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O15393 (TMPS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane protease serine 2

EC=3.4.21.-
Alternative name(s):
Serine protease 10
Gene names
Name:TMPRSS2
Synonyms:PRSS10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length492 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Subcellular location

Cell membrane; Single-pass type II membrane protein.

Transmembrane protease serine 2 catalytic chain: Secreted. Note: Activated by cleavage and secreted.

Tissue specificity

Expressed strongly in small intestine. Also expressed in prostate, colon, stomach and salivary gland. Ref.9

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 LDL-receptor class A domain.

Contains 1 peptidase S1 domain.

Contains 1 SRCR domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15393-1)

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: O15393-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 255255Transmembrane protease serine 2 non-catalytic chain
PRO_0000027855
Chain256 – 492237Transmembrane protease serine 2 catalytic chain
PRO_0000027856

Regions

Topological domain1 – 8484Cytoplasmic Potential
Transmembrane85 – 10521Helical; Signal-anchor for type II membrane protein; Potential
Topological domain106 – 492387Extracellular Potential
Domain112 – 14938LDL-receptor class A
Domain150 – 24293SRCR
Domain256 – 489234Peptidase S1

Sites

Active site2961Charge relay system By similarity
Active site3451Charge relay system By similarity
Active site4411Charge relay system
Site255 – 2562Cleavage Potential

Amino acid modifications

Glycosylation2131N-linked (GlcNAc...) Potential
Glycosylation2491N-linked (GlcNAc...) Potential
Disulfide bond113 ↔ 126 By similarity
Disulfide bond120 ↔ 139 By similarity
Disulfide bond133 ↔ 148 By similarity
Disulfide bond172 ↔ 231 By similarity
Disulfide bond185 ↔ 241 By similarity
Disulfide bond244 ↔ 365Interchain (between non-catalytic and catalytic chains) By similarity
Disulfide bond281 ↔ 297 By similarity
Disulfide bond410 ↔ 426 By similarity
Disulfide bond437 ↔ 465 By similarity

Natural variations

Alternative sequence11M → MPPAPPGGESGCEERGAAGH IEHSRYLSLLDAVDNSKM in isoform 2.
VSP_045083
Natural variant1601V → M. Ref.1 Ref.2 Ref.10
Corresponds to variant rs12329760 [ dbSNP | Ensembl ].
VAR_027674
Natural variant2541S → C. Ref.10
VAR_038002
Natural variant3291E → Q. Ref.1 Ref.10
VAR_038003
Natural variant4491K → N.
Corresponds to variant rs1056602 [ dbSNP | Ensembl ].
VAR_011692
Natural variant4911D → N. Ref.10
VAR_038004

Experimental info

Mutagenesis2551R → Q: Loss of cleavage.
Mutagenesis4411S → A: Loss of activity.
Sequence conflict261Y → H in BAF84502. Ref.4
Sequence conflict621N → S in BAH12445. Ref.4
Sequence conflict1631S → P in BAF84502. Ref.4
Sequence conflict2421I → L in AAC51784. Ref.1
Sequence conflict489 – 4913RAD → KAN in AAC51784. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2006. Version 3.
Checksum: C05B5531C8A311C7

FASTA49253,859
        10         20         30         40         50         60 
MALNSGSPPA IGPYYENHGY QPENPYPAQP TVVPTVYEVH PAQYYPSPVP QYAPRVLTQA 

        70         80         90        100        110        120 
SNPVVCTQPK SPSGTVCTSK TKKALCITLT LGTFLVGAAL AAGLLWKFMG SKCSNSGIEC 

       130        140        150        160        170        180 
DSSGTCINPS NWCDGVSHCP GGEDENRCVR LYGPNFILQV YSSQRKSWHP VCQDDWNENY 

       190        200        210        220        230        240 
GRAACRDMGY KNNFYSSQGI VDDSGSTSFM KLNTSAGNVD IYKKLYHSDA CSSKAVVSLR 

       250        260        270        280        290        300 
CIACGVNLNS SRQSRIVGGE SALPGAWPWQ VSLHVQNVHV CGGSIITPEW IVTAAHCVEK 

       310        320        330        340        350        360 
PLNNPWHWTA FAGILRQSFM FYGAGYQVEK VISHPNYDSK TKNNDIALMK LQKPLTFNDL 

       370        380        390        400        410        420 
VKPVCLPNPG MMLQPEQLCW ISGWGATEEK GKTSEVLNAA KVLLIETQRC NSRYVYDNLI 

       430        440        450        460        470        480 
TPAMICAGFL QGNVDSCQGD SGGPLVTSKN NIWWLIGDTS WGSGCAKAYR PGVYGNVMVF 

       490 
TDWIYRQMRA DG 

« Hide

Isoform 2 [UniParc].

Checksum: 444EBB1FFF3ACDFA
Show »

FASTA52957,690

References

« Hide 'large scale' references
[1]"Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3."
Paoloni-Giacobino A., Chen H., Peitsch M.C., Rossier C., Antonarakis S.E.
Genomics 44:309-320(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MET-160 AND GLN-329.
[2]"Mutation analyses of 268 candidate genes in human tumor cell lines."
Teng D.-H., Chen Y., Lian L., Ha P.C., Tavtigian S.V., Wong A.K.C.
Genomics 74:352-364(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-160.
[3]"Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia."
Afar D.E.H., Vivanco I., Hubert R.S., Kuo J., Chen E., Saffran D.C., Raitano A.B., Jakobovits A.
Cancer Res. 61:1686-1692(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Prostate, Testis and Tongue.
[5]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[6]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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).
Tissue: PNS.
[9]"Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues."
Vaarala M.H., Porvari K.S., Kellokumpu S., Kyllonen A.P., Vihko P.T.
J. Pathol. 193:134-140(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss."
Guipponi M., Toh M.-Y., Tan J., Park D., Hanson K., Ballana E., Kwong D., Cannon P.Z.F., Wu Q., Gout A., Delorenzi M., Speed T.P., Smith R.J.H., Dahl H.-H.M., Petersen M., Teasdale R.D., Estivill X., Park W.J., Scott H.S.
Hum. Mutat. 29:130-141(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MET-160; CYS-254; GLN-329 AND ASN-491.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001128571.1. NM_001135099.1.
NP_005647.3. NM_005656.3.
UniGeneHs.439309.

3D structure databases

ProteinModelPortalO15393.
SMRO15393. Positions 85-491.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000330330.

Chemistry

BindingDBO15393.
ChEMBLCHEMBL1795140.

Protein family/group databases

MEROPSS01.247.

PTM databases

PhosphoSiteO15393.

Proteomic databases

PaxDbO15393.
PRIDEO15393.

Protocols and materials databases

DNASU7113.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332149; ENSP00000330330; ENSG00000184012. [O15393-1]
ENST00000398585; ENSP00000381588; ENSG00000184012. [O15393-2]
ENST00000458356; ENSP00000391216; ENSG00000184012. [O15393-1]
GeneID7113.
KEGGhsa:7113.
UCSCuc002yzj.3. human. [O15393-1]

Organism-specific databases

CTD7113.
GeneCardsGC21M042836.
HGNCHGNC:11876. TMPRSS2.
HPAHPA013182.
MIM602060. gene.
neXtProtNX_O15393.
PharmGKBPA36577.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG013304.
KOK09633.
OMAKSWHPVC.
OrthoDBEOG75B84T.
PhylomeDBO15393.
TreeFamTF351678.

Gene expression databases

ArrayExpressO15393.
BgeeO15393.
CleanExHS_TMPRSS2.
GenevestigatorO15393.

Family and domain databases

Gene3D3.10.250.10. 1 hit.
4.10.400.10. 1 hit.
InterProIPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00192. LDLa. 1 hit.
SM00202. SR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
SSF57424. SSF57424. 1 hit.
PROSITEPS01209. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTMPRSS2. human.
GeneWikiTMPRSS2.
GenomeRNAi7113.
NextBio27847.
PROO15393.
SOURCESearch...

Entry information

Entry nameTMPS2_HUMAN
AccessionPrimary (citable) accession number: O15393
Secondary accession number(s): A8K6Z8 expand/collapse secondary AC list , B2R8E5, B7Z459, D3DSJ2, F8WES1, Q6GTK7, Q9BXX1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2006
Last modified: April 16, 2014
This is version 140 of the entry and version 3 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM