Skip Header

Contribute Send feedback
Read comments (?) or add your own

P98073 (ENTK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 142. 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
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Enteropeptidase
EC=3.4.21.9
Alternative name(s):
Enterokinase
Serine protease 7
Transmembrane protease serine 15

Cleaved into the following 2 chains:

  1. Enteropeptidase non-catalytic heavy chain
  2. Enteropeptidase catalytic light chain
Gene names
Name:TMPRSS15
Synonyms:ENTK, PRSS7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1019 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.

Catalytic activity

Activation of trypsinogen by selective cleavage of 6-Lys-|-Ile-7 bond.

Subunit structure

Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.

Subcellular location

Membrane; Single-pass type II membrane protein Probable.

Tissue specificity

Intestinal brush border.

Post-translational modification

The chains are derived from a single precursor that is cleaved by a trypsin-like protease.

Involvement in disease

Enterokinase deficiency (ENTKD) [MIM:226200]: Life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Sequence similarities

Belongs to the peptidase S1 family.

Contains 2 CUB domains.

Contains 2 LDL-receptor class A domains.

Contains 1 MAM domain.

Contains 1 peptidase S1 domain.

Contains 1 SEA domain.

Contains 1 SRCR domain.

Sequence caution

The sequence CAB90389.1 differs from that shown. Reason: Erroneous gene model prediction.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 784784Enteropeptidase non-catalytic heavy chain
PRO_0000027719
Chain785 – 1019235Enteropeptidase catalytic light chain
PRO_0000027720

Regions

Topological domain1 – 1818Cytoplasmic Potential
Transmembrane19 – 4729Helical; Signal-anchor for type II membrane protein; Potential
Topological domain48 – 1019972Extracellular Potential
Domain52 – 169118SEA
Domain182 – 22342LDL-receptor class A 1
Domain225 – 334110CUB 1
Domain342 – 504163MAM
Domain524 – 634111CUB 2
Domain641 – 67939LDL-receptor class A 2
Domain678 – 77194SRCR
Domain785 – 1019235Peptidase S1

Sites

Active site8251Charge relay system By similarity
Active site8761Charge relay system By similarity
Active site9711Charge relay system By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine Potential
Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation1791N-linked (GlcNAc...) Potential
Glycosylation3281N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation3881N-linked (GlcNAc...) Potential
Glycosylation4401N-linked (GlcNAc...) Potential
Glycosylation4701N-linked (GlcNAc...) Potential
Glycosylation5031N-linked (GlcNAc...) Potential
Glycosylation5341N-linked (GlcNAc...) Potential
Glycosylation6301N-linked (GlcNAc...) Potential
Glycosylation6821N-linked (GlcNAc...) Potential
Glycosylation7061N-linked (GlcNAc...) Potential
Glycosylation7251N-linked (GlcNAc...) Potential
Glycosylation8481N-linked (GlcNAc...) Potential
Glycosylation8871N-linked (GlcNAc...) Potential
Glycosylation9091N-linked (GlcNAc...) Potential
Glycosylation9491N-linked (GlcNAc...) Potential
Disulfide bond184 ↔ 197 By similarity
Disulfide bond191 ↔ 210 By similarity
Disulfide bond204 ↔ 221 By similarity
Disulfide bond225 ↔ 253 By similarity
Disulfide bond524 ↔ 552 By similarity
Disulfide bond643 ↔ 655 By similarity
Disulfide bond650 ↔ 668 By similarity
Disulfide bond662 ↔ 677 By similarity
Disulfide bond757 ↔ 767 By similarity
Disulfide bond772 ↔ 896Interchain (between heavy and light chains) By similarity
Disulfide bond810 ↔ 826 Ref.6
Disulfide bond910 ↔ 977 Ref.6
Disulfide bond941 ↔ 956 Ref.6
Disulfide bond967 ↔ 995 Ref.6

Natural variations

Natural variant651T → I.
Corresponds to variant rs35987974 [ dbSNP | Ensembl ].
VAR_031686
Natural variant771K → R.
Corresponds to variant rs2824804 [ dbSNP | Ensembl ].
VAR_021940
Natural variant1341E → Q. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2824790 [ dbSNP | Ensembl ].
VAR_031687
Natural variant5451S → C.
Corresponds to variant rs8134187 [ dbSNP | Ensembl ].
VAR_031688
Natural variant6411E → K.
Corresponds to variant rs2273204 [ dbSNP | Ensembl ].
VAR_020175
Natural variant6601N → H.
Corresponds to variant rs11088674 [ dbSNP | Ensembl ].
VAR_024292
Natural variant7321P → S. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2824721 [ dbSNP | Ensembl ].
VAR_031689
Natural variant8281Y → C.
Corresponds to variant rs8130110 [ dbSNP | Ensembl ].
VAR_031690

Secondary structure

1 ..................................... 1019
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P98073 [UniParc].

Last modified January 11, 2011. Version 3.
Checksum: 45288F0636E5EC52

FASTA1,019112,935
        10         20         30         40         50         60 
MGSKRGISSR HHSLSSYEIM FAALFAILVV LCAGLIAVSC LTIKESQRGA ALGQSHEARA 

        70         80         90        100        110        120 
TFKITSGVTY NPNLQDKLSV DFKVLAFDLQ QMIDEIFLSS NLKNEYKNSR VLQFENGSII 

       130        140        150        160        170        180 
VVFDLFFAQW VSDENVKEEL IQGLEANKSS QLVTFHIDLN SVDILDKLTT TSHLATPGNV 

       190        200        210        220        230        240 
SIECLPGSSP CTDALTCIKA DLFCDGEVNC PDGSDEDNKM CATVCDGRFL LTGSSGSFQA 

       250        260        270        280        290        300 
THYPKPSETS VVCQWIIRVN QGLSIKLSFD DFNTYYTDIL DIYEGVGSSK ILRASIWETN 

       310        320        330        340        350        360 
PGTIRIFSNQ VTATFLIESD ESDYVGFNAT YTAFNSSELN NYEKINCNFE DGFCFWVQDL 

       370        380        390        400        410        420 
NDDNEWERIQ GSTFSPFTGP NFDHTFGNAS GFYISTPTGP GGRQERVGLL SLPLDPTLEP 

       430        440        450        460        470        480 
ACLSFWYHMY GENVHKLSIN ISNDQNMEKT VFQKEGNYGD NWNYGQVTLN ETVKFKVAFN 

       490        500        510        520        530        540 
AFKNKILSDI ALDDISLTYG ICNGSLYPEP TLVPTPPPEL PTDCGGPFEL WEPNTTFSST 

       550        560        570        580        590        600 
NFPNSYPNLA FCVWILNAQK GKNIQLHFQE FDLENINDVV EIRDGEEADS LLLAVYTGPG 

       610        620        630        640        650        660 
PVKDVFSTTN RMTVLLITND VLARGGFKAN FTTGYHLGIP EPCKADHFQC KNGECVPLVN 

       670        680        690        700        710        720 
LCDGHLHCED GSDEADCVRF FNGTTNNNGL VRFRIQSIWH TACAENWTTQ ISNDVCQLLG 

       730        740        750        760        770        780 
LGSGNSSKPI FPTDGGPFVK LNTAPDGHLI LTPSQQCLQD SLIRLQCNHK SCGKKLAAQD 

       790        800        810        820        830        840 
ITPKIVGGSN AKEGAWPWVV GLYYGGRLLC GASLVSSDWL VSAAHCVYGR NLEPSKWTAI 

       850        860        870        880        890        900 
LGLHMKSNLT SPQTVPRLID EIVINPHYNR RRKDNDIAMM HLEFKVNYTD YIQPICLPEE 

       910        920        930        940        950        960 
NQVFPPGRNC SIAGWGTVVY QGTTANILQE ADVPLLSNER CQQQMPEYNI TENMICAGYE 

       970        980        990       1000       1010 
EGGIDSCQGD SGGPLMCQEN NRWFLAGVTS FGYKCALPNR PGVYARVSRF TEWIQSFLH

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence and chromosomal localization of human enterokinase, the proteolytic activator of trypsinogen."
Kitamoto Y., Veile R.A., Donis-Keller H., Sadler J.E.
Biochemistry 34:4562-4568(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLN-134 AND SER-732.
Tissue: Duodenum.
[2]"Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency."
Holzinger A., Maier E.M., Buck C., Mayerhofer P.U., Kappler M., Haworth J.C., Moroz S.P., Hadorn H.-B., Sadler J.E., Roscher A.A.
Am. J. Hum. Genet. 70:20-25(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-134 AND SER-732, INVOLVEMENT IN ENTKD.
[3]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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], VARIANTS GLN-134 AND SER-732.
[5]"Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains."
Kitamoto Y., Yuan X., Wu Q., McCourt D.W., Sadler J.E.
Proc. Natl. Acad. Sci. U.S.A. 91:7588-7592(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 749-1019.
Tissue: Duodenum.
[6]"Crystal structure of a supercharged variant of the human enteropeptidase light chain."
Simeonov P., Zahn M., Strater N., Zuchner T.
Proteins 80:1907-1910(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 785-1019, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U09860 mRNA. Translation: AAC50138.1.
Y19124 expand/collapse EMBL AC list , Y19125, Y19126, Y19127, Y19128, Y19129, Y19130, Y19131, Y19132, Y19133, Y19134, Y19135, Y19136, Y19137, Y19138, Y19139, Y19140, Y19141, Y19142, Y19143 Genomic DNA. Translation: CAB65555.1.
AL163217 Genomic DNA. Translation: CAB90389.1. Sequence problems.
AL163218 Genomic DNA. Translation: CAB90392.1.
BC111749 mRNA. Translation: AAI11750.1.
IPIIPI00023788.
PIRA56318.
RefSeqNP_002763.2. NM_002772.2.
UniGeneHs.149473.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DGJX-ray1.90A/B/C/D785-1019[»]
ProteinModelPortalP98073.
SMRP98073. Positions 271-510, 523-1019.
ModBaseSearch...

Protein family/group databases

MEROPSS01.156.

PTM databases

PhosphoSiteP98073.

Polymorphism databases

DMDM259016225.

Proteomic databases

PaxDbP98073.
PRIDEP98073.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284885; ENSP00000284885; ENSG00000154646.
GeneID5651.
KEGGhsa:5651.
UCSCuc002ykw.3. human.

Organism-specific databases

CTD5651.
GeneCardsGC21M019641.
HGNCHGNC:9490. TMPRSS15.
HPAHPA015611.
MIM226200. phenotype.
606635. gene.
neXtProtNX_P98073.
Orphanet168601. Congenital enteropathy due to enteropeptidase deficiency.
PharmGKBPA33839.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000112380.
HOVERGENHBG005588.
InParanoidP98073.
KOK01316.
OMAFEDGFCF.
OrthoDBEOG4QC14Q.
PhylomeDBP98073.

Enzyme and pathway databases

BRENDA3.4.21.9. 2681.

Gene expression databases

ArrayExpressP98073.
BgeeP98073.
CleanExHS_PRSS7.
GenevestigatorP98073.
GermOnlineENSG00000154646. Homo sapiens.

Family and domain databases

Gene3D2.60.120.290. 2 hits.
4.10.400.10. 2 hits.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR000859. CUB_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR000998. MAM_dom.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000082. SEA.
IPR001190. Srcr_rcpt.
IPR017448. Srcr_rcpt-rel.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00431. CUB. 2 hits.
PF00057. Ldl_recept_a. 1 hit.
PF00629. MAM. 1 hit.
PF01390. SEA. 1 hit.
PF00530. SRCR. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00042. CUB. 2 hits.
SM00192. LDLa. 2 hits.
SM00137. MAM. 1 hit.
SM00200. SEA. 1 hit.
SM00202. SR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF49899. ConA_like_lec_gl. 1 hit.
SSF49854. CUB. 2 hits.
SSF57424. LDL_rcpt_classA_cys-rich. 2 hits.
SSF50494. Pept_Ser_Cys. 1 hit.
SSF56487. Srcr_receptor. 1 hit.
PROSITEPS01180. CUB. 2 hits.
PS01209. LDLRA_1. 2 hits.
PS50068. LDLRA_2. 2 hits.
PS00740. MAM_1. 1 hit.
PS50060. MAM_2. 1 hit.
PS50024. SEA. 1 hit.
PS00420. SRCR_1. False negative.
PS50287. SRCR_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChEMBLCHEMBL1741195.
GenomeRNAi5651.
NextBio21958.
SOURCESearch...

Entry information

Entry nameENTK_HUMAN
AccessionPrimary (citable) accession number: P98073
Secondary accession number(s): Q2NKL7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 11, 2011
Last modified: May 1, 2013
This is version 142 of the entry and version 3 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

Peptidase families

Classification of peptidase families and list of entries

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents