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P35030 (TRY3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length304 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processDigestion
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Sulfation
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcobalamin 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

proteolysis

Inferred from direct assay PubMed 9099703. Source: GOC

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_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 6698368. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from direct assay PubMed 6698368. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10PubMed 6698368. Source: UniProtKB

serine-type endopeptidase activity

Inferred from direct assay Ref.10PubMed 6698368. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – ? Potential
Propeptide? – 80Activation peptidePRO_0000028201
Chain81 – 304224Trypsin-3
PRO_0000028202

Regions

Domain81 – 301221Peptidase S1

Sites

Active site1201Charge relay system
Active site1641Charge relay system
Active site2571Charge relay system
Metal binding1321Calcium
Metal binding1341Calcium; via carbonyl oxygen
Metal binding1371Calcium; via carbonyl oxygen
Metal binding1421Calcium
Site2511Required for specificity By similarity

Amino acid modifications

Modified residue2111Sulfotyrosine By similarity
Disulfide bond87 ↔ 217
Disulfide bond105 ↔ 121
Disulfide bond196 ↔ 263
Disulfide bond228 ↔ 242
Disulfide bond253 ↔ 277

Natural variations

Alternative sequence1 – 7171MCGPD…ALGTV → MHMRETSGFTLKKGRSAPLV FHPPDALI in isoform 4.
VSP_005409
Alternative sequence1 – 7070MCGPD…EALGT → MNPFLILAFVGAA in isoform 3.
VSP_005410
Alternative sequence1 – 7070MCGPD…EALGT → MGPAGE in isoform 5.
VSP_053779
Alternative sequence1 – 4545MCGPD…GGAGL → M in isoform 2.
VSP_042074
Natural variant1741A → V.
Corresponds to variant rs11547028 [ dbSNP | Ensembl ].
VAR_067459
Natural variant1881T → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs855581 [ dbSNP | Ensembl ].
VAR_046794
Natural variant2241T → S.
Corresponds to variant rs1063273 [ dbSNP | Ensembl ].
VAR_059788
Natural variant2321Y → C. Ref.2
Corresponds to variant rs1048379 [ dbSNP | Ensembl ].
VAR_046795

Experimental info

Sequence conflict891Missing in CAA50484. Ref.1
Sequence conflict224 – 2252TQ → RE in CAA33527. Ref.2
Sequence conflict253 – 2542CQ → WK in CAA33527. Ref.2

Secondary structure

............................................... 304
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) [UniParc].

Last modified October 14, 2008. Version 2.
Checksum: 4C4303C310B7BFFC

FASTA30432,529
        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 

« Hide

Isoform 2 (B) [UniParc].

Checksum: CD8AA6E8072BCE56
Show »

FASTA26028,161
Isoform 3 (C) [UniParc].

Checksum: 01563656780A6607
Show »

FASTA24726,727
Isoform 4 (D) [UniParc].

Checksum: 5908225118767A4A
Show »

FASTA26128,402
Isoform 5 (E) [UniParc].

Checksum: E8DF46CFF536DB74
Show »

FASTA24025,924

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS47958.1. [P35030-1]
CCDS56571.1. [P35030-4]
CCDS6545.1. [P35030-3]
PIRS12764.
S33496.
RefSeqNP_001184026.2. NM_001197097.2.
NP_001184027.1. NM_001197098.1.
NP_002762.2. NM_002771.3.
NP_031369.2. NM_007343.3.
UniGeneHs.654513.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4WX-ray1.70A81-304[»]
2R9PX-ray1.40A/B/C/D81-304[»]
3L33X-ray2.48A/B/C/D81-304[»]
3L3TX-ray2.38A/B/C/D81-304[»]
3P92X-ray1.60A81-304[»]
3P95X-ray1.30A81-304[»]
4DG4X-ray1.40A/B/D/G81-304[»]
ProteinModelPortalP35030.
SMRP35030. Positions 81-304.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111628. 20 interactions.
IntActP35030. 4 interactions.
STRING9606.ENSP00000354280.

Chemistry

BindingDBP35030.
ChEMBLCHEMBL2095204.

Protein family/group databases

MEROPSS01.174.

PTM databases

PhosphoSiteP35030.

Polymorphism databases

DMDM209572698.

Proteomic databases

MaxQBP35030.
PaxDbP35030.
PRIDEP35030.

Protocols and materials databases

DNASU5646.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342836; ENSP00000340889; ENSG00000010438. [P35030-4]
ENST00000361005; ENSP00000354280; ENSG00000010438. [P35030-1]
ENST00000379405; ENSP00000368715; ENSG00000010438. [P35030-3]
ENST00000429677; ENSP00000401828; ENSG00000010438.
GeneID5646.
KEGGhsa:5646.
UCSCuc003zti.4. human. [P35030-4]
uc003ztj.4. human. [P35030-1]

Organism-specific databases

CTD5646.
GeneCardsGC09P033750.
H-InvDBHIX0035151.
HGNCHGNC:9486. PRSS3.
MIM613578. gene.
neXtProtNX_P35030.
PharmGKBPA33838.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP35030.
KOK01312.
OMAWIQATID.
OrthoDBEOG75B84T.
PhylomeDBP35030.
TreeFamTF331065.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP35030.
BgeeP35030.
CleanExHS_PRSS3.
GenevestigatorP35030.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP35030.
GenomeRNAi5646.
NextBio21934.
PROP35030.
SOURCESearch...

Entry information

Entry nameTRY3_HUMAN
AccessionPrimary (citable) accession number: P35030
Secondary accession number(s): A8CED1 expand/collapse secondary AC list , 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: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM