Reviewed, UniProtKB/Swiss-Prot O15393 (TMPS2_HUMAN)

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- Recommended name:
            Transmembrane protease, serine 2 non-catalytic chain
    2- Recommended name:
            Transmembrane protease, serine 2 catalytic chain

Gene names

Name:	TMPRSS2
Synonyms:	PRSS10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.6
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	Polymorphism
Domain	Signal-anchor Transmembrane
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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	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
	Natural variant	160	1	V → M: dbSNP rs12329760. Ref.1 Ref.2 Ref.7		VAR_027674
	Natural variant	254	1	S → C Ref.7		VAR_038002
	Natural variant	329	1	E → Q Ref.1 Ref.7		VAR_038003
	Natural variant	449	1	K → N: dbSNP rs1056602.		VAR_011692
	Natural variant	491	1	D → N Ref.7		VAR_038004
Experimental info
	Mutagenesis	255	1	R → Q: Loss of cleavage.
	Mutagenesis	441	1	S → A: Loss of activity.
	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)
	O15393-1 [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

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: 9325052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 11414763] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 11245484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
[4]	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]. Tissue: Liver.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: PNS.
[6]	"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: 11169526] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"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: 17918732] [Abstract] Cited for: VARIANTS MET-160; CYS-254; GLN-329 AND ASN-491.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U75329 mRNA. Translation: AAC51784.1. AF123453 mRNA. Translation: AAD37117.1. AF270487 mRNA. Translation: AAK29280.1. AK222784 mRNA. Translation: BAD96504.1. BC051839 mRNA. Translation: AAH51839.1.
IPI	IPI00006212.
RefSeq	NP_005647.3.
UniGene	Hs.439309
3D structure databases
HSSP	HSSP built from PDB template 1EZX based on UniProtKB P00760.
ModBase	Search...
Protein family/group databases
MEROPS	S01.247.
Proteomic databases
PRIDE	O15393.
Genome annotation databases
Ensembl	ENSG00000184012. Homo sapiens. [Contig view]
GeneID	7113.
KEGG	hsa:7113.
Organism-specific databases
GeneCards	GC21M041750.
H-InvDB	HIX0016128.
HGNC	HGNC:11876. TMPRSS2.
HPA	HPA013182.
MIM	602060. gene.
PharmGKB	PA36577.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O15393.
HOVERGEN	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.
GermOnline	ENSG00000184012. Homo sapiens.
Family and domain databases
InterPro	IPR002172. LDL_rcpt_classA_cys-rich. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. IPR001190. Srcr_rcpt. IPR017448. Srcr_rcpt-rel. [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]
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 Resources
SOURCE	Search...

Entry information

Entry name

TMPS2_HUMAN

Accession

Primary (citable) accession number: O15393
Secondary accession number(s): Q6GTK7, Q9BXX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 3, 2006
Last modified:	June 16, 2009
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)