DB code: M00348

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain -.-.-.- :
3.30.70.960 : Alpha-Beta Plaits
2.60.120.290 : Jelly Rolls
2.60.120.290 : Jelly Rolls
4.10.100.10 :
4.10.100.10 :
4.10.100.10 :
4.10.100.10 :
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.109
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 D00214 M00167 D00426 M00133 D00428 D00429 D00430 D00431 D00432 D00433 D00434 D00435 M00227 M00209 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00349 T00074 T00410 T00411
2.60.120.290 : Jelly Rolls M00139 M00227 M00315 M00316 M00317
3.30.70.960 : Alpha-Beta Plaits M00227

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
Q9Y5Y6 Suppressor of tumorigenicity 14 protein
EC 3.4.21.109
Matriptase
Membrane-type serine protease 1
MT-SP1
Prostamin
Serine protease 14
Serine protease TADG-15
Tumor-associated differentially-expressed gene 15 protein
NP_068813.1 (Protein)
NM_021978.3 (DNA/RNA sequence)
S01.302 (Serine)
PF00431 (CUB)
PF00057 (Ldl_recept_a)
PF01390 (SEA)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Matriptase
Serine protease 14
Membrane-type serine protease 1
MT-SP1
Prostamin
Serine protease TADG-15
Tumor-associated differentially-expressed gene 15 protein
ST14
Breast cancer 80 kDa protease
Epithin
Serine endopeptidase SNC19

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9Y5Y6 ST14_HUMAN Cleaves various synthetic substrates with Arg or Lys at the P1 position and prefers small side-chain amino acids, such as Ala and Gly, at the P2 position. Interacts with CDCP1. May interact with TMEFF1. Membrane, Single-pass type II membrane protein (Probable).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00001 C00017 I00087 I00085 I00086
E.C.
Compound Protein H2O Protein Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1eawA01 Bound:LYS_15-ALA_16(chain B) Unbound Unbound Unbound Unbound
1eawC01 Bound:LYS_15-ALA_16(chain D) Unbound Unbound Unbound Unbound
1eaxA01 Unbound Unbound Unbound Unbound Unbound
2gv6A01 Unbound Unbound Unbound Unbound Unbound
2gv7A01 Unbound Unbound Unbound Unbound Unbound
3bn9A01 Unbound Unbound Unbound Unbound Unbound
3bn9B01 Unbound Unbound Unbound Unbound Unbound
3nclA01 Unbound Unbound Transition-state-analogue:CCZ Unbound Unbound
3npsA01 Unbound Unbound Unbound Unbound Unbound
3p8fA01 Bound:LYS_5-SER_6(chain I) Unbound Unbound Unbound Unbound
3p8gA01 Unbound Unbound Unbound Unbound Unbound
3so3A01 Unbound Unbound Unbound Unbound Unbound
1eawA02 Unbound Unbound Unbound Unbound Unbound
1eawC02 Unbound Unbound Unbound Unbound Unbound
1eaxA02 Unbound Unbound Unbound Unbound Unbound
2gv6A02 Unbound Unbound Unbound Unbound Unbound
2gv7A02 Unbound Unbound Unbound Unbound Unbound
3bn9A02 Unbound Unbound Unbound Unbound Unbound
3bn9B02 Unbound Unbound Unbound Unbound Unbound
3nclA02 Unbound Unbound Unbound Unbound Unbound
3npsA02 Unbound Unbound Unbound Unbound Unbound
3p8fA02 Unbound Unbound Unbound Unbound Unbound
3p8gA02 Unbound Unbound Unbound Unbound Unbound
3so3A02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [4] & Swiss-prot;Q9Y5Y6

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eawA01 SER 195 GLY 193;SER 195
1eawC01 SER 195 GLY 193;SER 195
1eaxA01 SER 195 GLY 193;SER 195
2gv6A01 SER 195 GLY 193;SER 195
2gv7A01 SER 195 GLY 193;SER 195
3bn9A01 SER 195 GLY 193;SER 195
3bn9B01 SER 195 GLY 193;SER 195
3nclA01 SER 208 GLY 206;SER 208
3npsA01 SER 195 GLY 193;SER 195
3p8fA01 SER 195 GLY 193;SER 195
3p8gA01 SER 195 GLY 193;SER 195
3so3A01 SER 195 GLY 193;SER 195
1eawA02 HIS 57;ASP 102
1eawC02 HIS 57;ASP 102
1eaxA02 HIS 57;ASP 102
2gv6A02 HIS 57;ASP 102
2gv7A02 HIS 57;ASP 102
3bn9A02 HIS 57;ASP 102
3bn9B02 HIS 57;ASP 102
3nclA02 HIS 52;ASP 107
3npsA02 HIS 57;ASP 102
3p8fA02 HIS 57;ASP 102
3p8gA02 HIS 57;ASP 102
3so3A02 HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Figure 5

References
[1]
Resource
Comments
Medline ID
PubMed ID 9374470
Journal J Biol Chem
Year 1997
Volume 272
Pages 29987-90
Authors Perona JJ, Craik CS
Title Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10831593
Journal J Biol Chem
Year 2000
Volume 275
Pages 26333-42
Authors Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR, Craik CS
Title Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12475199
Journal Chem Rev
Year 2002
Volume 102
Pages 4501-24
Authors Hedstrom L
Title Serine protease mechanism and specificity.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11696548
Journal J Biol Chem
Year 2002
Volume 277
Pages 2160-8
Authors Friedrich R, Fuentes-Prior P, Ong E, Coombs G, Hunter M, Oehler R, Pierson D, Gonzalez R, Huber R, Bode W, Madison EL
Title Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase.
Related PDB 1eaw 1eax
Related UniProtKB Q9Y5Y6
[5]
Resource
Comments
Medline ID
PubMed ID 12696750
Journal Curr Top Dev Biol
Year 2003
Volume 54
Pages 167-206
Authors Wu Q
Title Type II transmembrane serine proteases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12738778
Journal J Biol Chem
Year 2003
Volume 278
Pages 26773-9
Authors Oberst MD, Williams CA, Dickson RB, Johnson MD, Lin CY
Title The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16821772
Journal J Med Chem
Year 2006
Volume 49
Pages 4116-26
Authors Steinmetzer T, Schweinitz A, Sturzebecher A, Donnecke D, Uhland K, Schuster O, Steinmetzer P, Muller F, Friedrich R, Than ME, Bode W, Sturzebecher J
Title Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase.
Related PDB 2gv6 2gv7
Related UniProtKB Q9Y5Y6
[8]
Resource
Comments
Medline ID
PubMed ID 17981566
Journal Front Biosci
Year 2008
Volume 13
Pages 528-39
Authors Darragh MR, Bhatt AS, Craik CS
Title MT-SP1 proteolysis and regulation of cell-microenvironment interactions.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 18514224
Journal J Mol Biol
Year 2008
Volume 380
Pages 351-60
Authors Farady CJ, Egea PF, Schneider EL, Darragh MR, Craik CS
Title Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition.
Related PDB 3bn9
Related UniProtKB Q9Y5Y6
[10]
Resource
Comments
Medline ID
PubMed ID 20507279
Journal Biochem J
Year 2010
Volume 428
Pages 325-46
Authors Antalis TM, Buzza MS, Hodge KM, Hooper JD, Netzel-Arnett S
Title The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 21276938
Journal Chem Biol
Year 2011
Volume 18
Pages 48-57
Authors Brown CM, Ray M, Eroy-Reveles AA, Egea P, Tajon C, Craik CS
Title Peptide length and leaving-group sterics influence potency of peptide phosphonate protease inhibitors.
Related PDB 3ncl
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 21693064
Journal BMC Struct Biol
Year 2011
Volume 11
Pages 30
Authors Yuan C, Chen L, Meehan EJ, Daly N, Craik DJ, Huang M, Ngo JC
Title Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1.
Related PDB 3p8f 3p8g
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 22154938
Journal J Mol Biol
Year 2012
Volume 415
Pages 699-715
Authors Schneider EL, Lee MS, Baharuddin A, Goetz DH, Farady CJ, Ward M, Wang CI, Craik CS
Title A reverse binding motif that contributes to specific protease inhibition by antibodies.
Related PDB 3nps 3so3
Related UniProtKB

Comments
This enzyme belongs to peptidase family-S1.
This enzyme is composed of several non-catalytic domains in the N-terminal region and C-terminal trypsin-like catalytic domain. Although the structures of the non-catalytic domains have not been solved yet, their homologous domains have been elucidated.
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

Created Updated
2011-03-09 2012-08-02