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P83110

- HTRA3_HUMAN

UniProt

P83110 - HTRA3_HUMAN

Protein

Serine protease HTRA3

Gene

HTRA3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (20 Jun 2002)
      Previous versions | rss
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    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. protein binding Source: UniProtKB
    3. serine-type endopeptidase activity Source: InterPro
    4. 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

    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-SubCell

    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. 1 interaction.
    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 S1B 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.
    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

    MQARALLLAA LAALALAREP PAAPCPARCD VSRCPSPRCP GGYVPDLCNC    50
    CLVCAASEGE PCGGPLDSPC GESLECVRGL CRCRWSHAVC GTDGHTYANV 100
    CALQAASRRA LQLSGTPVRQ LQKGACPLGL HQLSSPRYKF NFIADVVEKI 150
    APAVVHIELF LRHPLFGRNV PLSSGSGFIM SEAGLIITNA HVVSSNSAAP 200
    GRQQLKVQLQ NGDSYEATIK DIDKKSDIAT IKIHPKKKLP VLLLGHSADL 250
    RPGEFVVAIG SPFALQNTVT TGIVSTAQRE GRELGLRDSD MDYIQTDAII 300
    NYGNSGGPLV NLDGEVIGIN TLKVTAGISF AIPSDRITRF LTEFQDKQIK 350
    DWKKRFIGIR MRTITPSLVD ELKASNPDFP EVSSGIYVQE VAPNSPSQRG 400
    GIQDGDIIVK VNGRPLVDSS ELQEAVLTES PLLLEVRRGN DDLLFSIAPE 450
    VVM 453
    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]
    RefSeqiNP_444272.1. NM_053044.3. [P83110-1]
    XP_005248097.1. XM_005248040.1. [P83110-2]
    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 ]
    RefSeqi NP_444272.1. NM_053044.3. [P83110-1 ]
    XP_005248097.1. XM_005248040.1. [P83110-2 ]
    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. 1 interaction.
    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 GC04P008191.
    HGNCi HGNC:30406. HTRA3.
    HPAi HPA021187.
    MIMi 608785. gene.
    neXtProti NX_P83110.
    PharmGKBi PA134908281.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0265.
    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

    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 1, 2014
    This is version 120 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