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Q92989

- CLP1_HUMAN

UniProt

Q92989 - CLP1_HUMAN

Protein

Polyribonucleotide 5'-hydroxyl-kinase Clp1

Gene

CLP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Feb 1997)
      Previous versions | rss
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    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

    Magnesium, manganese or nickel.1 PublicationUniRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei22 – 221ATPUniRule annotation
    Binding sitei62 – 621ATP; via carbonyl oxygenUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi124 – 1296ATPUniRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity Source: UniProtKB-EC
    3. ATP-dependent polyribonucleotide 5'-hydroxyl-kinase activity Source: UniProtKB
    4. polydeoxyribonucleotide kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell death Source: UniProtKB-KW
    2. cerebellar cortex development Source: UniProtKB
    3. gene expression Source: Reactome
    4. mRNA 3'-end processing Source: UniProtKB
    5. mRNA splicing, via spliceosome Source: Reactome
    6. RNA splicing Source: Reactome
    7. siRNA loading onto RISC involved in RNA interference Source: UniProtKB
    8. targeting of mRNA for destruction involved in RNA interference Source: UniProtKB
    9. termination of RNA polymerase II transcription Source: Reactome
    10. transcription from RNA polymerase II promoter Source: Reactome
    11. tRNA splicing, via endonucleolytic cleavage and ligation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    mRNA processing, tRNA processing

    Keywords - Ligandi

    ATP-binding, Magnesium, Manganese, Nickel, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_1096. Processing of Intronless Pre-mRNAs.
    REACT_1849. mRNA 3'-end processing.
    REACT_467. mRNA Splicing - Major Pathway.

    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
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:16999. CLP1.

    Subcellular locationi

    Nucleus 2 PublicationsUniRule annotation

    GO - Cellular componenti

    1. mRNA cleavage factor complex Source: UniProtKB-HAMAP
    2. nucleoplasm Source: Reactome
    3. nucleus Source: UniProtKB
    4. tRNA-intron endonuclease complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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 (PubMed:24766809, PubMed:24766810).2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi127 – 1282KS → AA: Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-128. 2 Publications
    Mutagenesisi127 – 1271K → A: Abrogates RNA kinase activity and tRNA splicing activity. 2 Publications
    Mutagenesisi151 – 1511D → A: Abrogates complementation of tRNA splicing activity in yeast. 2 Publications

    Keywords - Diseasei

    Disease mutation, Neurodegeneration

    Organism-specific databases

    PharmGKBiPA162382477.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 425425Polyribonucleotide 5'-hydroxyl-kinase Clp1PRO_0000089863Add
    BLAST

    Proteomic databases

    MaxQBiQ92989.
    PaxDbiQ92989.
    PRIDEiQ92989.

    PTM databases

    PhosphoSiteiQ92989.

    Expressioni

    Gene expression databases

    ArrayExpressiQ92989.
    BgeeiQ92989.
    CleanExiHS_CLP1.
    GenevestigatoriQ92989.

    Organism-specific databases

    HPAiHPA049957.
    HPA057770.

    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

    Protein-protein interaction databases

    BioGridi116174. 15 interactions.
    IntActiQ92989. 2 interactions.
    MINTiMINT-3049820.
    STRINGi9606.ENSP00000304704.

    Structurei

    3D structure databases

    ProteinModelPortaliQ92989.
    SMRiQ92989. Positions 14-423.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the Clp1 family. Clp1 subfamily.UniRule annotation

    Phylogenomic databases

    eggNOGiCOG5623.
    HOGENOMiHOG000231935.
    HOVERGENiHBG000921.
    InParanoidiQ92989.
    KOiK14399.
    PhylomeDBiQ92989.
    TreeFamiTF105795.

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    HAMAPiMF_03035. Clp1.
    InterProiIPR028606. Clp1.
    IPR029007. MobB-typ_P-loop.
    IPR027417. P-loop_NTPase.
    IPR010655. Pre-mRNA_cleavage_cplxII_Clp1.
    [Graphical view]
    PfamiPF06807. Clp1. 1 hit.
    PF03205. MobB. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 3 hits.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    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

    MGEEANDDKK PTTKFELERE TELRFEVEAS QSVQLELLTG MAEIFGTELT    50
    RNKKFTFDAG AKVAVFTWHG CSVQLSGRTE VAYVSKDTPM LLYLNTHTAL 100
    EQMRRQAEKE EERGPRVMVV GPTDVGKSTV CRLLLNYAVR LGRRPTYVEL 150
    DVGQGSVSIP GTMGALYIER PADVEEGFSI QAPLVYHFGS TTPGTNIKLY 200
    NKITSRLADV FNQRCEVNRR ASVSGCVINT CGWVKGSGYQ ALVHAASAFE 250
    VDVVVVLDQE RLYNELKRDL PHFVRTVLLP KSGGVVERSK DFRRECRDER 300
    IREYFYGFRG CFYPHAFNVK FSDVKIYKVG APTIPDSCLP LGMSQEDNQL 350
    KLVPVTPGRD MVHHLLSVST AEGTEENLSE TSVAGFIVVT SVDLEHQVFT 400
    VLSPAPRPLP KNFLLIMDIR FMDLK 425
    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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti140 – 1401R → H in NBA1; decreased kinase activity, impaired formation of the tRNA splicing endonuclease complex and impaired ability to mediate tRNA splicing and maturation. 2 Publications
    VAR_070952

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei139 – 20264Missing in isoform 2. 1 PublicationVSP_041164Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    XP_006718488.1. XM_006718425.1. [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.3. human. [Q92989-1]
    uc010rjw.2. human. [Q92989-2]

    Polymorphism databases

    DMDMi13431366.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS44600.1. [Q92989-2 ]
    CCDS7964.1. [Q92989-1 ]
    RefSeqi NP_001136069.1. NM_001142597.1. [Q92989-2 ]
    NP_006822.1. NM_006831.2. [Q92989-1 ]
    XP_006718488.1. XM_006718425.1. [Q92989-1 ]
    UniGenei Hs.523687.

    3D structure databases

    ProteinModelPortali Q92989.
    SMRi Q92989. Positions 14-423.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116174. 15 interactions.
    IntActi Q92989. 2 interactions.
    MINTi MINT-3049820.
    STRINGi 9606.ENSP00000304704.

    PTM databases

    PhosphoSitei Q92989.

    Polymorphism databases

    DMDMi 13431366.

    Proteomic databases

    MaxQBi Q92989.
    PaxDbi Q92989.
    PRIDEi Q92989.

    Protocols and materials databases

    DNASUi 10978.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302731 ; ENSP00000304704 ; ENSG00000172409 . [Q92989-2 ]
    ENST00000525602 ; ENSP00000436066 ; ENSG00000172409 . [Q92989-1 ]
    ENST00000533682 ; ENSP00000434995 ; ENSG00000172409 . [Q92989-1 ]
    GeneIDi 10978.
    KEGGi hsa:10978.
    UCSCi uc001nkw.3. human. [Q92989-1 ]
    uc010rjw.2. human. [Q92989-2 ]

    Organism-specific databases

    CTDi 10978.
    GeneCardsi GC11P057425.
    HGNCi HGNC:16999. CLP1.
    HPAi HPA049957.
    HPA057770.
    MIMi 608757. gene.
    neXtProti NX_Q92989.
    PharmGKBi PA162382477.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5623.
    HOGENOMi HOG000231935.
    HOVERGENi HBG000921.
    InParanoidi Q92989.
    KOi K14399.
    PhylomeDBi Q92989.
    TreeFami TF105795.

    Enzyme and pathway databases

    Reactomei REACT_1096. Processing of Intronless Pre-mRNAs.
    REACT_1849. mRNA 3'-end processing.
    REACT_467. mRNA Splicing - Major Pathway.

    Miscellaneous databases

    GenomeRNAii 10978.
    NextBioi 41710.
    PROi Q92989.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92989.
    Bgeei Q92989.
    CleanExi HS_CLP1.
    Genevestigatori Q92989.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    HAMAPi MF_03035. Clp1.
    InterProi IPR028606. Clp1.
    IPR029007. MobB-typ_P-loop.
    IPR027417. P-loop_NTPase.
    IPR010655. Pre-mRNA_cleavage_cplxII_Clp1.
    [Graphical view ]
    Pfami PF06807. Clp1. 1 hit.
    PF03205. MobB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 3 hits.
    ProtoNeti Search...

    Publicationsi

    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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. Cited for: VARIANT NBA1 HIS-140, FUNCTION, IDENTIFICATION IN THE TRNA SPLICING ENDONUCLEASE COMPLEX, MUTAGENESIS OF LYS-127.
    11. Cited for: VARIANT NBA1 HIS-140, FUNCTION, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiCLP1_HUMAN
    AccessioniPrimary (citable) accession number: Q92989
    Secondary accession number(s): B2R7J6, B4DTI8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: February 1, 1997
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 of the sequence. [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. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3