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
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

Although assigned as two separate genes (DIS3L2 and FAM6A), it is quite clear that the gene FAM6A described by PubMed:11352565 is a fragmentary prediction of DIS3L2.Curated

Cofactori

Mg2+1 Publication1 Publication, Mn2+1 Publication1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi383MagnesiumUniRule annotation1
Sitei391Important for catalytic activityUniRule annotation1
Metal bindingi392MagnesiumUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease, RNA-binding
Biological processCell cycle, Cell division, Mitosis
LigandMagnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DIS3-like exonuclease 2UniRule annotation (EC:3.1.13.-UniRule annotation)
Short name:
hDIS3L2
Gene namesi
Name:DIS3L2UniRule annotation
Synonyms:FAM6A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000144535.19
HGNCiHGNC:28648 DIS3L2
MIMi614184 gene
neXtProtiNX_Q8IYB7

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Perlman syndrome (PRLMNS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive congenital overgrowth syndrome. Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor. Histologic examination of the kidneys in affected children shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor.
See also OMIM:267000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079527443M → K in PRLMNS; unknown pathological significance. 1 Publication1
Natural variantiVAR_067578489C → Y in PRLMNS. 1 PublicationCorresponds to variant dbSNP:rs387907116EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi391D → N: Loss of exoribonuclease activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi129563
MalaCardsiDIS3L2
MIMi267000 phenotype
OpenTargetsiENSG00000144535
Orphaneti654 Nephroblastoma
2849 Perlman syndrome
PharmGKBiPA162383714

Polymorphism and mutation databases

BioMutaiDIS3L2
DMDMi296439471

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003148171 – 885DIS3-like exonuclease 2Add BLAST885

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31PhosphoserineCombined sources1
Modified residuei173PhosphoserineCombined sources1
Modified residuei252N6-acetyllysineCombined sources1
Modified residuei875PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8IYB7
MaxQBiQ8IYB7
PaxDbiQ8IYB7
PeptideAtlasiQ8IYB7
PRIDEiQ8IYB7
ProteomicsDBi71148
71149 [Q8IYB7-2]
71150 [Q8IYB7-3]
71151 [Q8IYB7-4]
71152 [Q8IYB7-5]

PTM databases

iPTMnetiQ8IYB7
PhosphoSitePlusiQ8IYB7

Expressioni

Gene expression databases

BgeeiENSG00000144535 Expressed in 183 organ(s), highest expression level in corpus callosum
CleanExiHS_DIS3L2
ExpressionAtlasiQ8IYB7 baseline and differential
GenevisibleiQ8IYB7 HS

Organism-specific databases

HPAiHPA035796
HPA035797

Interactioni

Protein-protein interaction databases

BioGridi126199, 11 interactors
IntActiQ8IYB7, 6 interactors
STRINGi9606.ENSP00000315569

Structurei

3D structure databases

ProteinModelPortaliQ8IYB7
SMRiQ8IYB7
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.UniRule annotation

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2102 Eukaryota
COG0557 LUCA
GeneTreeiENSGT00530000063106
HOVERGENiHBG107810
InParanoidiQ8IYB7
KOiK18758
OMAiREFEAFC
OrthoDBiEOG091G06EJ
PhylomeDBiQ8IYB7
TreeFamiTF315191

Family and domain databases

HAMAPiMF_03045 DIS3L2, 1 hit
InterProiView protein in InterPro
IPR028591 DIS3L2
IPR012340 NA-bd_OB-fold
IPR001900 RNase_II/R
IPR022966 RNase_II/R_CS
IPR033771 Rrp44_CSD1
PfamiView protein in Pfam
PF00773 RNB, 1 hit
PF17216 Rrp44_CSD1, 1 hit
SMARTiView protein in SMART
SM00955 RNB, 1 hit
SUPFAMiSSF50249 SSF50249, 3 hits
PROSITEiView protein in PROSITE
PS01175 RIBONUCLEASE_II, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8IYB7-1) [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
MSHPDYRMNL RPLGTPRGVS AVAGPHDIGA SPGDKKSKNR STRGKKKSIF
60 70 80 90 100
ETYMSKEDVS EGLKRGTLIQ GVLRINPKKF HEAFIPSPDG DRDIFIDGVV
110 120 130 140 150
ARNRALNGDL VVVKLLPEEH WKVVKPESND KETEAAYESD IPEELCGHHL
160 170 180 190 200
PQQSLKSYND SPDVIVEAQF DGSDSEDGHG ITQNVLVDGV KKLSVCVSEK
210 220 230 240 250
GREDGDAPVT KDETTCISQD TRALSEKSLQ RSAKVVYILE KKHSRAATGF
260 270 280 290 300
LKLLADKNSE LFRKYALFSP SDHRVPRIYV PLKDCPQDFV ARPKDYANTL
310 320 330 340 350
FICRIVDWKE DCNFALGQLA KSLGQAGEIE PETEGILTEY GVDFSDFSSE
360 370 380 390 400
VLECLPQGLP WTIPPEEFSK RRDLRKDCIF TIDPSTARDL DDALSCKPLA
410 420 430 440 450
DGNFKVGVHI ADVSYFVPEG SDLDKVAAER ATSVYLVQKV VPMLPRLLCE
460 470 480 490 500
ELCSLNPMSD KLTFSVIWTL TPEGKILDEW FGRTIIRSCT KLSYEHAQSM
510 520 530 540 550
IESPTEKIPA KELPPISPEH SSEEVHQAVL NLHGIAKQLR QQRFVDGALR
560 570 580 590 600
LDQLKLAFTL DHETGLPQGC HIYEYRESNK LVEEFMLLAN MAVAHKIHRA
610 620 630 640 650
FPEQALLRRH PPPQTRMLSD LVEFCDQMGL PVDFSSAGAL NKSLTQTFGD
660 670 680 690 700
DKYSLARKEV LTNMCSRPMQ MALYFCSGLL QDPAQFRHYA LNVPLYTHFT
710 720 730 740 750
SPIRRFADVL VHRLLAAALG YRERLDMAPD TLQKQADHCN DRRMASKRVQ
760 770 780 790 800
ELSTSLFFAV LVKESGPLES EAMVMGILKQ AFDVLVLRYG VQKRIYCNAL
810 820 830 840 850
ALRSHHFQKV GKKPELTLVW EPEDMEQEPA QQVITIFSLV EVVLQAESTA
860 870 880
LKYSAILKRP GTQGHLGPEK EEEESDGEPE DSSTS
Length:885
Mass (Da):99,279
Last modified:May 18, 2010 - v4
Checksum:i0F6757DCD1975412
GO
Isoform 2 (identifier: Q8IYB7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     581-619: LVEEFMLLAN...HPPPQTRMLS → PCCAGTPRPK...SAPQEPSIKA
     620-885: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:619
Mass (Da):69,046
Checksum:i343D7E3F9701AA00
GO
Isoform 3 (identifier: Q8IYB7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     528-603: AVLNLHGIAK...AHKIHRAFPE → QNADKDGAAH...VEEQTTQLQI
     604-885: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:603
Mass (Da):67,255
Checksum:i1402E1BA371A3E59
GO
Isoform 4 (identifier: Q8IYB7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     236-249: VYILEKKHSRAATG → IAYRFSPRVQMAFT
     250-885: Missing.

Show »
Length:249
Mass (Da):27,459
Checksum:i6255FF7B3A6D6656
GO
Isoform 5 (identifier: Q8IYB7-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     201-356: GREDGDAPVT...FSSEVLECLP → DNEIEAQRSS...VKLSLKQKEY
     357-885: Missing.

Note: No experimental confirmation available.
Show »
Length:356
Mass (Da):40,480
Checksum:iB1D4AA448B6A069E
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C440H7C440_HUMAN
DIS3-like exonuclease 2
DIS3L2
383Annotation score:
C9JGP4C9JGP4_HUMAN
DIS3-like exonuclease 2
DIS3L2
144Annotation score:
H7C1Q8H7C1Q8_HUMAN
DIS3-like exonuclease 2
DIS3L2
166Annotation score:
H7C036H7C036_HUMAN
DIS3-like exonuclease 2
DIS3L2
196Annotation score:
H7C302H7C302_HUMAN
DIS3-like exonuclease 2
DIS3L2
68Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16P → H in AAH36113 (PubMed:15489334).Curated1
Sequence conflicti16P → H in AAH26166 (PubMed:15489334).Curated1
Sequence conflicti96I → F in AAP97321 (Ref. 3) Curated1

Polymorphismi

Disrupted by a t(2;7)(q37.1;q21.3) chromosomal translocation found in a patient suffering from Marfanoid habitus and skeletal anomalies. However, its absence does not seem to be the cause of the disease.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03805912P → S1 PublicationCorresponds to variant dbSNP:rs723044EnsemblClinVar.1
Natural variantiVAR_079527443M → K in PRLMNS; unknown pathological significance. 1 Publication1
Natural variantiVAR_067577483R → G Probable disease-associated mutation found in a patient with Wilms tumor; does not suppress anchorage-independent cell growth. 1 PublicationCorresponds to variant dbSNP:rs186865544EnsemblClinVar.1
Natural variantiVAR_067578489C → Y in PRLMNS. 1 PublicationCorresponds to variant dbSNP:rs387907116EnsemblClinVar.1
Natural variantiVAR_067579576R → H Probable disease-associated mutation found in a patient with Wilms tumor; does not suppress anchorage-independent cell growth. 1 PublicationCorresponds to variant dbSNP:rs200386096EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030371201 – 356GREDG…LECLP → DNEIEAQRSSWAYPVSHRKS EERMVMHRLQKMRPPAFHKT QELYRRNPCKDQQRWFTSWR KNILEQQPASSNSWLIRTAN CLGNTPCFLPQTTECLEFMC LSRTVPRTLWHGLKIMPTHC SSAALWTGRRTAILPWGSWL RVLGRLVKLSLKQKEY in isoform 5. 1 PublicationAdd BLAST156
Alternative sequenceiVSP_030372236 – 249VYILE…RAATG → IAYRFSPRVQMAFT in isoform 4. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_030373250 – 885Missing in isoform 4. 2 PublicationsAdd BLAST636
Alternative sequenceiVSP_030374357 – 885Missing in isoform 5. 1 PublicationAdd BLAST529
Alternative sequenceiVSP_030375528 – 603AVLNL…RAFPE → QNADKDGAAHLQASHSPSAE DAEAQPSTEERLPETRGICD RDPDTRLFFLQQQSRVLEAK PQNTIRVEEQTTQLQI in isoform 3. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_030376581 – 619LVEEF…TRMLS → PCCAGTPRPKQGCSVTWWNS ATRWGCPWTSAPQEPSIKA in isoform 2. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_030377604 – 885Missing in isoform 3. 1 PublicationAdd BLAST282
Alternative sequenceiVSP_030378620 – 885Missing in isoform 2. 1 PublicationAdd BLAST266

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK094293 mRNA Translation: BAC04324.1
AL834174 mRNA Translation: CAH10694.1
BX648325 mRNA Translation: CAH10545.1
AF443854 mRNA Translation: AAP97321.1
AC019130 Genomic DNA No translation available.
AC068134 Genomic DNA Translation: AAY24086.1
AC093374 Genomic DNA Translation: AAX82031.1
AC138658 Genomic DNA No translation available.
BC026166 mRNA Translation: AAH26166.1
BC036113 mRNA Translation: AAH36113.2
CCDSiCCDS42834.1 [Q8IYB7-1]
CCDS58752.1 [Q8IYB7-3]
CCDS58753.1 [Q8IYB7-4]
RefSeqiNP_001244210.1, NM_001257281.1 [Q8IYB7-3]
NP_001244211.1, NM_001257282.1 [Q8IYB7-4]
NP_689596.4, NM_152383.4 [Q8IYB7-1]
UniGeneiHs.732236

Genome annotation databases

EnsembliENST00000273009; ENSP00000273009; ENSG00000144535 [Q8IYB7-3]
ENST00000325385; ENSP00000315569; ENSG00000144535 [Q8IYB7-1]
ENST00000390005; ENSP00000374655; ENSG00000144535 [Q8IYB7-2]
ENST00000409307; ENSP00000386799; ENSG00000144535 [Q8IYB7-1]
ENST00000409401; ENSP00000386594; ENSG00000144535 [Q8IYB7-4]
ENST00000433430; ENSP00000391175; ENSG00000144535 [Q8IYB7-5]
ENST00000445090; ENSP00000388999; ENSG00000144535 [Q8IYB7-4]
GeneIDi129563
KEGGihsa:129563
UCSCiuc002vso.4 human [Q8IYB7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK094293 mRNA Translation: BAC04324.1
AL834174 mRNA Translation: CAH10694.1
BX648325 mRNA Translation: CAH10545.1
AF443854 mRNA Translation: AAP97321.1
AC019130 Genomic DNA No translation available.
AC068134 Genomic DNA Translation: AAY24086.1
AC093374 Genomic DNA Translation: AAX82031.1
AC138658 Genomic DNA No translation available.
BC026166 mRNA Translation: AAH26166.1
BC036113 mRNA Translation: AAH36113.2
CCDSiCCDS42834.1 [Q8IYB7-1]
CCDS58752.1 [Q8IYB7-3]
CCDS58753.1 [Q8IYB7-4]
RefSeqiNP_001244210.1, NM_001257281.1 [Q8IYB7-3]
NP_001244211.1, NM_001257282.1 [Q8IYB7-4]
NP_689596.4, NM_152383.4 [Q8IYB7-1]
UniGeneiHs.732236

3D structure databases

ProteinModelPortaliQ8IYB7
SMRiQ8IYB7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126199, 11 interactors
IntActiQ8IYB7, 6 interactors
STRINGi9606.ENSP00000315569

PTM databases

iPTMnetiQ8IYB7
PhosphoSitePlusiQ8IYB7

Polymorphism and mutation databases

BioMutaiDIS3L2
DMDMi296439471

Proteomic databases

EPDiQ8IYB7
MaxQBiQ8IYB7
PaxDbiQ8IYB7
PeptideAtlasiQ8IYB7
PRIDEiQ8IYB7
ProteomicsDBi71148
71149 [Q8IYB7-2]
71150 [Q8IYB7-3]
71151 [Q8IYB7-4]
71152 [Q8IYB7-5]

Protocols and materials databases

DNASUi129563
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273009; ENSP00000273009; ENSG00000144535 [Q8IYB7-3]
ENST00000325385; ENSP00000315569; ENSG00000144535 [Q8IYB7-1]
ENST00000390005; ENSP00000374655; ENSG00000144535 [Q8IYB7-2]
ENST00000409307; ENSP00000386799; ENSG00000144535 [Q8IYB7-1]
ENST00000409401; ENSP00000386594; ENSG00000144535 [Q8IYB7-4]
ENST00000433430; ENSP00000391175; ENSG00000144535 [Q8IYB7-5]
ENST00000445090; ENSP00000388999; ENSG00000144535 [Q8IYB7-4]
GeneIDi129563
KEGGihsa:129563
UCSCiuc002vso.4 human [Q8IYB7-1]

Organism-specific databases

CTDi129563
DisGeNETi129563
EuPathDBiHostDB:ENSG00000144535.19
GeneCardsiDIS3L2
H-InvDBiHIX0002923
HGNCiHGNC:28648 DIS3L2
HPAiHPA035796
HPA035797
MalaCardsiDIS3L2
MIMi267000 phenotype
614184 gene
neXtProtiNX_Q8IYB7
OpenTargetsiENSG00000144535
Orphaneti654 Nephroblastoma
2849 Perlman syndrome
PharmGKBiPA162383714
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2102 Eukaryota
COG0557 LUCA
GeneTreeiENSGT00530000063106
HOVERGENiHBG107810
InParanoidiQ8IYB7
KOiK18758
OMAiREFEAFC
OrthoDBiEOG091G06EJ
PhylomeDBiQ8IYB7
TreeFamiTF315191

Miscellaneous databases

ChiTaRSiDIS3L2 human
GeneWikiiDIS3L2_(gene)
GenomeRNAii129563
PROiPR:Q8IYB7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144535 Expressed in 183 organ(s), highest expression level in corpus callosum
CleanExiHS_DIS3L2
ExpressionAtlasiQ8IYB7 baseline and differential
GenevisibleiQ8IYB7 HS

Family and domain databases

HAMAPiMF_03045 DIS3L2, 1 hit
InterProiView protein in InterPro
IPR028591 DIS3L2
IPR012340 NA-bd_OB-fold
IPR001900 RNase_II/R
IPR022966 RNase_II/R_CS
IPR033771 Rrp44_CSD1
PfamiView protein in Pfam
PF00773 RNB, 1 hit
PF17216 Rrp44_CSD1, 1 hit
SMARTiView protein in SMART
SM00955 RNB, 1 hit
SUPFAMiSSF50249 SSF50249, 3 hits
PROSITEiView protein in PROSITE
PS01175 RIBONUCLEASE_II, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDI3L2_HUMAN
AccessioniPrimary (citable) accession number: Q8IYB7
Secondary accession number(s): Q53S79
, Q580W6, Q5XKH0, Q69YG5, Q6AW99, Q7Z4T6, Q8N9K9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 132 of the entry and version 4 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 chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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