DB code: D00212

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.35
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 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq MEROPS
P00752 Glandular kallikrein
EC 3.4.21.35
Tissue kallikrein
PF00089 (Trypsin)
[Graphical View]
Q6H321 Kallikrein-1E2
EC 3.4.21.35
Glandular kallikrein
HPK
PF00089 (Trypsin)
[Graphical View] 		NP_001075362.1 (Protein)
NM_001081893.1 (DNA/RNA sequence)
S01.171 (Serine)
P06870 Kallikrein-1
EC 3.4.21.35
Tissue kallikrein
Kidney/pancreas/salivary gland kallikrein
PF00089 (Trypsin)
[Graphical View] 		NP_002248.1 (Protein)
NM_002257.2 (DNA/RNA sequence)

KEGG enzyme name
tissue kallikrein
glandular kallikrein
pancreatic kallikrein
submandibular kallikrein
submaxillary kallikrein
kidney kallikrein
urinary kallikrein
kallikrein
salivary kallikrein
kininogenin
kininogenase
callicrein
glumorin
padreatin
padutin
kallidinogenase
bradykininogenase
depot-padutin
urokallikrein
dilminal D
onokrein P

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00752 KLK_PIG Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. Monomer.
Q6H321 KLK2_HORSE Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. Secreted.
P06870 KLK1_HUMAN Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00769 C00001 C00012 C01505 C00306 I00087 I00085 I00086
E.C.
Compound Protein Peptide Kininogen H2O Peptide Kallidin Bradykinin Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein peptide/protein peptide/protein H2O peptide/protein amino acids,amine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,imine group,lipid,peptide/protein amino acids,amine group,aromatic ring (only carbon atom),carbohydrate,carboxyl group,imine group,lipid,peptide/protein
ChEBI 15377
 15377
 		6102
 6102
 		3165
 3165
PubChem 22247451
 962
 22247451
 962
 		5311111
 5311111
 		439201
 439201
1hiaB Unbound Analogue:ARG_30-ILE_31(chain I) Unbound Unbound Unbound Unbound
1hiaY Unbound Analogue:ARG_30-ILE_31(chain J) Unbound Unbound Unbound Unbound
2kaiB Unbound Analogue:LYS_15-ALA_16(chain I) Unbound Unbound Unbound Unbound
2pkaB Unbound Unbound Unbound Unbound Unbound Unbound
2pkaY Unbound Unbound Unbound Unbound Unbound Unbound
1gvzA01 Unbound Unbound Unbound Unbound Unbound Unbound
1spjA01 Unbound Unbound Unbound Unbound Unbound Unbound
1hiaA Unbound Unbound Unbound Unbound Unbound Unbound
1hiaX Unbound Unbound Unbound Unbound Unbound Unbound
2kaiA Unbound Unbound Unbound Unbound Unbound Unbound
2pkaA Unbound Unbound Unbound Unbound Unbound Unbound
2pkaX Unbound Unbound Unbound Unbound Unbound Unbound
1gvzA02 Unbound Unbound Unbound Unbound Unbound Unbound
1spjA02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1hiaB ASP 102;SER 195 GLY 193;SER 195
1hiaY ASP 102;SER 195 GLY 193;SER 195
2kaiB ASP 102;SER 195 GLY 193;SER 195
2pkaB ASP 102;SER 195 GLY 193;SER 195
2pkaY ASP 102;SER 195 GLY 193;SER 195
1gvzA01 SER 195 GLY 193;SER 195
1spjA01 SER 195 GLY 193;SER 195
1hiaA HIS 57
1hiaX HIS 57
2kaiA HIS 57
2pkaA HIS 57
2pkaX HIS 57
1gvzA02 HIS 57;ASP 102
1spjA02 HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
[13]
Scheme 3, Scheme 10, Scheme 11, p.94-104
[14]
p.2039
[21]
p.258-259
[29]
p.27277-27278
[30]
p.329-332

References
[1]
Resource
Comments REVIEW.
Medline ID 82194877
PubMed ID 7043199
Journal Methods Enzymol
Year 1981
Volume 80 Pt C
Pages 493-532
Authors Fiedler F, Fink E, Tschesche H, Fritz H
Title Porcine glandular kallikreins.
Related PDB
Related UniProtKB P00752
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS), AND REVISIONS.
Medline ID 83189107
PubMed ID 6551452
Journal J Mol Biol
Year 1983
Volume 164
Pages 237-82
Authors Bode W, Chen Z, Bartels K, Kutzbach C, Schmidt-Kastner G, Bartunik H
Title Refined 2 A X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin.
Related PDB 2pka
Related UniProtKB P00752
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF COMPLEX WITH BOVINE PANCREATIC TRYPSIN INHIBITOR.
Medline ID 83189108
PubMed ID 6188842
Journal J Mol Biol
Year 1983
Volume 164
Pages 283-311
Authors Chen Z, Bode W
Title Refined 2.5 A X-ray crystal structure of the complex formed by porcine kallikrein A and the bovine pancreatic trypsin inhibitor. Crystallization, Patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex.
Related PDB 2kai
Related UniProtKB P00752
[4]
Resource
Comments
Medline ID
PubMed ID 2954262
Journal Thromb Res
Year 1987
Volume 45
Pages 451-62
Authors Hijikata-Okunomiya A, Okamoto S, Kikumoto R, Tamao Y, Ohkubo K, Tezuka T, Tonomura S, Matsumoto O
Title Similarity and dissimilarity in the stereogeometry of the active sites of thrombin, trypsin, plasmin and glandular kallikrein.
Related PDB
Related UniProtKB
[5]
Resource
Comments STRUCTURE OF CARBOHYDRATES.
Medline ID 89062455
PubMed ID 3196708
Journal Biochemistry
Year 1988
Volume 27
Pages 7146-54
Authors Tomiya N, Yamaguchi T, Awaya J, Kurono M, Endo S, Arata Y, Takahashi N, Ishihara H, Mori M, Tejima S
Title Structural analyses of asparagine-linked oligosaccharides of porcine pancreatic kallikrein.
Related PDB
Related UniProtKB P00752
[6]
Resource
Comments
Medline ID
PubMed ID 2012805
Journal Biochemistry
Year 1991
Volume 30
Pages 3443-50
Authors Fahnestock M, Woo JE, Lopez GA, Snow J, Walz DA, Arici MJ, Mobley WC
Title beta-NGF-endopeptidase: structure and activity of a kallikrein encoded by the gene mGK-22.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1868047
Journal Biochemistry
Year 1991
Volume 30
Pages 7666-72
Authors Hatala MA, DiPippo VA, Powers CA
Title Biological thiols elicit prolactin proteolysis by glandular kallikrein and permit regulation by biochemical pathways linked to redox control.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1507198
Journal J Med Chem
Year 1992
Volume 35
Pages 3094-102
Authors Deshpande MS, Burton J
Title Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8148470
Journal Drug Des Discov
Year 1993
Volume 10
Pages 297-317
Authors Barth A, Wahab M, Brandt W, Frost K
Title Classification of serine proteases derived from steric comparisons of their active sites.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8254673
Journal J Mol Biol
Year 1993
Volume 234
Pages 779-815
Authors Sali A, Blundell TL
Title Comparative protein modelling by satisfaction of spatial restraints.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7526861
Journal Biochem Biophys Res Commun
Year 1994
Volume 204
Pages 1251-6
Authors Vihinen M
Title Modeling of prostate specific antigen and human glandular kallikrein structures.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7749384
Journal Braz J Med Biol Res
Year 1994
Volume 27
Pages 1935-42
Authors Sueiras-Diaz J, Jones DM, Ashworth D, Horton J, Evans DM, Szelke M
Title Cleavage of human kininogen fragments at Met-Lys by human tissue kallikrein.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9116171
Journal Drug Des Discov
Year 1994
Volume 12
Pages 89-111
Authors Barth A, Frost K, Wahab M, Brandt W, Schadler HD, Franke R
Title Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins".
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7535613
Journal Protein Sci
Year 1994
Volume 3
Pages 2033-44
Authors Villoutreix BO, Getzoff ED, Griffin JH
Title A structural model for the prostate disease marker, human prostate-specific antigen.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 7864830
Journal Biochem J
Year 1995
Volume 306
Pages 63-9
Authors Chagas JR, Portaro FC, Hirata IY, Almeida PC, Juliano MA, Juliano L, Prado ES
Title Determinants of the unusual cleavage specificity of lysyl-bradykinin-releasing kallikreins.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 7538242
Journal Urology
Year 1995
Volume 45
Pages 801-6
Authors Bridon DP, Dowell BL
Title Structural comparison of prostate-specific antigen and human glandular kallikrein using molecular modeling.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 8961351
Journal Protein Eng
Year 1996
Volume 9
Pages 987-95
Authors Moreau T, Gauthier F
Title Homology modelling of rat kallikrein rK9, a member of the tissue kallikrein family: implications for substrate specificity and inhibitor binding.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9208936
Journal Eur J Biochem
Year 1997
Volume 246
Pages 440-6
Authors Mikolajczyk SD, Millar LS, Marker KM, Grauer LS, Goel A, Cass MM, Kumar A, Saedi MS
Title Ala217 is important for the catalytic function and autoactivation of prostate-specific human kallikrein 2.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9491347
Journal J Comput Aided Mol Des
Year 1997
Volume 11
Pages 547-56
Authors Henriques EF, Ramos MJ, Reynolds CA
Title Inclusion of conserved buried water molecules in the model structure of rat submaxillary kallikrein.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID 97376615
PubMed ID 9232643
Journal Protein Sci
Year 1997
Volume 6
Pages 1418-25
Authors Timm DE
Title The crystal structure of the mouse glandular kallikrein-13 (prorenin converting enzyme).
Related PDB 1ao5
Related UniProtKB P36368
[21]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF COMPLEX WITH HIRUSTASIN.
Medline ID 97184690
PubMed ID 9032072
Journal Structure
Year 1997
Volume 5
Pages 253-64
Authors Mittl PR, Di Marco S, Fendrich G, Pohlig G, Heim J, Sommerhoff C, Fritz H, Priestle JP, Grutter MG
Title A new structural class of serine protease inhibitors revealed by the structure of the hirustasin-kallikrein complex.
Related PDB 1hia
Related UniProtKB P00752
[22]
Resource
Comments
Medline ID
PubMed ID 9568894
Journal Protein Sci
Year 1998
Volume 7
Pages 875-85
Authors Katz BA, Liu B, Barnes M, Springman EB
Title Crystal structure of recombinant human tissue kallikrein at 2.0 A resolution.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 9521101
Journal Protein Sci
Year 1998
Volume 7
Pages 259-69
Authors Piironen T, Villoutreix BO, Becker C, Hollingsworth K, Vihinen M, Bridon D, Qiu X, Rapp J, Dowell B, Lovgren T, Pettersson K, Lilja H
Title Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9933620
Journal J Biol Chem
Year 1999
Volume 274
Pages 4220-4
Authors Kishi T, Kato M, Shimizu T, Kato K, Matsumoto K, Yoshida S, Shiosaka S, Hakoshima T
Title Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10195448
Journal J Pept Res
Year 1999
Volume 53
Pages 109-19
Authors Juliano MA, Filira F, Gobbo M, Rocchi R, Del Nery E, Juliano L
Title Chromogenic and fluorogenic glycosylated and acetylglycosylated peptides as substrates for serine, thiol and aspartyl proteases.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10993887
Journal J Biol Chem
Year 2000
Volume 275
Pages 38457-66
Authors Chen VC, Chao L, Chao J
Title Roles of the P1, P2, and P3 residues in determining inhibitory specificity of kallistatin toward human tissue kallikrein.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10991942
Journal J Biol Chem
Year 2000
Volume 275
Pages 40371-7
Authors Chen VC, Chao L, Chao J
Title A positively charged loop on the surface of kallistatin functions to enhance tissue kallikrein inhibition by acting as a secondary binding site for kallikrein.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11983703
Journal J Biol Chem
Year 2002
Volume 277
Pages 24562-70
Authors Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M
Title Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12016211
Journal J Biol Chem
Year 2002
Volume 277
Pages 27273-81
Authors Gomis-Ruth FX, Bayes A, Sotiropoulou G, Pampalakis G, Tsetsenis T, Villegas V, Aviles FX, Coll M
Title The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family.
Related PDB
Related UniProtKB
[30]
Resource
Comments NUCLEOTIDE SEQUENCE [MRNA] OF 62-252, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 25-261.
Medline ID
PubMed ID 12217694
Journal J Mol Biol
Year 2002
Volume 322
Pages 325-37
Authors Carvalho AL, Sanz L, Barettino D, Romero A, Calvete JJ, Romao MJ
Title Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: a homologue of human PSA.
Related PDB 1gvz
Related UniProtKB Q6H321
[31]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 15651049
Journal Proteins
Year 2005
Volume 58
Pages 802-14
Authors Laxmikanthan G, Blaber SI, Bernett MJ, Scarisbrick IA, Juliano MA, Blaber M
Title 1.70 A X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding.
Related PDB 1spj
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1.
According to the literature, this enzyme has got a catalytic triad, composed of Ser/His/Asp and an oxyanionhole of mainchain amide groups. Thus, it must have a similar reaction mechanism to that of trypsin (D00197 in EzCatDB).

Created Updated
2006-01-10 2011-02-18