ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1

ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1
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Topology in Endoplasmic reticulum membrane
Topologylumenal side
cytoplasmic side
ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1 » Endoplasmic reticulum-to-nucleus signaling 1;Inositol-requiring protein 1;hIRE1p; Ire1-alpha;IRE1a;
Hydrophobic Thickness 28.4 ± 3.2 Å
Tilt Angle 0 ± 0°
ΔGtransfer -31.2 kcal/mol
ΔGfold -17.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology Out
TM Segments 444-464 (444-464)
Pathways

Alzheimer's disease (KEGG)

Protein processing in endoplasmic reticulum (KEGG)

PDB 4u6r (547-977), 3p23 (A/B/C/D=547-977), 2hz6 (A=24-390)
OPM none
Complexes

ERN1:ERN1_HUMAN

Interactions

BAK, Complex: BAK:ERN1, PubMed

BAX, Complex: ERN1:BAX, PubMed

ERN1, Complex: Homodimer of kinase/endoribonuclease, PDBID: 3P23

RNF13, Complex: RNF13:ERN1

SE1L1, Complex: ERN1:SE1L1, PubMed

TNR1A, Complex: TNR1A:ERN1:AGFG1, PubMed

TNR1A, Complex: TNR1A:ERN1, PubMed

Domains

AA: 571-832, PDBID: 3P23, Subunit A, Seq Identity:100%, Protein kinase domain

AA: 838-961, PDBID: 3P23, Subunit D, Seq Identity:100%, Ribonuclease 2-5A

UniProt annotation for ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1
FUNCTION: Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto- activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

ENZYME REGULATION: The kinase domain is activated by trans- autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain.

SUBUNIT: Interacts with DAB2IP (via PH domain); the interaction occurs in a ER stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1 (By similarity). Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of ERN1. Interacts with TAOK3 and TRAF2.

TISSUE SPECIFICITY: Ubiquitously expressed. High levels observed in pancreatic tissue.

UniProt features for ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1
SIGNAL 1 18 Potential.
CHAIN 19 977 Serine/threonine-protein kinase/endoribonuclease IRE1.
DOMAIN 571 832 Protein kinase.
DOMAIN 835 963 KEN.
ACT_SITE 688 688 Proton acceptor (By similarity).
Amino Acid Sequence for ERN1_HUMAN » Serine/threonine-protein kinase/endoribonuclease IRE1
MPARRLLLLL TLLLPGLGIF GSTSTVTLPE TLLFVSTLDG SLHAVSKRTG SIKWTLKEDP VLQVPTHVEE PAFLPDPNDG SLYTLGSKNN EGLTKLPFTI PELVQASPCR SSDGILYMGK KQDIWYVIDL LTGEKQQTLS SAFADSLCPS TSLLYLGRTE YTITMYDTKT RELRWNATYF DYAASLPEDD VDYKMSHFVS NGDGLVVTVD SESGDVLWIQ NYASPVVAFY VWQREGLRKV MHINVAVETL RYLTFMSGEV GRITKWKYPF PKETEAKSKL TPTLYVGKYS TSLYASPSMV HEGVAVVPRG STLPLLEGPQ TDGVTIGDKG ECVITPSTDV KFDPGLKSKN KLNYLRNYWL LIGHHETPLS ASTKMLERFP NNLPKHRENV IPADSEKKSF EEVINLVDQT SENAPTTVSR DVEEKPAHAP ARPEAPVDSM LKDMATIILS TFLLIGWVAF IITYPLSMHQ QQQLQHQQFQ KELEKIQLLQ QQQQQLPFHP PGDTAQDGEL LDTSGPYSES SGTSSPSTSP RASNHSLCSG SSASKAGSSP SLEQDDGDEE TSVVIVGKIS FCPKDVLGHG AEGTIVYRGM FDNRDVAVKR ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH LGLEPITLLQ QTTSGLAHLH SLNIVHRDLK PHNILISMPN AHGKIKAMIS DFGLCKKLAV GRHSFSRRSG VPGTEGWIAP EMLSEDCKEN PTYTVDIFSA GCVFYYVISE GSHPFGKSLQ RQANILLGAC SLDCLHPEKH EDVIARELIE KMIAMDPQKR PSAKHVLKHP FFWSLEKQLQ FFQDVSDRIE KESLDGPIVK QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL LRAMRNKKHH YRELPAEVRE TLGSLPDDFV CYFTSRFPHL LAHTYRAMEL CSHERLFQPY YFHEPPEPQP PVTPDAL