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Protein

Enteropeptidase

Gene

TMPRSS15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei825Charge relay systemBy similarity1
Active sitei876Charge relay systemBy similarity1
Active sitei971Charge relay systemBy similarity1

GO - Molecular functioni

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.9 2681

Protein family/group databases

MEROPSiS01.156

Names & Taxonomyi

Protein namesi
Recommended name:
Enteropeptidase (EC:3.4.21.9)
Alternative name(s):
Enterokinase
Serine protease 7
Transmembrane protease serine 15
Cleaved into the following 2 chains:
Gene namesi
Name:TMPRSS15
Synonyms:ENTK, PRSS7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000154646.8
HGNCiHGNC:9490 TMPRSS15
MIMi606635 gene
neXtProtiNX_P98073

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 18CytoplasmicSequence analysisAdd BLAST17
Transmembranei19 – 47Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST29
Topological domaini48 – 1019ExtracellularSequence analysisAdd BLAST972

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Enterokinase deficiency (ENTKD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionLife-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive.
See also OMIM:226200

Organism-specific databases

DisGeNETi5651
MalaCardsiTMPRSS15
MIMi226200 phenotype
OpenTargetsiENSG00000154646
Orphaneti168601 Congenital enteropathy due to enteropeptidase deficiency
PharmGKBiPA33839

Chemistry databases

ChEMBLiCHEMBL1741195

Polymorphism and mutation databases

BioMutaiTMPRSS15
DMDMi317373442

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00000277192 – 784Enteropeptidase non-catalytic heavy chainAdd BLAST783
ChainiPRO_0000027720785 – 1019Enteropeptidase catalytic light chainAdd BLAST235

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineSequence analysis1
Glycosylationi116N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi147N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi184 ↔ 197By similarity
Disulfide bondi191 ↔ 210By similarity
Disulfide bondi204 ↔ 221By similarity
Disulfide bondi225 ↔ 253By similarity
Glycosylationi328N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi335N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi388N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi440N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi470N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi503N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi524 ↔ 552By similarity
Glycosylationi534N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi630N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi643 ↔ 655By similarity
Disulfide bondi650 ↔ 668By similarity
Disulfide bondi662 ↔ 677By similarity
Glycosylationi682N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi706N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi725N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi757 ↔ 767By similarity
Disulfide bondi772 ↔ 896Interchain (between heavy and light chains)PROSITE-ProRule annotation
Disulfide bondi810 ↔ 8261 Publication
Glycosylationi848N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi887N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi909N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi910 ↔ 9771 Publication
Disulfide bondi941 ↔ 9561 Publication
Glycosylationi949N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi967 ↔ 9951 Publication

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Zymogen

Proteomic databases

PaxDbiP98073
PeptideAtlasiP98073
PRIDEiP98073
ProteomicsDBi57784

PTM databases

iPTMnetiP98073
PhosphoSitePlusiP98073

Expressioni

Tissue specificityi

Intestinal brush border.

Gene expression databases

BgeeiENSG00000154646
CleanExiHS_PRSS7
ExpressionAtlasiP98073 baseline and differential
GenevisibleiP98073 HS

Organism-specific databases

HPAiHPA015611
HPA072934

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi111632, 1 interactor
IntActiP98073, 3 interactors
MINTiP98073
STRINGi9606.ENSP00000284885

Chemistry databases

BindingDBiP98073

Structurei

Secondary structure

11019
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi799 – 804Combined sources6
Beta strandi807 – 814Combined sources8
Beta strandi816 – 822Combined sources7
Helixi824 – 827Combined sources4
Helixi834 – 836Combined sources3
Beta strandi837 – 842Combined sources6
Beta strandi855 – 864Combined sources10
Turni870 – 873Combined sources4
Beta strandi878 – 884Combined sources7
Beta strandi909 – 919Combined sources11
Beta strandi929 – 936Combined sources8
Helixi938 – 944Combined sources7
Beta strandi954 – 957Combined sources4
Beta strandi974 – 979Combined sources6
Beta strandi982 – 991Combined sources10
Beta strandi993 – 996Combined sources4
Beta strandi1002 – 1006Combined sources5
Helixi1007 – 1009Combined sources3
Helixi1011 – 1015Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DGJX-ray1.90A/B/C/D785-1019[»]
ProteinModelPortaliP98073
SMRiP98073
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 169SEAPROSITE-ProRule annotationAdd BLAST116
Domaini182 – 223LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST42
Domaini225 – 334CUB 1PROSITE-ProRule annotationAdd BLAST110
Domaini342 – 504MAMPROSITE-ProRule annotationAdd BLAST163
Domaini524 – 634CUB 2PROSITE-ProRule annotationAdd BLAST111
Domaini641 – 679LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST39
Domaini678 – 771SRCRPROSITE-ProRule annotationAdd BLAST94
Domaini785 – 1019Peptidase S1PROSITE-ProRule annotationAdd BLAST235

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118962
HOGENOMiHOG000112380
HOVERGENiHBG005588
InParanoidiP98073
KOiK01316
OMAiNWNYGQV
OrthoDBiEOG091G0DF7
PhylomeDBiP98073
TreeFamiTF351678

Family and domain databases

CDDicd00041 CUB, 2 hits
cd00112 LDLa, 2 hits
cd06263 MAM, 1 hit
cd00190 Tryp_SPc, 1 hit
Gene3Di2.60.120.290, 2 hits
3.10.250.10, 1 hit
3.30.70.960, 1 hit
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR000859 CUB_dom
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR002172 LDrepeatLR_classA_rpt
IPR000998 MAM_dom
IPR011163 Pept_S1A_enterop
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR000082 SEA_dom
IPR036364 SEA_dom_sf
IPR035914 Sperma_CUB_dom_sf
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00431 CUB, 2 hits
PF00057 Ldl_recept_a, 2 hits
PF00629 MAM, 1 hit
PF01390 SEA, 1 hit
PF15494 SRCR_2, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001138 Enteropeptidase, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00042 CUB, 2 hits
SM00192 LDLa, 2 hits
SM00137 MAM, 1 hit
SM00200 SEA, 1 hit
SM00202 SR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF49854 SSF49854, 2 hits
SSF49899 SSF49899, 1 hit
SSF50494 SSF50494, 1 hit
SSF56487 SSF56487, 1 hit
SSF57424 SSF57424, 2 hits
SSF82671 SSF82671, 1 hit
PROSITEiView protein in PROSITE
PS01180 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
PS50287 SRCR_2, 1 hit
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P98073-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSKRGISSR HHSLSSYEIM FAALFAILVV LCAGLIAVSC LTIKESQRGA
60 70 80 90 100
ALGQSHEARA TFKITSGVTY NPNLQDKLSV DFKVLAFDLQ QMIDEIFLSS
110 120 130 140 150
NLKNEYKNSR VLQFENGSII VVFDLFFAQW VSDENVKEEL IQGLEANKSS
160 170 180 190 200
QLVTFHIDLN SVDILDKLTT TSHLATPGNV SIECLPGSSP CTDALTCIKA
210 220 230 240 250
DLFCDGEVNC PDGSDEDNKM CATVCDGRFL LTGSSGSFQA THYPKPSETS
260 270 280 290 300
VVCQWIIRVN QGLSIKLSFD DFNTYYTDIL DIYEGVGSSK ILRASIWETN
310 320 330 340 350
PGTIRIFSNQ VTATFLIESD ESDYVGFNAT YTAFNSSELN NYEKINCNFE
360 370 380 390 400
DGFCFWVQDL NDDNEWERIQ GSTFSPFTGP NFDHTFGNAS GFYISTPTGP
410 420 430 440 450
GGRQERVGLL SLPLDPTLEP ACLSFWYHMY GENVHKLSIN ISNDQNMEKT
460 470 480 490 500
VFQKEGNYGD NWNYGQVTLN ETVKFKVAFN AFKNKILSDI ALDDISLTYG
510 520 530 540 550
ICNGSLYPEP TLVPTPPPEL PTDCGGPFEL WEPNTTFSST NFPNSYPNLA
560 570 580 590 600
FCVWILNAQK GKNIQLHFQE FDLENINDVV EIRDGEEADS LLLAVYTGPG
610 620 630 640 650
PVKDVFSTTN RMTVLLITND VLARGGFKAN FTTGYHLGIP EPCKADHFQC
660 670 680 690 700
KNGECVPLVN LCDGHLHCED GSDEADCVRF FNGTTNNNGL VRFRIQSIWH
710 720 730 740 750
TACAENWTTQ ISNDVCQLLG LGSGNSSKPI FPTDGGPFVK LNTAPDGHLI
760 770 780 790 800
LTPSQQCLQD SLIRLQCNHK SCGKKLAAQD ITPKIVGGSN AKEGAWPWVV
810 820 830 840 850
GLYYGGRLLC GASLVSSDWL VSAAHCVYGR NLEPSKWTAI LGLHMKSNLT
860 870 880 890 900
SPQTVPRLID EIVINPHYNR RRKDNDIAMM HLEFKVNYTD YIQPICLPEE
910 920 930 940 950
NQVFPPGRNC SIAGWGTVVY QGTTANILQE ADVPLLSNER CQQQMPEYNI
960 970 980 990 1000
TENMICAGYE EGGIDSCQGD SGGPLMCQEN NRWFLAGVTS FGYKCALPNR
1010
PGVYARVSRF TEWIQSFLH
Length:1,019
Mass (Da):112,935
Last modified:January 11, 2011 - v3
Checksum:i45288F0636E5EC52
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03168665T → I. Corresponds to variant dbSNP:rs35987974Ensembl.1
Natural variantiVAR_02194077K → R. Corresponds to variant dbSNP:rs2824804Ensembl.1
Natural variantiVAR_031687134E → Q3 PublicationsCorresponds to variant dbSNP:rs2824790Ensembl.1
Natural variantiVAR_031688545S → C. Corresponds to variant dbSNP:rs8134187Ensembl.1
Natural variantiVAR_020175641E → K. Corresponds to variant dbSNP:rs2273204Ensembl.1
Natural variantiVAR_024292660N → H. Corresponds to variant dbSNP:rs11088674Ensembl.1
Natural variantiVAR_031689732P → S3 PublicationsCorresponds to variant dbSNP:rs2824721Ensembl.1
Natural variantiVAR_031690828Y → C. Corresponds to variant dbSNP:rs8130110Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09860 mRNA Translation: AAC50138.1
Y19124
, 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
CCDSiCCDS13571.1
PIRiA56318
RefSeqiNP_002763.2, NM_002772.2
UniGeneiHs.149473

Genome annotation databases

EnsembliENST00000284885; ENSP00000284885; ENSG00000154646
GeneIDi5651
KEGGihsa:5651
UCSCiuc002ykw.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiENTK_HUMAN
AccessioniPrimary (citable) accession number: P98073
Secondary accession number(s): Q2NKL7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 11, 2011
Last modified: June 20, 2018
This is version 189 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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