HTRA1

Protein identityUniProt · HPA

UniProt accession

Q92743

Gene

HTRA1

Ensembl

ENSG00000166033

Chromosome

10

Canonical length

480 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Plasma membrane

Secretome location

Secreted to blood

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

480 residues, UniProt reviewed canonical sequence.

>Q92743|HTRA1
     1  MQIPRAALLP LLLLLLAAPA SAQLSRAGRS APLAAGCPDR CEPARCPPQP EHCEGGRARD
    61  ACGCCEVCGA PEGAACGLQE GPCGEGLQCV VPFGVPASAT VRRRAQAGLC VCASSEPVCG
   121  SDANTYANLC QLRAASRRSE RLHRPPVIVL QRGACGQGQE DPNSLRHKYN FIADVVEKIA
   181  PAVVHIELFR KLPFSKREVP VASGSGFIVS EDGLIVTNAH VVTNKHRVKV ELKNGATYEA
   241  KIKDVDEKAD IALIKIDHQG KLPVLLLGRS SELRPGEFVV AIGSPFSLQN TVTTGIVSTT
   301  QRGGKELGLR NSDMDYIQTD AIINYGNSGG PLVNLDGEVI GINTLKVTAG ISFAIPSDKI
   361  KKFLTESHDR QAKGKAITKK KYIGIRMMSL TSSKAKELKD RHRDFPDVIS GAYIIEVIPD
   421  TPAEAGGLKE NDVIISINGQ SVVSANDVSD VIKRESTLNM VVRRGNEDIM ITVIPEEIDP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HTRA1 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

751 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HTRA1.

Disease | AllUniProt

Conditions HTRA1 is implicated in, by any mechanism.

• Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 2 (CARASIL2) MIM:600142
• Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 2 (CADASIL2) MIM:616779

Disease | GeneticClinVar

40 pathogenic / likely-pathogenic of 377 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2
• CARASIL syndrome
• HTRA1-related cerebral small vessel disease
• HTRA1-related disorder
• HTRA1-related autosomal dominant cerebral small vessel disease

ReferencesPubMed · IEDB

Publications for HTRA1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.75

gnomAD pLI

0

gnomAD missense Z

1.05

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chorionic trophoblast cell differentiation
• negative regulation of BMP signaling pathway
• negative regulation of transforming growth factor beta receptor signaling pathway
• placenta development
• positive regulation of apoptotic process
• programmed cell death
• proteolysis

Molecular functions

• growth factor binding
• identical protein binding
• molecular function activator activity
• serine-type endopeptidase activity
• serine-type peptidase activity

Cellular components

• cytosol
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• plasma membrane

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
• PDZ domain 6
• Insulin-like growth factor binding protein
• Kazal-type serine protease inhibitor domain
• Trypsin-like peptidase domain
• PDZ domain

KeywordsUniProt

• Age-related macular degeneration
• Cell membrane
• Cytoplasm
• Disulfide bond
• Growth factor binding
• Hydrolase
• Membrane
• Protease
• Secreted
• Serine protease
• Signal

InteractionsUniProt · HPA

Protein binding partners of HTRA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GDF5
• TGFB1
• TGFB2
• BMP4