardsGC14M024974.
HGNCHGNC:2097. CMA1.
HPACAB000363.
HPA052634.
MIM118938. gene.
neXtProtNX_P23946.
PharmGKBPA26623.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP23946.
KOK01329.
OMATLHHDIM.
OrthoDBEOG7RRF7Z.
PhylomeDBP23946.
TreeFamTF333630.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
SABIO-RKP23946.

Gene expression databases

ArrayExpressP23946.
BgeeP23946.
CleanExHS_CMA1.
GenevestigatorP23946.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23946.
GeneWikiCMA1.
GenomeRNAi1215.
NextBio5003.
PMAP-CutDBP23946.
PROP23946.
SOURCESearch...

Entry information

Entry nameCMA1_HUMAN
AccessionPrimary (citable) accession number: P23946
Secondary accession number(s): B5BUM8 expand/collapse secondary AC list , Q16018, Q3SY36, Q9UDH5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM