HTRA4

Protein identityUniProt · HPA

UniProt accession

P83105

Gene

HTRA4

Ensembl

ENSG00000169495

Chromosome

8

Canonical length

476 aa

Protein class

Enzymes, Predicted secreted proteins

Secretome location

Secreted in female reproductive system

OverviewNCBI Gene

This gene encodes a member of the HtrA family of proteases. The encoded protein contains a putative signal peptide, an insulin growth factor binding domain, a Kazal protease inhibitor domain, a conserved trypsin domain and a PDZ domain. Based on studies on other related family members, this enzyme may function as a secreted oligomeric chaperone protease to degrade misfolded secretory proteins. Other human HtrA proteins have been implicated in arthritis, tumor suppression, unfolded stress response, apoptosis, and aging. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

476 residues, UniProt reviewed canonical sequence.

>P83105|HTRA4
     1  MIRPQLRTAG LGRCLLPGLL LLLVPVLWAG AEKLHTQPSC PAVCQPTRCP ALPTCALGTT
    61  PVFDLCRCCR VCPAAEREVC GGAQGQPCAP GLQCLQPLRP GFPSTCGCPT LGGAVCGSDR
   121  RTYPSMCALR AENRAARRLG KVPAVPVQWG NCGDTGTRSA GPLRRNYNFI AAVVEKVAPS
   181  VVHVQLWGRL LHGSRLVPVY SGSGFIVSED GLIITNAHVV RNQQWIEVVL QNGARYEAVV
   241  KDIDLKLDLA VIKIESNAEL PVLMLGRSSD LRAGEFVVAL GSPFSLQNTA TAGIVSTKQR
   301  GGKELGMKDS DMDYVQIDAT INYGNSGGPL VNLDGDVIGV NSLRVTDGIS FAIPSDRVRQ
   361  FLAEYHEHQM KGKAFSNKKY LGLQMLSLTV PLSEELKMHY PDFPDVSSGV YVCKVVEGTA
   421  AQSSGLRDHD VIVNINGKPI TTTTDVVKAL DSDSLSMAVL RGKDNLLLTV IPETIN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HTRA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

63 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.34

gnomAD pLI

0

gnomAD missense Z

0.97

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of transforming growth factor beta receptor signaling pathway
• positive regulation of apoptotic process
• programmed cell death
• proteolysis

Molecular functions

• endopeptidase activity
• identical protein binding
• serine-type endopeptidase activity

Cellular components

• extracellular region

Protein domainsUniProt · Pfam · InterPro

• Insulin-like growth factor-binding protein, IGFBP
• PDZ domain
• Peptidase S1C
• Kazal domain
• Peptidase S1, PA clan
• Growth factor receptor cysteine-rich domain superfamily
• PDZ superfamily
• Kazal domain superfamily
• Insulin-like growth factor binding protein
• Kazal-type serine protease inhibitor domain
• PDZ domain
• Trypsin-like peptidase domain

KeywordsUniProt

• Disulfide bond
• Hydrolase
• Protease
• Secreted
• Serine protease
• Signal

InteractionsUniProt · HPA

Protein binding partners of HTRA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TCP1
• XIAP