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Q92989 (CLP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Polyribonucleotide 5'-hydroxyl-kinase Clp1

EC=2.7.1.78
Alternative name(s):
Polyadenylation factor Clp1
Polynucleotide kinase Clp1
Pre-mRNA cleavage complex II protein Clp1
Gene names
Name:CLP1
Synonyms:HEAB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length425 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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 (Ref.10, Ref.11). Its role in tRNA splicing and maturation is required for cerebellar development (Ref.10, Ref.11). 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. Ref.7 Ref.8 Ref.10 Ref.11

Catalytic activity

ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA. Ref.7 Ref.8

ATP + 5'-dephospho-RNA = ADP + 5'-phospho-RNA. Ref.7 Ref.8

Cofactor

Magnesium, manganese or nickel. Ref.7

Subunit structure

Component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54 (Ref.10). 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. Ref.6 Ref.7 Ref.10

Subcellular location

Nucleus Ref.5 Ref.11.

Involvement in disease

Neurodegeneration with progressive brain atrophy 1 (NBA1): A neurological syndrome affecting both the central and peripheral nervous systems characterized by onset of slow, progressive, neurodegenerative features and/or static encephalopathy after 6 months of age. Clinical features include brain malformations and microcephaly, developmental delays, severe intellectual disabilities, absent or delayed speech and spontaneous epileptic seizures. Brain displays mild atrophy of the cerebellum, pons and corpus callosum together with progressive microcephaly. A progressive spinal motor neuron loss is observed, due to increased neural precursor cell susceptibility to apoptosis. The disease is caused by mutations affecting the gene represented in this entry. Neurodegeneration is due to defects in tRNA splicing (Ref.10, Ref.11). Ref.10 Ref.11

Sequence similarities

Belongs to the Clp1 family. Clp1 subfamily.

Ontologies

Keywords
   Biological processmRNA processing
tRNA processing
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Neurodegeneration
   LigandATP-binding
Magnesium
Manganese
Nickel
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Traceable author statement. Source: Reactome

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cerebellar cortex development

Inferred from mutant phenotype Ref.10Ref.11. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

mRNA 3'-end processing

Traceable author statement Ref.7. Source: UniProtKB

mRNA splicing, via spliceosome

Traceable author statement. Source: Reactome

siRNA loading onto RISC involved in RNA interference

Inferred from direct assay Ref.7. Source: UniProtKB

tRNA splicing, via endonucleolytic cleavage and ligation

Inferred from direct assay Ref.7. Source: UniProtKB

targeting of mRNA for destruction involved in RNA interference

Inferred from mutant phenotype Ref.7. Source: UniProtKB

termination of RNA polymerase II transcription

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentmRNA cleavage factor complex

Inferred from electronic annotation. Source: UniProtKB-HAMAP

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.11. Source: UniProtKB

tRNA-intron endonuclease complex

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionATP binding

Traceable author statement Ref.1. Source: UniProtKB

ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

ATP-dependent polyribonucleotide 5'-hydroxyl-kinase activity

Inferred from direct assay Ref.7. Source: UniProtKB

polydeoxyribonucleotide kinase activity

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92989-1)

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.
Isoform 2 (identifier: Q92989-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 425425Polyribonucleotide 5'-hydroxyl-kinase Clp1 HAMAP-Rule MF_03035
PRO_0000089863

Regions

Nucleotide binding124 – 1296ATP By similarity

Sites

Binding site221ATP By similarity
Binding site621ATP; via carbonyl oxygen By similarity

Natural variations

Alternative sequence139 – 20264Missing in isoform 2.
VSP_041164
Natural variant1401R → H in NBA1; decreased kinase activity, impaired formation of the tRNA splicing endonuclease complex and impaired ability to mediate tRNA splicing and maturation. Ref.10 Ref.11
VAR_070952

Experimental info

Mutagenesis127 – 1282KS → AA: Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-128. Ref.7 Ref.10
Mutagenesis1271K → A: Abrogates RNA kinase activity and tRNA splicing activity. Ref.7 Ref.10
Mutagenesis1511D → A: Abrogates complementation of tRNA splicing activity in yeast. Ref.7 Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 640AF4768994CFE6

FASTA42547,646
        10         20         30         40         50         60 
MGEEANDDKK PTTKFELERE TELRFEVEAS QSVQLELLTG MAEIFGTELT RNKKFTFDAG 

        70         80         90        100        110        120 
AKVAVFTWHG CSVQLSGRTE VAYVSKDTPM LLYLNTHTAL EQMRRQAEKE EERGPRVMVV 

       130        140        150        160        170        180 
GPTDVGKSTV CRLLLNYAVR LGRRPTYVEL DVGQGSVSIP GTMGALYIER PADVEEGFSI 

       190        200        210        220        230        240 
QAPLVYHFGS TTPGTNIKLY NKITSRLADV FNQRCEVNRR ASVSGCVINT CGWVKGSGYQ 

       250        260        270        280        290        300 
ALVHAASAFE VDVVVVLDQE RLYNELKRDL PHFVRTVLLP KSGGVVERSK DFRRECRDER 

       310        320        330        340        350        360 
IREYFYGFRG CFYPHAFNVK FSDVKIYKVG APTIPDSCLP LGMSQEDNQL KLVPVTPGRD 

       370        380        390        400        410        420 
MVHHLLSVST AEGTEENLSE TSVAGFIVVT SVDLEHQVFT VLSPAPRPLP KNFLLIMDIR 


FMDLK 

« Hide

Isoform 2 [UniParc].

Checksum: 661F193326BCB711
Show »

FASTA36140,696

References

« Hide 'large scale' references
[1]"AF10 is split by MLL and HEAB, a human homolog to a putative Caenorhabditis elegans ATP/GTP-binding protein in an invins(10;11)(p12;q23q12)."
Tanabe S., Bohlander S.K., Vignon C.V., Espinosa R. III, Zhao N., Strissel P.L., Zeleznik-Le N.J., Rowley J.D.
Blood 88:3535-3545(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Cerebellum and Placenta.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[5]"Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors."
de Vries H., Rueegsegger U., Huebner W., Friedlein A., Langen H., Keller W.
EMBO J. 19:5895-5904(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION AS A COMPONENT OF THE PRE-MRNA CLEAVAGE COMPLEX II, ASSOCIATION WITH THE PRE-MRNA CLEAVAGE COMPLEX I, SUBCELLULAR LOCATION.
[6]"Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3' end formation."
Paushkin S.V., Patel M., Furia B.S., Peltz S.W., Trotta C.R.
Cell 117:311-321(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH TSEN2; TSEN15; TSEN34 TSEN54, INTERACTION WITH CSTF2 AND SYMPK.
[7]"The human RNA kinase hClp1 is active on 3' transfer RNA exons and short interfering RNAs."
Weitzer S., Martinez J.
Nature 447:222-226(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, IDENTIFICATION IN A COMPLEX WITH TSEN2; TSEN15; TSEN34 TSEN54, MUTAGENESIS OF 127-LYS-SER-128.
[8]"Human RNA 5'-kinase (hClp1) can function as a tRNA splicing enzyme in vivo."
Ramirez A., Shuman S., Schwer B.
RNA 14:1737-1745(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF 127-LYS-SER-128 AND ASP-151.
[9]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function."
Baylor Hopkins Center for Mendelian Genomics
Karaca E., Weitzer S., Pehlivan D., Shiraishi H., Gogakos T., Hanada T., Jhangiani S.N., Wiszniewski W., Withers M., Campbell I.M., Erdin S., Isikay S., Franco L.M., Gonzaga-Jauregui C., Gambin T., Gelowani V., Hunter J.V., Yesil G. expand/collapse author list , Koparir E., Yilmaz S., Brown M., Briskin D., Hafner M., Morozov P., Farazi T.A., Bernreuther C., Glatzel M., Trattnig S., Friske J., Kronnerwetter C., Bainbridge M.N., Gezdirici A., Seven M., Muzny D.M., Boerwinkle E., Ozen M., Clausen T., Tuschl T., Yuksel A., Hess A., Gibbs R.A., Martinez J., Penninger J.M., Lupski J.R.
Cell 157:636-650(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NBA1 HIS-140, FUNCTION, IDENTIFICATION IN THE TRNA SPLICING ENDONUCLEASE COMPLEX, MUTAGENESIS OF LYS-127.
[11]"CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration."
Schaffer A.E., Eggens V.R., Caglayan A.O., Reuter M.S., Scott E., Coufal N.G., Silhavy J.L., Xue Y., Kayserili H., Yasuno K., Rosti R.O., Abdellateef M., Caglar C., Kasher P.R., Cazemier J.L., Weterman M.A., Cantagrel V., Cai N. expand/collapse author list , Zweier C., Altunoglu U., Satkin N.B., Aktar F., Tuysuz B., Yalcinkaya C., Caksen H., Bilguvar K., Fu X.D., Trotta C.R., Gabriel S., Reis A., Gunel M., Baas F., Gleeson J.G.
Cell 157:651-663(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NBA1 HIS-140, FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS44600.1. [Q92989-2]
CCDS7964.1. [Q92989-1]
RefSeqNP_001136069.1. NM_001142597.1. [Q92989-2]
NP_006822.1. NM_006831.2. [Q92989-1]
XP_006718488.1. XM_006718425.1. [Q92989-1]
UniGeneHs.523687.

3D structure databases

ProteinModelPortalQ92989.
SMRQ92989. Positions 14-423.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116174. 15 interactions.
IntActQ92989. 2 interactions.
MINTMINT-3049820.
STRING9606.ENSP00000304704.

PTM databases

PhosphoSiteQ92989.

Polymorphism databases

DMDM13431366.

Proteomic databases

MaxQBQ92989.
PaxDbQ92989.
PRIDEQ92989.

Protocols and materials databases

DNASU10978.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302731; ENSP00000304704; ENSG00000172409. [Q92989-2]
ENST00000525602; ENSP00000436066; ENSG00000172409. [Q92989-1]
ENST00000533682; ENSP00000434995; ENSG00000172409. [Q92989-1]
GeneID10978.
KEGGhsa:10978.
UCSCuc001nkw.3. human. [Q92989-1]
uc010rjw.2. human. [Q92989-2]

Organism-specific databases

CTD10978.
GeneCardsGC11P057425.
HGNCHGNC:16999. CLP1.
HPAHPA049957.
HPA057770.
MIM608757. gene.
neXtProtNX_Q92989.
PharmGKBPA162382477.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5623.
HOGENOMHOG000231935.
HOVERGENHBG000921.
InParanoidQ92989.
KOK14399.
PhylomeDBQ92989.
TreeFamTF105795.

Enzyme and pathway databases

ReactomeREACT_1788. Transcription.
REACT_71. Gene Expression.
REACT_78. Post-Elongation Processing of the Transcript.

Gene expression databases

ArrayExpressQ92989.
BgeeQ92989.
CleanExHS_CLP1.
GenevestigatorQ92989.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
HAMAPMF_03035. Clp1.
InterProIPR028606. Clp1.
IPR029007. MobB-typ_P-loop.
IPR027417. P-loop_NTPase.
IPR010655. Pre-mRNA_cleavage_cplxII_Clp1.
[Graphical view]
PfamPF06807. Clp1. 1 hit.
PF03205. MobB. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 3 hits.
ProtoNetSearch...

Other

GenomeRNAi10978.
NextBio41710.
PROQ92989.
SOURCESearch...

Entry information

Entry nameCLP1_HUMAN
AccessionPrimary (citable) accession number: Q92989
Secondary accession number(s): B2R7J6, B4DTI8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: February 1, 1997
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM