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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei548 – 5481ATP
Active sitei637 – 6371Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi526 – 5349ATPPROSITE-ProRule annotation

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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 430396LumenalSequence analysisAdd
BLAST
Transmembranei431 – 45121HelicalSequence analysisAdd
BLAST
Topological domaini452 – 926475CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi548 – 5481K → A: Loss of autophosphorylation, of induction of apoptosis and of 28S rRNA cleavage, attenuation of repression of protein synthesis. 1 Publication

Organism-specific databases

PharmGKBiPA134889542.

Polymorphism and mutation databases

BioMutaiERN2.
DMDMi327478597.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3434Sequence analysisAdd
BLAST
Chaini35 – 926892Serine/threonine-protein kinase/endoribonuclease IRE2PRO_0000024329Add
BLAST

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ76MJ5.
PeptideAtlasiQ76MJ5.
PRIDEiQ76MJ5.

PTM databases

iPTMnetiQ76MJ5.
PhosphoSiteiQ76MJ5.

Expressioni

Gene expression databases

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

Organism-specific databases

HPAiHPA016558.

Interactioni

Protein-protein interaction databases

BioGridi115843. 1 interaction.
STRINGi9606.ENSP00000256797.

Structurei

3D structure databases

ProteinModelPortaliQ76MJ5.
SMRiQ76MJ5. Positions 32-191, 465-910.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini520 – 781262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini784 – 912129KENPROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 991Q → L in BAB21297 (PubMed:11175748).Curated
Sequence conflicti150 – 1501E → A in BAB21297 (PubMed:11175748).Curated
Sequence conflicti215 – 2151G → E in BAB21297 (PubMed:11175748).Curated
Sequence conflicti218 – 2181T → A in BAB21297 (PubMed:11175748).Curated
Sequence conflicti227 – 2271V → M in BAB21297 (PubMed:11175748).Curated
Sequence conflicti279 – 2791T → A in BAB21297 (PubMed:11175748).Curated
Sequence conflicti320 – 3201A → T in BAB21297 (PubMed:11175748).Curated
Sequence conflicti380 – 3801L → P in BAB21297 (PubMed:11175748).Curated
Sequence conflicti421 – 4211T → I in BAB21297 (PubMed:11175748).Curated
Sequence conflicti453 – 4531Missing in BAB21297 (PubMed:11175748).Curated
Sequence conflicti468 – 4681A → V in BAB21297 (PubMed:11175748).Curated
Sequence conflicti472 – 4743FAH → TAD in BAB21297 (PubMed:11175748).Curated
Sequence conflicti486 – 4861A → V in BAB21297 (PubMed:11175748).Curated
Sequence conflicti488 – 4914RRSQ → LRSK in BAB21297 (PubMed:11175748).Curated
Sequence conflicti528 – 5281R → H in BAB21297 (PubMed:11175748).Curated
Sequence conflicti650 – 6501S → T in BAB21297 (PubMed:11175748).Curated
Sequence conflicti698 – 6981D → N in BAB21297 (PubMed:11175748).Curated
Sequence conflicti738 – 7381A → V in BAB21297 (PubMed:11175748).Curated
Sequence conflicti759 – 7591G → A in BAB21297 (PubMed:11175748).Curated
Sequence conflicti764 – 7641P → L in BAB21297 (PubMed:11175748).Curated
Sequence conflicti768 – 7681P → A in BAB21297 (PubMed:11175748).Curated
Sequence conflicti808 – 8081V → M in BAB21297 (PubMed:11175748).Curated
Sequence conflicti817 – 8171A → T in BAB21297 (PubMed:11175748).Curated
Sequence conflicti833 – 8331T → I in BAB21297 (PubMed:11175748).Curated
Sequence conflicti888 – 8881R → Q in BAB21297 (PubMed:11175748).Curated
Sequence conflicti896 – 8961A → V in BAB21297 (PubMed:11175748).Curated
Sequence conflicti918 – 9181R → G in BAB21297 (PubMed:11175748).Curated
Sequence conflicti924 – 9241T → A in BAB21297 (PubMed:11175748).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti69 – 691V → I.1 Publication
Corresponds to variant rs9932495 [ dbSNP | Ensembl ].
VAR_040495
Natural varianti118 – 1181R → C.1 Publication
Corresponds to variant rs56117885 [ dbSNP | Ensembl ].
VAR_040496
Natural varianti184 – 1841R → C.1 Publication
Corresponds to variant rs34683474 [ dbSNP | Ensembl ].
VAR_040497
Natural varianti271 – 2711R → Q.2 Publications
Corresponds to variant rs55772851 [ dbSNP | Ensembl ].
VAR_040498
Natural varianti318 – 3181A → T.1 Publication
Corresponds to variant rs56191901 [ dbSNP | Ensembl ].
VAR_040499
Natural varianti410 – 4101L → F.1 Publication
Corresponds to variant rs55687638 [ dbSNP | Ensembl ].
VAR_040500
Natural varianti487 – 4871S → T.2 Publications
Corresponds to variant rs26764 [ dbSNP | Ensembl ].
VAR_040501
Natural varianti504 – 5041L → F.1 Publication
VAR_040502
Natural varianti537 – 5371R → Q.1 Publication
Corresponds to variant rs56176960 [ dbSNP | Ensembl ].
VAR_040503
Natural varianti858 – 8581H → Y.1 Publication
VAR_040504

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.
CCDSiCCDS32407.1.
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.
CCDSiCCDS32407.1.
RefSeqiNP_001295149.2. NM_001308220.1.
NP_150296.4. NM_033266.3.
UniGeneiHs.592041.

3D structure databases

ProteinModelPortaliQ76MJ5.
SMRiQ76MJ5. Positions 32-191, 465-910.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115843. 1 interaction.
STRINGi9606.ENSP00000256797.

PTM databases

iPTMnetiQ76MJ5.
PhosphoSiteiQ76MJ5.

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

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 125 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.