PTRH2

Protein identityUniProt · HPA

UniProt accession

Q9Y3E5

Gene

PTRH2

Ensembl

ENSG00000141378

Chromosome

17

Canonical length

179 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

The protein encoded by this gene is a mitochondrial protein with two putative domains, an N-terminal mitochondrial localization sequence, and a UPF0099 domain. In vitro assays suggest that this protein possesses peptidyl-tRNA hydrolase activity, to release the peptidyl moiety from tRNA, thereby preventing the accumulation of dissociated peptidyl-tRNA that could reduce the efficiency of translation. This protein also plays a role regulating cell survival and death. It promotes survival as part of an integrin-signaling pathway for cells attached to the extracellular matrix (ECM), but also promotes apoptosis in cells that have lost their attachment to the ECM, a process called anoikos. After loss of cell attachment to the ECM, this protein is phosphorylated, is released from the mitochondria into the cytosol, and promotes caspase-independent apoptosis through interactions with transcriptional regulators. This gene has been implicated in the development and progression of tumors, and mutations in this gene have been associated with an infantile multisystem neurologic, endocrine, and pancreatic disease (INMEPD) characterized by intellectual disability, postnatal microcephaly, progressive cerebellar atrophy, hearing impairment, polyneuropathy, failure to thrive, and organ fibrosis with exocrine pancreas insufficiency (PMID: 25574476). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

Canonical amino-acid sequenceUniProt

179 residues, UniProt reviewed canonical sequence.

>Q9Y3E5|PTRH2
     1  MPSKSLVMEY LAHPSTLGLA VGVACGMCLG WSLRVCFGML PKSKTSKTHT DTESEASILG
    61  DSGEYKMILV VRNDLKMGKG KVAAQCSHAA VSAYKQIQRR NPEMLKQWEY CGQPKVVVKA
   121  PDEETLIALL AHAKMLGLTV SLIQDAGRTQ IAPGSQTVLG IGPGPADLID KVTGHLKLY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PTRH2 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

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

46 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PTRH2.

Disease | AllUniProt

Conditions PTRH2 is implicated in, by any mechanism.

• Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (IMNEPD1) MIM:616263

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 51 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1
• Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset
• Cerebellar ataxia
• Hearing impairment
• Global developmental delay

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)

1.7

gnomAD pLI

0

gnomAD missense Z

0.43

DepMap mean gene effect

-0.19

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• negative regulation of anoikis
• negative regulation of gene expression
• positive regulation of anoikis

Molecular functions

• peptidyl-tRNA hydrolase activity

Cellular components

• cytosol
• membrane
• mitochondrial outer membrane
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Peptidyl-tRNA hydrolase, PTH2
• Peptidyl-tRNA hydrolase II domain superfamily
• Peptidyl-tRNA hydrolase PTH2

KeywordsUniProt

• Apoptosis
• Hydrolase
• Isopeptide bond
• Membrane
• Mitochondrion
• Mitochondrion outer membrane
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of PTRH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TLE5