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Protein

Trypsin-3

Gene

PRSS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.2 Publications

Catalytic activityi

Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

Cofactori

Ca2+Note: Binds 1 Ca2+ ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei120Charge relay system1
Metal bindingi132Calcium1
Metal bindingi134Calcium; via carbonyl oxygen1
Metal bindingi137Calcium; via carbonyl oxygen1
Metal bindingi142Calcium1
Active sitei164Charge relay system1
Sitei251Required for specificityBy similarity1
Active sitei257Charge relay system1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  • cobalamin metabolic process Source: Reactome
  • digestion Source: UniProtKB
  • endothelial cell migration Source: UniProtKB
  • proteolysis Source: UniProtKB
  • zymogen activation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Digestion

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS00287-MONOMER.
ReactomeiR-HSA-1462054. Alpha-defensins.
R-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6803157. Antimicrobial peptides.

Protein family/group databases

MEROPSiS01.174.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PRSS3
Synonyms:PRSS4, TRY3, TRY4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:9486. PRSS3.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5646.
OpenTargetsiENSG00000010438.
PharmGKBiPA33838.

Chemistry databases

ChEMBLiCHEMBL4551.
GuidetoPHARMACOLOGYi2399.

Polymorphism and mutation databases

BioMutaiPRSS3.
DMDMi209572698.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000028201? – 80Activation peptide
Signal peptidei1 – ?Sequence analysis
ChainiPRO_000002820281 – 304Trypsin-3Add BLAST224

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi87 ↔ 217
Disulfide bondi105 ↔ 121
Disulfide bondi196 ↔ 263
Modified residuei211SulfotyrosineBy similarity1
Disulfide bondi228 ↔ 242
Disulfide bondi253 ↔ 277

Keywords - PTMi

Disulfide bond, Sulfation, Zymogen

Proteomic databases

EPDiP35030.
MaxQBiP35030.
PaxDbiP35030.
PeptideAtlasiP35030.
PRIDEiP35030.

PTM databases

iPTMnetiP35030.
PhosphoSitePlusiP35030.

Expressioni

Tissue specificityi

Expressed in pancreas and brain. Also expressed in Paneth cells, at the base of small intestinal crypts.1 Publication

Gene expression databases

BgeeiENSG00000010438.
CleanExiHS_PRSS3.
ExpressionAtlasiP35030. baseline and differential.
GenevisibleiP35030. HS.

Organism-specific databases

HPAiHPA062452.
HPA063471.

Interactioni

Protein-protein interaction databases

BioGridi111628. 9 interactors.
IntActiP35030. 8 interactors.
STRINGi9606.ENSP00000354280.

Chemistry databases

BindingDBiP35030.

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi89 – 91Combined sources3
Beta strandi95 – 111Combined sources17
Beta strandi114 – 117Combined sources4
Helixi119 – 121Combined sources3
Beta strandi127 – 131Combined sources5
Beta strandi133 – 137Combined sources5
Beta strandi143 – 152Combined sources10
Turni158 – 160Combined sources3
Beta strandi166 – 172Combined sources7
Beta strandi177 – 180Combined sources4
Beta strandi195 – 201Combined sources7
Beta strandi206 – 208Combined sources3
Beta strandi216 – 222Combined sources7
Helixi225 – 231Combined sources7
Turni233 – 235Combined sources3
Beta strandi240 – 244Combined sources5
Beta strandi246 – 249Combined sources4
Turni254 – 258Combined sources5
Beta strandi260 – 263Combined sources4
Beta strandi266 – 273Combined sources8
Beta strandi275 – 278Combined sources4
Beta strandi284 – 288Combined sources5
Helixi289 – 292Combined sources4
Helixi293 – 302Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4U30X-ray2.50A/B/C/D81-304[»]
4U32X-ray1.65A81-304[»]
5C67X-ray1.83A/B81-304[»]
ProteinModelPortaliP35030.
SMRiP35030.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35030.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 301Peptidase S1PROSITE-ProRule annotationAdd BLAST221

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP35030.
KOiK01312.
OMAiCYETHIQ.
OrthoDBiEOG091G0DF7.
PhylomeDBiP35030.
TreeFamiTF331065.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35030-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MCGPDDRCPA RWPGPGRAVK CGKGLAAARP GRVERGGAQR GGAGLELHPL
60 70 80 90 100
LGGRTWRAAR DADGCEALGT VAVPFDDDDK IVGGYTCEEN SLPYQVSLNS
110 120 130 140 150
GSHFCGGSLI SEQWVVSAAH CYKTRIQVRL GEHNIKVLEG NEQFINAAKI
160 170 180 190 200
IRHPKYNRDT LDNDIMLIKL SSPAVINARV STISLPTTPP AAGTECLISG
210 220 230 240 250
WGNTLSFGAD YPDELKCLDA PVLTQAECKA SYPGKITNSM FCVGFLEGGK
260 270 280 290 300
DSCQRDSGGP VVCNGQLQGV VSWGHGCAWK NRPGVYTKVY NYVDWIKDTI

AANS
Length:304
Mass (Da):32,529
Last modified:October 14, 2008 - v2
Checksum:i4C4303C310B7BFFC
GO
Isoform 2 (identifier: P35030-2) [UniParc]FASTAAdd to basket
Also known as: B

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

Show »
Length:260
Mass (Da):28,161
Checksum:iCD8AA6E8072BCE56
GO
Isoform 3 (identifier: P35030-3) [UniParc]FASTAAdd to basket
Also known as: C

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

Show »
Length:247
Mass (Da):26,727
Checksum:i01563656780A6607
GO
Isoform 4 (identifier: P35030-4) [UniParc]FASTAAdd to basket
Also known as: D

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

Show »
Length:261
Mass (Da):28,402
Checksum:i5908225118767A4A
GO
Isoform 5 (identifier: P35030-5) [UniParc]FASTAAdd to basket
Also known as: E

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

Show »
Length:240
Mass (Da):25,924
Checksum:iE8DF46CFF536DB74
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti89Missing in CAA50484 (PubMed:8294000).Curated1
Sequence conflicti224 – 225TQ → RE in CAA33527 (PubMed:2326201).Curated2
Sequence conflicti253 – 254CQ → WK in CAA33527 (PubMed:2326201).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067459174A → V.Corresponds to variant rs11547028dbSNPEnsembl.1
Natural variantiVAR_046794188T → A.7 PublicationsCorresponds to variant rs855581dbSNPEnsembl.1
Natural variantiVAR_059788224T → S.Corresponds to variant rs1063273dbSNPEnsembl.1
Natural variantiVAR_046795232Y → C.1 PublicationCorresponds to variant rs1048379dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0054091 – 71MCGPD…ALGTV → MHMRETSGFTLKKGRSAPLV FHPPDALI in isoform 4. CuratedAdd BLAST71
Alternative sequenceiVSP_0054101 – 70MCGPD…EALGT → MNPFLILAFVGAA in isoform 3. 3 PublicationsAdd BLAST70
Alternative sequenceiVSP_0537791 – 70MCGPD…EALGT → MGPAGE in isoform 5. 1 PublicationAdd BLAST70
Alternative sequenceiVSP_0420741 – 45MCGPD…GGAGL → M in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47958.1. [P35030-1]
CCDS56570.1. [P35030-5]
CCDS56571.1. [P35030-4]
CCDS6545.1. [P35030-3]
PIRiS12764.
S33496.
RefSeqiNP_001184026.2. NM_001197097.2.
NP_001184027.1. NM_001197098.1.
NP_002762.2. NM_002771.3.
NP_031369.2. NM_007343.3.
UniGeneiHs.654513.

Genome annotation databases

EnsembliENST00000342836; ENSP00000340889; ENSG00000010438. [P35030-4]
ENST00000361005; ENSP00000354280; ENSG00000010438. [P35030-1]
ENST00000379405; ENSP00000368715; ENSG00000010438. [P35030-3]
ENST00000429677; ENSP00000401828; ENSG00000010438. [P35030-5]
GeneIDi5646.
KEGGihsa:5646.
UCSCiuc003zti.5. human. [P35030-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47958.1. [P35030-1]
CCDS56570.1. [P35030-5]
CCDS56571.1. [P35030-4]
CCDS6545.1. [P35030-3]
PIRiS12764.
S33496.
RefSeqiNP_001184026.2. NM_001197097.2.
NP_001184027.1. NM_001197098.1.
NP_002762.2. NM_002771.3.
NP_031369.2. NM_007343.3.
UniGeneiHs.654513.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4U30X-ray2.50A/B/C/D81-304[»]
4U32X-ray1.65A81-304[»]
5C67X-ray1.83A/B81-304[»]
ProteinModelPortaliP35030.
SMRiP35030.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111628. 9 interactors.
IntActiP35030. 8 interactors.
STRINGi9606.ENSP00000354280.

Chemistry databases

BindingDBiP35030.
ChEMBLiCHEMBL4551.
GuidetoPHARMACOLOGYi2399.

Protein family/group databases

MEROPSiS01.174.

PTM databases

iPTMnetiP35030.
PhosphoSitePlusiP35030.

Polymorphism and mutation databases

BioMutaiPRSS3.
DMDMi209572698.

Proteomic databases

EPDiP35030.
MaxQBiP35030.
PaxDbiP35030.
PeptideAtlasiP35030.
PRIDEiP35030.

Protocols and materials databases

DNASUi5646.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342836; ENSP00000340889; ENSG00000010438. [P35030-4]
ENST00000361005; ENSP00000354280; ENSG00000010438. [P35030-1]
ENST00000379405; ENSP00000368715; ENSG00000010438. [P35030-3]
ENST00000429677; ENSP00000401828; ENSG00000010438. [P35030-5]
GeneIDi5646.
KEGGihsa:5646.
UCSCiuc003zti.5. human. [P35030-1]

Organism-specific databases

CTDi5646.
DisGeNETi5646.
GeneCardsiPRSS3.
H-InvDBHIX0035151.
HGNCiHGNC:9486. PRSS3.
HPAiHPA062452.
HPA063471.
MIMi613578. gene.
neXtProtiNX_P35030.
OpenTargetsiENSG00000010438.
PharmGKBiPA33838.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP35030.
KOiK01312.
OMAiCYETHIQ.
OrthoDBiEOG091G0DF7.
PhylomeDBiP35030.
TreeFamiTF331065.

Enzyme and pathway databases

BioCyciZFISH:HS00287-MONOMER.
ReactomeiR-HSA-1462054. Alpha-defensins.
R-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6803157. Antimicrobial peptides.

Miscellaneous databases

EvolutionaryTraceiP35030.
GenomeRNAii5646.
PROiP35030.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000010438.
CleanExiHS_PRSS3.
ExpressionAtlasiP35030. baseline and differential.
GenevisibleiP35030. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRY3_HUMAN
AccessioniPrimary (citable) accession number: P35030
Secondary accession number(s): A8CED1
, A8CED3, A9Z1Y4, E7ES07, F8W7P3, P15951, Q15665, Q5VXV0, Q6ISJ4, Q9UQV3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 171 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.