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O60235

- TM11D_HUMAN

UniProt

O60235 - TM11D_HUMAN

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Protein

Transmembrane protease serine 11D

Gene
TMPRSS11D, HAT
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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 regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei227 – 2271Charge relay system By similarity
Active sitei272 – 2721Charge relay system By similarity
Active sitei368 – 3681Charge relay system By similarity

GO - Molecular functioni

  1. peptidase activity Source: ProtInc
  2. serine-type endopeptidase activity Source: InterPro

GO - Biological processi

  1. proteolysis Source: UniProtKB
  2. respiratory gaseous exchange Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.047.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 11D (EC:3.4.21.-)
Alternative name(s):
Airway trypsin-like protease
Cleaved into the following 2 chains:
Gene namesi
Synonyms:HAT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:24059. TMPRSS11D.

Subcellular locationi

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2020Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei21 – 4121Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini42 – 418377Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: ProtInc
  2. extracellular vesicular exosome Source: UniProt
  3. integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142670728.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 186186Transmembrane protease serine 11D non-catalytic chainPRO_0000027885Add
BLAST
Chaini187 – 418232Transmembrane protease serine 11D catalytic chainPRO_0000027886Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi144 – 1441N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi173 ↔ 292Interchain (between non-catalytic and catalytic chains) By similarity
Disulfide bondi212 ↔ 228 By similarity
Disulfide bondi337 ↔ 353 By similarity
Disulfide bondi364 ↔ 393 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiO60235.
PRIDEiO60235.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiO60235.
BgeeiO60235.
CleanExiHS_TMPRSS11D.
GenevestigatoriO60235.

Organism-specific databases

HPAiHPA052834.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

IntActiO60235. 1 interaction.
MINTiMINT-8302106.
STRINGi9606.ENSP00000283916.

Structurei

3D structure databases

ProteinModelPortaliO60235.
SMRiO60235. Positions 45-418.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 163118SEAAdd
BLAST
Domaini187 – 417231Peptidase S1Add
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.
Contains 1 SEA domain.

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG5640.
HOGENOMiHOG000251823.
HOVERGENiHBG013304.
InParanoidiO60235.
KOiK09641.
OMAiSNLRNQF.
OrthoDBiEOG75B84T.
PhylomeDBiO60235.
TreeFamiTF351684.

Family and domain databases

Gene3Di3.30.70.960. 1 hit.
InterProiIPR017329. Pept_S1A_HAT/DESC1.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF037941. TMPRSS11ABCDE. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00200. SEA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEiPS50024. SEA. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O60235-1 [UniParc]FASTAAdd to Basket

« Hide

MYRPARVTST SRFLNPYVVC FIVVAGVVIL AVTIALLVYF LAFDQKSYFY    50
RSSFQLLNVE YNSQLNSPAT QEYRTLSGRI ESLITKTFKE SNLRNQFIRA 100
HVAKLRQDGS GVRADVVMKF QFTRNNNGAS MKSRIESVLR QMLNNSGNLE 150
INPSTEITSL TDQAAANWLI NECGAGPDLI TLSEQRILGG TEAEEGSWPW 200
QVSLRLNNAH HCGGSLINNM WILTAAHCFR SNSNPRDWIA TSGISTTFPK 250
LRMRVRNILI HNNYKSATHE NDIALVRLEN SVTFTKDIHS VCLPAATQNI 300
PPGSTAYVTG WGAQEYAGHT VPELRQGQVR IISNDVCNAP HSYNGAILSG 350
MLCAGVPQGG VDACQGDSGG PLVQEDSRRL WFIVGIVSWG DQCGLPDKPG 400
VYTRVTAYLD WIRQQTGI 418
Length:418
Mass (Da):46,263
Last modified:August 1, 1998 - v1
Checksum:iF4BC1DB020CFBBD0
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB002134 mRNA. Translation: BAA28691.1.
BC125195 mRNA. Translation: AAI25196.1.
BC125196 mRNA. Translation: AAI25197.1.
CCDSiCCDS3518.1.
RefSeqiNP_004253.1. NM_004262.2.
UniGeneiHs.132195.

Genome annotation databases

EnsembliENST00000283916; ENSP00000283916; ENSG00000153802.
GeneIDi9407.
KEGGihsa:9407.
UCSCiuc003hdq.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB002134 mRNA. Translation: BAA28691.1 .
BC125195 mRNA. Translation: AAI25196.1 .
BC125196 mRNA. Translation: AAI25197.1 .
CCDSi CCDS3518.1.
RefSeqi NP_004253.1. NM_004262.2.
UniGenei Hs.132195.

3D structure databases

ProteinModelPortali O60235.
SMRi O60235. Positions 45-418.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O60235. 1 interaction.
MINTi MINT-8302106.
STRINGi 9606.ENSP00000283916.

Chemistry

BindingDBi O60235.
ChEMBLi CHEMBL1795138.

Protein family/group databases

MEROPSi S01.047.

Proteomic databases

PaxDbi O60235.
PRIDEi O60235.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000283916 ; ENSP00000283916 ; ENSG00000153802 .
GeneIDi 9407.
KEGGi hsa:9407.
UCSCi uc003hdq.3. human.

Organism-specific databases

CTDi 9407.
GeneCardsi GC04M068686.
HGNCi HGNC:24059. TMPRSS11D.
HPAi HPA052834.
MIMi 605369. gene.
neXtProti NX_O60235.
PharmGKBi PA142670728.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5640.
HOGENOMi HOG000251823.
HOVERGENi HBG013304.
InParanoidi O60235.
KOi K09641.
OMAi SNLRNQF.
OrthoDBi EOG75B84T.
PhylomeDBi O60235.
TreeFami TF351684.

Miscellaneous databases

GeneWikii TMPRSS11D.
GenomeRNAii 9407.
NextBioi 35242.
PROi O60235.
SOURCEi Search...

Gene expression databases

ArrayExpressi O60235.
Bgeei O60235.
CleanExi HS_TMPRSS11D.
Genevestigatori O60235.

Family and domain databases

Gene3Di 3.30.70.960. 1 hit.
InterProi IPR017329. Pept_S1A_HAT/DESC1.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view ]
PIRSFi PIRSF037941. TMPRSS11ABCDE. 1 hit.
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00200. SEA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEi PS50024. SEA. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiTM11D_HUMAN
AccessioniPrimary (citable) accession number: O60235
Secondary accession number(s): Q08AF6
Entry historyi
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 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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