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O60235 (TM11D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane protease serine 11D

EC=3.4.21.-
Alternative name(s):
Airway trypsin-like protease
Gene names
Name:TMPRSS11D
Synonyms:HAT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. Plays a role in the proteolytic processing of ACE2. Proteolytically cleaves and activates the human coronavirus 229E (HCoV-229E) spike glycoprotein 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. Ref.4 Ref.5

Catalytic activity

Preferentially cleaves the C-terminal side of arginine residues at the P1 position of certain peptides, cleaving Boc-Phe-Ser-Arg-4-methylcoumaryl-7-amide most efficiently and having an optimum pH of 8.6 with this substrate.

Enzyme regulation

Strongly inhibited by diisopropyl fluorophosphate, leupeptin, antipain, aprotinin, and soybean trypsin inhibitor, but hardly inhibited by secretory leukocyte protease inhibitor at 10 microM.

Subunit structure

Monomer.

Subcellular location

Cell membrane; Single-pass type II membrane protein. Note: Activated by cleavage and secreted.

Transmembrane protease serine 11D catalytic chain: Secreted. Note: Activated by cleavage and secreted.

Tissue specificity

Located in the cells of the submucosal serous glands of the bronchi and trachea.

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 peptidase S1 domain.

Contains 1 SEA domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 186186Transmembrane protease serine 11D non-catalytic chain
PRO_0000027885
Chain187 – 418232Transmembrane protease serine 11D catalytic chain
PRO_0000027886

Regions

Topological domain1 – 2020Cytoplasmic Potential
Transmembrane21 – 4121Helical; Signal-anchor for type II membrane protein; Potential
Topological domain42 – 418377Extracellular Potential
Domain46 – 163118SEA
Domain187 – 417231Peptidase S1

Sites

Active site2271Charge relay system By similarity
Active site2721Charge relay system By similarity
Active site3681Charge relay system By similarity

Amino acid modifications

Glycosylation1441N-linked (GlcNAc...) Potential
Disulfide bond173 ↔ 292Interchain (between non-catalytic and catalytic chains) By similarity
Disulfide bond212 ↔ 228 By similarity
Disulfide bond337 ↔ 353 By similarity
Disulfide bond364 ↔ 393 By similarity

Sequences

Sequence LengthMass (Da)Tools
O60235 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: F4BC1DB020CFBBD0

FASTA41846,263
        10         20         30         40         50         60 
MYRPARVTST SRFLNPYVVC FIVVAGVVIL AVTIALLVYF LAFDQKSYFY RSSFQLLNVE 

        70         80         90        100        110        120 
YNSQLNSPAT QEYRTLSGRI ESLITKTFKE SNLRNQFIRA HVAKLRQDGS GVRADVVMKF 

       130        140        150        160        170        180 
QFTRNNNGAS MKSRIESVLR QMLNNSGNLE INPSTEITSL TDQAAANWLI NECGAGPDLI 

       190        200        210        220        230        240 
TLSEQRILGG TEAEEGSWPW QVSLRLNNAH HCGGSLINNM WILTAAHCFR SNSNPRDWIA 

       250        260        270        280        290        300 
TSGISTTFPK LRMRVRNILI HNNYKSATHE NDIALVRLEN SVTFTKDIHS VCLPAATQNI 

       310        320        330        340        350        360 
PPGSTAYVTG WGAQEYAGHT VPELRQGQVR IISNDVCNAP HSYNGAILSG MLCAGVPQGG 

       370        380        390        400        410 
VDACQGDSGG PLVQEDSRRL WFIVGIVSWG DQCGLPDKPG VYTRVTAYLD WIRQQTGI 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of the cDNA for human airway trypsin-like protease."
Yamaoka K., Masuda K., Ogawa H., Takagi K., Umemoto N., Yasuoka S.
J. Biol. Chem. 273:11895-11901(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
[3]"Purification, characterization, and localization of a novel trypsin-like protease found in the human airway."
Yasuoka S., Ohnishi T., Kawano S., Tsuchihashi S., Ogawara M., Masuda K., Yamaoka K., Takahashi M., Sano T.
Am. J. Respir. Cell Mol. Biol. 16:300-308(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 187-206, CHARACTERIZATION.
[4]"TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium."
Bertram S., Dijkman R., Habjan M., Heurich A., Gierer S., Glowacka I., Welsch K., Winkler M., Schneider H., Hofmann-Winkler H., Thiel V., Pohlmann S.
J. Virol. 87:6150-6160(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB002134 mRNA. Translation: BAA28691.1.
BC125195 mRNA. Translation: AAI25196.1.
BC125196 mRNA. Translation: AAI25197.1.
CCDSCCDS3518.1.
RefSeqNP_004253.1. NM_004262.2.
UniGeneHs.132195.

3D structure databases

ProteinModelPortalO60235.
SMRO60235. Positions 45-418.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO60235. 1 interaction.
MINTMINT-8302106.
STRING9606.ENSP00000283916.

Chemistry

BindingDBO60235.
ChEMBLCHEMBL1795138.

Protein family/group databases

MEROPSS01.047.

Proteomic databases

PaxDbO60235.
PRIDEO60235.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283916; ENSP00000283916; ENSG00000153802.
GeneID9407.
KEGGhsa:9407.
UCSCuc003hdq.3. human.

Organism-specific databases

CTD9407.
GeneCardsGC04M068686.
HGNCHGNC:24059. TMPRSS11D.
HPAHPA052834.
MIM605369. gene.
neXtProtNX_O60235.
PharmGKBPA142670728.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251823.
HOVERGENHBG013304.
InParanoidO60235.
KOK09641.
OMASNLRNQF.
OrthoDBEOG75B84T.
PhylomeDBO60235.
TreeFamTF351684.

Gene expression databases

ArrayExpressO60235.
BgeeO60235.
CleanExHS_TMPRSS11D.
GenevestigatorO60235.

Family and domain databases

Gene3D3.30.70.960. 1 hit.
InterProIPR017329. Pept_S1A_HAT/DESC1.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF037941. TMPRSS11ABCDE. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00200. SEA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEPS50024. SEA. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTMPRSS11D.
GenomeRNAi9407.
NextBio35242.
PROO60235.
SOURCESearch...

Entry information

Entry nameTM11D_HUMAN
AccessionPrimary (citable) accession number: O60235
Secondary accession number(s): Q08AF6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM