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Protein

Transmembrane protease serine 4

Gene

TMPRSS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

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

EuPathDBiHostDB:ENSG00000137648.16
HGNCiHGNC:11878 TMPRSS4
MIMi606565 gene
neXtProtiNX_Q9NRS4

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

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...) asparagineSequence analysis1
Disulfide bondi140 ↔ 193By similarity
Glycosylationi178N-linked (GlcNAc...) asparagineSequence 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

iPTMnetiQ9NRS4
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

Show more details

Protein-protein interaction databases

BioGridi121163, 5 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

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

CDDicd00112 LDLa, 1 hit
cd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR036055 LDL_receptor-like_sf
IPR002172 LDrepeatLR_classA_rpt
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF15494 SRCR_2, 1 hit
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00192 LDLa, 1 hit
SM00202 SR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF56487 SSF56487, 1 hit
SSF57424 SSF57424, 1 hit
PROSITEiView protein in PROSITE
PS50287 SRCR_2, 1 hit
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

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 dbSNP:rs1894176Ensembl.1
Natural variantiVAR_046505198K → E. Corresponds to variant dbSNP:rs12270001Ensembl.1
Natural variantiVAR_046506208V → G5 PublicationsCorresponds to variant dbSNP:rs1941635Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTMPS4_HUMAN
AccessioniPrimary (citable) accession number: Q9NRS4
Secondary accession number(s): A8MU84
, B0YJB0, B7Z8C5, E7ERX8, Q5XKQ6, Q6UX37, Q9NZA5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 11, 2011
Last modified: May 23, 2018
This is version 167 of the entry and version 2 of the sequence. See 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

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