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Protein

Transmembrane protease serine 2

Gene

TMPRSS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Enzyme and pathway databases

SIGNORiO15393

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
MIMi602060 gene
neXtProtiNX_O15393

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
ProteomicsDBi48634

PTM databases

GlyConnecti1848
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 Expressed in 142 organ(s), highest expression level in mucosa of transverse colon
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

Protein-protein interaction databases

BioGridi112968, 2 interactors
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
OMAiPAQYYPS
OrthoDBiEOG091G0DF7
PhylomeDBiO15393
TreeFamiTF351678

Family and domain databases

CDDicd00112 LDLa, 1 hit
cd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR002172 LDrepeatLR_classA_rpt
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JKZ3C9JKZ3_HUMAN
Transmembrane protease serine 2
TMPRSS2
489Annotation score:
C9J5Y1C9J5Y1_HUMAN
Transmembrane protease serine 2
TMPRSS2
219Annotation score:
C9JB05C9JB05_HUMAN
Transmembrane protease serine 2
TMPRSS2
79Annotation score:

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
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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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
UniGeneiHs.439309

3D structure databases

ProteinModelPortaliO15393
SMRiO15393
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112968, 2 interactors
IntActiO15393, 57 interactors
STRINGi9606.ENSP00000381588

Chemistry databases

BindingDBiO15393
ChEMBLiCHEMBL1795140
GuidetoPHARMACOLOGYi2421

Protein family/group databases

MEROPSiS01.247

PTM databases

GlyConnecti1848
iPTMnetiO15393
PhosphoSitePlusiO15393

Polymorphism and mutation databases

BioMutaiTMPRSS2

Proteomic databases

MaxQBiO15393
PaxDbiO15393
PeptideAtlasiO15393
PRIDEiO15393
ProteomicsDBi48634

Protocols and materials databases

DNASUi7113
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi7113
DisGeNETi7113
EuPathDBiHostDB:ENSG00000184012.11
GeneCardsiTMPRSS2
HGNCiHGNC:11876 TMPRSS2
HPAiHPA034493
HPA035787
MIMi602060 gene
neXtProtiNX_O15393
OpenTargetsiENSG00000184012
PharmGKBiPA36577
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SIGNORiO15393

Miscellaneous databases

ChiTaRSiTMPRSS2 human
GeneWikiiTMPRSS2
GenomeRNAii7113
PROiPR:O15393
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184012 Expressed in 142 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_TMPRSS2
ExpressionAtlasiO15393 baseline and differential
GenevisibleiO15393 HS

Family and domain databases

CDDicd00112 LDLa, 1 hit
cd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR002172 LDrepeatLR_classA_rpt
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 178 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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