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

DIS3-like exonuclease 2

Gene

Dis3l2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation.UniRule annotation2 Publications

Cofactori

Mg2+UniRule annotation1 Publication, Mn2+UniRule annotation1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi381 – 3811Magnesium1 Publication
Sitei389 – 3891Important for catalytic activity1 Publication
Metal bindingi390 – 3901Magnesium1 Publication

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • poly(U) RNA binding Source: UniProtKB
  • ribonuclease activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

Magnesium, Metal-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DIS3-like exonuclease 2UniRule annotation (EC:3.1.13.-UniRule annotation)
Gene namesi
Name:Dis3l2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2442555. Dis3l2.

Subcellular locationi

  • Cytoplasm UniRule annotation1 Publication
  • CytoplasmP-body UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 741R → A: Loss of enzyme activity and polyuridylated RNA-binding; when associated with A-612. 1 Publication
Mutagenesisi389 – 3891D → N: Loss of exoribonuclease activity. 1 Publication
Mutagenesisi548 – 5536RLDQLK → AAAAAA: 40% decreased enzyme activity. 1 Publication
Mutagenesisi612 – 6121Q → A: Loss of enzyme activity and polyuridylated RNA-binding; when associated with A-74. 1 Publication
Mutagenesisi777 – 7771N → A: 40% increased enzyme activity. 1 Publication
Mutagenesisi778 – 7781Q → A: Impaired enzyme activity and polyuridylated RNA-binding. 1 Publication
Mutagenesisi796 – 7961N → A: Does not affect enzyme activity. 1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 870870DIS3-like exonuclease 2PRO_0000314818Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei31 – 311PhosphoserineBy similarity
Modified residuei172 – 1721PhosphoserineBy similarity
Modified residuei250 – 2501N6-acetyllysineBy similarity
Modified residuei864 – 8641PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8CI75.
MaxQBiQ8CI75.
PaxDbiQ8CI75.
PeptideAtlasiQ8CI75.
PRIDEiQ8CI75.

PTM databases

iPTMnetiQ8CI75.
PhosphoSiteiQ8CI75.

Expressioni

Gene expression databases

BgeeiQ8CI75.
ExpressionAtlasiQ8CI75. baseline and differential.
GenevisibleiQ8CI75. MM.

Interactioni

Protein-protein interaction databases

DIPiDIP-60224N.
STRINGi10090.ENSMUSP00000132673.

Structurei

Secondary structure

1
870
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi56 – 6510Combined sources
Beta strandi66 – 727Combined sources
Beta strandi82 – 854Combined sources
Beta strandi94 – 974Combined sources
Turni98 – 1047Combined sources
Beta strandi110 – 1156Combined sources
Beta strandi231 – 2388Combined sources
Beta strandi243 – 2508Combined sources
Beta strandi262 – 2709Combined sources
Beta strandi276 – 2794Combined sources
Helixi280 – 2823Combined sources
Helixi285 – 2895Combined sources
Helixi291 – 2944Combined sources
Beta strandi297 – 3059Combined sources
Beta strandi311 – 32313Combined sources
Helixi327 – 33711Combined sources
Helixi347 – 3504Combined sources
Beta strandi356 – 3583Combined sources
Helixi363 – 3686Combined sources
Beta strandi369 – 3713Combined sources
Beta strandi378 – 3814Combined sources
Beta strandi390 – 3967Combined sources
Beta strandi402 – 4098Combined sources
Helixi411 – 4144Combined sources
Helixi420 – 4289Combined sources
Helixi444 – 4474Combined sources
Turni448 – 4503Combined sources
Beta strandi457 – 46812Combined sources
Beta strandi474 – 48512Combined sources
Beta strandi488 – 4914Combined sources
Helixi492 – 5009Combined sources
Helixi520 – 54324Combined sources
Beta strandi554 – 5585Combined sources
Turni560 – 5623Combined sources
Beta strandi565 – 5706Combined sources
Helixi575 – 59824Combined sources
Beta strandi604 – 6085Combined sources
Helixi613 – 62412Combined sources
Helixi625 – 6273Combined sources
Helixi635 – 6417Combined sources
Helixi650 – 66213Combined sources
Beta strandi671 – 6744Combined sources
Helixi675 – 6773Combined sources
Helixi681 – 6844Combined sources
Turni687 – 6904Combined sources
Beta strandi701 – 7033Combined sources
Helixi704 – 71613Combined sources
Helixi727 – 76236Combined sources
Beta strandi766 – 77510Combined sources
Beta strandi777 – 7848Combined sources
Turni785 – 7873Combined sources
Beta strandi790 – 7945Combined sources
Beta strandi800 – 8067Combined sources
Beta strandi809 – 8113Combined sources
Beta strandi813 – 8186Combined sources
Beta strandi821 – 8255Combined sources
Beta strandi829 – 8335Combined sources
Beta strandi837 – 8448Combined sources
Beta strandi851 – 8544Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4PMWX-ray2.95A/B37-856[»]
ProteinModelPortaliQ8CI75.
SMRiQ8CI75. Positions 49-124, 228-856.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Specifically recognizes and binds polyuridylated RNAs via 3 RNA-binding regions (named U-zone 1, U-zone 2 and U-zone 3) that form an open funnel on one face of the catalytic domain, allowing RNA to navigate a path to the active site.1 Publication

Sequence similaritiesi

Belongs to the RNR ribonuclease family. DIS3L2 subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG2102. Eukaryota.
COG0557. LUCA.
GeneTreeiENSGT00530000063106.
HOGENOMiHOG000017705.
HOVERGENiHBG107810.
InParanoidiQ8CI75.
KOiK18758.
OMAiDQAQFRH.
OrthoDBiEOG7WDN1X.
PhylomeDBiQ8CI75.
TreeFamiTF315191.

Family and domain databases

HAMAPiMF_03045. DIS3L2.
InterProiIPR028591. DIS3L2.
IPR012340. NA-bd_OB-fold.
IPR022966. RNase_II/R_CS.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 3 hits.
PROSITEiPS01175. RIBONUCLEASE_II. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8CI75-1) [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
MNHPDYKLNL RSPGTPRGVS SVVGPSAVGA SPGDKKSKNK SMRGKKKSIF
60 70 80 90 100
ETYMSKEDVS EGLKRGTLIQ GVLRINPKKF HEAFIPSPDG DRDIFIDGVV
110 120 130 140 150
ARNRALNGDL VVVKLLPEDQ WKAVKPESND KEIEATYEAD IPEEGCGHHP
160 170 180 190 200
LQQSRKGWSG PDVIIEAQFD DSDSEDRHGN TSGLVDGVKK LSISTPDRGK
210 220 230 240 250
EDSSTPVMKD ENTPIPQDTR GLSEKSLQKS AKVVYILEKK HSRAATGILK
260 270 280 290 300
LLADKNSDLF KKYALFSPSD HRVPRIYVPL KDCPQDFMTR PKDFANTLFI
310 320 330 340 350
CRIIDWKEDC NFALGQLAKS LGQAGEIEPE TEGILTEYGV DFSDFSSEVL
360 370 380 390 400
ECLPQSLPWT IPPDEVGKRR DLRKDCIFTI DPSTARDLDD ALACRRLTDG
410 420 430 440 450
TFEVGVHIAD VSYFVPEGSS LDKVAAERAT SVYLVQKVVP MLPRLLCEEL
460 470 480 490 500
CSLNPMTDKL TFSVIWKLTP EGKILEEWFG RTIIRSCTKL SYDHAQSMIE
510 520 530 540 550
NPTEKIPEEE LPPISPEHSV EEVHQAVLNL HSIAKQLRRQ RFVDGALRLD
560 570 580 590 600
QLKLAFTLDH ETGLPQGCHI YEYRDSNKLV EEFMLLANMA VAHKIFRTFP
610 620 630 640 650
EQALLRRHPP PQTKMLSDLV EFCDQMGLPM DVSSAGALNK SLTKTFGDDK
660 670 680 690 700
YSLARKEVLT NMYSRPMQMA LYFCSGMLQD QEQFRHYALN VPLYTHFTSP
710 720 730 740 750
IRRFADVIVH RLLAAALGYS EQPDVEPDTL QKQADHCNDR RMASKRVQEL
760 770 780 790 800
SIGLFFAVLV KESGPLESEA MVMGVLNQAF DVLVLRFGVQ KRIYCNALAL
810 820 830 840 850
RSYSFQKVGK KPELTLVWEP DDLEEEPTQQ VITIFSLVDV VLQAEATALK
860 870
YSAILKRPGL EKASDEEPED
Length:870
Mass (Da):97,775
Last modified:March 1, 2003 - v1
Checksum:iE54474450DCD363F
GO
Isoform 2 (identifier: Q8CI75-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     122-122: K → KPRITLSLPGVLGLQ

Note: No experimental confirmation available.
Show »
Length:884
Mass (Da):99,220
Checksum:iFDD0AEB9C4F05712
GO

Sequence cautioni

The sequence BAC27292.1 differs from that shown. Reason: Frameshift at position 53. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei122 – 1221K → KPRITLSLPGVLGLQ in isoform 2. 1 PublicationVSP_030379

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK031180 mRNA. Translation: BAC27292.1. Frameshift.
BC036177 mRNA. Translation: AAH36177.1.
CCDSiCCDS15124.1. [Q8CI75-1]
CCDS48304.1. [Q8CI75-2]
RefSeqiNP_001165628.1. NM_001172157.1. [Q8CI75-2]
NP_705758.1. NM_153530.2. [Q8CI75-1]
UniGeneiMm.389152.

Genome annotation databases

EnsembliENSMUST00000065694; ENSMUSP00000070506; ENSMUSG00000053333. [Q8CI75-1]
ENSMUST00000168237; ENSMUSP00000132673; ENSMUSG00000053333. [Q8CI75-2]
GeneIDi208718.
KEGGimmu:208718.
UCSCiuc007bvu.2. mouse. [Q8CI75-1]
uc007bvw.2. mouse. [Q8CI75-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK031180 mRNA. Translation: BAC27292.1. Frameshift.
BC036177 mRNA. Translation: AAH36177.1.
CCDSiCCDS15124.1. [Q8CI75-1]
CCDS48304.1. [Q8CI75-2]
RefSeqiNP_001165628.1. NM_001172157.1. [Q8CI75-2]
NP_705758.1. NM_153530.2. [Q8CI75-1]
UniGeneiMm.389152.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4PMWX-ray2.95A/B37-856[»]
ProteinModelPortaliQ8CI75.
SMRiQ8CI75. Positions 49-124, 228-856.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60224N.
STRINGi10090.ENSMUSP00000132673.

PTM databases

iPTMnetiQ8CI75.
PhosphoSiteiQ8CI75.

Proteomic databases

EPDiQ8CI75.
MaxQBiQ8CI75.
PaxDbiQ8CI75.
PeptideAtlasiQ8CI75.
PRIDEiQ8CI75.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000065694; ENSMUSP00000070506; ENSMUSG00000053333. [Q8CI75-1]
ENSMUST00000168237; ENSMUSP00000132673; ENSMUSG00000053333. [Q8CI75-2]
GeneIDi208718.
KEGGimmu:208718.
UCSCiuc007bvu.2. mouse. [Q8CI75-1]
uc007bvw.2. mouse. [Q8CI75-2]

Organism-specific databases

CTDi129563.
MGIiMGI:2442555. Dis3l2.

Phylogenomic databases

eggNOGiKOG2102. Eukaryota.
COG0557. LUCA.
GeneTreeiENSGT00530000063106.
HOGENOMiHOG000017705.
HOVERGENiHBG107810.
InParanoidiQ8CI75.
KOiK18758.
OMAiDQAQFRH.
OrthoDBiEOG7WDN1X.
PhylomeDBiQ8CI75.
TreeFamiTF315191.

Miscellaneous databases

PROiQ8CI75.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CI75.
ExpressionAtlasiQ8CI75. baseline and differential.
GenevisibleiQ8CI75. MM.

Family and domain databases

HAMAPiMF_03045. DIS3L2.
InterProiIPR028591. DIS3L2.
IPR012340. NA-bd_OB-fold.
IPR022966. RNase_II/R_CS.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 3 hits.
PROSITEiPS01175. RIBONUCLEASE_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Forelimb.
  2. "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).
    Strain: FVB/N-3.
    Tissue: Mammary tumor.
  3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-864, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-864, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen and Testis.
  5. "A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway."
    Chang H.M., Triboulet R., Thornton J.E., Gregory R.I.
    Nature 497:244-248(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-389.
  6. "Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway."
    Faehnle C.R., Walleshauser J., Joshua-Tor L.
    Nature 514:252-256(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 37-856 OF MUTANT ASN-389 IN COMPLEX WITH MAGNESIUM AND POLY(U) RNA, FUNCTION, DOMAIN, COFACTOR, RNA BINDING, MUTAGENESIS OF ARG-74; ASP-389; 548-ARG--LYS-553; GLN-612; ASN-777; GLN-778 AND ASN-796.

Entry informationi

Entry nameiDI3L2_MOUSE
AccessioniPrimary (citable) accession number: Q8CI75
Secondary accession number(s): Q8BMG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: March 1, 2003
Last modified: July 6, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.