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Protein

Transmembrane protease serine 2

Gene

TMPRSS2

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

Functioni

Serine protease that proteolytically cleaves and activates the viral spike glycoproteins which facilitate virus-cell membrane fusions; spike proteins are synthesized and maintained in precursor intermediate folding states and proteolysis permits the refolding and energy release required to create stable virus-cell linkages and membrane coalescence. Facilitates human SARS coronavirus (SARS-CoV) infection via two independent mechanisms, proteolytic cleavage of ACE2, which might promote viral uptake, and cleavage of coronavirus spike glycoprotein which activates the glycoprotein for cathepsin L-independent host cell entry. Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei296Charge relay systemBy similarity1
Active sitei345Charge relay systemBy similarity1
Active sitei441Charge relay system1

GO - Molecular functioni

  • scavenger receptor activity Source: InterPro
  • serine-type endopeptidase activity Source: InterPro
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • positive regulation of viral entry into host cell Source: UniProtKB
  • protein autoprocessing Source: UniProtKB
  • proteolysis Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.247.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 2 (EC:3.4.21.-)
Alternative name(s):
Serine protease 10
Cleaved into the following 2 chains:
Gene namesi
Name:TMPRSS2
Synonyms:PRSS10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000184012.11.
HGNCiHGNC:11876. TMPRSS2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 84CytoplasmicSequence analysisAdd BLAST84
Transmembranei85 – 105Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini106 – 492ExtracellularSequence analysisAdd BLAST387

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi255R → Q: Loss of cleavage. 1 Publication1
Mutagenesisi441S → A: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi7113.
OpenTargetsiENSG00000184012.
PharmGKBiPA36577.

Chemistry databases

ChEMBLiCHEMBL1795140.
GuidetoPHARMACOLOGYi2421.

Polymorphism and mutation databases

BioMutaiTMPRSS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000278551 – 255Transmembrane protease serine 2 non-catalytic chainAdd BLAST255
ChainiPRO_0000027856256 – 492Transmembrane protease serine 2 catalytic chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi113 ↔ 126By similarity
Disulfide bondi120 ↔ 139By similarity
Disulfide bondi133 ↔ 148By similarity
Disulfide bondi172 ↔ 231By similarity
Disulfide bondi185 ↔ 241By similarity
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi244 ↔ 365Interchain (between non-catalytic and catalytic chains)PROSITE-ProRule annotation
Glycosylationi249N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi281 ↔ 297By similarity
Disulfide bondi410 ↔ 426By similarity
Disulfide bondi437 ↔ 465By similarity

Post-translational modificationi

Proteolytically processed; by an autocatalytic mechanism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei255 – 256CleavageSequence analysis2

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiO15393.
PaxDbiO15393.
PeptideAtlasiO15393.
PRIDEiO15393.

PTM databases

iPTMnetiO15393.
PhosphoSitePlusiO15393.

Expressioni

Tissue specificityi

Highly expressed in prostate epithelial cells and in prostate cancers. Expressed in type II pneumocytes in the lung (at protein level). Expressed strongly in small intestine. Also expressed in colon, stomach and salivary gland.3 Publications

Gene expression databases

BgeeiENSG00000184012.
CleanExiHS_TMPRSS2.
ExpressionAtlasiO15393. baseline and differential.
GenevisibleiO15393. HS.

Organism-specific databases

HPAiHPA034493.
HPA035787.

Interactioni

Subunit structurei

The catalytically active form interacts with ACE2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TMEM128Q5BJH2-24EBI-12345267,EBI-10694905

Protein-protein interaction databases

BioGridi112968. 1 interactor.
IntActiO15393. 57 interactors.
STRINGi9606.ENSP00000381588.

Chemistry databases

BindingDBiO15393.

Structurei

3D structure databases

ProteinModelPortaliO15393.
SMRiO15393.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini112 – 149LDL-receptor class APROSITE-ProRule annotationAdd BLAST38
Domaini150 – 242SRCRPROSITE-ProRule annotationAdd BLAST93
Domaini256 – 489Peptidase S1PROSITE-ProRule annotationAdd BLAST234

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000251822.
HOVERGENiHBG013304.
InParanoidiO15393.
KOiK09633.
OMAiQVYSSQR.
OrthoDBiEOG091G0DF7.
PhylomeDBiO15393.
TreeFamiTF351678.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di3.10.250.10. 1 hit.
InterProiView protein in InterPro
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
PfamiView protein in Pfam
PF15494. SRCR_2. 1 hit.
PF00089. Trypsin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiView protein in SMART
SM00192. LDLa. 1 hit.
SM00202. SR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
SSF57424. SSF57424. 1 hit.
PROSITEiView protein in PROSITE
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
PS50287. SRCR_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15393-1) [UniParc]FASTAAdd to basket

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
MALNSGSPPA IGPYYENHGY QPENPYPAQP TVVPTVYEVH PAQYYPSPVP
60 70 80 90 100
QYAPRVLTQA SNPVVCTQPK SPSGTVCTSK TKKALCITLT LGTFLVGAAL
110 120 130 140 150
AAGLLWKFMG SKCSNSGIEC DSSGTCINPS NWCDGVSHCP GGEDENRCVR
160 170 180 190 200
LYGPNFILQV YSSQRKSWHP VCQDDWNENY GRAACRDMGY KNNFYSSQGI
210 220 230 240 250
VDDSGSTSFM KLNTSAGNVD IYKKLYHSDA CSSKAVVSLR CIACGVNLNS
260 270 280 290 300
SRQSRIVGGE SALPGAWPWQ VSLHVQNVHV CGGSIITPEW IVTAAHCVEK
310 320 330 340 350
PLNNPWHWTA FAGILRQSFM FYGAGYQVEK VISHPNYDSK TKNNDIALMK
360 370 380 390 400
LQKPLTFNDL VKPVCLPNPG MMLQPEQLCW ISGWGATEEK GKTSEVLNAA
410 420 430 440 450
KVLLIETQRC NSRYVYDNLI TPAMICAGFL QGNVDSCQGD SGGPLVTSKN
460 470 480 490
NIWWLIGDTS WGSGCAKAYR PGVYGNVMVF TDWIYRQMRA DG
Length:492
Mass (Da):53,859
Last modified:October 3, 2006 - v3
Checksum:iC05B5531C8A311C7
GO
Isoform 2 (identifier: O15393-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:529
Mass (Da):57,690
Checksum:i444EBB1FFF3ACDFA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26Y → H in BAF84502 (PubMed:14702039).Curated1
Sequence conflicti62N → S in BAH12445 (PubMed:14702039).Curated1
Sequence conflicti163S → P in BAF84502 (PubMed:14702039).Curated1
Sequence conflicti242I → L in AAC51784 (PubMed:9325052).Curated1
Sequence conflicti489 – 491RAD → KAN in AAC51784 (PubMed:9325052).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027674160V → M3 PublicationsCorresponds to variant dbSNP:rs12329760Ensembl.1
Natural variantiVAR_038002254S → C1 Publication1
Natural variantiVAR_038003329E → Q2 PublicationsCorresponds to variant dbSNP:rs775137340Ensembl.1
Natural variantiVAR_011692449K → N. Corresponds to variant dbSNP:rs1056602Ensembl.1
Natural variantiVAR_038004491D → N1 PublicationCorresponds to variant dbSNP:rs779875214Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0450831M → MPPAPPGGESGCEERGAAGH IEHSRYLSLLDAVDNSKM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75329 mRNA. Translation: AAC51784.1.
AF123453 mRNA. Translation: AAD37117.1.
AF270487 mRNA. Translation: AAK29280.1.
AK291813 mRNA. Translation: BAF84502.1.
AK296860 mRNA. Translation: BAH12445.1.
AK313338 mRNA. Translation: BAG36142.1.
AK222784 mRNA. Translation: BAD96504.1.
AP001610 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09597.1.
CH471079 Genomic DNA. Translation: EAX09598.1.
BC051839 mRNA. Translation: AAH51839.1.
CCDSiCCDS33564.1. [O15393-1]
CCDS54486.1. [O15393-2]
RefSeqiNP_001128571.1. NM_001135099.1. [O15393-2]
NP_005647.3. NM_005656.3. [O15393-1]
XP_011528033.1. XM_011529731.2. [O15393-1]
UniGeneiHs.439309.

Genome annotation databases

EnsembliENST00000332149; ENSP00000330330; ENSG00000184012. [O15393-1]
ENST00000398585; ENSP00000381588; ENSG00000184012. [O15393-2]
ENST00000458356; ENSP00000391216; ENSG00000184012. [O15393-1]
GeneIDi7113.
KEGGihsa:7113.
UCSCiuc002yzj.4. human. [O15393-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTMPS2_HUMAN
AccessioniPrimary (citable) accession number: O15393
Secondary accession number(s): A8K6Z8
, B2R8E5, B7Z459, D3DSJ2, F8WES1, Q6GTK7, Q9BXX1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2006
Last modified: September 27, 2017
This is version 171 of the entry and version 3 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families