Reviewed, UniProtKB/Swiss-Prot P35030 (TRY3_HUMAN)

Names and origin

Protein names

Recommended name:
    Trypsin-3
    EC=3.4.21.4
Alternative name(s):
    Trypsin III
    Brain trypsinogen
    Mesotrypsinogen
    Trypsin IV
    Serine protease 3
    Serine protease 4

Gene names

Name:	PRSS3
Synonyms:	PRSS4, TRY3, TRY4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	304 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)

Catalytic activity	Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
Cofactor	Binds 1 calcium ion per subunit.
Subcellular location	Secreted.
Tissue specificity	Pancreas and brain.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Digestion
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Sulfation Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	digestion Ref.2 Traceable author statement. Source: UniProtKB endothelial cell migration Inferred from mutant phenotype. Source: UniProtKB proteolysis Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB zymogen activation Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: UniProtKB
Molecular function	calcium ion binding Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P35030-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: P35030-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGL → M

Isoform C (identifier: P35030-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: MCGPDDRCPA...DADGCEALGT → MNPFLILAFVGAA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – ?

Potential

Propeptide

? – 80

Activation peptide

PRO_0000028201

Chain

81 – 304

224

Trypsin-3

PRO_0000028202

Regions

Domain

81 – 301

221

Peptidase S1

Sites

Active site

120

1

Charge relay system

Active site

164

1

Charge relay system

Active site

257

1

Charge relay system

Metal binding

132

1

Calcium

Metal binding

134

1

Calcium; via carbonyl oxygen

Metal binding

137

1

Calcium; via carbonyl oxygen

Metal binding

142

1

Calcium

Site

251

1

Required for specificity By similarity

Amino acid modifications

Modified residue

211

1

Sulfotyrosine By similarity

Disulfide bond

87 ↔ 217

Disulfide bond

105 ↔ 121

Disulfide bond

196 ↔ 263

Disulfide bond

228 ↔ 242

Disulfide bond

253 ↔ 277

Natural variations

Alternative sequence

1 – 70

70

MCGPD…EALGT → MNPFLILAFVGAA in isoform C.

VSP_005410

Alternative sequence

1 – 45

45

MCGPD…GGAGL → M in isoform B.

VSP_005409

Natural variant

188

1

T → A: dbSNP rs855581. Ref.1 Ref.2 Ref.3

VAR_046794

Natural variant

232

1

Y → C: dbSNP rs1048379. Ref.2

VAR_046795

Experimental info

Sequence conflict

89

1

Missing in CAA50484. Ref.1

Sequence conflict

224 – 225

2

TQ → RE in CAA33527. Ref.2

Sequence conflict

253 – 254

2

CQ → WK in CAA33527. Ref.2

Secondary structure

1

.

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304

Helix Strand Turn

Details...

Beta strand

95 – 109

15

Beta strand

111 – 117

7

Helix

119 – 121

3

Beta strand

127 – 131

5

Beta strand

133 – 137

5

Beta strand

143 – 152

10

Turn

158 – 160

3

Beta strand

166 – 172

7

Beta strand

195 – 201

7

Beta strand

206 – 208

3

Beta strand

216 – 222

7

Helix

225 – 231

7

Turn

233 – 235

3

Beta strand

240 – 244

5

Beta strand

260 – 263

4

Beta strand

266 – 273

8

Beta strand

275 – 279

5

Beta strand

284 – 288

5

Helix

289 – 292

4

Helix

293 – 301

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 4C4303C310B7BFFC	FASTA	304	32,529
	10 20 30 40 50 60 MCGPDDRCPA RWPGPGRAVK CGKGLAAARP GRVERGGAQR GGAGLELHPL LGGRTWRAAR 70 80 90 100 110 120 DADGCEALGT VAVPFDDDDK IVGGYTCEEN SLPYQVSLNS GSHFCGGSLI SEQWVVSAAH 130 140 150 160 170 180 CYKTRIQVRL GEHNIKVLEG NEQFINAAKI IRHPKYNRDT LDNDIMLIKL SSPAVINARV 190 200 210 220 230 240 STISLPTTPP AAGTECLISG WGNTLSFGAD YPDELKCLDA PVLTQAECKA SYPGKITNSM 250 260 270 280 290 300 FCVGFLEGGK DSCQRDSGGP VVCNGQLQGV VSWGHGCAWK NRPGVYTKVY NYVDWIKDTI AANS
	Isoform B. Checksum: CD8AA6E8072BCE56	FASTA	260	28,161
	10 20 30 40 50 60 MELHPLLGGR TWRAARDADG CEALGTVAVP FDDDDKIVGG YTCEENSLPY QVSLNSGSHF 70 80 90 100 110 120 CGGSLISEQW VVSAAHCYKT RIQVRLGEHN IKVLEGNEQF INAAKIIRHP KYNRDTLDND 130 140 150 160 170 180 IMLIKLSSPA VINARVSTIS LPTTPPAAGT ECLISGWGNT LSFGADYPDE LKCLDAPVLT 190 200 210 220 230 240 QAECKASYPG KITNSMFCVG FLEGGKDSCQ RDSGGPVVCN GQLQGVVSWG HGCAWKNRPG 250 260 VYTKVYNYVD WIKDTIAANS
	Isoform C. Checksum: 01563656780A6607	FASTA	247	26,727
	10 20 30 40 50 60 MNPFLILAFV GAAVAVPFDD DDKIVGGYTC EENSLPYQVS LNSGSHFCGG SLISEQWVVS 70 80 90 100 110 120 AAHCYKTRIQ VRLGEHNIKV LEGNEQFINA AKIIRHPKYN RDTLDNDIML IKLSSPAVIN 130 140 150 160 170 180 ARVSTISLPT TPPAAGTECL ISGWGNTLSF GADYPDELKC LDAPVLTQAE CKASYPGKIT 190 200 210 220 230 240 NSMFCVGFLE GGKDSCQRDS GGPVVCNGQL QGVVSWGHGC AWKNRPGVYT KVYNYVDWIK DTIAANS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA encoding human brain trypsinogen and characterization of its product." Wiegand U., Corbach S., Minn A., Kang J., Mueller-Hill B. Gene 136:167-175(1993) [PubMed: 8294000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), VARIANT ALA-188. Tissue: Brain.
[2]	"Nucleotide sequence of the human pancreatic trypsinogen III cDNA." Tani T., Kawashima I., Mita K., Takiguchi Y. Nucleic Acids Res. 18:1631-1631(1990) [PubMed: 2326201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), VARIANTS ALA-188 AND CYS-232. Tissue: Pancreas.
[3]	Fukuoka S. Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), VARIANT ALA-188.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Crystal structure reveals basis for the inhibitor resistance of human brain trypsin." Katona G., Berglund G.I., Hajdu J., Graf L., Szilagyi L. J. Mol. Biol. 315:1209-1218(2002) [PubMed: 11827488] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) (ISOFORM A).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X72781 mRNA. Translation: CAB58178.1.
X71345 mRNA. Translation: CAA50484.1.
X15505 mRNA. Translation: CAA33527.1.
D45417 mRNA. Translation: BAA08257.1.
AL356489, AL139113, AL358573 Genomic DNA. Translation: CAH69873.1.
AL358573, AL139113, AL356489 Genomic DNA. Translation: CAI39515.1.
AL139113, AL356489, AL358573 Genomic DNA. Translation: CAI39658.1.

IPI

IPI00015614.
IPI00220839.
IPI00843764.

PIR

S12764.
S33496.

UniGene

Hs.654513

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H4W	X-ray	1.70	A	81-304	[»]
2R9P	X-ray	1.40	A/B/C/D	81-304	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.174.

Proteomic databases

PRIDE

P35030.

Genome annotation databases

Ensembl

ENSG00000010438. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC09P033740.

H-InvDB

HIX0034806.

HGNC

HGNC:9486. PRSS3.

PharmGKB

PA33838.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P35030.

HOVERGEN

P35030.

OMA

P35030. RCPARWP.

Enzyme and pathway databases

BRENDA

3.4.21.4. 247.

Gene expression databases

ArrayExpress

P35030.

Bgee

P35030.

CleanEx

HS_PRSS3.

GermOnline

ENSG00000010438. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

21934.

Entry information

Entry name

TRY3_HUMAN

Accession

Primary (citable) accession number: P35030
Secondary accession number(s): P15951 , Q15665, Q5VXV0, Q9UQV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	October 14, 2008
Last modified:	June 16, 2009
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)