Q8IV48 (ERI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3'-5' exoribonuclease 1
EC=3.1.-.-

Alternative name(s):
3'-5' exonuclease ERI1
Eri-1 homolog
Histone mRNA 3'-end-specific exoribonuclease
Histone mRNA 3'-exonuclease 1
Protein 3'hExo
Short name=HEXO

Gene names

Name:	ERI1
Synonyms:	3'EXO, THEX1

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	349 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA exonuclease that binds to the 3'-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication. A 2' and 3'-hydroxyl groups at the last nucleotide of the histone 3'-end is required for efficient degradation of RNA substrates. Also able to degrade the 3'-overhangs of short interfering RNAs (siRNAs) in vitro, suggesting a possible role as regulator of RNA interference (RNAi). Requires for binding the 5'-ACCCA-3' sequence present in stem-loop structure. Able to bind other mRNAs. Required for 5.8S rRNA 3'-end processing. Also binds to 5.8s ribosomal RNA. Binds with high affinity to the stem-loop structure of replication-dependent histone pre-mRNAs. Ref.1 Ref.6
Cofactor	Binds 2 magnesium ions per subunit.
Enzyme regulation	Although it can bind simultaneously with SLBP to the 3'-end of histone mRNA, the presence of SLBP prevents the exonuclease activity. Ref.1
Subunit structure	Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Interacts in a cooperative manner with SLBP to the mature 3'-end of histone mRNAs By similarity. Binds to 40S and 60S ribosomal subunits and to 80S assembled ribosomes. Found in a ternary complex with SLBP and the stem-loop structure of the 3'-end of histone mRNAs. Ref.6
Subcellular location	Cytoplasm. Nucleus. Nucleus › nucleolus Ref.6.
Domain	The SAP domain is necessary for binding to the stem-loop structure of histone mRNAs and to form the ternary complex with SLBP, but not for 3'-end histone mRNA exonuclease activity.
Sequence similarities	Contains 1 exonuclease domain. Contains 1 SAP domain.
Sequence caution	The sequence CAB70871.2 differs from that shown. Reason: Erroneous termination at position 159. Translated as Leu. The sequence CAB70871.2 differs from that shown. Reason: Frameshift at position 117.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing rRNA processing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding RNA-binding
Molecular function	Exonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	gene silencing by RNA Inferred from electronic annotation. Source: UniProtKB-KW rRNA 3'-end processing Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB histone pre-mRNA 3'end processing complex Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	3'-5' exonuclease activity Inferred from direct assay Ref.1Ref.6. Source: UniProtKB histone pre-mRNA stem-loop binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW rRNA binding Inferred from sequence or structural similarity. Source: UniProtKB ribosome binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Probable

Chain

2 – 349

348

3'-5' exoribonuclease 1

PRO_0000187007

Regions

Domain

76 – 110

35

SAP

Domain

130 – 306

177

Exonuclease

Sites

Active site

136

1

Proton acceptor Potential

Active site

293

1

Proton acceptor Potential

Metal binding

134

1

Magnesium 1

Metal binding

134

1

Magnesium 2

Metal binding

136

1

Magnesium 1

Metal binding

234

1

Magnesium 2

Metal binding

298

1

Magnesium 1

Binding site

136

1

AMP

Binding site

137

1

AMP; via amide nitrogen and carbonyl oxygen

Binding site

293

1

AMP

Amino acid modifications

Modified residue

62

1

Phosphoserine Ref.7

Natural variations

Natural variant

16

1

L → P. Ref.2
Corresponds to variant rs2288672 [ dbSNP | Ensembl ].

VAR_018107

Experimental info

Mutagenesis

92

1

K → A: Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-104. Ref.6

Mutagenesis

96

1

R → A: Does not inhibit RNA-binding to the stem-loop structure. Ref.6

Mutagenesis

99

1

K → A: Reduces slightly RNA-binding to the stem-loop structure. Ref.6

Mutagenesis

104

1

K → A: Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-92. Ref.6

Mutagenesis

105

1

R → A: Inhibits RNA-binding to the stem-loop structure. Ref.6

Mutagenesis

109

1

Y → A: Reduces slightly RNA-binding to the stem-loop structure; when associated with A-110. Ref.6

Mutagenesis

110

1

Y → A: Reduces slightly RNA-binding to the stem-loop structure; when associated with A-109. Ref.6

Mutagenesis

111

1

K → A: Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-112. Ref.6

Mutagenesis

112

1

K → A: Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-111. Ref.6

Mutagenesis

234

1

D → A: Inhibits 3'-end histone mRNA exonuclease activity. Ref.6

Mutagenesis

235

1

M → A: Inhibits RNA-binding to the stem-loop structure and 3'-end histone mRNA exonuclease activity. Ref.6

Mutagenesis

298

1

D → A: Inhibits 3'-end histone mRNA exonuclease activity. Ref.6

Secondary structure

1

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349

Helix Strand Turn

Details...

Helix

64 – 77

14

Helix

81 – 90

10

Helix

99 – 114

16

Beta strand

126 – 132

7

Beta strand

151 – 160

10

Turn

161 – 163

3

Beta strand

165 – 174

10

Beta strand

177 – 179

3

Helix

184 – 190

7

Helix

194 – 198

5

Beta strand

200 – 202

3

Helix

203 – 216

14

Turn

220 – 222

3

Beta strand

225 – 231

7

Turn

232 – 235

4

Helix

236 – 246

11

Helix

252 – 254

3

Beta strand

255 – 259

5

Helix

260 – 268

9

Helix

272 – 274

3

Helix

277 – 283

7

Helix

295 – 311

17

Beta strand

320 – 329

10

Beta strand

332 – 334

3

Sequences

	Sequence		Length	Mass (Da)
	Q8IV48 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: D5837AA05F09410C	FASTA	349	40,064
	10 20 30 40 50 60 MEDPQSKEPA GEAVALALLE SPRPEGGEEP PRPSPEETQQ CKFDGQETKG SKFITSSASD 70 80 90 100 110 120 FSDPVYKEIA ITNGCINRMS KEELRAKLSE FKLETRGVKD VLKKRLKNYY KKQKLMLKES 130 140 150 160 170 180 NFADSYYDYI CIIDFEATCE EGNPPEFVHE IIEFPVVLLN THTLEIEDTF QQYVRPEINT 190 200 210 220 230 240 QLSDFCISLT GITQDQVDRA DTFPQVLKKV IDWMKLKELG TKYKYSLLTD GSWDMSKFLN 250 260 270 280 290 300 IQCQLSRLKY PPFAKKWINI RKSYGNFYKV PRSQTKLTIM LEKLGMDYDG RPHCGLDDSK 310 320 330 340 NIARIAVRML QDGCELRINE KMHAGQLMSV SSSLPIEGTP PPQMPHFRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A 3' exonuclease that specifically interacts with the 3' end of histone mRNA." Dominski Z., Yang X.-C., Kaygun H., Dadlez M., Marzluff W.F. Mol. Cell 12:295-305(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-23; 43-48; 53-67; 161-172; 200-208; 225-237; 263-269 AND 284-291, FUNCTION, ENZYME REGULATION, ENZYME ACTIVITY, RNA-BINDING.
[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], VARIANT PRO-16.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[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].
[5]	"A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans." Kennedy S., Wang D., Ruvkun G. Nature 427:645-649(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY IN VITRO.
[6]	"Characterization of 3'hExo, a 3' exonuclease specifically interacting with the 3' end of histone mRNA." Yang X.-C., Purdy M., Marzluff W.F., Dominski Z. J. Biol. Chem. 281:30447-30454(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A TERNARY COMPLEX, ENZYME ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-92; ARG-96; LYS-99; LYS-104; ARG-105; THY-109; THY-110; LYS-111; LYS-112; ASP-234; MET-235 AND ASP-298, RNA-BINDING.
[7]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystallographic structure of the nuclease domain of 3'hExo, a DEDDh family member, bound to rAMP." Cheng Y., Patel D.J. J. Mol. Biol. 343:305-312(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 123-322 IN COMPLEX WITH MAGNESIUM IONS AND AMP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY310909 mRNA. Translation: AAQ21219.1.
AK291062 mRNA. Translation: BAF83751.1.
AL137679 mRNA. Translation: CAB70871.2. Sequence problems.
BC035279 mRNA. Translation: AAH35279.1.

IPI

IPI00216873.

PIR

T46432.

RefSeq

NP_699163.2. NM_153332.3.

UniGene

Hs.20000.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W0H	X-ray	1.59	A	123-322	[»]
1ZBH	X-ray	3.00	A/B/C/D	51-348	[»]
1ZBU	X-ray	3.00	A/B/C/D	2-348	[»]
4HXH	X-ray	2.60	B/E	55-349	[»]

ProteinModelPortal

Q8IV48.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000250263.

PTM databases

PhosphoSite

Q8IV48.

Polymorphism databases

DMDM

45476938.

Proteomic databases

PaxDb

Q8IV48.

PeptideAtlas

Q8IV48.

PRIDE

Q8IV48.

Protocols and materials databases

DNASU

90459.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000250263; ENSP00000250263; ENSG00000104626.
ENST00000519292; ENSP00000430190; ENSG00000104626.
ENST00000523898; ENSP00000429615; ENSG00000104626.

GeneID

90459.

KEGG

hsa:90459.

UCSC

uc003wsk.2. human.

Organism-specific databases

CTD

90459.

GeneCards

GC08P008900.

HGNC

HGNC:23994. ERI1.

HPA

CAB033838.

MIM

608739. gene.

neXtProt

NX_Q8IV48.

PharmGKB

PA164719226.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5018.

HOGENOM

HOG000006635.

HOVERGEN

HBG048925.

InParanoid

Q8IV48.

KO

K01175.

OMA

ICVIDFE.

OrthoDB

EOG4NGGN1.

PhylomeDB

Q8IV48.

Gene expression databases

ArrayExpress

Q8IV48.

Bgee

Q8IV48.

CleanEx

HS_ERI1.

Genevestigator

Q8IV48.

GermOnline

ENSG00000104626. Homo sapiens.

Family and domain databases

InterPro

IPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
IPR003034. SAP_dom.
[Graphical view]

Pfam

PF00929. RNase_T. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]

SMART

SM00479. EXOIII. 1 hit.
SM00513. SAP. 1 hit.
[Graphical view]

SUPFAM

SSF53098. RNaseH_fold. 1 hit.

PROSITE

PS50800. SAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00131. Adenosine monophosphate.

EvolutionaryTrace

Q8IV48.

GenomeRNAi

90459.

NextBio

76770.

SOURCE

Search...

Entry information

Entry name

ERI1_HUMAN

Accession

Primary (citable) accession number: Q8IV48
Secondary accession number(s): A8K4U7, Q9NSX3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 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.