Q92989 (CLP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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. Ref.7 Ref.8
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. 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
Subcellular location	Nucleus Ref.5.
Sequence similarities	Belongs to the Clp1 family. Clp1 subfamily.

Ontologies

Keywords
Biological process	mRNA processing tRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Manganese Nickel Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome tRNA-intron endonuclease complex Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ATP binding Traceable author statement Ref.1. Source: UniProtKB ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity Inferred from electronic annotation. Source: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 425	425	Polyribonucleotide 5'-hydroxyl-kinase Clp1 HAMAP-Rule MF_03035		PRO_0000089863
Regions
	Nucleotide binding	124 – 129	6	ATP By similarity
Sites
	Binding site	22	1	ATP By similarity
	Binding site	62	1	ATP; via carbonyl oxygen By similarity
Natural variations
	Alternative sequence	139 – 202	64	Missing in isoform 2.		VSP_041164
Experimental info
	Mutagenesis	127	1	K → A: Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-128. Ref.7
	Mutagenesis	128	1	S → A: Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-127. Ref.7
	Mutagenesis	151	1	D → A: Abrogates complementation of tRNA splicing activity in yeast. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 640AF4768994CFE6	FASTA	425	47,646
	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
	Isoform 2 [UniParc]. Checksum: 661F193326BCB711	FASTA	361	40,696
	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 CRLLLNYAIT SRLADVFNQR CEVNRRASVS GCVINTCGWV KGSGYQALVH 190 200 210 220 230 240 AASAFEVDVV VVLDQERLYN ELKRDLPHFV RTVLLPKSGG VVERSKDFRR ECRDERIREY 250 260 270 280 290 300 FYGFRGCFYP HAFNVKFSDV KIYKVGAPTI PDSCLPLGMS QEDNQLKLVP VTPGRDMVHH 310 320 330 340 350 360 LLSVSTAEGT EENLSETSVA GFIVVTSVDL EHQVFTVLSP APRPLPKNFL LIMDIRFMDL K

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 LYS-127 AND 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.
+	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.
IPI	IPI00024381. IPI00908312.
RefSeq	NP_001136069.1. NM_001142597.1. NP_006822.1. NM_006831.2.
UniGene	Hs.523687.
3D structure databases
ProteinModelPortal	Q92989.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92989. 1 interaction.
STRING	9606.ENSP00000304704.
PTM databases
PhosphoSite	Q92989.
Polymorphism databases
DMDM	13431366.
Proteomic databases
PaxDb	Q92989.
PRIDE	Q92989.
Protocols and materials databases
DNASU	10978.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000302731; ENSP00000304704; ENSG00000172409. ENST00000525602; ENSP00000436066; ENSG00000172409. ENST00000533682; ENSP00000434995; ENSG00000172409.
GeneID	10978.
KEGG	hsa:10978.
UCSC	uc001nkw.3. human. uc010rjw.2. human.
Organism-specific databases
CTD	10978.
GeneCards	GC11P057425.
HGNC	HGNC:16999. CLP1.
MIM	608757. gene.
neXtProt	NX_Q92989.
PharmGKB	PA162382477.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5623.
HOGENOM	HOG000231935.
HOVERGEN	HBG000921.
InParanoid	Q92989.
KO	K14399.
OrthoDB	EOG4K0QNF.
PhylomeDB	Q92989.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_1788. Transcription. REACT_71. Gene Expression. REACT_78. Post-Elongation Processing of the Transcript.
Gene expression databases
ArrayExpress	Q92989.
Bgee	Q92989.
CleanEx	HS_CLP1.
Genevestigator	Q92989.
GermOnline	ENSG00000172409. Homo sapiens.
Family and domain databases
HAMAP	MF_03035. Clp1.
InterPro	IPR010655. Pre-mRNA_cleavage_cplxII_Clp1. [Graphical view]
Pfam	PF06807. Clp1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10978.
NextBio	41710.
SOURCE	Search...

Entry information

Entry name

CLP1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.