P35030 (TRY3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Trypsin-3
EC=3.4.21.4

Alternative name(s):
Brain trypsinogen
Mesotrypsinogen
Serine protease 3
Serine protease 4
Trypsin III
Trypsin IV

Gene names

Name:	PRSS3
Synonyms:	PRSS4, TRY3, TRY4

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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)

Function	Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5. Ref.9 Ref.10
Catalytic activity	Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
Cofactor	Binds 1 calcium ion per subunit.
Subcellular location	Secreted.
Tissue specificity	Expressed in pancreas and brain. Also expressed in Paneth cells, at the base of small intestinal crypts. Ref.9
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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cobalamin metabolic process Traceable author statement. Source: Reactome digestion Traceable author statement Ref.10PubMed 6698368. Source: UniProtKB endothelial cell migration Inferred from mutant phenotype PubMed 15313892. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome metabolic process Inferred from direct assay. Source: GOC proteolysis Inferred from electronic annotation. Source: UniProtKB-KW small molecule metabolic process Traceable author statement. Source: Reactome vitamin metabolic process Traceable author statement. Source: Reactome water-soluble vitamin metabolic process Traceable author statement. Source: Reactome zymogen activation Inferred from direct assay PubMed 6698368. Source: UniProtKB
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 6698368. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay PubMed 6698368. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Inferred from direct assay PubMed 9099703. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35030-1)

Also known as: A;

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 2 (identifier: P35030-2)

Also known as: B;

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

Isoform 3 (identifier: P35030-3)

Also known as: C;

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

Isoform 4 (identifier: P35030-4)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MCGPDDRCPA...ADGCEALGTV → MHMRETSGFTLKKGRSAPLVFHPPDALI

Isoform 5 (identifier: P35030-5)

Also known as: E;

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

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 – 71

71

MCGPD…ALGTV → MHMRETSGFTLKKGRSAPLV FHPPDALI in isoform 4.

VSP_005409

Alternative sequence

1 – 70

70

MCGPD…EALGT → MNPFLILAFVGAA in isoform 3.

VSP_005410

Alternative sequence

1 – 70

70

MCGPD…EALGT → MGPAGE in isoform 5.

VSP_053779

Alternative sequence

1 – 45

45

MCGPD…GGAGL → M in isoform 2.

VSP_042074

Natural variant

174

1

A → V.
Corresponds to variant rs11547028 [ dbSNP | Ensembl ].

VAR_067459

Natural variant

188

1

T → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs855581 [ dbSNP | Ensembl ].

VAR_046794

Natural variant

224

1

T → S.
Corresponds to variant rs1063273 [ dbSNP | Ensembl ].

VAR_059788

Natural variant

232

1

Y → C. Ref.2
Corresponds to variant rs1048379 [ dbSNP | Ensembl ].

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

89 – 91

3

Beta strand

95 – 111

17

Beta strand

114 – 117

4

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

177 – 180

4

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

246 – 249

4

Turn

254 – 258

5

Beta strand

260 – 263

4

Beta strand

266 – 273

8

Beta strand

275 – 278

4

Beta strand

284 – 288

5

Helix

289 – 292

4

Helix

293 – 302

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (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 2 (B) [UniParc]. 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 3 (C) [UniParc]. 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
	Isoform 4 (D) [UniParc]. Checksum: 5908225118767A4A	FASTA	261	28,402
	10 20 30 40 50 60 MHMRETSGFT LKKGRSAPLV FHPPDALIAV PFDDDDKIVG GYTCEENSLP YQVSLNSGSH 70 80 90 100 110 120 FCGGSLISEQ WVVSAAHCYK TRIQVRLGEH NIKVLEGNEQ FINAAKIIRH PKYNRDTLDN 130 140 150 160 170 180 DIMLIKLSSP AVINARVSTI SLPTTPPAAG TECLISGWGN TLSFGADYPD ELKCLDAPVL 190 200 210 220 230 240 TQAECKASYP GKITNSMFCV GFLEGGKDSC QRDSGGPVVC NGQLQGVVSW GHGCAWKNRP 250 260 GVYTKVYNYV DWIKDTIAAN S
	Isoform 5 (E) [UniParc]. Checksum: E8DF46CFF536DB74	FASTA	240	25,924
	10 20 30 40 50 60 MGPAGEVAVP FDDDDKIVGG YTCEENSLPY QVSLNSGSHF CGGSLISEQW VVSAAHCYKT 70 80 90 100 110 120 RIQVRLGEHN IKVLEGNEQF INAAKIIRHP KYNRDTLDND IMLIKLSSPA VINARVSTIS 130 140 150 160 170 180 LPTTPPAAGT ECLISGWGNT LSFGADYPDE LKCLDAPVLT QAECKASYPG KITNSMFCVG 190 200 210 220 230 240 FLEGGKDSCQ RDSGGPVVCN GQLQGVVSWG HGCAWKNRPG VYTKVYNYVD WIKDTIAANS

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), 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 3), VARIANT ALA-188.
[4]	"Sequence of a large duplication from human chromosome 7 to chromosome 9 containing a portion of the T cell receptor beta locus and trypsinogen locus." Rowen L., Trask B., Boysen C., Qin S., Wang K., Ahearn M.E., Hood L. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), VARIANT ALA-188.
[5]	"Keratinocytes synthesize enteropeptidase and multiple forms of trypsinogen during terminal differentiation." Nakanishi J., Yamamoto M., Koyama J., Sato J., Hibino T. J. Invest. Dermatol. 130:944-952(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5), VARIANT ALA-188.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-188.
[8]	"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] (ISOFORM 3), VARIANT ALA-188.
[9]	"Paneth cell trypsin is the processing enzyme for human defensin-5." Ghosh D., Porter E., Shen B., Lee S.K., Wilk D., Drazba J., Yadav S.P., Crabb J.W., Ganz T., Bevins C.L. Nat. Immunol. 3:583-590(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors." Szmola R., Kukor Z., Sahin-Toth M. J. Biol. Chem. 278:48580-48589(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) (ISOFORM A).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X72781 mRNA. Translation: CAB58178.1.
X71345 mRNA. Translation: CAA50484.1.
X15505 mRNA. Translation: CAA33527.1.
D45417 mRNA. Translation: BAA08257.1.
AF029308 Genomic DNA. Translation: AAC13322.1.
AB298285 mRNA. Translation: BAF80324.1.
AB298286 mRNA. Translation: BAF80325.1.
AL139113 Genomic DNA. No translation available.
AL356489 Genomic DNA. No translation available.
AL358573 Genomic DNA. No translation available.
CH471071 Genomic DNA. Translation: EAW58482.1.
CH471071 Genomic DNA. Translation: EAW58484.1.
BC069476 mRNA. Translation: AAH69476.1.
BC069494 mRNA. Translation: AAH69494.1.

PIR

S12764.
S33496.

RefSeq

NP_001184026.2. NM_001197097.2.
NP_001184027.1. NM_001197098.1.
NP_002762.2. NM_002771.3.
NP_031369.2. NM_007343.3.

UniGene

Hs.654513.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3L33	X-ray	2.48	A/B/C/D	81-304	[»]
3L3T	X-ray	2.38	A/B/C/D	81-304	[»]
3P92	X-ray	1.60	A	81-304	[»]
3P95	X-ray	1.30	A	81-304	[»]
4DG4	X-ray	1.40	A/B/D/G	81-304	[»]

ProteinModelPortal

P35030.

SMR

P35030. Positions 81-304.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

111628. 20 interactions.

IntAct

P35030. 3 interactions.

STRING

9606.ENSP00000354280.

Chemistry

BindingDB

P35030.

ChEMBL

CHEMBL2095204.

Protein family/group databases

MEROPS

S01.174.

PTM databases

PhosphoSite

P35030.

Polymorphism databases

DMDM

209572698.

Proteomic databases

PaxDb

P35030.

PRIDE

P35030.

Protocols and materials databases

DNASU

5646.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342836; ENSP00000340889; ENSG00000010438. [P35030-4]
ENST00000361005; ENSP00000354280; ENSG00000010438. [P35030-1]
ENST00000379405; ENSP00000368715; ENSG00000010438. [P35030-3]
ENST00000429677; ENSP00000401828; ENSG00000010438.

GeneID

5646.

KEGG

hsa:5646.

UCSC

uc003zti.4. human. [P35030-4]
uc003ztj.4. human. [P35030-1]

Organism-specific databases

CTD

5646.

GeneCards

GC09P033750.

H-InvDB

HIX0035151.

HGNC

HGNC:9486. PRSS3.

MIM

613578. gene.

neXtProt

NX_P35030.

PharmGKB

PA33838.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P35030.

KO

K01312.

OMA

WIQATID.

OrthoDB

EOG75B84T.

PhylomeDB

P35030.

TreeFam

TF331065.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P35030.

Bgee

P35030.

CleanEx

HS_PRSS3.

Genevestigator

P35030.

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. SSF50494. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P35030.

GenomeRNAi

5646.

NextBio

21934.

PRO

P35030.

SOURCE

Search...

Entry information

Entry name

TRY3_HUMAN

Accession

Primary (citable) accession number: P35030
Secondary accession number(s): A8CED1 , A8CED3, A9Z1Y4, E7ES07, F8W7P3, P15951, Q15665, Q5VXV0, Q6ISJ4, Q9UQV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	October 14, 2008
Last modified:	April 16, 2014
This is version 145 of the entry and version 2 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.