Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Polyribonucleotide 5'-hydroxyl-kinase Clp1

Gene

CLP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Plays a key role 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 (PubMed:24766809, PubMed:24766810). Its role in tRNA splicing and maturation is required for cerebellar development (PubMed:24766809, PubMed:24766810). 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.4 Publications

Catalytic activityi

ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.UniRule annotation
ATP + 5'-dephospho-RNA = ADP + 5'-phospho-RNA.UniRule annotation

Cofactori

Mg2+UniRule annotation1 Publication, Mn2+UniRule annotation1 Publication, Ni2+UniRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei22ATPUniRule annotation1
Binding sitei62ATP; via carbonyl oxygenUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi124 – 129ATPUniRule annotation6

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processmRNA processing, tRNA processing
LigandATP-binding, Magnesium, Manganese, Nickel, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-109688 Cleavage of Growing Transcript in the Termination Region
R-HSA-6784531 tRNA processing in the nucleus
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-72187 mRNA 3'-end processing
R-HSA-77595 Processing of Intronless Pre-mRNAs

Names & Taxonomyi

Protein namesi
Recommended name:
Polyribonucleotide 5'-hydroxyl-kinase Clp1UniRule annotation (EC:2.7.1.78UniRule annotation)
Alternative name(s):
Polyadenylation factor Clp1UniRule annotation
Polynucleotide kinase Clp1UniRule annotation
Pre-mRNA cleavage complex II protein Clp1UniRule annotation
Gene namesi
Name:CLP1UniRule annotation
Synonyms:HEAB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000172409.5
HGNCiHGNC:16999 CLP1
MIMi608757 gene
neXtProtiNX_Q92989

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Pontocerebellar hypoplasia 10 (PCH10)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. Neurodegeneration is due to defects in tRNA splicing (PubMed:24766809, PubMed:24766810).2 Publications
Disease descriptionA form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH10 features include cortical dysgenesis marked by a simplified gyral pattern, cortical atrophy, mild or focal cerebellar vermian volume loss, delayed myelination, progressive microcephaly, global growth and developmental delays, severe intellectual disabilities, and seizures refractory to treatment.
See also OMIM:615803
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070952140R → H in PCH10; decreases kinase activity, impairs formation of the tRNA splicing endonuclease complex and impairs ability to mediate tRNA splicing and maturation. 2 PublicationsCorresponds to variant dbSNP:rs587777616EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi127 – 128KS → AA: Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-128. 2 Publications2
Mutagenesisi127K → A: Abrogates RNA kinase activity and tRNA splicing activity. 1 Publication1
Mutagenesisi151D → A: Abrogates complementation of tRNA splicing activity in yeast. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi10978
MalaCardsiCLP1
MIMi615803 phenotype
OpenTargetsiENSG00000172409
Orphaneti411493 Pontocerebellar hypoplasia type 10
PharmGKBiPA162382477

Polymorphism and mutation databases

BioMutaiCLP1
DMDMi13431366

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000898631 – 425Polyribonucleotide 5'-hydroxyl-kinase Clp1Add BLAST425

Proteomic databases

EPDiQ92989
MaxQBiQ92989
PaxDbiQ92989
PeptideAtlasiQ92989
PRIDEiQ92989
ProteomicsDBi75650
75651 [Q92989-2]

PTM databases

iPTMnetiQ92989
PhosphoSitePlusiQ92989

Expressioni

Gene expression databases

BgeeiENSG00000172409 Expressed in 212 organ(s), highest expression level in secondary oocyte
CleanExiHS_CLP1
ExpressionAtlasiQ92989 baseline and differential
GenevisibleiQ92989 HS

Organism-specific databases

HPAiHPA057770

Interactioni

Subunit structurei

Component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54 (PubMed:24766809). 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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TSEN54Q7Z6J94EBI-2559831,EBI-2559824

Protein-protein interaction databases

BioGridi116174, 23 interactors
CORUMiQ92989
IntActiQ92989, 13 interactors
MINTiQ92989
STRINGi9606.ENSP00000434995

Structurei

3D structure databases

ProteinModelPortaliQ92989
SMRiQ92989
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Clp1 family. Clp1 subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG2749 Eukaryota
COG5623 LUCA
GeneTreeiENSGT00390000000344
HOGENOMiHOG000231935
HOVERGENiHBG000921
KOiK14399
PhylomeDBiQ92989
TreeFamiTF105795

Family and domain databases

Gene3Di2.60.120.1030, 1 hit
3.30.70.2410, 1 hit
HAMAPiMF_03035 Clp1, 1 hit
InterProiView protein in InterPro
IPR028606 Clp1
IPR010655 Clp1_C
IPR038238 Clp1_C_sf
IPR032324 Clp1_N
IPR038239 Clp1_N_sf
IPR032319 CLP1_P
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF06807 Clp1, 1 hit
PF16573 CLP1_N, 1 hit
PF16575 CLP1_P, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q92989-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGEEANDDKK PTTKFELERE TELRFEVEAS QSVQLELLTG MAEIFGTELT
60 70 80 90 100
RNKKFTFDAG AKVAVFTWHG CSVQLSGRTE VAYVSKDTPM LLYLNTHTAL
110 120 130 140 150
EQMRRQAEKE EERGPRVMVV GPTDVGKSTV CRLLLNYAVR LGRRPTYVEL
160 170 180 190 200
DVGQGSVSIP GTMGALYIER PADVEEGFSI QAPLVYHFGS TTPGTNIKLY
210 220 230 240 250
NKITSRLADV FNQRCEVNRR ASVSGCVINT CGWVKGSGYQ ALVHAASAFE
260 270 280 290 300
VDVVVVLDQE RLYNELKRDL PHFVRTVLLP KSGGVVERSK DFRRECRDER
310 320 330 340 350
IREYFYGFRG CFYPHAFNVK FSDVKIYKVG APTIPDSCLP LGMSQEDNQL
360 370 380 390 400
KLVPVTPGRD MVHHLLSVST AEGTEENLSE TSVAGFIVVT SVDLEHQVFT
410 420
VLSPAPRPLP KNFLLIMDIR FMDLK
Length:425
Mass (Da):47,646
Last modified:February 1, 1997 - v1
Checksum:i640AF4768994CFE6
GO
Isoform 2 (identifier: Q92989-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     139-202: Missing.

Show »
Length:361
Mass (Da):40,696
Checksum:i661F193326BCB711
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PL17E9PL17_HUMAN
Polyribonucleotide 5'-hydroxyl-kina...
CLP1
436Annotation score:
E9PJM4E9PJM4_HUMAN
Polyribonucleotide 5'-hydroxyl-kina...
CLP1
132Annotation score:
E9PKV5E9PKV5_HUMAN
Polyribonucleotide 5'-hydroxyl-kina...
CLP1
92Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070952140R → H in PCH10; decreases kinase activity, impairs formation of the tRNA splicing endonuclease complex and impairs ability to mediate tRNA splicing and maturation. 2 PublicationsCorresponds to variant dbSNP:rs587777616EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041164139 – 202Missing in isoform 2. 1 PublicationAdd BLAST64

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73524 mRNA Translation: AAC50780.1
AK300232 mRNA Translation: BAG62000.1
AK313007 mRNA Translation: BAG35843.1
CH471076 Genomic DNA Translation: EAW73770.1
BC000446 mRNA Translation: AAH00446.1
CCDSiCCDS44600.1 [Q92989-2]
CCDS7964.1 [Q92989-1]
RefSeqiNP_001136069.1, NM_001142597.1 [Q92989-2]
NP_006822.1, NM_006831.2 [Q92989-1]
UniGeneiHs.523687

Genome annotation databases

EnsembliENST00000302731; ENSP00000304704; ENSG00000172409 [Q92989-2]
ENST00000525602; ENSP00000436066; ENSG00000172409 [Q92989-1]
ENST00000533682; ENSP00000434995; ENSG00000172409 [Q92989-1]
GeneIDi10978
KEGGihsa:10978
UCSCiuc001nkw.4 human [Q92989-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73524 mRNA Translation: AAC50780.1
AK300232 mRNA Translation: BAG62000.1
AK313007 mRNA Translation: BAG35843.1
CH471076 Genomic DNA Translation: EAW73770.1
BC000446 mRNA Translation: AAH00446.1
CCDSiCCDS44600.1 [Q92989-2]
CCDS7964.1 [Q92989-1]
RefSeqiNP_001136069.1, NM_001142597.1 [Q92989-2]
NP_006822.1, NM_006831.2 [Q92989-1]
UniGeneiHs.523687

3D structure databases

ProteinModelPortaliQ92989
SMRiQ92989
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116174, 23 interactors
CORUMiQ92989
IntActiQ92989, 13 interactors
MINTiQ92989
STRINGi9606.ENSP00000434995

PTM databases

iPTMnetiQ92989
PhosphoSitePlusiQ92989

Polymorphism and mutation databases

BioMutaiCLP1
DMDMi13431366

Proteomic databases

EPDiQ92989
MaxQBiQ92989
PaxDbiQ92989
PeptideAtlasiQ92989
PRIDEiQ92989
ProteomicsDBi75650
75651 [Q92989-2]

Protocols and materials databases

DNASUi10978
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302731; ENSP00000304704; ENSG00000172409 [Q92989-2]
ENST00000525602; ENSP00000436066; ENSG00000172409 [Q92989-1]
ENST00000533682; ENSP00000434995; ENSG00000172409 [Q92989-1]
GeneIDi10978
KEGGihsa:10978
UCSCiuc001nkw.4 human [Q92989-1]

Organism-specific databases

CTDi10978
DisGeNETi10978
EuPathDBiHostDB:ENSG00000172409.5
GeneCardsiCLP1
HGNCiHGNC:16999 CLP1
HPAiHPA057770
MalaCardsiCLP1
MIMi608757 gene
615803 phenotype
neXtProtiNX_Q92989
OpenTargetsiENSG00000172409
Orphaneti411493 Pontocerebellar hypoplasia type 10
PharmGKBiPA162382477
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2749 Eukaryota
COG5623 LUCA
GeneTreeiENSGT00390000000344
HOGENOMiHOG000231935
HOVERGENiHBG000921
KOiK14399
PhylomeDBiQ92989
TreeFamiTF105795

Enzyme and pathway databases

ReactomeiR-HSA-109688 Cleavage of Growing Transcript in the Termination Region
R-HSA-6784531 tRNA processing in the nucleus
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-72187 mRNA 3'-end processing
R-HSA-77595 Processing of Intronless Pre-mRNAs

Miscellaneous databases

GenomeRNAii10978
PROiPR:Q92989
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172409 Expressed in 212 organ(s), highest expression level in secondary oocyte
CleanExiHS_CLP1
ExpressionAtlasiQ92989 baseline and differential
GenevisibleiQ92989 HS

Family and domain databases

Gene3Di2.60.120.1030, 1 hit
3.30.70.2410, 1 hit
HAMAPiMF_03035 Clp1, 1 hit
InterProiView protein in InterPro
IPR028606 Clp1
IPR010655 Clp1_C
IPR038238 Clp1_C_sf
IPR032324 Clp1_N
IPR038239 Clp1_N_sf
IPR032319 CLP1_P
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF06807 Clp1, 1 hit
PF16573 CLP1_N, 1 hit
PF16575 CLP1_P, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCLP1_HUMAN
AccessioniPrimary (citable) accession number: Q92989
Secondary accession number(s): B2R7J6, B4DTI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: February 1, 1997
Last modified: November 7, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again