Q15661 (TRYB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tryptase alpha/beta-1
Short name=Tryptase-1
EC=3.4.21.59

Alternative name(s):
Tryptase I
Tryptase alpha-1

Gene names

Name:	TPSAB1
Synonyms:	TPS1, TPS2, TPSB1

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 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.11
Subcellular location	Secreted. Note: Released from the secretory granules upon mast cell activation By similarity.
Polymorphism	There are two alleles alpha and beta-I. The sequence shown is that of allele beta-I.
Sequence similarities	Belongs to the peptidase S1 family. Tryptase subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response Traceable author statement Ref.1. Source: ProtInc extracellular matrix disassembly Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL
Molecular_function	serine-type endopeptidase activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1761369,EBI-389883
PIK3R1	P27986	2	EBI-1761369,EBI-79464

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15661-1)

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 2 (identifier: Q15661-2)

The sequence of this isoform differs from the canonical sequence as follows:
     79-87: Missing.

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 By similarity

PRO_0000027479

Chain

31 – 275

245

Tryptase alpha/beta-1

PRO_0000027480

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

Glycosylation

132

1

N-linked (GlcNAc...) Potential

Glycosylation

233

1

N-linked (GlcNAc...) Ref.12

Disulfide bond

59 ↔ 75

Disulfide bond

155 ↔ 230

Disulfide bond

188 ↔ 211

Disulfide bond

220 ↔ 248

Natural variations

Alternative sequence

79 – 87

9

Missing in isoform 2.

VSP_005375

Natural variant

3

1

N → S in allele alpha.

VAR_064277

Natural variant

15

1

R → P. Ref.5 Ref.6 Ref.14
Corresponds to variant rs61729112 [ dbSNP | Ensembl ].

VAR_064278

Natural variant

18

1

A → V. Ref.14
Corresponds to variant rs1800984 [ dbSNP | Ensembl ].

VAR_014557

Natural variant

23

1

G → V in allele alpha. Ref.14
Corresponds to variant rs1141965 [ dbSNP | Ensembl ].

VAR_014558

Natural variant

28

1

R → Q in allele alpha.
Corresponds to variant rs1064770 [ dbSNP | Ensembl ].

VAR_064279

Natural variant

29

1

V → A in allele alpha.
Corresponds to variant rs1064771 [ dbSNP | Ensembl ].

VAR_064280

Natural variant

51

1

H → R in allele alpha.
Corresponds to variant rs1060281 [ dbSNP | Ensembl ].

VAR_064281

Natural variant

52

1

G → D in allele alpha.
Corresponds to variant rs17841227 [ dbSNP | Ensembl ].

VAR_064282

Natural variant

53

1

P → R in allele alpha.
Corresponds to variant rs17841226 [ dbSNP | Ensembl ].

VAR_064283

Natural variant

76

1

V → L in allele alpha.
Corresponds to variant rs71384640 [ dbSNP | Ensembl ].

VAR_064284

Natural variant

85

1

A → T. Ref.1 Ref.5 Ref.14
Corresponds to variant rs1141968 [ dbSNP | Ensembl ].

VAR_014559

Natural variant

115

1

T → I in allele alpha.
Corresponds to variant rs1064774 [ dbSNP | Ensembl ].

VAR_064285

Natural variant

116

1

A → I in allele alpha; requires 2 nucleotide substitutions.

VAR_064286

Natural variant

118

1

I → T in allele alpha.
Corresponds to variant rs71376589 [ dbSNP | Ensembl ].

VAR_064287

Natural variant

132

1

N → K. Ref.8 Ref.14
Corresponds to variant rs1800991 [ dbSNP | Ensembl ].

VAR_016102

Natural variant

133

1

V → I in allele alpha.
Corresponds to variant rs1064779 [ dbSNP | Ensembl ].

VAR_064288

Natural variant

136

1

H → R in allele alpha.
Corresponds to variant rs1064780 [ dbSNP | Ensembl ].

VAR_051830

Natural variant

141

1

T → A. Ref.14
Corresponds to variant rs1800992 [ dbSNP | Ensembl ].

VAR_014560

Natural variant

141

1

T → M in allele alpha.

VAR_064289

Natural variant

162

1

D → N. Ref.14
Corresponds to variant rs2234641 [ dbSNP | Ensembl ].

VAR_014561

Natural variant

168

1

R → P in allele alpha.
Corresponds to variant rs1141969 [ dbSNP | Ensembl ].

VAR_064290

Natural variant

170

1

P → S. Ref.6 Ref.14
Corresponds to variant rs2234904 [ dbSNP | Ensembl ].

VAR_014562

Natural variant

205

1

V → I in allele alpha.
Corresponds to variant rs1060284 [ dbSNP | Ensembl ].

VAR_064291

Natural variant

215

1

T → S. Ref.1 Ref.6 Ref.14
Corresponds to variant rs2234905 [ dbSNP | Ensembl ].

VAR_014563

Natural variant

216

1

R → Q. Ref.1 Ref.6 Ref.14
Corresponds to variant rs2234906 [ dbSNP | Ensembl ].

VAR_014564

Natural variant

221

1

Q → K. Ref.1 Ref.6 Ref.14
Corresponds to variant rs17841224 [ dbSNP | Ensembl ].

VAR_064292

Natural variant

245

1

G → D in allele alpha.
Corresponds to variant rs1060292 [ dbSNP | Ensembl ].

VAR_064293

Natural variant

263

1

Y → N. Ref.14
Corresponds to variant rs2234646 [ dbSNP | Ensembl ].

VAR_064294

Experimental info

Sequence conflict

129

1

E → K in ACZ98912. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

275

Helix Strand Turn

Details...

Beta strand

32 – 36

5

Beta strand

45 – 65

21

Beta strand

68 – 71

4

Helix

73 – 76

4

Helix

83 – 85

3

Beta strand

86 – 89

4

Turn

95 – 98

4

Beta strand

104 – 109

6

Turn

116 – 118

3

Beta strand

123 – 129

7

Beta strand

135 – 137

3

Beta strand

155 – 160

6

Beta strand

176 – 179

4

Helix

185 – 193

9

Beta strand

196 – 198

3

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 – 270

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. 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
	Isoform 2 [UniParc]. Checksum: 04F79FEB4ABF517D	FASTA	266	29,533
	10 20 30 40 50 60 MLNLLLLALP VLASRAYAAP APGQALQRVG IVGGQEAPRS KWPWQVSLRV HGPYWMHFCG 70 80 90 100 110 120 GSLIHPQWVL TAAHCVGPVQ LREQHLYYQD QLLPVSRIIV HPQFYTAQIG ADIALLELEE 130 140 150 160 170 180 PVNVSSHVHT VTLPPASETF PPGMPCWVTG WGDVDNDERL PPPFPLKQVK VPIMENHICD 190 200 210 220 230 240 AKYHLGAYTG DDVRIVRDDM LCAGNTRRDS CQGDSGGPLV CKVNGTWLQA GVVSWGEGCA 250 260 QPNRPGIYTR VTYYLDWIHH YVPKKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of complementary DNA for human tryptase." Miller J.S., Westin E.H., Schwartz L.B. J. Clin. Invest. 84:1188-1195(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-85; SER-215; GLN-216 AND LYS-221. Tissue: Lung.
[2]	Schwartz L.B. Submitted (MAR-1990) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 89-93 AND 108.
[3]	"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 [GENOMIC DNA / MRNA] (ALLELE BETA-I) (ISOFORM 1).
[4]	"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] (ALLELES ALPHA AND BETA-I) (ISOFORM 1).
[5]	"Molecular cloning and characterization of novel human tryptase cDNAs and splicing variants." Wang H.W., McNeil H.P., Thomas P.S., Murphy B.N., Webster M.J., Hettiaratchi A., King G., Heywood G.J., Huang C., Stevens R.L., Hunt J.E. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 16-275 (ALLELE ALPHA; ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 54-275 (ALLELE BETA-I; ISOFORM 2), VARIANTS PRO-15 AND THR-85.
[6]	"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] (ISOFORM 1), VARIANTS PRO-15; SER-170; SER-215; GLN-216 AND LYS-221.
[7]	"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].
[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 1), VARIANT LYS-132.
[9]	"Human pituitary tryptase: molecular forms, NH2-terminal sequence, immunocytochemical localization, and specificity with prohormone and fluorogenic substrates." Cromlish J.A., Seidah N.G., Marcinkiewcz M., Hamelin J., Johnson D.A., Chretein M. J. Biol. Chem. 262:1363-1373(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-50, PROTEIN SEQUENCE OF 31-38. Tissue: Lung.
[10]	"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.
[11]	"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.
[12]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-233, MASS SPECTROMETRY. Tissue: Liver.
[13]	"The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region." Marquardt U., Zettl F., Huber R., Bode W., Sommerhoff C. J. Mol. Biol. 321:491-502(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 31-275.
[14]	"Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog." Guida M., Riedy M., Lee D., Hall J. Pharmacogenetics 10:389-396(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-15; VAL-18; VAL-23; THR-85; LYS-132; ALA-141; ASN-162; SER-170; SER-215; GLN-216; LYS-221 AND ASN-263.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M30038 mRNA. Translation: AAA86934.1.
M33494 Genomic DNA. Translation: AAC83172.1.
M33491 mRNA. Translation: AAA36778.1.
AF098328 Genomic DNA. Translation: AAD17846.1.
AF099144 Genomic DNA. Translation: AAD17860.1.
AF206665 mRNA. Translation: AAG35695.1.
AF206666 mRNA. Translation: AAG35696.1.
AF206667 mRNA. Translation: AAG35697.1.
FJ931116 Genomic DNA. Translation: ACZ98910.1.
FJ931118 mRNA. Translation: ACZ98912.1.
AC120498 Genomic DNA. No translation available.
BC074974 mRNA. Translation: AAH74974.1.

IPI

IPI00419942.
IPI00472739.

PIR

A35863.
A45754.
C35863.

RefSeq

NP_003285.2. NM_003294.3.

UniGene

Hs.405479.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LTO	X-ray	2.20	A/B/C/D	31-275	[»]
2F9N	X-ray	1.60	A/B/C/D	31-275	[»]
2F9O	X-ray	2.10	A/B/C/D	31-275	[»]
2F9P	X-ray	2.30	A/B/C/D	31-275	[»]
2ZEB	X-ray	2.50	A/B/C/D	31-273	[»]
2ZEC	X-ray	2.06	A/B/C/D	31-273	[»]
4A6L	X-ray	2.05	A/B/C/D	31-275	[»]

ProteinModelPortal

Q15661.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15661. 2 interactions.

STRING

9606.ENSP00000343577.

Protein family/group databases

MEROPS

S01.143.

PTM databases

PhosphoSite

Q15661.

Polymorphism databases

DMDM

18202508.

Proteomic databases

PaxDb

Q15661.

PRIDE

Q15661.

Protocols and materials databases

DNASU

7177.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338844; ENSP00000343577; ENSG00000172236.
ENST00000561736; ENSP00000456821; ENSG00000172236.

GeneID

7177.

KEGG

hsa:7177.

UCSC

uc002ckz.3. human.
uc010uux.2. human.

Organism-specific databases

CTD

7177.

GeneCards

GC16P001290.

H-InvDB

HIX0012676.

HGNC

HGNC:12019. TPSAB1.

HPA

CAB016369.
CAB022175.

MIM

191080. gene.

neXtProt

NX_Q15661.

PharmGKB

PA36698.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOVERGEN

HBG013304.

InParanoid

Q15661.

KO

K01340.

OrthoDB

EOG4P8FJQ.

PhylomeDB

Q15661.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpress

Q15661.

Bgee

Q15661.

CleanEx

HS_TPSAB1.

Genevestigator

Q15661.

GermOnline

ENSG00000172236. Homo sapiens.
ENSG00000197253. 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

Q15661.

ChEMBL

CHEMBL2617.

ChiTaRS

TPSAB1. human.

EvolutionaryTrace

Q15661.

GenomeRNAi

7177.

NextBio

28132.

SOURCE

Search...

Entry information

Entry name

TRYB1_HUMAN

Accession

Primary (citable) accession number: Q15661
Secondary accession number(s): D2E6R9 , D2E6S1, P15157, Q15663, Q6B052, Q9H2Y4, Q9H2Y5, Q9UQI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 121 of the entry and version 1 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.