O15393 (TMPS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane protease serine 2
EC=3.4.21.-

Alternative name(s):
Serine protease 10

Cleaved into the following 2 chains:

1. Transmembrane protease serine 2 non-catalytic chain
2. Transmembrane protease serine 2 catalytic chain

Gene names

Name:	TMPRSS2
Synonyms:	PRSS10

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	492 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 255	255	Transmembrane protease serine 2 non-catalytic chain		PRO_0000027855
	Chain	256 – 492	237	Transmembrane protease serine 2 catalytic chain		PRO_0000027856
Regions
	Topological domain	1 – 84	84	Cytoplasmic Potential
	Transmembrane	85 – 105	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	106 – 492	387	Extracellular Potential
	Domain	112 – 149	38	LDL-receptor class A
	Domain	150 – 242	93	SRCR
	Domain	256 – 489	234	Peptidase S1
Sites
	Active site	296	1	Charge relay system By similarity
	Active site	345	1	Charge relay system By similarity
	Active site	441	1	Charge relay system
	Site	255 – 256	2	Cleavage Potential
Amino acid modifications
	Glycosylation	213	1	N-linked (GlcNAc...) Potential
	Glycosylation	249	1	N-linked (GlcNAc...) Potential
	Disulfide bond	113 ↔ 126		By similarity
	Disulfide bond	120 ↔ 139		By similarity
	Disulfide bond	133 ↔ 148		By similarity
	Disulfide bond	172 ↔ 231		By similarity
	Disulfide bond	185 ↔ 241		By similarity
	Disulfide bond	244 ↔ 365		Interchain (between non-catalytic and catalytic chains) By similarity
	Disulfide bond	281 ↔ 297		By similarity
	Disulfide bond	410 ↔ 426		By similarity
	Disulfide bond	437 ↔ 465		By similarity
Natural variations
	Alternative sequence	1	1	M → MPPAPPGGESGCEERGAAGH IEHSRYLSLLDAVDNSKM in isoform 2.		VSP_045083
	Natural variant	160	1	V → M. Ref.1 Ref.2 Ref.10 Corresponds to variant rs12329760 [ dbSNP | Ensembl ].		VAR_027674
	Natural variant	254	1	S → C. Ref.10		VAR_038002
	Natural variant	329	1	E → Q. Ref.1 Ref.10		VAR_038003
	Natural variant	449	1	K → N. Corresponds to variant rs1056602 [ dbSNP | Ensembl ].		VAR_011692
	Natural variant	491	1	D → N. Ref.10		VAR_038004
Experimental info
	Mutagenesis	255	1	R → Q: Loss of cleavage.
	Mutagenesis	441	1	S → A: Loss of activity.
	Sequence conflict	26	1	Y → H in BAF84502. Ref.4
	Sequence conflict	62	1	N → S in BAH12445. Ref.4
	Sequence conflict	163	1	S → P in BAF84502. Ref.4
	Sequence conflict	242	1	I → L in AAC51784. Ref.1
	Sequence conflict	489 – 491	3	RAD → KAN in AAC51784. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 3, 2006. Version 3. Checksum: C05B5531C8A311C7	FASTA	492	53,859
	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
	Isoform 2 [UniParc]. Checksum: 444EBB1FFF3ACDFA	FASTA	529	57,690
	10 20 30 40 50 60 MPPAPPGGES GCEERGAAGH IEHSRYLSLL DAVDNSKMAL NSGSPPAIGP YYENHGYQPE 70 80 90 100 110 120 NPYPAQPTVV PTVYEVHPAQ YYPSPVPQYA PRVLTQASNP VVCTQPKSPS GTVCTSKTKK 130 140 150 160 170 180 ALCITLTLGT FLVGAALAAG LLWKFMGSKC SNSGIECDSS GTCINPSNWC DGVSHCPGGE 190 200 210 220 230 240 DENRCVRLYG PNFILQVYSS QRKSWHPVCQ DDWNENYGRA ACRDMGYKNN FYSSQGIVDD 250 260 270 280 290 300 SGSTSFMKLN TSAGNVDIYK KLYHSDACSS KAVVSLRCIA CGVNLNSSRQ SRIVGGESAL 310 320 330 340 350 360 PGAWPWQVSL HVQNVHVCGG SIITPEWIVT AAHCVEKPLN NPWHWTAFAG ILRQSFMFYG 370 380 390 400 410 420 AGYQVEKVIS HPNYDSKTKN NDIALMKLQK PLTFNDLVKP VCLPNPGMML QPEQLCWISG 430 440 450 460 470 480 WGATEEKGKT SEVLNAAKVL LIETQRCNSR YVYDNLITPA MICAGFLQGN VDSCQGDSGG 490 500 510 520 PLVTSKNNIW WLIGDTSWGS GCAKAYRPGV YGNVMVFTDW IYRQMRADG

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00006212. IPI00871690.
RefSeq	NP_001128571.1. NM_001135099.1. NP_005647.3. NM_005656.3.
UniGene	Hs.439309.
3D structure databases
ProteinModelPortal	O15393.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000330330.
Protein family/group databases
MEROPS	S01.247.
PTM databases
PhosphoSite	O15393.
Proteomic databases
PaxDb	O15393.
PRIDE	O15393.
Protocols and materials databases
DNASU	7113.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332149; ENSP00000330330; ENSG00000184012. ENST00000398585; ENSP00000381588; ENSG00000184012. ENST00000458356; ENSP00000391216; ENSG00000184012.
GeneID	7113.
KEGG	hsa:7113.
UCSC	uc002yzj.3. human. uc010gor.3. human.
Organism-specific databases
CTD	7113.
GeneCards	GC21M042836.
HGNC	HGNC:11876. TMPRSS2.
HPA	HPA013182.
MIM	602060. gene.
neXtProt	NX_O15393.
PharmGKB	PA36577.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5640.
HOVERGEN	HBG013304.
KO	K09633.
OMA	FYSSQGI.
OrthoDB	EOG4J6RQN.
PhylomeDB	O15393.
Enzyme and pathway databases
Pathway_Interaction_DB	ar_pathway. Coregulation of Androgen receptor activity. ar_tf_pathway. Regulation of Androgen receptor activity.
Gene expression databases
ArrayExpress	O15393.
Bgee	O15393.
CleanEx	HS_TMPRSS2.
Genevestigator	O15393.
GermOnline	ENSG00000184012. Homo sapiens.
Family and domain databases
Gene3D	4.10.400.10. 1 hit.
InterPro	IPR023415. LDLR_class-A_CS. IPR002172. LDrepeatLR_classA_rpt. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR001190. Srcr_rcpt. IPR017448. Srcr_rcpt-rel. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00530. SRCR. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00192. LDLa. 1 hit. SM00202. SR. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57424. LDL_rcpt_classA_cys-rich. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit. SSF56487. Srcr_receptor. 1 hit.
PROSITE	PS01209. LDLRA_1. 1 hit. PS50068. LDLRA_2. 1 hit. PS00420. SRCR_1. False negative. PS50287. SRCR_2. 1 hit. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O15393.
ChEMBL	CHEMBL1795140.
ChiTaRS	TMPRSS2. human.
GenomeRNAi	7113.
NextBio	27847.
SOURCE	Search...

Entry information

Entry name

TMPS2_HUMAN

Accession

Primary (citable) accession number: O15393
Secondary accession number(s): A8K6Z8 , B2R8E5, B7Z459, D3DSJ2, F8WES1, Q6GTK7, Q9BXX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 3, 2006
Last modified:	May 29, 2013
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.