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Protein

5'-3' exoribonuclease 1

Gene

XRN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Major 5'-3' exoribonuclease involved in mRNA decay. Required for the 5'-3'-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Binds to RNA and DNA (By similarity). Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS).By similarity1 Publication

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • exonuclease activity Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • histone mRNA catabolic process Source: UniProtKB
  • nuclear mRNA surveillance Source: UniProtKB
  • nuclear-transcribed mRNA catabolic process Source: UniProtKB
  • regulation of mRNA stability Source: Reactome
  • rRNA catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Ligandi

DNA-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-430039. mRNA decay by 5' to 3' exoribonuclease.
R-HSA-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
R-HSA-450513. Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-3' exoribonuclease 1 (EC:3.1.13.-)
Alternative name(s):
Strand-exchange protein 1 homolog
Gene namesi
Name:XRN1
Synonyms:SEP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:30654. XRN1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi54464.
OpenTargetsiENSG00000114127.
PharmGKBiPA134878471.

Polymorphism and mutation databases

BioMutaiXRN1.
DMDMi74714582.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000713921 – 17065'-3' exoribonuclease 1Add BLAST1706

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1348PhosphoserineBy similarity1
Modified residuei1645PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8IZH2.
MaxQBiQ8IZH2.
PaxDbiQ8IZH2.
PeptideAtlasiQ8IZH2.
PRIDEiQ8IZH2.

PTM databases

iPTMnetiQ8IZH2.
PhosphoSitePlusiQ8IZH2.

Expressioni

Tissue specificityi

Expressed in heart, brain, pancreas, spleen, testis, osteogenic sarcoma (OGS) biopsy and primary cell lines.1 Publication

Inductioni

By GDNF/glial cell line-derived neurotrophic factor.1 Publication

Gene expression databases

BgeeiENSG00000114127.
CleanExiHS_XRN1.
ExpressionAtlasiQ8IZH2. baseline and differential.
GenevisibleiQ8IZH2. HS.

Organism-specific databases

HPAiHPA035005.
HPA035006.

Interactioni

Subunit structurei

Found in a mRNP complex with UPF1, UPF2, UPF3B and XRN1 (PubMed:14527413). Associates with alpha and beta tubulins (By similarity). Interacts with DIS3L2 (PubMed:23756462). Interacts with ZC3HAV1 in an RNA-dependent manner (PubMed:21876179). Interacts with ZFP36L1 (PubMed:15687258).By similarity4 Publications

Protein-protein interaction databases

BioGridi119970. 109 interactors.
DIPiDIP-31174N.
IntActiQ8IZH2. 50 interactors.
STRINGi9606.ENSP00000264951.

Structurei

3D structure databases

ProteinModelPortaliQ8IZH2.
SMRiQ8IZH2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the 5'-3' exonuclease family.Curated

Phylogenomic databases

eggNOGiKOG2044. Eukaryota.
KOG2045. Eukaryota.
COG5049. LUCA.
GeneTreeiENSGT00670000098080.
HOVERGENiHBG094164.
KOiK12618.
OMAiYRLFDRV.
OrthoDBiEOG091G00A4.
PhylomeDBiQ8IZH2.
TreeFamiTF105757.

Family and domain databases

InterProiIPR027073. 5_3_exoribonuclease.
IPR004859. Put_53exo.
[Graphical view]
PANTHERiPTHR12341. PTHR12341. 3 hits.
PfamiPF03159. XRN_N. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IZH2-1) [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
MGVPKFYRWI SERYPCLSEV VKEHQIPEFD NLYLDMNGII HQCSHPNDDD
60 70 80 90 100
VHFRISDDKI FTDIFHYLEV LFRIIKPRKV FFMAVDGVAP RAKMNQQRGR
110 120 130 140 150
RFRSAKEAED KIKKAIEKGE TLPTEARFDS NCITPGTEFM ARLHEHLKYF
160 170 180 190 200
VNMKISTDKS WQGVTIYFSG HETPGEGEHK IMEFIRSEKA KPDHDPNTRH
210 220 230 240 250
CLYGLDADLI MLGLTSHEAH FSLLREEVRF GGKKTQRVCA PEETTFHLLH
260 270 280 290 300
LSLMREYIDY EFSVLKEKIT FKYDIERIID DWILMGFLVG NDFIPHLPHL
310 320 330 340 350
HINHDALPLL YGTYVTILPE LGGYINESGH LNLPRFEKYL VKLSDFDREH
360 370 380 390 400
FSEVFVDLKW FESKVGNKYL NEAAGVAAEE ARNYKEKKKL KGQENSLCWT
410 420 430 440 450
ALDKNEGEMI TSKDNLEDET EDDDLFETEF RQYKRTYYMT KMGVDVVSDD
460 470 480 490 500
FLADQAACYV QAIQWILHYY YHGVQSWSWY YPYHYAPFLS DIHNISTLKI
510 520 530 540 550
HFELGKPFKP FEQLLAVLPA ASKNLLPACY QHLMTNEDSP IIEYYPPDFK
560 570 580 590 600
TDLNGKQQEW EAVVLIPFID EKRLLEAMET CNHSLKKEER KRNQHSECLM
610 620 630 640 650
CWYDRDTEFI YPSPWPEKFP AIERCCTRYK IISLDAWRVD INKNKITRID
660 670 680 690 700
QKALYFCGFP TLKHIRHKFF LKKSGVQVFQ QSSRGENMML EILVDAESDE
710 720 730 740 750
LTVENVASSV LGKSVFVNWP HLEEARVVAV SDGETKFYLE EPPGTQKLYS
760 770 780 790 800
GRTAPPSKVV HLGDKEQSNW AKEVQGISEH YLRRKGIIIN ETSAVVYAQL
810 820 830 840 850
LTGRKYQINQ NGEVRLEKQW SKQVVPFVYQ TIVKDIRAFD SRFSNIKTLD
860 870 880 890 900
DLFPLRSMVF MLGTPYYGCT GEVQDSGDVI TEGRIRVIFS IPCEPNLDAL
910 920 930 940 950
IQNQHKYSIK YNPGYVLASR LGVSGYLVSR FTGSIFIGRG SRRNPHGDHK
960 970 980 990 1000
ANVGLNLKFN KKNEEVPGYT KKVGSEWMYS SAAEQLLAEY LERAPELFSY
1010 1020 1030 1040 1050
IAKNSQEDVF YEDDIWPGEN ENGAEKVQEI ITWLKGHPVS TLSRSSCDLQ
1060 1070 1080 1090 1100
ILDAAIVEKI EEEVEKCKQR KNNKKVRVTV KPHLLYRPLE QQHGVIPDRD
1110 1120 1130 1140 1150
AEFCLFDRVV NVRENFSVPV GLRGTIIGIK GANREADVLF EVLFDEEFPG
1160 1170 1180 1190 1200
GLTIRCSPGR GYRLPTSALV NLSHGSRSET GNQKLTAIVK PQPAVHQHSS
1210 1220 1230 1240 1250
SSSVSSGHLG ALNHSPQSLF VPTQVPTKDD DEFCNIWQSL QGSGKMQYFQ
1260 1270 1280 1290 1300
PTIQEKGAVL PQEISQVNQH HKSGFNDNSV KYQQRKHDPH RKFKEECKSP
1310 1320 1330 1340 1350
KAECWSQKMS NKQPNSGIEN FLASLNISKE NEVQSSHHGE PPSEEHLSPQ
1360 1370 1380 1390 1400
SFAMGTRMLK EILKIDGSNT VDHKNEIKQI ANEIPVSSNR RDEYGLPSQP
1410 1420 1430 1440 1450
KQNKKLASYM NKPHSANEYH NVQSMDNMCW PAPSQIPPVS TPVTELSRIC
1460 1470 1480 1490 1500
SLVGMPQPDF SFLRMPQTMT VCQVKLSNGL LVHGPQCHSE NEAKEKAALF
1510 1520 1530 1540 1550
ALQQLGSLGM NFPLPSQVFA NYPSAVPPGT IPPAFPPPTG WDHYGSNYAL
1560 1570 1580 1590 1600
GAANIMPSSS HLFGSMPWGP SVPVPGKPFH HTLYSGTMPM AGGIPGGVHN
1610 1620 1630 1640 1650
QFIPLQVTKK RVANKKNFEN KEAQSSQATP VQTSQPDSSN IVKVSPRESS
1660 1670 1680 1690 1700
SASLKSSPIA QPASSFQVET ASQGHSISHH KSTPISSSRR KSRKLAVNFG

VSKPSE
Length:1,706
Mass (Da):194,107
Last modified:March 1, 2003 - v1
Checksum:iD06A76208DE78698
GO
Isoform 2 (identifier: Q8IZH2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1354-1354: M → MK
     1540-1552: Missing.

Show »
Length:1,694
Mass (Da):192,843
Checksum:i25AD7CD0191A4E05
GO
Isoform 3 (identifier: Q8IZH2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     449-459: DDFLADQAACY → EYVFANAFILK
     460-1706: Missing.

Show »
Length:459
Mass (Da):53,818
Checksum:i2C546FA5EDB81BC3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48D → G in CAE45950 (PubMed:17974005).Curated1
Sequence conflicti55I → T in BAC04718 (PubMed:14702039).Curated1
Sequence conflicti113K → E in CAH18332 (PubMed:17974005).Curated1
Sequence conflicti142R → K in AAH48104 (PubMed:15489334).Curated1
Sequence conflicti148K → E in CAH18332 (PubMed:17974005).Curated1
Sequence conflicti572Missing in CAB63749 (PubMed:17974005).Curated1
Sequence conflicti722L → I in CAE45950 (PubMed:17974005).Curated1
Sequence conflicti834K → R in CAH18332 (PubMed:17974005).Curated1
Sequence conflicti1250Q → R in CAH18332 (PubMed:17974005).Curated1
Sequence conflicti1463L → F in CAE45950 (PubMed:17974005).Curated1
Sequence conflicti1686S → P in CAH18332 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053000674S → G.Corresponds to variant rs35214510dbSNPEnsembl.1
Natural variantiVAR_0530011259V → A.Corresponds to variant rs35902661dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016692449 – 459DDFLADQAACY → EYVFANAFILK in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_016693460 – 1706Missing in isoform 3. 1 PublicationAdd BLAST1247
Alternative sequenceiVSP_0166941354M → MK in isoform 2. 1 Publication1
Alternative sequenceiVSP_0166951540 – 1552Missing in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY137776 mRNA. Translation: AAN11306.1.
AL133623 mRNA. Translation: CAB63749.1.
BX640905 mRNA. Translation: CAE45950.1.
CR627396 mRNA. Translation: CAH10490.1.
CR749518 mRNA. Translation: CAH18332.1.
BC039314 mRNA. Translation: AAH39314.1.
BC048104 mRNA. Translation: AAH48104.1.
AK096177 mRNA. Translation: BAC04718.1.
CCDSiCCDS3123.1. [Q8IZH2-1]
CCDS63801.1. [Q8IZH2-2]
CCDS75028.1. [Q8IZH2-3]
PIRiT43461.
RefSeqiNP_001269786.1. NM_001282857.1. [Q8IZH2-2]
NP_001269788.1. NM_001282859.1. [Q8IZH2-3]
NP_061874.3. NM_019001.4. [Q8IZH2-1]
UniGeneiHs.435103.

Genome annotation databases

EnsembliENST00000264951; ENSP00000264951; ENSG00000114127. [Q8IZH2-1]
ENST00000392981; ENSP00000376707; ENSG00000114127. [Q8IZH2-2]
ENST00000463916; ENSP00000418404; ENSG00000114127. [Q8IZH2-3]
GeneIDi54464.
KEGGihsa:54464.
UCSCiuc003eus.4. human. [Q8IZH2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY137776 mRNA. Translation: AAN11306.1.
AL133623 mRNA. Translation: CAB63749.1.
BX640905 mRNA. Translation: CAE45950.1.
CR627396 mRNA. Translation: CAH10490.1.
CR749518 mRNA. Translation: CAH18332.1.
BC039314 mRNA. Translation: AAH39314.1.
BC048104 mRNA. Translation: AAH48104.1.
AK096177 mRNA. Translation: BAC04718.1.
CCDSiCCDS3123.1. [Q8IZH2-1]
CCDS63801.1. [Q8IZH2-2]
CCDS75028.1. [Q8IZH2-3]
PIRiT43461.
RefSeqiNP_001269786.1. NM_001282857.1. [Q8IZH2-2]
NP_001269788.1. NM_001282859.1. [Q8IZH2-3]
NP_061874.3. NM_019001.4. [Q8IZH2-1]
UniGeneiHs.435103.

3D structure databases

ProteinModelPortaliQ8IZH2.
SMRiQ8IZH2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119970. 109 interactors.
DIPiDIP-31174N.
IntActiQ8IZH2. 50 interactors.
STRINGi9606.ENSP00000264951.

PTM databases

iPTMnetiQ8IZH2.
PhosphoSitePlusiQ8IZH2.

Polymorphism and mutation databases

BioMutaiXRN1.
DMDMi74714582.

Proteomic databases

EPDiQ8IZH2.
MaxQBiQ8IZH2.
PaxDbiQ8IZH2.
PeptideAtlasiQ8IZH2.
PRIDEiQ8IZH2.

Protocols and materials databases

DNASUi54464.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264951; ENSP00000264951; ENSG00000114127. [Q8IZH2-1]
ENST00000392981; ENSP00000376707; ENSG00000114127. [Q8IZH2-2]
ENST00000463916; ENSP00000418404; ENSG00000114127. [Q8IZH2-3]
GeneIDi54464.
KEGGihsa:54464.
UCSCiuc003eus.4. human. [Q8IZH2-1]

Organism-specific databases

CTDi54464.
DisGeNETi54464.
GeneCardsiXRN1.
HGNCiHGNC:30654. XRN1.
HPAiHPA035005.
HPA035006.
MIMi607994. gene.
neXtProtiNX_Q8IZH2.
OpenTargetsiENSG00000114127.
PharmGKBiPA134878471.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2044. Eukaryota.
KOG2045. Eukaryota.
COG5049. LUCA.
GeneTreeiENSGT00670000098080.
HOVERGENiHBG094164.
KOiK12618.
OMAiYRLFDRV.
OrthoDBiEOG091G00A4.
PhylomeDBiQ8IZH2.
TreeFamiTF105757.

Enzyme and pathway databases

ReactomeiR-HSA-430039. mRNA decay by 5' to 3' exoribonuclease.
R-HSA-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
R-HSA-450513. Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.

Miscellaneous databases

ChiTaRSiXRN1. human.
GenomeRNAii54464.
PROiQ8IZH2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114127.
CleanExiHS_XRN1.
ExpressionAtlasiQ8IZH2. baseline and differential.
GenevisibleiQ8IZH2. HS.

Family and domain databases

InterProiIPR027073. 5_3_exoribonuclease.
IPR004859. Put_53exo.
[Graphical view]
PANTHERiPTHR12341. PTHR12341. 3 hits.
PfamiPF03159. XRN_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiXRN1_HUMAN
AccessioniPrimary (citable) accession number: Q8IZH2
Secondary accession number(s): Q4G0S3
, Q68D88, Q6AI24, Q6MZS8, Q86WS7, Q8N8U4, Q9UF39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 126 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

Miscellaneous

Down-regulated in OGS biopsy.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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

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.