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Protein

Serine protease HTRA1

Gene

Htra1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, but it is unclear whether it leads to the proteolytic degradation of TGF-beta proteins themselves (PubMed:18551132) or not (PubMed:14973287). By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169Involved in trimer stabilizationBy similarity1
Sitei171Involved in trimer stabilizationBy similarity1
Active sitei220Charge relay systemBy similarity1
Active sitei250Charge relay systemBy similarity1
Sitei278Involved in trimer stabilizationBy similarity1
Active sitei328Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

  • chorionic trophoblast cell differentiation Source: MGI
  • dentinogenesis Source: Ensembl
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of defense response to virus Source: Ensembl
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  • placenta development Source: MGI
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • proteolysis Source: UniProtKB
  • regulation of cell growth Source: InterPro

Keywordsi

Molecular functionGrowth factor binding, Hydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.277

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease HTRA1 (EC:3.4.21.-)
Alternative name(s):
High-temperature requirement A serine peptidase 1
Serine protease 11
Gene namesi
Name:Htra1
Synonyms:Htra, Prss11
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1929076 Htra1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Mutants mice exhibit reduced retinal capillary density, as compared to wild type animals, in all 3 retinal layers, nerve fiber layer, as well as inner and outer plexiform layers.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi171F → D: Loss of efficient trimer formation. 1 Publication1
Mutagenesisi328S → A: Loss of enzymatic activity. No effect on BMP4-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000002694423 – 480Serine protease HTRA1Add BLAST458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi110 ↔ 130PROSITE-ProRule annotation
Disulfide bondi119 ↔ 155PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiQ9R118
PaxDbiQ9R118
PeptideAtlasiQ9R118
PRIDEiQ9R118

PTM databases

CarbonylDBiQ9R118
PhosphoSitePlusiQ9R118

Expressioni

Tissue specificityi

In the brain, mainly expressed in cortical areas both in glial cells and neurons (at protein level). In bones, deposited in the matrix, with higher level in newly formed bone compared to fully calcified bone (at protein level). Also expressed in the tendons (at protein level). In the articular cartilage, detected only in the deepest zone of the joint cartilage. Not detected in the chondrocytes of the growth plate (at protein level). In an experimental arthritis model, at early disease stages, up-regulated in articular chondrocytes in the deep layers of the cartilage (at protein level). As arthritis progresses, chondrocyte expression expands toward the surface.3 Publications

Developmental stagei

First detected at 10.5 dpc. At 11.5 dpc, in the developing heart, expressed in the atrioventricular endocardial cushion and the outflow tract (at protein level). At 14.5 dpc, strong expression in the outflow tracts, including valves. In the developing skeleton, expressed at 12.5 dpc in the vertebral column and limbs. At 14.5 dpc, expressed in rudiments of tendons and ligaments along the vertebrae, as well as in mesenchymal cells surrounding precartilage condensations. Not detected in precartilage condensations, nor in chondrocytes, but strongly expressed in ossification centers. At 17.5 dpc, in the hind limb, significant expression persists in tendons and ligaments, but expression in the forming joints is reduced. At this stage, weakly detected in the thin layer of articular surfaces. Postnatally, in long bones, expressed by terminally differentiated hypertrophic chondrocytes that are committed to degeneration and eventually replaced by bone, as well as by osteoblasts at late differentiation stages and by mature osteocytes. In the developing brain, expressed in specific regions of the neuroepithelium in the forebrain and hindbrain adjacent to the forming choroid plexus. From 17.5 dpc till birth, expressed in neurogenic areas including ventricular zones (at protein level). At 12.5 and 14.5 dpc, expressed in Muellerian duct cells and in the surrounding mesenchyme in both male and female gonads. In the lung, detected in the mesenchymal cells. Expressed at 12.5 dpc in abdominal skin, both in epidermis and dermis. Also expressed in the epithelium of developing whiskers at 14.5 dpc. At later stages, localized in the basal layer of epidermis and in the invading epidermal cells that formed the whisker rudiments (at protein level). 9 days after birth, detected in the whisker outer root sheet (at protein level).3 Publications

Gene expression databases

BgeeiENSMUSG00000006205
CleanExiMM_HTRA1
GenevisibleiQ9R118 MM

Interactioni

Subunit structurei

Forms homotrimers. In the presence of substrate, may form higher-order multimers in a PDZ-independent manner (By similarity). Interacts with TGF-beta family members, including BMP4, TGFB1, TGFB2, activin A and GDF5.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207847, 5 interactors
STRINGi10090.ENSMUSP00000006367

Structurei

3D structure databases

ProteinModelPortaliQ9R118
SMRiQ9R118
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 100IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST68
Domaini98 – 157Kazal-likePROSITE-ProRule annotationAdd BLAST60
Domaini365 – 467PDZPROSITE-ProRule annotationAdd BLAST103

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni204 – 364Serine proteaseAdd BLAST161

Domaini

The IGFBP N-terminal domain mediates interaction with TSC2 substrate.By similarity

Sequence similaritiesi

Belongs to the peptidase S1C family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1320 Eukaryota
COG0265 LUCA
GeneTreeiENSGT00510000046315
HOGENOMiHOG000223641
HOVERGENiHBG052044
InParanoidiQ9R118
KOiK08784
OMAiTYANLCQ
OrthoDBiEOG091G0LXR
TreeFamiTF323480

Family and domain databases

InterProiView protein in InterPro
IPR009030 Growth_fac_rcpt_cys_sf
IPR000867 IGFBP-like
IPR002350 Kazal_dom
IPR036058 Kazal_dom_sf
IPR001478 PDZ
IPR036034 PDZ_sf
IPR009003 Peptidase_S1_PA
IPR001940 Peptidase_S1C
PfamiView protein in Pfam
PF00219 IGFBP, 1 hit
PF07648 Kazal_2, 1 hit
PF00595 PDZ, 1 hit
PRINTSiPR00834 PROTEASES2C
SMARTiView protein in SMART
SM00121 IB, 1 hit
SM00280 KAZAL, 1 hit
SM00228 PDZ, 1 hit
SUPFAMiSSF100895 SSF100895, 1 hit
SSF50156 SSF50156, 1 hit
SSF50494 SSF50494, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS51323 IGFBP_N_2, 1 hit
PS51465 KAZAL_2, 1 hit
PS50106 PDZ, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9R118-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSLRTTLLS LLLLLLAAPS LALPSGTGRS APAATVCPEH CDPTRCAPPP
60 70 80 90 100
TDCEGGRVRD ACGCCEVCGA LEGAACGLQE GPCGEGLQCV VPFGVPASAT
110 120 130 140 150
VRRRAQAGLC VCASSEPVCG SDAKTYTNLC QLRAASRRSE KLRQPPVIVL
160 170 180 190 200
QRGACGQGQE DPNSLRHKYN FIADVVEKIA PAVVHIELYR KLPFSKREVP
210 220 230 240 250
VASGSGFIVS EDGLIVTNAH VVTNKNRVKV ELKNGATYEA KIKDVDEKAD
260 270 280 290 300
IALIKIDHQG KLPVLLLGRS SELRPGEFVV AIGSPFSLQN TVTTGIVSTT
310 320 330 340 350
QRGGKELGLR NSDMDYIQTD AIINYGNSGG PLVNLDGEVI GINTLKVTAG
360 370 380 390 400
ISFAIPSDKI KKFLTESHDR QAKGKAVTKK KYIGIRMMSL TSSKAKELKD
410 420 430 440 450
RHRDFPDVLS GAYIIEVIPD TPAEAGGLKE NDVIISINGQ SVVTANDVSD
460 470 480
VIKKENTLNM VVRRGNEDIV ITVIPEEIDP
Length:480
Mass (Da):51,214
Last modified:July 27, 2011 - v2
Checksum:i92BDDA85CF5B12B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91V → L in AAD49422 (PubMed:14973287).Curated1
Sequence conflicti143R → P in AAD49422 (PubMed:14973287).Curated1
Sequence conflicti179I → F in AAD49422 (PubMed:14973287).Curated1
Sequence conflicti182A → D in AAD49422 (PubMed:14973287).Curated1
Sequence conflicti185 – 186HI → KH in AAD49422 (PubMed:14973287).Curated2
Sequence conflicti241K → I in AAD49422 (PubMed:14973287).Curated1
Sequence conflicti259Q → K in BAC41168 (PubMed:16141072).Curated1
Sequence conflicti366E → Q in AAH13516 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172994 mRNA Translation: AAD49422.1
AF179369 mRNA Translation: AAD52682.1
CH466531 Genomic DNA Translation: EDL17689.1
BC013516 mRNA Translation: AAH13516.1
AK090320 mRNA Translation: BAC41168.1
AK090321 mRNA Translation: BAC41169.1
CCDSiCCDS21908.1
RefSeqiNP_062510.2, NM_019564.3
UniGeneiMm.30156

Genome annotation databases

EnsembliENSMUST00000006367; ENSMUSP00000006367; ENSMUSG00000006205
GeneIDi56213
KEGGimmu:56213
UCSCiuc009kau.2 mouse

Similar proteinsi

Entry informationi

Entry nameiHTRA1_MOUSE
AccessioniPrimary (citable) accession number: Q9R118
Secondary accession number(s): Q8BN04
, Q8BN05, Q91WS3, Q9QZK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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