Q16651 (PRSS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prostasin
EC=3.4.21.-

Alternative name(s):
Channel-activating protease 1
Short name=CAP1
Serine protease 8

Cleaved into the following 2 chains:

1. Prostasin light chain
2. Prostasin heavy chain

Gene names

Name:

PRSS8

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	343 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	Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G). Ref.4 Ref.5
Subunit structure	Heterodimer of two chains, light and heavy, held by a disulfide bond.
Subcellular location	Prostasin: Cell membrane; Single-pass membrane protein. Prostasin light chain: Secreted › extracellular space. Note: Found in the seminal fluid. Secreted after cleavage of its C-terminus. Prostasin heavy chain: Secreted › extracellular space. Note: Found in the seminal fluid. Secreted after cleavage of its C-terminus.
Tissue specificity	Found in prostate, liver, salivary gland, kidney, lung, pancreas, colon, bronchus and renal proximal tubular cells. In the prostate gland it may be synthesized in epithelial cells, secreted into the ducts, and excreted into the seminal fluid.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of sodium ion transport Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Traceable author statement PubMed 10077646. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 19911255. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Potential

Propeptide

30 – 32

3

Activation peptide

PRO_0000028027

Chain

33 – 343

311

Prostasin

PRO_0000240511

Chain

33 – 44

12

Prostasin light chain

PRO_0000028028

Chain

45 – 322

278

Prostasin heavy chain

PRO_0000028029

Propeptide

323 – 343

21

PRO_0000028030

Regions

Transmembrane

320 – 340

21

Helical; Potential

Domain

45 – 286

242

Peptidase S1

Sites

Active site

85

1

Charge relay system

Active site

134

1

Charge relay system

Active site

238

1

Charge relay system

Amino acid modifications

Glycosylation

159

1

N-linked (GlcNAc...) Potential

Disulfide bond

37 ↔ 154

Interchain (between light and heavy chains) By similarity

Disulfide bond

70 ↔ 86

Ref.6

Disulfide bond

168 ↔ 244

Ref.6

Disulfide bond

201 ↔ 223

Ref.6

Disulfide bond

234 ↔ 262

Ref.6

Secondary structure

1

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343

Helix Strand Turn

Details...

Beta strand

59 – 64

6

Beta strand

67 – 74

8

Beta strand

76 – 82

7

Helix

84 – 86

3

Helix

93 – 95

3

Beta strand

96 – 101

6

Beta strand

113 – 115

3

Beta strand

117 – 122

6

Helix

124 – 128

5

Beta strand

130 – 132

3

Beta strand

136 – 142

7

Beta strand

148 – 150

3

Beta strand

167 – 174

8

Beta strand

189 – 196

8

Helix

198 – 205

8

Turn

206 – 208

3

Turn

218 – 220

3

Beta strand

221 – 225

5

Beta strand

227 – 230

4

Turn

235 – 239

5

Beta strand

241 – 246

6

Beta strand

249 – 256

8

Beta strand

260 – 263

4

Beta strand

269 – 273

5

Helix

274 – 277

4

Helix

278 – 288

11

Sequences

	Sequence		Length	Mass (Da)
	Q16651 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 98DD6447F5A8C1B2	FASTA	343	36,431
	10 20 30 40 50 60 MAQKGVLGPG QLGAVAILLY LGLLRSGTGA EGAEAPCGVA PQARITGGSS AVAGQWPWQV 70 80 90 100 110 120 SITYEGVHVC GGSLVSEQWV LSAAHCFPSE HHKEAYEVKL GAHQLDSYSE DAKVSTLKDI 130 140 150 160 170 180 IPHPSYLQEG SQGDIALLQL SRPITFSRYI RPICLPAANA SFPNGLHCTV TGWGHVAPSV 190 200 210 220 230 240 SLLTPKPLQQ LEVPLISRET CNCLYNIDAK PEEPHFVQED MVCAGYVEGG KDACQGDSGG 250 260 270 280 290 300 PLSCPVEGLW YLTGIVSWGD ACGARNRPGV YTLASSYASW IQSKVTELQP RVVPQTQESQ 310 320 330 340 PDSNLCGSHL AFSSAPAQGL LRPILFLPLG LALGLLSPWL SEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA." Yu J.X., Chao L., Chao J. J. Biol. Chem. 270:13483-13489(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Prostate.
[2]	"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: Placenta.
[3]	"Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland." Yu J.X., Chao L., Chao J. J. Biol. Chem. 269:18843-18848(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 45-64. Tissue: Semen.
[4]	"Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line." Tong Z., Illek B., Bhagwandin V.J., Verghese G.M., Caughey G.H. Am. J. Physiol. 287:L928-L935(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SODIUM CHANNELS ACTIVATION.
[5]	"Biochemical characterization of prostasin, a channel activating protease." Shipway A., Danahay H., Williams J.A., Tully D.C., Backes B.J., Harris J.L. Biochem. Biophys. Res. Commun. 324:953-963(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY.
[6]	"Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations." Spraggon G., Hornsby M., Shipway A., Tully D.C., Bursulaya B., Danahay H., Harris J.L., Lesley S.A. Protein Sci. 18:1081-1094(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 45-305 IN COMPLEX WITH INHIBITOR, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L41351 mRNA. Translation: AAC41759.1.
U33446 Genomic DNA. Translation: AAB19071.1.
BC001462 mRNA. Translation: AAH01462.1.

IPI

IPI00329538.

PIR

A57014.

RefSeq

NP_002764.1. NM_002773.3.

UniGene

Hs.75799.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DFJ	X-ray	1.45	A	45-289	[»]
3DFL	X-ray	2.00	A	45-289	[»]
3E0N	X-ray	1.70	B	45-305	[»]
3E0P	X-ray	1.70	B	45-305	[»]
3E16	X-ray	1.60	B	45-305	[»]
3E1X	X-ray	1.70	B	45-305	[»]
3FVF	X-ray	1.60	B	45-305	[»]
3GYL	X-ray	1.30	B	45-305	[»]
3GYM	X-ray	2.80	A/B	45-305	[»]

ProteinModelPortal

Q16651.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-5000236.

STRING

9606.ENSP00000319730.

Protein family/group databases

MEROPS

S01.159.

Polymorphism databases

DMDM

2833277.

Proteomic databases

PaxDb

Q16651.

PRIDE

Q16651.

Protocols and materials databases

DNASU

5652.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000317508; ENSP00000319730; ENSG00000052344.

GeneID

5652.

KEGG

hsa:5652.

UCSC

uc002ebc.4. human.

Organism-specific databases

CTD

5652.

GeneCards

GC16M031142.

HGNC

HGNC:9491. PRSS8.

HPA

HPA030436.

MIM

600823. gene.

neXtProt

NX_Q16651.

PharmGKB

PA33840.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

Q16651.

KO

K08664.

OMA

HFVQEDM.

OrthoDB

EOG4FN4J9.

Gene expression databases

ArrayExpress

Q16651.

Bgee

Q16651.

CleanEx

HS_PRSS8.

Genevestigator

Q16651.

GermOnline

ENSG00000052344. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16651.

ChEMBL

CHEMBL5610.

ChiTaRS

PRSS8. human.

EvolutionaryTrace

Q16651.

GenomeRNAi

5652.

NextBio

21962.

SOURCE

Search...

Entry information

Entry name

PRSS8_HUMAN

Accession

Primary (citable) accession number: Q16651
Secondary accession number(s): Q9UCA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 116 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.