Q8K1T0 (TMPS3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane protease serine 3
EC=3.4.21.-

Gene names

Name:

Tmprss3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable serine protease that play a role in hearing. Acts as a permissive factor for cochlear hair cells survival and activation at the onset of hearing and is required for saccular hair cell survival. Activates ENaC (in vitro). Ref.1 Ref.3
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.1 Ref.3.
Tissue specificity	Strongly expressed in liver, cochlea, brain, cerebellum, spleen, lung, and muscle and at a lower degree in retina, kidney, and heart. Expressed in the spiral ganglion, the cells supporting the organ of Corti and the stria vascularis. Isoform 2 is strongly expressed only in the cochlea with very faint expression in the cerebellum, spleen and muscle. Ref.3
Post-translational modification	Undergoes autoproteolytic activation.
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	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
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	cellular sodium ion homeostasis Inferred from sequence orthology Ref.1. Source: MGI proteolysis Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Inferred from mutant phenotype Ref.3. Source: UniProtKB
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.3. Source: UniProtKB endoplasmic reticulum membrane Inferred from sequence orthology Ref.1. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from direct assay PubMed 17918732. Source: UniProtKB
Molecular_function	scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro sodium channel regulator activity Inferred from sequence orthology Ref.1. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8K1T0-1)

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: Q8K1T0-2)

Also known as: F;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAASEMVEVEPEPNIRGPEIVTM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 453	453	Transmembrane protease serine 3		PRO_0000088691
Regions
	Topological domain	1 – 48	48	Cytoplasmic Potential
	Transmembrane	49 – 69	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	70 – 453	384	Extracellular Potential
	Domain	72 – 108	37	LDL-receptor class A
	Domain	104 – 205	102	SRCR
	Domain	217 – 448	232	Peptidase S1
Sites
	Active site	257	1	Charge relay system By similarity
	Active site	304	1	Charge relay system By similarity
	Active site	400	1	Charge relay system Probable
	Site	216 – 217	2	Cleavage Potential
Amino acid modifications
	Glycosylation	221	1	N-linked (GlcNAc...) Potential
	Disulfide bond	73 ↔ 85		By similarity
	Disulfide bond	79 ↔ 98		By similarity
	Disulfide bond	92 ↔ 107		By similarity
	Disulfide bond	129 ↔ 194		By similarity
	Disulfide bond	142 ↔ 204		By similarity
	Disulfide bond	207 ↔ 324		By similarity
	Disulfide bond	242 ↔ 258		By similarity
	Disulfide bond	338 ↔ 406		By similarity
	Disulfide bond	369 ↔ 385		By similarity
	Disulfide bond	396 ↔ 424		By similarity
Natural variations
	Alternative sequence	1	1	M → MAASEMVEVEPEPNIRGPEI VTM in isoform 2.		VSP_041581
Experimental info
	Sequence conflict	117	1	L → H in CAC83350. Ref.1
	Sequence conflict	246	1	I → V in CAD22137. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 1EE7ECD6CB3DD894	FASTA	453	49,506
	10 20 30 40 50 60 MGENDPPAAE APFSFRSLFG LDDLKISPVA PDGDAVAAQI LSLLPLKFFP IIVIGIIALI 70 80 90 100 110 120 LALAIGLGIH FDCSGKYRCH SSFKCIELTA RCDGVSDCKN AEDEYRCVRV SGQRAALQVF 130 140 150 160 170 180 TAAAWRTMCS DDWKSHYAKI ACAQLGFPSY VSSDHLRVDA LEEQFQGDFV SINHLLSDDK 190 200 210 220 230 240 VTALHHSVYM REGCTSGHVV TLKCSACGTR TGYSPRIVGG NMSSLTQWPW QVSLQFQGYH 250 260 270 280 290 300 LCGGSIITPL WIVTAAHCVY DLYHPKSWTV QVGLVSLMDS PVPSHLVEKI IYHSKYKPKR 310 320 330 340 350 360 LGNDIALMKL SEPLTFDETI QPICLPNSEE NFPDGKLCWT SGWGATEDGG DASPVLNHAA 370 380 390 400 410 420 VPLISNKICN HRDVYGGIIS PSMLCAGYLK GGVDSCQGDS GGPLVCQERR LWKLVGATSF 430 440 450 GIGCAEVNKP GVYTRITSFL DWIHEQLERD LKT
	Isoform 2 (F) [UniParc]. Checksum: 0214D1E550EC917B	FASTA	475	51,886
	10 20 30 40 50 60 MAASEMVEVE PEPNIRGPEI VTMGENDPPA AEAPFSFRSL FGLDDLKISP VAPDGDAVAA 70 80 90 100 110 120 QILSLLPLKF FPIIVIGIIA LILALAIGLG IHFDCSGKYR CHSSFKCIEL TARCDGVSDC 130 140 150 160 170 180 KNAEDEYRCV RVSGQRAALQ VFTAAAWRTM CSDDWKSHYA KIACAQLGFP SYVSSDHLRV 190 200 210 220 230 240 DALEEQFQGD FVSINHLLSD DKVTALHHSV YMREGCTSGH VVTLKCSACG TRTGYSPRIV 250 260 270 280 290 300 GGNMSSLTQW PWQVSLQFQG YHLCGGSIIT PLWIVTAAHC VYDLYHPKSW TVQVGLVSLM 310 320 330 340 350 360 DSPVPSHLVE KIIYHSKYKP KRLGNDIALM KLSEPLTFDE TIQPICLPNS EENFPDGKLC 370 380 390 400 410 420 WTSGWGATED GGDASPVLNH AAVPLISNKI CNHRDVYGGI ISPSMLCAGY LKGGVDSCQG 430 440 450 460 470 DSGGPLVCQE RRLWKLVGAT SFGIGCAEVN KPGVYTRITS FLDWIHEQLE RDLKT

References

[1]	"The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro." Guipponi M., Vuagniaux G., Wattenhofer M., Shibuya K., Vazquez M., Dougherty L., Scamuffa N., Guida E., Okui M., Rossier C., Hancock M., Buchet K., Reymond A., Hummler E., Marzella P.L., Kudoh J., Shimizu N., Scott H.S., Antonarakis S.E., Rossier B.C. Hum. Mol. Genet. 11:2829-2836(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, FUNCTION IN ENAC CLEAVAGE.
[2]	"Genomic organization of murine transmembrane proteinases." Rao N.V., Rao G.N., Hoidal J.R. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Tmprss3, a transmembrane serine protease deficient in human DFNB8/10 deafness, is critical for cochlear hair cell survival at the onset of hearing." Fasquelle L., Scott H.S., Lenoir M., Wang J., Rebillard G., Gaboyard S., Venteo S., Francois F., Mausset-Bonnefont A.L., Antonarakis S.E., Neidhart E., Chabbert C., Puel J.L., Guipponi M., Delprat B. J. Biol. Chem. 286:17383-17397(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING (ISOFORM 2).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ429216 Genomic DNA. Translation: CAD22137.1. AJ300738 mRNA. Translation: CAC83350.1. AY261383 Genomic DNA. Translation: AAO33581.1.
IPI	IPI00330042. IPI00831549.
RefSeq	NP_542765.2. NM_080727.2.
UniGene	Mm.214638.
3D structure databases
ProteinModelPortal	Q8K1T0.
SMR	Q8K1T0. Positions 72-448.
ModBase	Search...
Protein family/group databases
MEROPS	S01.079.
PTM databases
PhosphoSite	Q8K1T0.
Proteomic databases
PRIDE	Q8K1T0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000024833; ENSMUSP00000024833; ENSMUSG00000024034. ENSMUST00000114549; ENSMUSP00000110196; ENSMUSG00000024034.
GeneID	140765.
KEGG	mmu:140765.
UCSC	uc008bup.2. mouse.
Organism-specific databases
CTD	64699.
MGI	MGI:2155445. Tmprss3.
Phylogenomic databases
eggNOG	COG5640.
GeneTree	ENSGT00700000104118.
HOGENOM	HOG000251822.
HOVERGEN	HBG013304.
InParanoid	Q812A6.
KO	K09634.
OMA	TLKCTAC.
OrthoDB	EOG4XH002.
Gene expression databases
ArrayExpress	Q8K1T0.
Bgee	Q8K1T0.
CleanEx	MM_TMPRSS3.
Genevestigator	Q8K1T0.
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	PF00057. Ldl_recept_a. 1 hit. 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. 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
NextBio	369973.
SOURCE	Search...

Entry information

Entry name

TMPS3_MOUSE

Accession

Primary (citable) accession number: Q8K1T0
Secondary accession number(s): Q812A6, Q8VDE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2003
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program