P05981 (HEPS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine protease hepsin
EC=3.4.21.106

Alternative name(s):
Transmembrane protease serine 1

Cleaved into the following 2 chains:

1. Serine protease hepsin non-catalytic chain
2. Serine protease hepsin catalytic chain

Gene names

Name:	HPN
Synonyms:	TMPRSS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	417 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Ref.7 Ref.8
Catalytic activity	Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys.
Subcellular location	Membrane; Single-pass type II membrane protein.
Tissue specificity	Present in most tissues, with the highest level in liver.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 peptidase S1 domain. Contains 1 SRCR domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	basement membrane disassembly Inferred from direct assay PubMed 16908524. Source: UniProtKB cochlea morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB detection of mechanical stimulus involved in sensory perception of sound Inferred from sequence or structural similarity. Source: UniProtKB epithelium development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from direct assay PubMed 15614436. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from direct assay PubMed 19843851. Source: UniProtKB negative regulation of epithelial to mesenchymal transition Inferred from direct assay PubMed 19843851. Source: UniProtKB pilomotor reflex Inferred from sequence or structural similarity. Source: UniProtKB positive regulation by host of viral transcription Inferred from direct assay PubMed 15614436. Source: UniProtKB positive regulation of cell growth Inferred from mutant phenotype Ref.5. Source: UniProtKB positive regulation of gene expression Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of hepatocyte proliferation Inferred from direct assay PubMed 15614436. Source: UniProtKB positive regulation of plasminogen activation Inferred from direct assay PubMed 16908524. Source: UniProtKB positive regulation of thyroid hormone generation Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from direct assay PubMed 16908524PubMed 19843851PubMed 19911255. Source: UniProtKB regulation of cell shape Inferred from mutant phenotype Ref.5. Source: UniProtKB response to thyroid hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell surface Inferred from direct assay PubMed 16908524Ref.5. Source: UniProtKB cell-cell junction Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay PubMed 17918732. Source: UniProtKB integral to plasma membrane Inferred from direct assay Ref.4. Source: UniProtKB neuronal cell body Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium-activated potassium channel activity Inferred from sequence or structural similarity. Source: UniProtKB scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Inferred from direct assay PubMed 16908524. Source: UniProtKB serine-type exopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 162

162

Serine protease hepsin non-catalytic chain Potential

PRO_0000027841

Chain

163 – 417

255

Serine protease hepsin catalytic chain Potential

PRO_0000027842

Regions

Topological domain

1 – 23

23

Cytoplasmic Potential

Transmembrane

24 – 44

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

45 – 417

373

Extracellular Potential

Domain

54 – 151

98

SRCR

Domain

163 – 405

243

Peptidase S1

Sites

Active site

203

1

Charge relay system By similarity

Active site

257

1

Charge relay system By similarity

Active site

353

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

112

1

N-linked (GlcNAc...) Ref.6

Disulfide bond

77 ↔ 140

Ref.8

Disulfide bond

90 ↔ 150

Ref.8

Disulfide bond

119 ↔ 138

Ref.8

Disulfide bond

153 ↔ 277

Interchain (between non-catalytic and catalytic chains) By similarity

Disulfide bond

188 ↔ 204

Ref.8

Disulfide bond

291 ↔ 359

Ref.8

Disulfide bond

322 ↔ 338

Ref.8

Disulfide bond

349 ↔ 381

Ref.8

Secondary structure

1

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417

Helix Strand Turn

Details...

Beta strand

53 – 56

4

Turn

58 – 60

3

Beta strand

62 – 67

6

Turn

68 – 71

4

Beta strand

72 – 77

6

Helix

82 – 93

12

Beta strand

98 – 105

8

Helix

106 – 109

4

Beta strand

116 – 120

5

Turn

122 – 124

3

Helix

125 – 127

3

Helix

131 – 134

4

Beta strand

135 – 138

4

Beta strand

144 – 150

7

Beta strand

177 – 182

6

Beta strand

185 – 200

16

Helix

202 – 204

3

Helix

207 – 209

3

Helix

212 – 214

3

Beta strand

215 – 220

6

Beta strand

229 – 232

4

Beta strand

234 – 240

7

Helix

244 – 246

3

Beta strand

259 – 265

7

Beta strand

290 – 300

11

Beta strand

310 – 317

8

Helix

319 – 322

4

Turn

325 – 330

6

Beta strand

336 – 340

5

Beta strand

356 – 361

6

Beta strand

368 – 382

15

Beta strand

388 – 392

5

Helix

393 – 396

4

Helix

397 – 406

10

Turn

407 – 409

3

Beta strand

412 – 416

5

Sequences

	Sequence		Length	Mass (Da)
	P05981 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: B2086FF661E551D7	FASTA	417	45,011
	10 20 30 40 50 60 MAQKEGGRTV PCCSRPKVAA LTAGTLLLLT AIGAASWAIV AVLLRSDQEP LYPVQVSSAD 70 80 90 100 110 120 ARLMVFDKTE GTWRLLCSSR SNARVAGLSC EEMGFLRALT HSELDVRTAG ANGTSGFFCV 130 140 150 160 170 180 DEGRLPHTQR LLEVISVCDC PRGRFLAAIC QDCGRRKLPV DRIVGGRDTS LGRWPWQVSL 190 200 210 220 230 240 RYDGAHLCGG SLLSGDWVLT AAHCFPERNR VLSRWRVFAG AVAQASPHGL QLGVQAVVYH 250 260 270 280 290 300 GGYLPFRDPN SEENSNDIAL VHLSSPLPLT EYIQPVCLPA AGQALVDGKI CTVTGWGNTQ 310 320 330 340 350 360 YYGQQAGVLQ EARVPIISND VCNGADFYGN QIKPKMFCAG YPEGGIDACQ GDSGGPFVCE 370 380 390 400 410 DSISRTPRWR LCGIVSWGTG CALAQKPGVY TKVSDFREWI FQAIKTHSEA SGMVTQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells." Leytus S.P., Loeb K.R., Hagen F.S., Kurachi K., Davie E.W. Biochemistry 27:1067-1074(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Mammary gland.
[3]	"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]. Tissue: Pancreas and Spleen.
[4]	"Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization." Tsuji A., Torres-Rosado A., Arai T., le Beau M.M., Lemons R.S., Chou S.H., Kurachi K. J. Biol. Chem. 266:16948-16953(1991) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[5]	"Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth." Torres-Rosado A., O'Shea K.S., Tsuji A., Chou S.-H., Kurachi K. Proc. Natl. Acad. Sci. U.S.A. 90:7181-7185(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Proteolytic activation of pro-macrophage-stimulating protein by hepsin." Ganesan R., Kolumam G.A., Lin S.J., Xie M.H., Santell L., Wu T.D., Lazarus R.A., Chaudhuri A., Kirchhofer D. Mol. Cancer Res. 9:1175-1186(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers." Herter S., Piper D.E., Aaron W., Gabriele T., Cutler G., Cao P., Bhatt A.S., Choe Y., Craik C.S., Walker N., Meininger D., Hoey T., Austin R.J. Biochem. J. 390:125-136(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 46-417, DISULFIDE BONDS, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M18930 mRNA. Translation: AAA36013.1.
X07732 mRNA. Translation: CAA30558.1.
X07002 mRNA. Translation: CAA30058.1.
AK315655 mRNA. Translation: BAG38021.1.
BC025716 mRNA. Translation: AAH25716.1.

IPI

IPI00395826.

PIR

S00845.

RefSeq

NP_002142.1. NM_002151.2.
NP_892028.1. NM_182983.2.

UniGene

Hs.182385.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1O5E	X-ray	1.75	H	163-417	[»]
			L	46-159	[»]
1O5F	X-ray	1.78	H	163-417	[»]
			L	46-159	[»]
1P57	X-ray	1.75	A	46-159	[»]
			B	163-417	[»]
1Z8G	X-ray	1.55	A	46-417	[»]
3T2N	X-ray	2.55	A/B	46-417	[»]

ProteinModelPortal

P05981.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000262626.

Protein family/group databases

MEROPS

S01.224.

PTM databases

PhosphoSite

P05981.

Polymorphism databases

DMDM

123057.

Proteomic databases

PaxDb

P05981.

PeptideAtlas

P05981.

PRIDE

P05981.

Protocols and materials databases

DNASU

3249.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262626; ENSP00000262626; ENSG00000105707.
ENST00000392226; ENSP00000376060; ENSG00000105707.

GeneID

3249.

KEGG

hsa:3249.

UCSC

uc002nxq.2. human.

Organism-specific databases

CTD

3249.

GeneCards

GC19P035531.

H-InvDB

HIX0137465.

HGNC

HGNC:5155. HPN.

HPA

HPA006804.

MIM

142440. gene.

neXtProt

NX_P05981.

PharmGKB

PA29425.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251822.

HOVERGEN

HBG013304.

InParanoid

P05981.

KO

K08665.

OrthoDB

EOG4PRSQV.

PhylomeDB

P05981.

Enzyme and pathway databases

BRENDA

3.4.21.106. 2681.

Gene expression databases

ArrayExpress

P05981.

Bgee

P05981.

CleanEx

HS_HPN.

Genevestigator

P05981.

GermOnline

ENSG00000105707. Homo sapiens.

Family and domain databases

InterPro

IPR015352. Hepsin-SRCR.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR017448. Srcr_rcpt-rel.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF09272. Hepsin-SRCR. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

ProDom

PD021735. Hepsin-SRCR. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.
SSF56487. Srcr_receptor. 1 hit.

PROSITE

PS00420. SRCR_1. False negative.
PS50287. SRCR_2. False negative.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P05981.

DrugBank

DB00036. Coagulation factor VIIa.

EvolutionaryTrace

P05981.

GenomeRNAi

3249.

NextBio

12917.

PMAP-CutDB

P05981.

SOURCE

Search...

Entry information

Entry name

HEPS_HUMAN

Accession

Primary (citable) accession number: P05981
Secondary accession number(s): B2RDS4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.