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P83110

- HTRA3_HUMAN

UniProt

P83110 - HTRA3_HUMAN

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Protein

Serine protease HTRA3

Gene

HTRA3

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

Functioni

Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans By similarity. May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei191 – 1911Charge relay systemSequence Analysis
Active sitei227 – 2271Charge relay systemSequence Analysis
Active sitei305 – 3051Charge relay system

GO - Molecular functioni

  1. endopeptidase activity Source: BHF-UCL
  2. serine-type endopeptidase activity Source: InterPro
  3. serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  1. negative regulation of BMP signaling pathway Source: UniProtKB
  2. negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  3. proteolysis Source: UniProtKB
  4. regulation of cell growth Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.284.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease HTRA3 (EC:3.4.21.-)
Alternative name(s):
High-temperature requirement factor A3
Pregnancy-related serine protease
Gene namesi
Name:HTRA3
Synonyms:PRSP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:30406. HTRA3.

Subcellular locationi

Secreted 1 Publication
Note: Secretion increased during decidualization of endometrial stromal cells.

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi305 – 3051S → A: Abolishes protease activity. Stabilizes the protein. 1 Publication

Organism-specific databases

PharmGKBiPA134908281.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence AnalysisAdd
BLAST
Chaini18 – 453436Serine protease HTRA3PRO_0000026949Add
BLAST

Proteomic databases

MaxQBiP83110.
PaxDbiP83110.
PRIDEiP83110.

PTM databases

PhosphoSiteiP83110.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in both adult and fetal heart, ovary, uterus placenta, and bladder. In the endometrium, expressed in epithelial glands and the stroma. Also present in leukocytes. Isoform 1 is predominant in heart and skeletal muscle, whereas isoform 2 is predominant in placenta and kidney.3 Publications

Inductioni

Down-regulated in ovarian and endometrial cancers (EC). Decrease of 3.2-fold in endometrial cancer.2 Publications

Gene expression databases

BgeeiP83110.
CleanExiHS_HTRA3.
GenevestigatoriP83110.

Organism-specific databases

HPAiHPA021187.

Interactioni

Subunit structurei

Homotrimer By similarity. Interacts with TGFB1; the interaction inhibits TGFB-mediated signaling. Interacts with BMP4; the interaction inhibits BMP4-mediated signaling. Interacts with TGFB2 and GDF5 By similarity. Interacts with MYH9.By similarity2 Publications

Protein-protein interaction databases

BioGridi125099. 2 interactions.
IntActiP83110. 2 interactions.
MINTiMINT-4786544.
STRINGi9606.ENSP00000303766.

Structurei

Secondary structure

1
453
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi354 – 3563
Beta strandi359 – 3635
Helixi366 – 37510
Beta strandi384 – 3918
Helixi396 – 4005
Beta strandi407 – 4115
Helixi419 – 42810
Beta strandi430 – 4389
Beta strandi441 – 4477
Beta strandi450 – 4523

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2P3WX-ray1.70A/B354-453[»]
ProteinModelPortaliP83110.
SMRiP83110. Positions 25-125, 134-453.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP83110.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 7757IGFBP N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini64 – 12865Kazal-likePROSITE-ProRule annotationAdd
BLAST
Domaini359 – 44486PDZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni175 – 340166Serine proteaseAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1C family.Curated
Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
Contains 1 Kazal-like domain.PROSITE-ProRule annotation
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG0265.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiP83110.
KOiK08785.
OMAiTDGHTYA.
OrthoDBiEOG7V1FR7.
PhylomeDBiP83110.
TreeFamiTF323480.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_N_dom.
IPR000867. IGFBP-like.
IPR002350. Kazal_dom.
IPR001478. PDZ.
IPR001940. Peptidase_S1C.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF07648. Kazal_2. 1 hit.
PF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSiPR00834. PROTEASES2C.
SMARTiSM00121. IB. 1 hit.
SM00280. KAZAL. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS51323. IGFBP_N_2. 1 hit.
PS51465. KAZAL_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P83110-1) [UniParc]FASTAAdd to Basket

Also known as: Long, pL

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
MQARALLLAA LAALALAREP PAAPCPARCD VSRCPSPRCP GGYVPDLCNC
60 70 80 90 100
CLVCAASEGE PCGGPLDSPC GESLECVRGL CRCRWSHAVC GTDGHTYANV
110 120 130 140 150
CALQAASRRA LQLSGTPVRQ LQKGACPLGL HQLSSPRYKF NFIADVVEKI
160 170 180 190 200
APAVVHIELF LRHPLFGRNV PLSSGSGFIM SEAGLIITNA HVVSSNSAAP
210 220 230 240 250
GRQQLKVQLQ NGDSYEATIK DIDKKSDIAT IKIHPKKKLP VLLLGHSADL
260 270 280 290 300
RPGEFVVAIG SPFALQNTVT TGIVSTAQRE GRELGLRDSD MDYIQTDAII
310 320 330 340 350
NYGNSGGPLV NLDGEVIGIN TLKVTAGISF AIPSDRITRF LTEFQDKQIK
360 370 380 390 400
DWKKRFIGIR MRTITPSLVD ELKASNPDFP EVSSGIYVQE VAPNSPSQRG
410 420 430 440 450
GIQDGDIIVK VNGRPLVDSS ELQEAVLTES PLLLEVRRGN DDLLFSIAPE

VVM
Length:453
Mass (Da):48,608
Last modified:June 20, 2002 - v2
Checksum:i3046FCDA1AB24FA6
GO
Isoform 2 (identifier: P83110-2) [UniParc]FASTAAdd to Basket

Also known as: Short, pS

The sequence of this isoform differs from the canonical sequence as follows:
     351-357: DWKKRFI → APSLAVH
     358-453: Missing.

Show »
Length:357
Mass (Da):37,940
Checksum:i8A62D2B9823BC420
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei351 – 3577DWKKRFI → APSLAVH in isoform 2. 1 PublicationVSP_012570
Alternative sequencei358 – 45396Missing in isoform 2. 1 PublicationVSP_012571Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY280665 mRNA. Translation: AAP42282.1.
AY280666 mRNA. Translation: AAP42283.1.
AY040094 mRNA. Translation: AAK71475.2.
AC113611 Genomic DNA. No translation available.
BC034390 mRNA. Translation: AAH34390.1.
BC035717 mRNA. Translation: AAH35717.1.
CCDSiCCDS3400.1. [P83110-1]
CCDS75105.1. [P83110-2]
RefSeqiNP_001284488.1. NM_001297559.1. [P83110-2]
NP_444272.1. NM_053044.4. [P83110-1]
UniGeneiHs.479119.

Genome annotation databases

EnsembliENST00000307358; ENSP00000303766; ENSG00000170801. [P83110-1]
ENST00000382512; ENSP00000371952; ENSG00000170801. [P83110-2]
GeneIDi94031.
KEGGihsa:94031.
UCSCiuc003gkz.3. human. [P83110-2]
uc003gla.3. human. [P83110-1]

Polymorphism databases

DMDMi21542412.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY280665 mRNA. Translation: AAP42282.1 .
AY280666 mRNA. Translation: AAP42283.1 .
AY040094 mRNA. Translation: AAK71475.2 .
AC113611 Genomic DNA. No translation available.
BC034390 mRNA. Translation: AAH34390.1 .
BC035717 mRNA. Translation: AAH35717.1 .
CCDSi CCDS3400.1. [P83110-1 ]
CCDS75105.1. [P83110-2 ]
RefSeqi NP_001284488.1. NM_001297559.1. [P83110-2 ]
NP_444272.1. NM_053044.4. [P83110-1 ]
UniGenei Hs.479119.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2P3W X-ray 1.70 A/B 354-453 [» ]
ProteinModelPortali P83110.
SMRi P83110. Positions 25-125, 134-453.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 125099. 2 interactions.
IntActi P83110. 2 interactions.
MINTi MINT-4786544.
STRINGi 9606.ENSP00000303766.

Protein family/group databases

MEROPSi S01.284.

PTM databases

PhosphoSitei P83110.

Polymorphism databases

DMDMi 21542412.

Proteomic databases

MaxQBi P83110.
PaxDbi P83110.
PRIDEi P83110.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000307358 ; ENSP00000303766 ; ENSG00000170801 . [P83110-1 ]
ENST00000382512 ; ENSP00000371952 ; ENSG00000170801 . [P83110-2 ]
GeneIDi 94031.
KEGGi hsa:94031.
UCSCi uc003gkz.3. human. [P83110-2 ]
uc003gla.3. human. [P83110-1 ]

Organism-specific databases

CTDi 94031.
GeneCardsi GC04P008271.
HGNCi HGNC:30406. HTRA3.
HPAi HPA021187.
MIMi 608785. gene.
neXtProti NX_P83110.
PharmGKBi PA134908281.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0265.
GeneTreei ENSGT00510000046315.
HOGENOMi HOG000223641.
HOVERGENi HBG052044.
InParanoidi P83110.
KOi K08785.
OMAi TDGHTYA.
OrthoDBi EOG7V1FR7.
PhylomeDBi P83110.
TreeFami TF323480.

Miscellaneous databases

EvolutionaryTracei P83110.
GenomeRNAii 94031.
NextBioi 78335.
PROi P83110.
SOURCEi Search...

Gene expression databases

Bgeei P83110.
CleanExi HS_HTRA3.
Genevestigatori P83110.

Family and domain databases

Gene3Di 2.30.42.10. 1 hit.
InterProi IPR009030. Growth_fac_rcpt_N_dom.
IPR000867. IGFBP-like.
IPR002350. Kazal_dom.
IPR001478. PDZ.
IPR001940. Peptidase_S1C.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF07648. Kazal_2. 1 hit.
PF13180. PDZ_2. 1 hit.
[Graphical view ]
PRINTSi PR00834. PROTEASES2C.
SMARTi SM00121. IB. 1 hit.
SM00280. KAZAL. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view ]
SUPFAMi SSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEi PS51323. IGFBP_N_2. 1 hit.
PS51465. KAZAL_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2."
    Nie G.-Y., Hampton A., Li Y., Findlay J.K., Salamonsen L.A.
    Biochem. J. 371:39-48(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
    Tissue: Heart.
  2. Southan C., Punia P.K.
    Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain and Ovary.
  4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer."
    Bowden M.A., Di Nezza-Cossens L.A., Jobling T., Salamonsen L.A., Nie G.
    Gynecol. Oncol. 103:253-260(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, TISSUE SPECIFICITY.
  6. "Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer."
    Narkiewicz J., Lapinska-Szumczyk S., Zurawa-Janicka D., Skorko-Glonek J., Emerich J., Lipinska B.
    Oncol. Rep. 21:1529-1537(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  7. "Decidual HtrA3 negatively regulates trophoblast invasion during human placentation."
    Singh H., Endo Y., Nie G.
    Hum. Reprod. 26:748-757(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, POSSIBLE FUNCTION.
  8. "Application of the wheat-germ cell-free translation system to produce high temperature requirement A3 (HtrA3) proteases."
    Singh H., Makino S., Endo Y., Li Y., Stephens A.N., Nie G.
    BioTechniques 52:23-28(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MYH9, ENZYME ACTIVITY, MUTAGENESIS OF SER-305.
  9. "Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3."
    Runyon S.T., Zhang Y., Appleton B.A., Sazinsky S.L., Wu P., Pan B., Wiesmann C., Skelton N.J., Sidhu S.S.
    Protein Sci. 16:2454-2471(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 354-453 IN COMPLEX WITH SYNTHETIC PEPTIDES.

Entry informationi

Entry nameiHTRA3_HUMAN
AccessioniPrimary (citable) accession number: P83110
Secondary accession number(s): Q7Z7A2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: June 20, 2002
Last modified: October 29, 2014
This is version 121 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3