Human Gene PARN (ENST00000341484.11) from GENCODE V44
  Description: Homo sapiens poly(A)-specific ribonuclease (PARN), transcript variant 2, mRNA. (from RefSeq NM_001134477)
RefSeq Summary (NM_001134477): 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].
Gencode Transcript: ENST00000341484.11
Gencode Gene: ENSG00000140694.18
Transcript (Including UTRs)
   Position: hg38 chr16:14,436,605-14,630,276 Size: 193,672 Total Exon Count: 24 Strand: -
Coding Region
   Position: hg38 chr16:14,436,717-14,627,330 Size: 190,614 Coding Exon Count: 21 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:14,436,605-14,630,276)mRNA (may differ from genome)Protein (578 aa)
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-  Comments and Description Text from UniProtKB
  ID: PARN_HUMAN
DESCRIPTION: RecName: Full=Poly(A)-specific ribonuclease PARN; EC=3.1.13.4; AltName: Full=Deadenylating nuclease; AltName: Full=Deadenylation nuclease; AltName: Full=Polyadenylate-specific ribonuclease;
FUNCTION: 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization.
CATALYTIC ACTIVITY: Exonucleolytic cleavage of poly(A) to 5'-AMP.
COFACTOR: Divalent metal cations. Mg(2+) is the most probable.
SUBUNIT: Homodimer. Interacts with KHSRP and CELF1/CUGBP1. Found in a mRNA decay complex with RENT1, RENT2 and RENT3B. Interacts with ZC3HAV1 in an RNA-independent manner.
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus, nucleolus. Note=Some nuclear fraction is nucleolar.
TISSUE SPECIFICITY: Ubiquitous.
PTM: Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation after genotoxic stress.
SIMILARITY: Belongs to the CAF1 family.
SIMILARITY: Contains 1 R3H domain.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PARN
Diseases sorted by gene-association score: pulmonary fibrosis and/or bone marrow failure, telomere-related, 4* (1331), dyskeratosis congenita, autosomal recessive 6* (1229), parn-related dyskeratosis congenita* (500), dyskeratosis congenita* (460), pulmonary fibrosis (22), dyskeratosis congenita autosomal recessive (11), pulmonary fibrosis, idiopathic* (11), angelman syndrome (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.77 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 467.95 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -78.40251-0.312 Picture PostScript Text
3' UTR -28.30112-0.253 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012677 - Nucleotide-bd_a/b_plait
IPR014789 - PolyA-riboNase_RNA_binding
IPR001374 - R3H_ss-bd
IPR006941 - RNase_CAF1
IPR012337 - RNaseH-like_dom

Pfam Domains:
PF04857 - CAF1 family ribonuclease
PF01424 - R3H domain
PF08675 - RNA binding domain

Protein Data Bank (PDB) 3-D Structure
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2A1R - X-ray MuPIT 2A1S - X-ray MuPIT 3CTR - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O95453
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003676 nucleic acid binding
GO:0003723 RNA binding
GO:0003730 mRNA 3'-UTR binding
GO:0004518 nuclease activity
GO:0004527 exonuclease activity
GO:0004535 poly(A)-specific ribonuclease activity
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0019901 protein kinase binding
GO:0043169 cation binding
GO:0046872 metal ion binding
GO:0070034 telomerase RNA binding

Biological Process:
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening
GO:0006402 mRNA catabolic process
GO:0007292 female gamete generation
GO:0009451 RNA modification
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0043488 regulation of mRNA stability
GO:0051973 positive regulation of telomerase activity
GO:0090503 RNA phosphodiester bond hydrolysis, exonucleolytic
GO:0090669 telomerase RNA stabilization
GO:1904872 regulation of telomerase RNA localization to Cajal body

Cellular Component:
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  BC044763 - Homo sapiens poly(A)-specific ribonuclease (deadenylation nuclease), mRNA (cDNA clone IMAGE:4826198).
BC050029 - Homo sapiens poly(A)-specific ribonuclease (deadenylation nuclease), mRNA (cDNA clone MGC:41881 IMAGE:4825218), complete cds.
AK023866 - Homo sapiens cDNA FLJ13804 fis, clone THYRO1000197, highly similar to Poly(A)-specific ribonuclease PARN (EC 3.1.13.4).
AJ005698 - Homo sapiens mRNA for poly(A)-specific ribonuclease.
AK301648 - Homo sapiens cDNA FLJ57636 complete cds, highly similar to Poly(A)-specific ribonuclease PARN (EC 3.1.13.4).
AK293189 - Homo sapiens cDNA FLJ58764 complete cds, highly similar to Poly(A)-specific ribonuclease PARN (EC3.1.13.4).
AK299653 - Homo sapiens cDNA FLJ58618 complete cds, highly similar to Poly(A)-specific ribonuclease PARN (EC 3.1.13.4).
JF432357 - Synthetic construct Homo sapiens clone IMAGE:100073549 poly(A)-specific ribonuclease (deadenylation nuclease) (PARN) gene, encodes complete protein.
KJ891752 - Synthetic construct Homo sapiens clone ccsbBroadEn_01146 PARN gene, encodes complete protein.
AK315020 - Homo sapiens cDNA, FLJ95954, Homo sapiens poly(A)-specific ribonuclease (deadenylation nuclease)(PARN), mRNA.
JD283200 - Sequence 264224 from Patent EP1572962.
CU690630 - Synthetic construct Homo sapiens gateway clone IMAGE:100020940 5' read PARN mRNA.
AK303348 - Homo sapiens cDNA FLJ57461 complete cds, highly similar to Poly(A)-specific ribonuclease PARN (EC 3.1.13.4).

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03018 - RNA degradation

Reactome (by CSHL, EBI, and GO)

Protein O95453 (Reactome details) participates in the following event(s):

R-HSA-450422 KSRP recruits RNA degradation activities
R-HSA-429992 PARN deadenylates mRNA
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-429947 Deadenylation of mRNA
R-HSA-8953854 Metabolism of RNA
R-HSA-429914 Deadenylation-dependent mRNA decay

-  Other Names for This Gene
  Alternate Gene Symbols: B2RCB3, B4DDG8, B4DWR4, B4E1H6, DAN, ENST00000341484.1, ENST00000341484.10, ENST00000341484.2, ENST00000341484.3, ENST00000341484.4, ENST00000341484.5, ENST00000341484.6, ENST00000341484.7, ENST00000341484.8, ENST00000341484.9, NM_001134477, O95453, PARN_HUMAN, uc010uzc.1, uc010uzc.2, uc010uzc.3
UCSC ID: ENST00000341484.11
RefSeq Accession: NM_001134477
Protein: O95453 (aka PARN_HUMAN)
CCDS: CCDS45420.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PARN:
dkc (Dyskeratosis Congenita and Related Telomere Biology Disorders)
pf (Pulmonary Fibrosis Predisposition Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.