TARGETID

T01003

FORMERID

TTDI03172

UNIPROID

ERN1_HUMAN

TARGNAME

Endoplasmic reticulum to nucleus signaling 1 (ERN1)

GENENAME

ERN1

TARGTYPE

Clinical trial target

SYNONYMS

Serine/threonine-protein kinase/endoribonuclease IRE1; Ire1-alpha; IRE1a; IRE1; Inositol-requiring protein 1; hIRE1p; Endoplasmic reticulum-to-nucleus signaling 1

FUNCTION

In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity. The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA. The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes. Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A. Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR).

PDBSTRUC

6HX1; 6HV0; 5HGI; 4Z7H; 4Z7G

BIOCLASS

Kinase

SEQUENCE

MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYFDYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKVMHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWLLIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSRDVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQKELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSGSSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAVGRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQRQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDLLRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPYYFHEPPEPQPPVTPDAL

DRUGINFO

ORIN1001

DRUGINFO

879325-11-8

DRUGINFO

AC1LE05K

DRUGINFO

BB 0223767

DRUGINFO

T8361

DRUGINFO

US8614253, 29-1

DRUGINFO

US8614253, 29-19

DRUGINFO

US8614253, 32-4

DRUGINFO

US8614253, 32-5