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Protein

Serine/threonine-protein kinase/endoribonuclease IRE2

Gene

ERN2

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

Functioni

Induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. Pro-apoptotic. Appears to play no role in the unfolded-protein response, unlike closely related proteins.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Enzyme regulationi

The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei548ATP1
Active sitei637Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi526 – 534ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • endonuclease activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • ribonuclease activity Source: InterPro

GO - Biological processi

  • apoptotic chromosome condensation Source: UniProtKB
  • mRNA processing Source: InterPro
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • rRNA catabolic process Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS13528-MONOMER.
SignaLinkiQ76MJ5.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase/endoribonuclease IRE2
Alternative name(s):
Endoplasmic reticulum-to-nucleus signaling 2
Inositol-requiring protein 2
Short name:
hIRE2p
Ire1-beta
Short name:
IRE1b
Including the following 2 domains:
Gene namesi
Name:ERN2Imported
Synonyms:IRE2By similarity
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:16942. ERN2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 430LumenalSequence analysisAdd BLAST396
Transmembranei431 – 451HelicalSequence analysisAdd BLAST21
Topological domaini452 – 926CytoplasmicSequence analysisAdd BLAST475

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi548K → A: Loss of autophosphorylation, of induction of apoptosis and of 28S rRNA cleavage, attenuation of repression of protein synthesis. 1 Publication1

Organism-specific databases

DisGeNETi10595.
OpenTargetsiENSG00000134398.
PharmGKBiPA134889542.

Polymorphism and mutation databases

BioMutaiERN2.
DMDMi327478597.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000002432935 – 926Serine/threonine-protein kinase/endoribonuclease IRE2Add BLAST892

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ76MJ5.
PeptideAtlasiQ76MJ5.
PRIDEiQ76MJ5.

PTM databases

iPTMnetiQ76MJ5.
PhosphoSitePlusiQ76MJ5.

Expressioni

Gene expression databases

BgeeiENSG00000134398.
CleanExiHS_ERN2.
ExpressionAtlasiQ76MJ5. baseline and differential.
GenevisibleiQ76MJ5. HS.

Organism-specific databases

HPAiHPA016558.

Interactioni

Protein-protein interaction databases

BioGridi115843. 1 interactor.
STRINGi9606.ENSP00000256797.

Structurei

3D structure databases

ProteinModelPortaliQ76MJ5.
SMRiQ76MJ5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini520 – 781Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini784 – 912KENPROSITE-ProRule annotationAdd BLAST129

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 KEN domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
HOVERGENiHBG051506.
InParanoidiQ76MJ5.
KOiK11715.
OrthoDBiEOG091G049V.
PhylomeDBiQ76MJ5.
TreeFamiTF313986.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
InterProiIPR033523. IRE2.
IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR13954:SF15. PTHR13954:SF15. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 4 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q76MJ5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASAVRGSRP WPRLGLQLQF AALLLGTLSP QVHTLRPENL LLVSTLDGSL
60 70 80 90 100
HALSKQTGDL KWTLRDDPVI EGPMYVTEMA FLSDPADGSL YILGTQKQQG
110 120 130 140 150
LMKLPFTIPE LVHASPCRSS DGVFYTGRKQ DAWFVVDPES GETQMTLTTE
160 170 180 190 200
GPSTPRLYIG RTQYTVTMHD PRAPALRWNT TYRRYSAPPM DGSPGKYMSH
210 220 230 240 250
LASCGMGLLL TVDPGSGTVL WTQDLGVPVM GVYTWHQDGL RQLPHLTLAR
260 270 280 290 300
DTLHFLALRW GHIRLPASGP RDTATLFSTL DTQLLMTLYV GKDETGFYVS
310 320 330 340 350
KALVHTGVAL VPRGLTLAPA DGPTTDEVTL QVSGEREGSP STAVRYPSGS
360 370 380 390 400
VALPSQWLLI GHHELPPVLH TTMLRVHPTL GSGTAETRPP ENTQAPAFFL
410 420 430 440 450
ELLSLSREKL WDSELHPEEK TPDSYLGLGP QDLLAASLTA VLLGGWILFV
460 470 480 490 500
MRQQQPQVVE KQQETPLAPA DFAHISQDAQ SLHSGASRRS QKRLQSPSKQ
510 520 530 540 550
AQPLDDPEAE QLTVVGKISF NPKDVLGRGA GGTFVFRGQF EGRAVAVKRL
560 570 580 590 600
LRECFGLVRR EVQLLQESDR HPNVLRYFCT ERGPQFHYIA LELCRASLQE
610 620 630 640 650
YVENPDLDRG GLEPEVVLQQ LMSGLAHLHS LHIVHRDLKP GNILITGPDS
660 670 680 690 700
QGLGRVVLSD FGLCKKLPAG RCSFSLHSGI PGTEGWMAPE LLQLLPPDSP
710 720 730 740 750
TSAVDIFSAG CVFYYVLSGG SHPFGDSLYR QANILTGAPC LAHLEEEVHD
760 770 780 790 800
KVVARDLVGA MLSPLPQPRP SAPQVLAHPF FWSRAKQLQF FQDVSDWLEK
810 820 830 840 850
ESEQEPLVRA LEAGGCAVVR DNWHEHISMP LQTDLRKFRS YKGTSVRDLL
860 870 880 890 900
RAVRNKKHHY RELPVEVRQA LGQVPDGFVQ YFTNRFPRLL LHTHRAMRSC
910 920
ASESLFLPYY PPDSEARRPC PGATGR
Length:926
Mass (Da):102,480
Last modified:April 5, 2011 - v4
Checksum:iB580794191B66DA2
GO

Sequence cautioni

The sequence BAD18455 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99Q → L in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti150E → A in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti215G → E in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti218T → A in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti227V → M in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti279T → A in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti320A → T in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti380L → P in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti421T → I in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti453Missing in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti468A → V in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti472 – 474FAH → TAD in BAB21297 (PubMed:11175748).Curated3
Sequence conflicti486A → V in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti488 – 491RRSQ → LRSK in BAB21297 (PubMed:11175748).Curated4
Sequence conflicti528R → H in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti650S → T in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti698D → N in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti738A → V in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti759G → A in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti764P → L in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti768P → A in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti808V → M in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti817A → T in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti833T → I in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti888R → Q in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti896A → V in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti918R → G in BAB21297 (PubMed:11175748).Curated1
Sequence conflicti924T → A in BAB21297 (PubMed:11175748).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04049569V → I.1 PublicationCorresponds to variant rs9932495dbSNPEnsembl.1
Natural variantiVAR_040496118R → C.1 PublicationCorresponds to variant rs56117885dbSNPEnsembl.1
Natural variantiVAR_040497184R → C.1 PublicationCorresponds to variant rs34683474dbSNPEnsembl.1
Natural variantiVAR_040498271R → Q.2 PublicationsCorresponds to variant rs55772851dbSNPEnsembl.1
Natural variantiVAR_040499318A → T.1 PublicationCorresponds to variant rs56191901dbSNPEnsembl.1
Natural variantiVAR_040500410L → F.1 PublicationCorresponds to variant rs55687638dbSNPEnsembl.1
Natural variantiVAR_040501487S → T.2 PublicationsCorresponds to variant rs26764dbSNPEnsembl.1
Natural variantiVAR_040502504L → F.1 PublicationCorresponds to variant rs56001432dbSNPEnsembl.1
Natural variantiVAR_040503537R → Q.1 PublicationCorresponds to variant rs56176960dbSNPEnsembl.1
Natural variantiVAR_040504858H → Y.1 PublicationCorresponds to variant rs56137182dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB047079 mRNA. Translation: BAB21297.1.
AK131280 mRNA. Translation: BAD18455.1. Different initiation.
AC012317 Genomic DNA. No translation available.
CCDSiCCDS32407.2.
RefSeqiNP_001295149.2. NM_001308220.1.
NP_150296.4. NM_033266.3.
UniGeneiHs.592041.

Genome annotation databases

EnsembliENST00000256797; ENSP00000256797; ENSG00000134398.
GeneIDi10595.
KEGGihsa:10595.
UCSCiuc002dma.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB047079 mRNA. Translation: BAB21297.1.
AK131280 mRNA. Translation: BAD18455.1. Different initiation.
AC012317 Genomic DNA. No translation available.
CCDSiCCDS32407.2.
RefSeqiNP_001295149.2. NM_001308220.1.
NP_150296.4. NM_033266.3.
UniGeneiHs.592041.

3D structure databases

ProteinModelPortaliQ76MJ5.
SMRiQ76MJ5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115843. 1 interactor.
STRINGi9606.ENSP00000256797.

PTM databases

iPTMnetiQ76MJ5.
PhosphoSitePlusiQ76MJ5.

Polymorphism and mutation databases

BioMutaiERN2.
DMDMi327478597.

Proteomic databases

PaxDbiQ76MJ5.
PeptideAtlasiQ76MJ5.
PRIDEiQ76MJ5.

Protocols and materials databases

DNASUi10595.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256797; ENSP00000256797; ENSG00000134398.
GeneIDi10595.
KEGGihsa:10595.
UCSCiuc002dma.5. human.

Organism-specific databases

CTDi10595.
DisGeNETi10595.
GeneCardsiERN2.
HGNCiHGNC:16942. ERN2.
HPAiHPA016558.
MIMi604034. gene.
neXtProtiNX_Q76MJ5.
OpenTargetsiENSG00000134398.
PharmGKBiPA134889542.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
HOVERGENiHBG051506.
InParanoidiQ76MJ5.
KOiK11715.
OrthoDBiEOG091G049V.
PhylomeDBiQ76MJ5.
TreeFamiTF313986.

Enzyme and pathway databases

BioCyciZFISH:HS13528-MONOMER.
SignaLinkiQ76MJ5.

Miscellaneous databases

ChiTaRSiERN2. human.
GenomeRNAii10595.
PROiQ76MJ5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134398.
CleanExiHS_ERN2.
ExpressionAtlasiQ76MJ5. baseline and differential.
GenevisibleiQ76MJ5. HS.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
InterProiIPR033523. IRE2.
IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR13954:SF15. PTHR13954:SF15. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 4 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERN2_HUMAN
AccessioniPrimary (citable) accession number: Q76MJ5
Secondary accession number(s): Q6ZNC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: April 5, 2011
Last modified: November 2, 2016
This is version 127 of the entry and version 4 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, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.