DB code: M00227

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain -.-.-.- :
3.30.70.960 : Alpha-Beta Plaits
2.60.120.290 : Jelly Rolls
2.-.-.- :
2.60.120.290 : Jelly Rolls
-.-.-.- :
3.10.250.10 : Mac-2 Binding Protein
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.9
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 M00209 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411
2.60.120.290 : Jelly Rolls M00139 M00315 M00316 M00317 M00348
3.10.250.10 : Mac-2 Binding Protein M00349
3.30.70.960 : Alpha-Beta Plaits M00348

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P98072 Enteropeptidase
EC 3.4.21.9
Enterokinase
Serine protease 7
Enteropeptidase non-catalytic heavy chain
Enteropeptidase catalytic light chain
NP_776864.1 (Protein)
NM_174439.2 (DNA/RNA sequence)
S01.156 (Serine)
PF00431 (CUB)
PF00057 (Ldl_recept_a)
PF00629 (MAM)
PF01390 (SEA)
PF00530 (SRCR)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
enteropeptidase
enterokinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P98072 ENTK_BOVIN Activation of trypsinogen by selective cleavage of 6-Lys-|-Ile-7 bond. Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond. Membrane, Single-pass type II membrane protein (Probable).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id L00076 C00001 C00298 I00087 I00085 I00086
E.C.
Compound Trypsinogen H2O Trypsin Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 962
22247451
1ekbB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Intermediate-analogue:ASP-ASP-ASP-LYS (chain C)
1ekbB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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
1ekbB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;ASP 194;SER 195(mainchain amide)
1ekbB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.364

References
[1]
Resource
Comments
Medline ID
PubMed ID 12810
Journal Biochim Biophys Acta
Year 1976
Volume 452
Pages 488-96
Authors Baratti J, Maroux S
Title On the catalytic and binding sites of porcine enteropeptidase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8051081
Journal J Biol Chem
Year 1994
Volume 269
Pages 19976-82
Authors Matsushima M, Ichinose M, Yahagi N, Kakei N, Tsukada S, Miki K, Kurokawa K, Tashiro K, Shiokawa K, Shinomiya K, et al
Title Structural characterization of porcine enteropeptidase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8052624
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 7588-92
Authors Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE
Title Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8962677
Journal Biol Chem Hoppe Seyler
Year 1995
Volume 376
Pages 681-4
Authors Wang ZM, Rubin H, Schechter NM
Title Production of active recombinant human chymase from a construct containing the enterokinase cleavage site of trypsinogen in place of the native propeptide sequence.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9636275
Journal Biotechnology (N Y)
Year 1995
Volume 13
Pages 982-7
Authors Collins-Racie LA, McColgan JM, Grant KL, DiBlasio-Smith EA, McCoy JM, LaVallie ER
Title Production of recombinant bovine enterokinase catalytic subunit in Escherichia coli using the novel secretory fusion partner DsbA.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9636316
Journal Biotechnology (N Y)
Year 1996
Volume 14
Pages 77-81
Authors Vozza LA, Wittwer L, Higgins DR, Purcell TJ, Bergseid M, Collins-Racie LA, LaVallie ER, Hoeffler JP
Title Production of a recombinant bovine enterokinase catalytic subunit in the methylotrophic yeast Pichia pastoris.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9395456
Journal J Biol Chem
Year 1997
Volume 272
Pages 31293-300
Authors Lu D, Yuan X, Zheng X, Sadler JE
Title Bovine proenteropeptidase is activated by trypsin, and the specificity of enteropeptidase depends on the heavy chain.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10094769
Journal Anal Biochem
Year 1999
Volume 269
Pages 10-6
Authors Hosfield T, Lu Q
Title Influence of the amino acid residue downstream of (Asp)4Lys on enterokinase cleavage of a fusion protein.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9880538
Journal J Biol Chem
Year 1999
Volume 274
Pages 1596-605
Authors Zheng X, Lu D, Sadler JE
Title Apical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10493881
Journal J Mol Biol
Year 1999
Volume 292
Pages 361-73
Authors Lu D, Futterer K, Korolev S, Zheng X, Tan K, Waksman G, Sadler JE
Title Crystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptide.
Related PDB 1ekb
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10656339
Journal J Biotechnol
Year 2000
Volume 76
Pages 245-51
Authors Svetina M, Krasevec N, Gaberc-Porekar V, Komel R
Title Expression of catalytic subunit of bovine enterokinase in the filamentous fungus Aspergillus niger.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11719902
Journal Am J Hum Genet
Year 2002
Volume 70
Pages 20-5
Authors Holzinger A, Maier EM, Buck C, Mayerhofer PU, Kappler M, Haworth JC, Moroz SP, Hadorn HB, Sadler JE, Roscher AA
Title Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11913964
Journal Arch Biochem Biophys
Year 2002
Volume 400
Pages 1-6
Authors Song HW, Choi SI, Seong BL
Title Engineered recombinant enteropeptidase catalytic subunit: effect of N-terminal modification.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1.
This protein is composed of a non-catalytic heavy chain, which is a multidomain bound to membrane, and a catalytic light chain. These two chains are linked by a disulfide bond (see [3]). The tertiary strucutre of the catalytic chain has been determined so far. (The chain A in 1ekb is a C-terminal fragment of heavy chain.) However, the homologous domains have been elucidated. Moreover, this enzyme is a member of type II transmembrane serine protease family (see M00348, M00349 in EzCatDB).
According to the literature [10], this enzyme has got the catalytic triad, which is a signature of serine proteases; His57, Asp102 and Ser195. Moreover, the Ser195 is bound to the C-terminal of Lys residue, to form a tetrahedral hemiketal intermediate, which showed that Ser195 could function as nucleophile.

Created Updated
2004-03-26 2012-08-06