PARN

Protein identityUniProt · HPA

UniProt accession

O95453

Gene

PARN

Ensembl

ENSG00000140694

Chromosome

16

Canonical length

639 aa

Protein class

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

Subcellular location

Nuclear speckles

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a 3'-exoribonuclease, with similarity to the RNase D family of 3'-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Canonical amino-acid sequenceUniProt

639 residues, UniProt reviewed canonical sequence.

>O95453|PARN
     1  MEIIRSNFKS NLHKVYQAIE EADFFAIDGE FSGISDGPSV SALTNGFDTP EERYQKLKKH
    61  SMDFLLFQFG LCTFKYDYTD SKYITKSFNF YVFPKPFNRS SPDVKFVCQS SSIDFLASQG
   121  FDFNKVFRNG IPYLNQEEER QLREQYDEKR SQANGAGALS YVSPNTSKCP VTIPEDQKKF
   181  IDQVVEKIED LLQSEENKNL DLEPCTGFQR KLIYQTLSWK YPKGIHVETL ETEKKERYIV
   241  ISKVDEEERK RREQQKHAKE QEELNDAVGF SRVIHAIANS GKLVIGHNML LDVMHTVHQF
   301  YCPLPADLSE FKEMTTCVFP RLLDTKLMAS TQPFKDIINN TSLAELEKRL KETPFNPPKV
   361  ESAEGFPSYD TASEQLHEAG YDAYITGLCF ISMANYLGSF LSPPKIHVSA RSKLIEPFFN
   421  KLFLMRVMDI PYLNLEGPDL QPKRDHVLHV TFPKEWKTSD LYQLFSAFGN IQISWIDDTS
   481  AFVSLSQPEQ VKIAVNTSKY AESYRIQTYA EYMGRKQEEK QIKRKWTEDS WKEADSKRLN
   541  PQCIPYTLQN HYYRNNSFTA PSTVGKRNLS PSQEEAGLED GVSGEISDTE LEQTDSCAEP
   601  LSEGRKKAKK LKRMKKELSP AGSISKNSPA TLFEVPDTW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PARN 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

23 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PARN.

Disease | AllUniProt

Conditions PARN is implicated in, by any mechanism.

• Dyskeratosis congenita, autosomal recessive, 6 (DKCB6) MIM:616353
• Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 4 (PFBMFT4) MIM:616371

Disease | GeneticClinVar

86 pathogenic / likely-pathogenic of 977 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4
• Dyskeratosis congenita, autosomal recessive 6
• Pulmonary fibrosis
• Familial Interstitial Pneumonia
• Dyskeratosis congenita

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)

0.52

gnomAD pLI

0

gnomAD missense Z

0.79

DepMap mean gene effect

-0.24

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

• box H/ACA sno(s)RNA 3'-end processing
• female gamete generation
• lncRNA processing
• miRNA catabolic process
• nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
• nuclear-transcribed mRNA poly(A) tail shortening
• poly(A)-dependent snoRNA 3'-end processing
• positive regulation of telomere maintenance via telomerase
• priRNA 3'-end processing
• regulation of telomerase RNA localization to Cajal body
• RNA modification
• siRNA 3'-end processing
• telomerase RNA stabilization

Molecular functions

• 3'-5'-RNA exonuclease activity
• cation binding
• metal ion binding
• mRNA 3'-UTR binding
• nuclease activity
• poly(A)-specific ribonuclease activity
• protein kinase binding
• RNA binding
• telomerase RNA binding

Cellular components

• cytoplasm
• cytosol
• glutamatergic synapse
• nuclear speck
• nucleolus
• nucleus
• postsynapse

Protein domainsUniProt · Pfam · InterPro

• R3H domain
• Ribonuclease CAF1
• Ribonuclease H-like superfamily
• Nucleotide-binding alpha-beta plait domain superfamily
• RNA-binding domain superfamily
• Ribonuclease H superfamily
• R3H domain superfamily
• CAF1 family poly(A)-specific ribonucleases
• CAF1 family ribonuclease
• Poly(A)-specific ribonuclease, RNA-binding
• PARN, R3H domain
• RNA binding domain

KeywordsUniProt

• Acetylation
• Cytoplasm
• Dyskeratosis congenita
• Exonuclease
• Hydrolase
• Magnesium
• Metal-binding
• Nonsense-mediated mRNA decay
• Nuclease
• Nucleus
• Phosphoprotein
• RNA-binding

InteractionsUniProt · HPA

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

• DHX36
• KHSRP
• ZC3HAV1
• CELF1
• NCBP1
• BYSL