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P83110 (HTRA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine protease HTRA3

EC=3.4.21.-
Alternative name(s):
High-temperature requirement factor A3
Pregnancy-related serine protease
Gene names
Name:HTRA3
Synonyms:PRSP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length453 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Subunit structure

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. Ref.8

Subcellular location

Secreted. Note: Secretion increased during decidualization of endometrial stromal cells. Ref.7

Tissue specificity

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. Ref.1 Ref.5 Ref.7

Induction

Down-regulated in ovarian and endometrial cancers (EC). Decrease of 3.2-fold in endometrial cancer. Ref.5 Ref.6

Sequence similarities

Belongs to the peptidase S1B family.

Contains 1 IGFBP N-terminal domain.

Contains 1 Kazal-like domain.

Contains 1 PDZ (DHR) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P83110-1)

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.
Isoform 2 (identifier: P83110-2)

Also known as: Short; pS;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 453436Serine protease HTRA3
PRO_0000026949

Regions

Domain21 – 7757IGFBP N-terminal
Domain64 – 12865Kazal-like
Domain359 – 44486PDZ
Region175 – 340166Serine protease

Sites

Active site1911Charge relay system Potential
Active site2271Charge relay system Potential
Active site3051Charge relay system

Natural variations

Alternative sequence351 – 3577DWKKRFI → APSLAVH in isoform 2.
VSP_012570
Alternative sequence358 – 45396Missing in isoform 2.
VSP_012571

Experimental info

Mutagenesis3051S → A: Abolishes protease activity. Stabilizes the protein. Ref.8

Secondary structure

..................... 453
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) (pL) [UniParc].

Last modified June 20, 2002. Version 2.
Checksum: 3046FCDA1AB24FA6

FASTA45348,608
        10         20         30         40         50         60 
MQARALLLAA LAALALAREP PAAPCPARCD VSRCPSPRCP GGYVPDLCNC CLVCAASEGE 

        70         80         90        100        110        120 
PCGGPLDSPC GESLECVRGL CRCRWSHAVC GTDGHTYANV CALQAASRRA LQLSGTPVRQ 

       130        140        150        160        170        180 
LQKGACPLGL HQLSSPRYKF NFIADVVEKI APAVVHIELF LRHPLFGRNV PLSSGSGFIM 

       190        200        210        220        230        240 
SEAGLIITNA HVVSSNSAAP GRQQLKVQLQ NGDSYEATIK DIDKKSDIAT IKIHPKKKLP 

       250        260        270        280        290        300 
VLLLGHSADL RPGEFVVAIG SPFALQNTVT TGIVSTAQRE GRELGLRDSD MDYIQTDAII 

       310        320        330        340        350        360 
NYGNSGGPLV NLDGEVIGIN TLKVTAGISF AIPSDRITRF LTEFQDKQIK DWKKRFIGIR 

       370        380        390        400        410        420 
MRTITPSLVD ELKASNPDFP EVSSGIYVQE VAPNSPSQRG GIQDGDIIVK VNGRPLVDSS 

       430        440        450 
ELQEAVLTES PLLLEVRRGN DDLLFSIAPE VVM 

« Hide

Isoform 2 (Short) (pS) [UniParc].

Checksum: 8A62D2B9823BC420
Show »

FASTA35737,940

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_444272.1. NM_053044.3.
XP_005248097.1. XM_005248040.1.
UniGeneHs.479119.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2P3WX-ray1.70A/B354-453[»]
ProteinModelPortalP83110.
SMRP83110. Positions 25-125, 134-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125099. 1 interaction.
IntActP83110. 2 interactions.
MINTMINT-4786544.
STRING9606.ENSP00000303766.

Protein family/group databases

MEROPSS01.284.

PTM databases

PhosphoSiteP83110.

Polymorphism databases

DMDM21542412.

Proteomic databases

PaxDbP83110.
PRIDEP83110.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307358; ENSP00000303766; ENSG00000170801. [P83110-1]
ENST00000382512; ENSP00000371952; ENSG00000170801. [P83110-2]
GeneID94031.
KEGGhsa:94031.
UCSCuc003gkz.3. human. [P83110-2]
uc003gla.3. human. [P83110-1]

Organism-specific databases

CTD94031.
GeneCardsGC04P008191.
HGNCHGNC:30406. HTRA3.
HPAHPA021187.
MIM608785. gene.
neXtProtNX_P83110.
PharmGKBPA134908281.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0265.
HOGENOMHOG000223641.
HOVERGENHBG052044.
InParanoidP83110.
KOK08785.
OMATDGHTYA.
OrthoDBEOG7V1FR7.
PhylomeDBP83110.
TreeFamTF323480.

Gene expression databases

BgeeP83110.
CleanExHS_HTRA3.
GenevestigatorP83110.

Family and domain databases

Gene3D2.30.42.10. 1 hit.
InterProIPR009030. Growth_fac_rcpt_N_dom.
IPR000867. IGFBP-like.
IPR002350. Kazal_dom.
IPR001478. PDZ.
IPR001940. Peptidase_S1C.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF07648. Kazal_2. 1 hit.
PF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSPR00834. PROTEASES2C.
SMARTSM00121. IB. 1 hit.
SM00280. KAZAL. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS51323. IGFBP_N_2. 1 hit.
PS51465. KAZAL_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP83110.
GenomeRNAi94031.
NextBio78335.
PROP83110.
SOURCESearch...

Entry information

Entry nameHTRA3_HUMAN
AccessionPrimary (citable) accession number: P83110
Secondary accession number(s): Q7Z7A2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: June 20, 2002
Last modified: April 16, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM