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Protein

Transmembrane protease serine 4

Gene

TMPRSS4

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

Functioni

Probable protease. Seems to be capable of activating ENaC (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei245Charge relay systemBy similarity1
Active sitei290Charge relay systemBy similarity1
Active sitei387Charge relay systemBy similarity1

GO - Molecular functioni

  • scavenger receptor activity Source: InterPro
  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137648-MONOMER.

Protein family/group databases

MEROPSiS01.034.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 4 (EC:3.4.21.-)
Alternative name(s):
Channel-activating protease 2
Short name:
CAPH2
Membrane-type serine protease 2
Short name:
MT-SP2
Gene namesi
Name:TMPRSS4
Synonyms:TMPRSS3
ORF Names:UNQ776/PRO1570
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:11878. TMPRSS4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 32CytoplasmicSequence analysisAdd BLAST32
Transmembranei33 – 53Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini54 – 437ExtracellularSequence analysisAdd BLAST384

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi56649.
MalaCardsiTMPRSS4.
OpenTargetsiENSG00000137648.
Orphaneti363969. Autosomal recessive cerebral atrophy.
PharmGKBiPA36579.

Chemistry databases

ChEMBLiCHEMBL2331048.

Polymorphism and mutation databases

BioMutaiTMPRSS4.
DMDMi317373304.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000886921 – 437Transmembrane protease serine 4Add BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi64 ↔ 83By similarity
Disulfide bondi77 ↔ 92By similarity
Disulfide bondi127 ↔ 183By similarity
Glycosylationi130N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi140 ↔ 193By similarity
Glycosylationi178N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi196 ↔ 310By similarity
Disulfide bondi230 ↔ 246By similarity
Disulfide bondi356 ↔ 372By similarity
Disulfide bondi383 ↔ 410By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei204 – 205CleavageSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9NRS4.
PaxDbiQ9NRS4.
PeptideAtlasiQ9NRS4.
PRIDEiQ9NRS4.

PTM databases

PhosphoSitePlusiQ9NRS4.

Expressioni

Tissue specificityi

High levels in pancreatic, gastric, colorectal and ampullary cancer. Very weak expression in normal gastrointestinal and urogenital tract.

Gene expression databases

BgeeiENSG00000137648.
CleanExiHS_TMPRSS3.
HS_TMPRSS4.
ExpressionAtlasiQ9NRS4. baseline and differential.
GenevisibleiQ9NRS4. HS.

Organism-specific databases

HPAiHPA006238.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC155Q8N6L03EBI-10313040,EBI-749265
CLEC7AQ9BXN23EBI-10312990,EBI-3939278
SYNE4Q8N2053EBI-10312990,EBI-7131783
TMEM79Q9BSE23EBI-10313040,EBI-8649725

Protein-protein interaction databases

BioGridi121163. 4 interactors.
IntActiQ9NRS4. 5 interactors.
STRINGi9606.ENSP00000416037.

Chemistry databases

BindingDBiQ9NRS4.

Structurei

3D structure databases

ProteinModelPortaliQ9NRS4.
SMRiQ9NRS4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 93LDL-receptor class AAdd BLAST33
Domaini94 – 204SRCRPROSITE-ProRule annotationAdd BLAST111
Domaini205 – 434Peptidase S1PROSITE-ProRule annotationAdd BLAST230

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 LDL-receptor class A domain.Curated
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation
Contains 1 SRCR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000251822.
HOVERGENiHBG013304.
InParanoidiQ9NRS4.
KOiK09635.
OMAiHCLACGE.
OrthoDBiEOG091G0AH5.
PhylomeDBiQ9NRS4.
TreeFamiTF351678.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di3.10.250.10. 1 hit.
4.10.400.10. 1 hit.
InterProiIPR002172. LDrepeatLR_classA_rpt.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF15494. SRCR_2. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00192. LDLa. 1 hit.
SM00202. SR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
SSF57424. SSF57424. 1 hit.
PROSITEiPS50287. SRCR_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRS4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLQDPDSDQP LNSLDVKPLR KPRIPMETFR KVGIPIIIAL LSLASIIIVV
60 70 80 90 100
VLIKVILDKY YFLCGQPLHF IPRKQLCDGE LDCPLGEDEE HCVKSFPEGP
110 120 130 140 150
AVAVRLSKDR STLQVLDSAT GNWFSACFDN FTEALAETAC RQMGYSSKPT
160 170 180 190 200
FRAVEIGPDQ DLDVVEITEN SQELRMRNSS GPCLSGSLVS LHCLACGKSL
210 220 230 240 250
KTPRVVGVEE ASVDSWPWQV SIQYDKQHVC GGSILDPHWV LTAAHCFRKH
260 270 280 290 300
TDVFNWKVRA GSDKLGSFPS LAVAKIIIIE FNPMYPKDND IALMKLQFPL
310 320 330 340 350
TFSGTVRPIC LPFFDEELTP ATPLWIIGWG FTKQNGGKMS DILLQASVQV
360 370 380 390 400
IDSTRCNADD AYQGEVTEKM MCAGIPEGGV DTCQGDSGGP LMYQSDQWHV
410 420 430
VGIVSWGYGC GGPSTPGVYT KVSAYLNWIY NVWKAEL
Length:437
Mass (Da):48,246
Last modified:January 11, 2011 - v2
Checksum:i3CF55633361A2BE7
GO
Isoform 2 (identifier: Q9NRS4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     147-151: Missing.

Note: No experimental confirmation available.
Show »
Length:432
Mass (Da):47,686
Checksum:iD5FAC7E40798790C
GO
Isoform 3 (identifier: Q9NRS4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MLQ → M

Note: No experimental confirmation available.
Show »
Length:435
Mass (Da):48,005
Checksum:i14B3AF624CE8BEA6
GO
Isoform 4 (identifier: Q9NRS4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MLQ → M
     14-53: LDVKPLRKPRIPMETFRKVGIPIIIALLSLASIIIVVVLI → LV

Note: No experimental confirmation available.
Show »
Length:397
Mass (Da):43,786
Checksum:i135A735A29AB457C
GO

Sequence cautioni

The sequence AAF31436 differs from that shown. Reason: Frameshift at position 31.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2L → V in AAF31436 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024293177R → Q.Corresponds to variant rs1894176dbSNPEnsembl.1
Natural variantiVAR_046505198K → E.Corresponds to variant rs12270001dbSNPEnsembl.1
Natural variantiVAR_046506208V → G.5 PublicationsCorresponds to variant rs1941635dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0131161 – 3MLQ → M in isoform 3 and isoform 4. 2 Publications3
Alternative sequenceiVSP_05422914 – 53LDVKP…VVVLI → LV in isoform 4. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_013117147 – 151Missing in isoform 2. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF179224 mRNA. Translation: AAF74526.1.
AF216312 mRNA. Translation: AAF31436.1. Frameshift.
AK172766 mRNA. Translation: BAD18749.1.
AK303173 mRNA. Translation: BAH13911.1.
AY358530 mRNA. Translation: AAQ88894.1.
EF445038 Genomic DNA. Translation: ACA06088.1.
AP000665 Genomic DNA. No translation available.
AP002800 Genomic DNA. No translation available.
BC004855 mRNA. Translation: AAH04855.1.
BC011703 mRNA. Translation: AAH11703.1.
CCDSiCCDS31684.1. [Q9NRS4-1]
CCDS44743.1. [Q9NRS4-2]
CCDS53716.1. [Q9NRS4-3]
CCDS53717.1. [Q9NRS4-4]
RefSeqiNP_001077416.1. NM_001083947.1.
NP_001167023.1. NM_001173552.1.
NP_063947.1. NM_019894.3.
UniGeneiHs.161985.

Genome annotation databases

EnsembliENST00000437212; ENSP00000416037; ENSG00000137648. [Q9NRS4-1]
ENST00000522824; ENSP00000430547; ENSG00000137648. [Q9NRS4-2]
ENST00000523251; ENSP00000429209; ENSG00000137648. [Q9NRS4-4]
ENST00000534111; ENSP00000435184; ENSG00000137648. [Q9NRS4-3]
ENST00000618855; ENSP00000477949; ENSG00000137648. [Q9NRS4-1]
GeneIDi56649.
KEGGihsa:56649.
UCSCiuc010rxo.3. human. [Q9NRS4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF179224 mRNA. Translation: AAF74526.1.
AF216312 mRNA. Translation: AAF31436.1. Frameshift.
AK172766 mRNA. Translation: BAD18749.1.
AK303173 mRNA. Translation: BAH13911.1.
AY358530 mRNA. Translation: AAQ88894.1.
EF445038 Genomic DNA. Translation: ACA06088.1.
AP000665 Genomic DNA. No translation available.
AP002800 Genomic DNA. No translation available.
BC004855 mRNA. Translation: AAH04855.1.
BC011703 mRNA. Translation: AAH11703.1.
CCDSiCCDS31684.1. [Q9NRS4-1]
CCDS44743.1. [Q9NRS4-2]
CCDS53716.1. [Q9NRS4-3]
CCDS53717.1. [Q9NRS4-4]
RefSeqiNP_001077416.1. NM_001083947.1.
NP_001167023.1. NM_001173552.1.
NP_063947.1. NM_019894.3.
UniGeneiHs.161985.

3D structure databases

ProteinModelPortaliQ9NRS4.
SMRiQ9NRS4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121163. 4 interactors.
IntActiQ9NRS4. 5 interactors.
STRINGi9606.ENSP00000416037.

Chemistry databases

BindingDBiQ9NRS4.
ChEMBLiCHEMBL2331048.

Protein family/group databases

MEROPSiS01.034.

PTM databases

PhosphoSitePlusiQ9NRS4.

Polymorphism and mutation databases

BioMutaiTMPRSS4.
DMDMi317373304.

Proteomic databases

MaxQBiQ9NRS4.
PaxDbiQ9NRS4.
PeptideAtlasiQ9NRS4.
PRIDEiQ9NRS4.

Protocols and materials databases

DNASUi56649.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000437212; ENSP00000416037; ENSG00000137648. [Q9NRS4-1]
ENST00000522824; ENSP00000430547; ENSG00000137648. [Q9NRS4-2]
ENST00000523251; ENSP00000429209; ENSG00000137648. [Q9NRS4-4]
ENST00000534111; ENSP00000435184; ENSG00000137648. [Q9NRS4-3]
ENST00000618855; ENSP00000477949; ENSG00000137648. [Q9NRS4-1]
GeneIDi56649.
KEGGihsa:56649.
UCSCiuc010rxo.3. human. [Q9NRS4-1]

Organism-specific databases

CTDi56649.
DisGeNETi56649.
GeneCardsiTMPRSS4.
HGNCiHGNC:11878. TMPRSS4.
HPAiHPA006238.
MalaCardsiTMPRSS4.
MIMi606565. gene.
neXtProtiNX_Q9NRS4.
OpenTargetsiENSG00000137648.
Orphaneti363969. Autosomal recessive cerebral atrophy.
PharmGKBiPA36579.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000251822.
HOVERGENiHBG013304.
InParanoidiQ9NRS4.
KOiK09635.
OMAiHCLACGE.
OrthoDBiEOG091G0AH5.
PhylomeDBiQ9NRS4.
TreeFamiTF351678.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137648-MONOMER.

Miscellaneous databases

ChiTaRSiTMPRSS4. human.
GenomeRNAii56649.
PROiQ9NRS4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137648.
CleanExiHS_TMPRSS3.
HS_TMPRSS4.
ExpressionAtlasiQ9NRS4. baseline and differential.
GenevisibleiQ9NRS4. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di3.10.250.10. 1 hit.
4.10.400.10. 1 hit.
InterProiIPR002172. LDrepeatLR_classA_rpt.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF15494. SRCR_2. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00192. LDLa. 1 hit.
SM00202. SR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF56487. SSF56487. 1 hit.
SSF57424. SSF57424. 1 hit.
PROSITEiPS50287. SRCR_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTMPS4_HUMAN
AccessioniPrimary (citable) accession number: Q9NRS4
Secondary accession number(s): A8MU84
, B0YJB0, B7Z8C5, E7ERX8, Q5XKQ6, Q6UX37, Q9NZA5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 155 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.