P32361 (IRE1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase/endoribonuclease IRE1

Alternative name(s):
Endoplasmic reticulum-to-nucleus signaling 1

Including the following 2 domains:

1. Serine/threonine-protein kinase
   EC=2.7.11.1
2. Endoribonuclease
   EC=3.1.26.-

Gene names

Name:	IRE1
Synonyms:	ERN1
Ordered Locus Names:	YHR079C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	1115 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	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 HAC1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes. Ref.5 Ref.6 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain. Ref.5
Subunit structure	Homodimer; in response to the accumulation of unfolded proteins. Ref.5 Ref.6
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Post-translational modification	Autophosphorylated mainly on serine residues. Ref.6
Miscellaneous	Present with 259 molecules/cell in log phase SD medium. Ref.8
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 KEN domain. Contains 1 protein kinase domain.
Sequence caution	The sequence AAB68894.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	endoplasmic reticulum unfolded protein response Inferred from mutant phenotype Ref.2. Source: SGD fungal-type cell wall organization Inferred from mutant phenotype. Source: SGD inositol metabolic process Inferred from mutant phenotype Ref.1. Source: SGD mRNA processing Inferred from electronic annotation. Source: InterPro regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: SGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW endoribonuclease activity, producing 5'-phosphomonoesters Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Inferred from direct assay. Source: SGD protein serine/threonine kinase activity Inferred from direct assay Ref.5. Source: SGD unfolded protein binding Inferred from mutant phenotype. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-9364,EBI-9364

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 1115

1097

Serine/threonine-protein kinase/endoribonuclease IRE1

PRO_0000024338

Regions

Topological domain

19 – 526

508

Lumenal Potential

Transmembrane

527 – 555

29

Helical; Potential

Topological domain

556 – 1115

560

Cytoplasmic Potential

Domain

674 – 980

307

Protein kinase

Domain

983 – 1115

133

KEN

Nucleotide binding

680 – 688

9

ATP By similarity

Sites

Active site

797

1

Proton acceptor By similarity

Binding site

702

1

ATP

Amino acid modifications

Modified residue

840

1

Phosphoserine; by autocatalysis Probable

Modified residue

841

1

Phosphoserine; by autocatalysis Probable

Glycosylation

111

1

N-linked (GlcNAc...) Potential

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Glycosylation

298

1

N-linked (GlcNAc...) Potential

Glycosylation

397

1

N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis

702

1

K → A: Loss of autophosphorylation. Ref.5

Sequence conflict

368

1

N → S in CAA77763. Ref.1

Sequence conflict

625 – 626

2

ND → KH in CAA77763. Ref.1

Secondary structure

1

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1115

Helix Strand Turn

Details...

Beta strand

116 – 127

12

Beta strand

132 – 136

5

Turn

137 – 139

3

Beta strand

142 – 146

5

Helix

148 – 150

3

Beta strand

154 – 156

3

Turn

162 – 164

3

Beta strand

165 – 171

7

Turn

175 – 177

3

Beta strand

178 – 183

6

Turn

184 – 186

3

Beta strand

187 – 194

8

Helix

195 – 199

5

Beta strand

203 – 207

5

Beta strand

222 – 226

5

Beta strand

229 – 237

9

Turn

238 – 240

3

Beta strand

243 – 248

6

Beta strand

277 – 286

10

Beta strand

300 – 305

6

Turn

308 – 310

3

Helix

311 – 314

4

Beta strand

321 – 323

3

Beta strand

326 – 329

4

Turn

330 – 332

3

Beta strand

333 – 337

5

Beta strand

344 – 347

4

Beta strand

355 – 364

10

Turn

365 – 368

4

Beta strand

369 – 374

6

Beta strand

390 – 394

5

Beta strand

400 – 404

5

Turn

405 – 407

3

Helix

409 – 413

5

Helix

419 – 422

4

Helix

424 – 426

3

Helix

429 – 433

5

Helix

435 – 442

8

Beta strand

444 – 446

3

Beta strand

674 – 682

9

Beta strand

688 – 705

18

Helix

706 – 708

3

Helix

709 – 722

14

Beta strand

731 – 736

6

Beta strand

738 – 745

8

Beta strand

749 – 751

3

Helix

752 – 757

6

Helix

774 – 790

17

Helix

800 – 802

3

Beta strand

803 – 806

4

Helix

809 – 812

4

Beta strand

823 – 826

4

Helix

858 – 861

4

Helix

900 – 914

15

Turn

924 – 926

3

Helix

927 – 933

7

Helix

947 – 960

14

Helix

965 – 967

3

Helix

971 – 975

5

Helix

978 – 980

3

Helix

983 – 998

16

Turn

1002 – 1005

4

Helix

1007 – 1013

7

Helix

1016 – 1019

4

Helix

1025 – 1028

4

Helix

1048 – 1060

13

Helix

1062 – 1064

3

Helix

1067 – 1072

6

Helix

1078 – 1087

10

Helix

1091 – 1102

12

Turn

1107 – 1109

3

Helix

1110 – 1114

5

Sequences

	Sequence		Length	Mass (Da)
	P32361 [UniParc]. Last modified February 1, 1995. Version 2. Checksum: BD65D74E74365945	FASTA	1,115	126,976
	10 20 30 40 50 60 MRLLRRNMLV LTLLVCVFSS IISCSIPLSS RTSRRQIVED EVASTKKLNF NYGVDKNINS 70 80 90 100 110 120 PIPAPRTTEG LPNMKLSSYP TPNLLNTADN RRANKKGRRA ANSISVPYLE NRSLNELSLS 130 140 150 160 170 180 DILIAADVEG GLHAVDRRNG HIIWSIEPEN FQPLIEIQEP SRLETYETLI IEPFGDGNIY 190 200 210 220 230 240 YFNAHQGLQK LPLSIRQLVS TSPLHLKTNI VVNDSGKIVE DEKVYTGSMR TIMYTINMLN 250 260 270 280 290 300 GEIISAFGPG SKNGYFGSQS VDCSPEEKIK LQECENMIVI GKTIFELGIH SYDGASYNVT 310 320 330 340 350 360 YSTWQQNVLD VPLALQNTFS KDGMCIAPFR DKSLLASDLD FRIARWVSPT FPGIIVGLFD 370 380 390 400 410 420 VFNDLRTNEN ILVPHPFNPG DHESISSNKV YLDQTSNLSW FALSSQNFPS LVESAPISRY 430 440 450 460 470 480 ASSDRWRVSS IFEDETLFKN AIMGVHQIYN NEYDHLYENY EKTNSLDTTH KYPPLMIDSS 490 500 510 520 530 540 VDTTDLHQNN EMNSLKEYMS PEDLEAYRKK IHEQISRELD EKNQNSLLLK FGSLVYRIIE 550 560 570 580 590 600 TGVFLLLFLI FCAILQRFKI LPPLYVLLSK IGFMPEKEIP IVESKSLNCP SSSENVTKPF 610 620 630 640 650 660 DMKSGKQVVF EGAVNDGSLK SEKDNDDADE DDEKSLDLTT EKKKRKRGSR GGKKGRKSRI 670 680 690 700 710 720 ANIPNFEQSL KNLVVSEKIL GYGSSGTVVF QGSFQGRPVA VKRMLIDFCD IALMEIKLLT 730 740 750 760 770 780 ESDDHPNVIR YYCSETTDRF LYIALELCNL NLQDLVESKN VSDENLKLQK EYNPISLLRQ 790 800 810 820 830 840 IASGVAHLHS LKIIHRDLKP QNILVSTSSR FTADQQTGAE NLRILISDFG LCKKLDSGQS 850 860 870 880 890 900 SFRTNLNNPS GTSGWRAPEL LEESNNLQCQ VETEHSSSRH TVVSSDSFYD PFTKRRLTRS 910 920 930 940 950 960 IDIFSMGCVF YYILSKGKHP FGDKYSRESN IIRGIFSLDE MKCLHDRSLI AEATDLISQM 970 980 990 1000 1010 1020 IDHDPLKRPT AMKVLRHPLF WPKSKKLEFL LKVSDRLEIE NRDPPSALLM KFDAGSDFVI 1030 1040 1050 1060 1070 1080 PSGDWTVKFD KTFMDNLERY RKYHSSKLMD LLRALRNKYH HFMDLPEDIA ELMGPVPDGF 1090 1100 1110 YDYFTKRFPN LLIGVYMIVK ENLSDDQILR EFLYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae." Nikawa J., Yamashita S. Mol. Microbiol. 6:1441-1446(1992) [PubMed: 1625574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus." Mori K., Ma W., Gething M.J., Sambrook J. Cell 74:743-756(1993) [PubMed: 8358794] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII." Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P. , Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., Vaudin M. Science 265:2077-2082(1994) [PubMed: 8091229] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation." Welihinda A.A., Kaufman R.J. J. Biol. Chem. 271:18181-18187(1996) [PubMed: 8663458] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, HOMODIMERIZATION, MUTAGENESIS OF LYS-702.
[6]	"Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus." Shamu C.E., Walter P. EMBO J. 15:3028-3039(1996) [PubMed: 8670804] [Abstract] Cited for: FUNCTION, OLIGOMERIZATION, PHOSPHORYLATION.
[7]	"The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response." Sidrauski C., Walter P. Cell 90:1031-1039(1997) [PubMed: 9323131] [Abstract] Cited for: FUNCTION.
[8]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z11701 Genomic DNA. Translation: CAA77763.1.
L19640 Genomic DNA. Translation: AAA34489.1.
U10556 Genomic DNA. Translation: AAB68894.1. Different initiation.
BK006934 Genomic DNA. Translation: DAA06773.1.

PIR

A47541.

RefSeq

NP_011946.1. NM_001179209.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BE1	X-ray	2.98	A/B	111-449	[»]
2RIO	X-ray	2.40	A/B	658-1115	[»]
3FBV	X-ray	3.20	A/B/C/D/E/F/G/H/I/J/K/L/M/N	641-1115	[»]
3LJ0	X-ray	3.20	A/B	658-1115	[»]
3LJ1	X-ray	3.33	A/B	658-1115	[»]
3LJ2	X-ray	3.33	A/B	658-1115	[»]
3SDJ	X-ray	3.65	A/B/C/D/E/F/G/H/I/J/K/L/M/N	641-1115	[»]
3SDM	X-ray	6.60	A/B/C/D/E/F/G	641-1115	[»]

ProteinModelPortal

P32361.

SMR

P32361. Positions 111-449, 663-1115.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-233N.

IntAct

P32361. 5 interactions.

MINT

MINT-408165.

STRING

P32361.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YHR079C; YHR079C; YHR079C.

GeneID

856478.

KEGG

sce:YHR079C.

NMPDR

fig|4932.3.peg.3106.

Organism-specific databases

CYGD

YHR079c.

SGD

S000001121. IRE1.

Phylogenomic databases

eggNOG

fuNOG06834.

GeneTree

EFGT00050000000595.

HOGENOM

HBG203762.

OMA

PNNIDND.

OrthoDB

EOG4DBXNV.

Enzyme and pathway databases

BRENDA

2.7.11.1. 984.

Reactome

REACT_97252. Diabetes pathways.

Gene expression databases

ArrayExpress

P32361.

Genevestigator

P32361.

GermOnline

YHR079C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR010513. KEN_RNase_activator.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_cat_dom.
IPR006567. PUG-dom.
IPR011047. Quinonprotein_ADH-like.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Gene3D

G3DSA:2.140.10.10. Quinoprotein_alc_DH-like. 1 hit.

KO

K08852.

Pfam

PF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]

SMART

SM00564. PQQ. 3 hits.
SM00580. PUG. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50998. Quin_alc_DH_like. 1 hit.

PROSITE

PS51392. KEN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

982158.

Entry information

Entry name

IRE1_YEAST

Accession

Primary (citable) accession number: P32361
Secondary accession number(s): D3DL29

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	February 1, 1995
Last modified:	December 14, 2011
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program