Human Gene CLP1 (uc001nkw.3) Description and Page Index
  Description: Homo sapiens cleavage and polyadenylation factor I subunit 1 (CLP1), transcript variant 1, mRNA.
RefSeq Summary (NM_006831): This gene encodes a member of the Clp1 family. The encoded protein is a multifunctional kinase which is a component of the tRNA splicing endonuclease complex and a component of the pre-mRNA cleavage complex II. This protein is implicated in tRNA, mRNA, and siRNA maturation. Mutations in this gene are associated with pontocerebellar hypoplasia type 10 (PCH10). Alternatively splice transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014].
Transcript (Including UTRs)
   Position: hg19 chr11:57,425,216-57,429,337 Size: 4,122 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg19 chr11:57,426,949-57,428,908 Size: 1,960 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:57,425,216-57,429,337)mRNA (may differ from genome)Protein (425 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Polyribonucleotide 5'-hydroxyl-kinase Clp1; EC=; AltName: Full=Polynucleotide kinase Clp1; AltName: Full=Pre-mRNA cleavage complex II protein Clp1;
FUNCTION: Polynucleotide kinase that can phosphorylate the 5'- hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Appears to have roles in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex. Phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA. Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA- induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing.
CATALYTIC ACTIVITY: ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.
CATALYTIC ACTIVITY: ATP + 5'-dephospho-RNA = ADP + 5'-phospho-RNA.
COFACTOR: Magnesium, manganese or nickel.
SUBUNIT: Component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54. Component of pre-mRNA cleavage complex II (CF-II). Also associates with numerous components of the pre-mRNA cleavage complex I (CF- I/CFIm), including NUDT21, CPSF2, CPSF3, CPSF6 and CPSF7. Interacts with CSTF2 and SYMPK.
SIMILARITY: Belongs to the Clp1 family. Clp1 subfamily.

-  MalaCards Disease Associations
  MalaCards Gene Search: CLP1
Diseases sorted by gene-association score: pontocerebellar hypoplasia, type 10* (1269), anus disease (16), pontocerebellar hypoplasia (14), rectal disease (9)
* = Manually curated disease association

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

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.33 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 157.71 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -44.60139-0.321 Picture PostScript Text
3' UTR -109.08429-0.254 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
IPR010655 - Pre-mRNA_cleavage_cplxII_Clp1

Pfam Domains:
PF06807 - Pre-mRNA cleavage complex II protein Clp1
PF16573 - N-terminal beta-sandwich domain of polyadenylation factor
PF16575 - mRNA cleavage and polyadenylation factor CLP1 P-loop

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases

ModBase Predicted Comparative 3D Structure on Q92989
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0046404 ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity
GO:0051733 polydeoxyribonucleotide kinase activity
GO:0051736 ATP-dependent polyribonucleotide 5'-hydroxyl-kinase activity

Biological Process:
GO:0000398 mRNA splicing, via spliceosome
GO:0006369 termination of RNA polymerase II transcription
GO:0006378 mRNA polyadenylation
GO:0006379 mRNA cleavage
GO:0006388 tRNA splicing, via endonucleolytic cleavage and ligation
GO:0006397 mRNA processing
GO:0008033 tRNA processing
GO:0016310 phosphorylation
GO:0021695 cerebellar cortex development
GO:0030423 targeting of mRNA for destruction involved in RNA interference
GO:0031124 mRNA 3'-end processing
GO:0035087 siRNA loading onto RISC involved in RNA interference

Cellular Component:
GO:0000214 tRNA-intron endonuclease complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0005849 mRNA cleavage factor complex

-  Descriptions from all associated GenBank mRNAs
  U73524 - Human putative ATP/GTP-binding protein (HEAB) mRNA, complete cds.
AK313007 - Homo sapiens cDNA, FLJ93472, Homo sapiens ATP/GTP-binding protein (HEAB), mRNA.
AK300232 - Homo sapiens cDNA FLJ51305 complete cds, highly similar to Pre-mRNA cleavage complex II protein Clp1.
BC000446 - Homo sapiens CLP1, cleavage and polyadenylation factor I subunit, homolog (S. cerevisiae), mRNA (cDNA clone MGC:8442 IMAGE:2821321), complete cds.
JD226892 - Sequence 207916 from Patent EP1572962.
JD337142 - Sequence 318166 from Patent EP1572962.
KJ893189 - Synthetic construct Homo sapiens clone ccsbBroadEn_02583 CLP1 gene, encodes complete protein.
KJ893190 - Synthetic construct Homo sapiens clone ccsbBroadEn_02584 CLP1 gene, encodes complete protein.
JD331928 - Sequence 312952 from Patent EP1572962.
JD365730 - Sequence 346754 from Patent EP1572962.
JD474534 - Sequence 455558 from Patent EP1572962.
JD322401 - Sequence 303425 from Patent EP1572962.
JD265327 - Sequence 246351 from Patent EP1572962.
JD298738 - Sequence 279762 from Patent EP1572962.
JD551598 - Sequence 532622 from Patent EP1572962.
JD556904 - Sequence 537928 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q92989 (Reactome details) participates in the following event(s):

R-HSA-72231 Cleavage and Polyadenylation
R-HSA-77591 Binding of Cleavage factors and Poly(A)Polymerase to the CstF:CPSF:Pre-mRNA Complex
R-HSA-72180 Cleavage of mRNA at the 3'-end
R-HSA-77592 Cleavage of Intronless Pre-mRNA at 3'-end
R-HSA-77593 Cleavage and polyadenylation of Intronless Pre-mRNA
R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex
R-HSA-5696813 TSEN complex cleaves the intron from pre-tRNA
R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage
R-HSA-72139 Formation of the active Spliceosomal C (B*) complex
R-HSA-8849157 TREX complex binds spliced, capped mRNA:CBC:EJC cotranscriptionally
R-HSA-156661 Formation of Exon Junction Complex
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-77595 Processing of Intronless Pre-mRNAs
R-HSA-72187 mRNA 3'-end processing
R-HSA-109688 Cleavage of Growing Transcript in the Termination Region
R-HSA-72172 mRNA Splicing
R-HSA-75067 Processing of Capped Intronless Pre-mRNA
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73856 RNA Polymerase II Transcription Termination
R-HSA-6784531 tRNA processing in the nucleus
R-HSA-8953854 Metabolism of RNA
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-72306 tRNA processing
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: B2R7J6, B4DTI8, CLP1_HUMAN, HEAB, NM_006831, NP_006822, Q92989
UCSC ID: uc001nkw.3
RefSeq Accession: NM_006831
Protein: Q92989 (aka CLP1_HUMAN)
CCDS: CCDS7964.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_006831.2
exon count: 3CDS single in 3' UTR: no RNA size: 1864
ORF size: 1278CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2756.00frame shift in genome: no % Coverage: 99.03
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

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