P20231 (TRYB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tryptase beta-2
Short name=Tryptase-2
EC=3.4.21.59

Alternative name(s):
Tryptase II

Gene names

Name:	TPSB2
Synonyms:	TPS2

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	275 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	Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. Has an immunoprotective role during bacterial infection. Required to efficiently combat K.pneumoniae infection By similarity.
Catalytic activity	Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa, but with more restricted specificity than trypsin.
Subunit structure	Homotetramer. The active tetramer is converted to inactive monomers at neutral and acidic pH in the absence of heparin. Low concentrations of inactive monomers become active monomers at pH 6.0 in the presence of heparin. When the concentration of active monomers is higher, they convert to active monomers and then to active tetramers. These monomers are active and functionally distinct from the tetrameric enzyme. In contrast to the hidden active sites in the tetrameric form, the active site of the monomeric form is accessible for macromolecular proteins and inhibitors eg: fibrinogen which is a substrate for the monomeric but not for the tetrameric form. The monomeric form forms a complex with SERPINB6. Ref.10
Subcellular location	Secreted. Note: Released from the secretory granules upon mast cell activation.
Polymorphism	There are two alleles; beta-II and beta-III. Beta-II is the most commun allele. There are two forms of the beta-III allele, a short and a long form. The short form (also named frameshifted form) is carried by 23% and 19% of individuals of European and African ancestry but 0% of Asian subjects. In the human genome reference version GRCh37/hg19, the allele beta-III short form is represented.
Sequence similarities	Belongs to the peptidase S1 family. Tryptase subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Phosphoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Non-traceable author statement. Source: UniProtKB
Cellular_component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Propeptide

19 – 30

12

Activation peptide

PRO_0000027481

Chain

31 – 275

245

Tryptase beta-2

PRO_0000027482

Regions

Domain

31 – 272

242

Peptidase S1

Sites

Active site

74

1

Charge relay system

Active site

121

1

Charge relay system

Active site

224

1

Charge relay system

Amino acid modifications

Modified residue

97

1

Phosphotyrosine By similarity

Glycosylation

233

1

N-linked (GlcNAc...) Potential

Disulfide bond

59 ↔ 75

Disulfide bond

155 ↔ 230

Disulfide bond

188 ↔ 211

Disulfide bond

220 ↔ 248

Natural variations

Natural variant

51 – 53

3

HGP → RDR in beta-III.

VAR_012104

Experimental info

Sequence conflict

132

1

N → K in AAA51843. Ref.1

Sequence conflict

132

1

N → K in AAD13876. Ref.2

Sequence conflict

132

1

N → K in AAD17858. Ref.3

Sequence conflict

132

1

N → K in ACZ98911. Ref.5

Sequence conflict

132

1

N → K in AAH29356. Ref.7

Sequence conflict

132

1

N → K in AAA36779. Ref.8

Sequence conflict

132

1

N → K in AAA36780. Ref.8

Sequence conflict

141

1

T → A in ACZ98913. Ref.5

Sequence conflict

240

1

G → D in ACZ98913. Ref.5

Secondary structure

1

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275

Helix Strand Turn

Details...

Beta strand

32 – 36

5

Beta strand

39 – 41

3

Beta strand

45 – 50

6

Beta strand

52 – 54

3

Beta strand

56 – 65

10

Beta strand

68 – 71

4

Helix

73 – 76

4

Helix

83 – 85

3

Beta strand

86 – 89

4

Turn

95 – 98

4

Beta strand

102 – 109

8

Turn

116 – 118

3

Beta strand

123 – 129

7

Beta strand

135 – 137

3

Beta strand

154 – 161

8

Beta strand

176 – 183

8

Helix

185 – 193

9

Beta strand

209 – 212

4

Beta strand

215 – 218

4

Turn

221 – 225

5

Beta strand

227 – 232

6

Beta strand

235 – 244

10

Beta strand

246 – 250

5

Beta strand

255 – 259

5

Helix

260 – 263

4

Helix

264 – 267

4

Turn

268 – 270

3

Sequences

	Sequence		Length	Mass (Da)
	P20231 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: ADC48FDC51F37112	FASTA	275	30,515
	10 20 30 40 50 60 MLNLLLLALP VLASRAYAAP APGQALQRVG IVGGQEAPRS KWPWQVSLRV HGPYWMHFCG 70 80 90 100 110 120 GSLIHPQWVL TAAHCVGPDV KDLAALRVQL REQHLYYQDQ LLPVSRIIVH PQFYTAQIGA 130 140 150 160 170 180 DIALLELEEP VNVSSHVHTV TLPPASETFP PGMPCWVTGW GDVDNDERLP PPFPLKQVKV 190 200 210 220 230 240 PIMENHICDA KYHLGAYTGD DVRIVRDDML CAGNTRRDSC QGDSGGPLVC KVNGTWLQAG 250 260 270 VVSWGEGCAQ PNRPGIYTRV TYYLDWIHHY VPKKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a second complementary DNA for human tryptase." Miller J.S., Moxley G., Schwartz L.B. J. Clin. Invest. 86:864-870(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (VARIANT BETA-2). Tissue: Lung.
[2]	"Characterization of a tryptase mRNA expressed in the human basophil cell line KU812." Blom T., Hellman L. Scand. J. Immunol. 37:203-208(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (VARIANT BETA-2).
[3]	"Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3." Pallaoro M., Fejzo M.S., Shayesteh L., Blount J.L., Caughey G.H. J. Biol. Chem. 274:3355-3362(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANTS BETA-2 AND BETA-3).
[4]	Pallaoro M., Fejzo M.S., Shayesteh L., Blount J.L., Caughey G.H. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[5]	"Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations." Trivedi N.N., Tamraz B., Chu C., Kwok P.Y., Caughey G.H. J. Allergy Clin. Immunol. 124:1099-1105(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANT BETA-2), NUCLEOTIDE SEQUENCE [MRNA] OF 50-275 (VARIANT BETA-3).
[6]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (VARIANT BETA-2). Tissue: Lung.
[8]	"Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family." Vanderslice P., Ballinger S.M., Tam E.K., Goldstein S.M., Craik C.S., Caughey G.H. Proc. Natl. Acad. Sci. U.S.A. 87:3811-3815(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-275 (VARIANT BETA-2), NUCLEOTIDE SEQUENCE [MRNA] OF 9-275 (VARIANT BETA-3).
[9]	"Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers." Strik M.C., Wolbink A., Wouters D., Bladergroen B.A., Verlaan A.R., van Houdt I.S., Hijlkema S., Hack C.E., Kummer J.A. Blood 103:2710-2717(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FORMATION OF A COMPLEX WITH SERPINB6.
[10]	"Active monomers of human beta-tryptase have expanded substrate specificities." Fukuoka Y., Schwartz L.B. Int. Immunopharmacol. 7:1900-1908(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[11]	"Human beta-tryptase is a ring-like tetramer with active sites facing a central pore." Pereira P.J.B., Bergner A., Macedo-Ribeiro S., Huber R., Matschiner G., Fritz H., Sommerhoff C.P., Bode W. Nature 392:306-311(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[12]	"The structure of the human betaII-tryptase tetramer: fo(u)r better or worse." Sommerhoff C.P., Bode W., Pereira P.J.B., Stubbs M.T., Stuerzebecher J., Piechottka G.P., Matschiner G., Bergner A. Proc. Natl. Acad. Sci. U.S.A. 96:10984-10991(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M37488 mRNA. Translation: AAA51843.1.
S55551 mRNA. Translation: AAD13876.1.
AF099143 Genomic DNA. Translation: AAD17859.2.
AF099145 Genomic DNA. Translation: AAD17857.1.
AF099146 Genomic DNA. Translation: AAD17858.1.
FJ931117 Genomic DNA. Translation: ACZ98911.1.
FJ931120 mRNA. Translation: ACZ98913.1.
AC120498 Genomic DNA. No translation available.
BC029356 mRNA. Translation: AAH29356.1.
M33492 mRNA. Translation: AAA36779.1.
M33493 mRNA. Translation: AAA36780.1.

IPI

IPI00419942.

PIR

B35863.
C35863.

RefSeq

NP_003285.2. NM_003294.3.
NP_077078.5. NM_024164.5.

UniGene

Hs.405479.
Hs.592982.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A0L	X-ray	3.00	A/B/C/D	31-274	[»]
1AAO	model	-	A	31-275	[»]
2BM2	X-ray	2.20	A/B/C/D	31-275	[»]
2FPZ	X-ray	2.00	A/B/C/D	31-275	[»]
2FS8	X-ray	2.50	A/B/C/D	31-275	[»]
2FS9	X-ray	2.30	A/B/C/D	31-275	[»]
2FWW	X-ray	2.25	A/B/C/D	31-275	[»]
2FXR	X-ray	2.50	A/B/C/D	31-275	[»]
2GDD	X-ray	2.35	A/B/C/D	31-275	[»]
2ZA5	X-ray	2.30	A/B/C/D	31-275	[»]
3V7T	X-ray	2.09	A/B/C/D	31-275	[»]

ProteinModelPortal

P20231.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20231. 2 interactions.

STRING

9606.ENSP00000420825.

Protein family/group databases

MEROPS

S01.015.

PTM databases

PhosphoSite

P20231.

Proteomic databases

PaxDb

P20231.

PRIDE

P20231.

Protocols and materials databases

DNASU

64499.
7177.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

64499.
7177.

KEGG

hsa:64499.
hsa:7177.

Organism-specific databases

CTD

64499.
7177.

GeneCards

GC16M001281.

HGNC

HGNC:14120. TPSB2.

HPA

CAB016369.
CAB022175.

MIM

191081. gene.

neXtProt

NX_P20231.

PharmGKB

PA36698.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOVERGEN

HBG013304.

InParanoid

P20231.

KO

K01340.

PhylomeDB

P20231.

Gene expression databases

ArrayExpress

P20231.

Bgee

P20231.

CleanEx

HS_TPSB2.

Genevestigator

P20231.

GermOnline

ENSG00000172236. 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

P20231.

EvolutionaryTrace

P20231.

NextBio

28132.

SOURCE

Search...

Entry information

Entry name

TRYB2_HUMAN

Accession

Primary (citable) accession number: P20231
Secondary accession number(s): D2E6S0 , D2E6S2, O95827, Q15664, Q9UQI6, Q9UQI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 132 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.