O75460 (ERN1_HUMAN) 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
Inositol-requiring protein 1
Short name=hIRE1p
Ire1-alpha
Short name=IRE1a

Including the following 2 domains:

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

Gene names

Name:	ERN1
Synonyms:	IRE1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	977 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 XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis. Ref.1 Ref.8 Ref.9 UniProtKB Q9EQY0
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
Enzyme regulation	The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain. Ref.1 Ref.9
Subunit structure	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. Ref.7 Ref.9
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.1.
Tissue specificity	Ubiquitously expressed. High levels observed in pancreatic tissue. Ref.1
Post-translational modification	Autophosphorylated. Ref.1 ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 KEN domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Serine/threonine-protein kinase Transferase
PTM	ADP-ribosylation Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Inferred from direct assay Ref.1. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: InterPro positive regulation of endoplasmic reticulum unfolded protein response Inferred from mutant phenotype PubMed 16645094. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.1. Source: UniProtKB nuclear inner membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB endoribonuclease activity Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Bak1	O08734	2	EBI-371750,EBI-822441	From a different organism.
BAX	Q07812	2	EBI-371750,EBI-516580
Bax	Q07813	2	EBI-371750,EBI-700711	From a different organism.
Hspa5	P20029	2	EBI-371750,EBI-772325	From a different organism.
TAOK3	Q9H2K8	3	EBI-371750,EBI-1384100
TRAF2	Q12933	2	EBI-371750,EBI-355744

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75460-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75460-2)

The sequence of this isoform differs from the canonical sequence as follows:
     19-70: IFGSTSTVTL...VLQVPTHVEE → VSDRGAWGGG...SPAVGGSGRA
     71-977: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 977

959

Serine/threonine-protein kinase/endoribonuclease IRE1

PRO_0000024327

Regions

Topological domain

19 – 443

425

Lumenal Potential

Transmembrane

444 – 464

21

Helical; Potential

Topological domain

465 – 977

513

Cytoplasmic Potential

Domain

571 – 832

262

Protein kinase

Domain

835 – 963

129

KEN

Nucleotide binding

577 – 585

9

ATP By similarity UniProtKB P32361

Sites

Active site

688

1

Proton acceptor By similarity UniProtKB P32361

Binding site

599

1

ATP Ref.1

Amino acid modifications

Modified residue

973

1

Phosphothreonine Ref.10

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

19 – 70

52

IFGST…THVEE → VSDRGAWGGGQLATAGSGPG QRRGAGAGVRAGSATAAARC PVSPAVGGSGRA in isoform 2.

VSP_034582

Alternative sequence

71 – 977

907

Missing in isoform 2.

VSP_034583

Natural variant

244

1

N → S in a renal clear cell carcinoma sample; somatic mutation. Ref.14

VAR_040488

Natural variant

418

1

V → M. Ref.14
Corresponds to variant rs55869215 [ dbSNP | Ensembl ].

VAR_040489

Natural variant

474

1

L → R in a lung adenocarcinoma sample; somatic mutation. Ref.14

VAR_040490

Natural variant

635

1

R → W in a gastric adenocarcinoma sample; somatic mutation. Ref.14

VAR_040491

Natural variant

700

1

N → S. Ref.14

VAR_040492

Natural variant

769

1

S → F in a glioblastoma multiforme sample; somatic mutation. Ref.14

VAR_040493

Natural variant

830

1

P → L in an ovarian serous carcinoma sample; somatic mutation. Ref.14

VAR_040494

Experimental info

Mutagenesis

109

1

C → S: No effect on dimerization. Ref.9

Mutagenesis

148

1

C → S: No effect on dimerization. Weakens dimer; when associated with S-148. Ref.9

Mutagenesis

332

1

C → S: No effect on dimerization. Weakens dimer; when associated with S-332. Ref.9

Mutagenesis

599

1

K → A: Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest. Ref.1 Ref.8

Sequence conflict

190 – 191

2

DV → EG in AAC25991. Ref.1

Sequence conflict

768

1

I → V in AAC25991. Ref.1

Sequence conflict

816

1

D → G in BAF85092. Ref.2

Sequence conflict

824 – 825

2

KH → ND in AAC25991. Ref.1

Sequence conflict

880

1

V → D in AAC25991. Ref.1

Sequence conflict

904

1

M → T in BAF85092. Ref.2

Sequence conflict

924

1

S → T in AAC25991. Ref.1

Secondary structure

1

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977

Helix Strand Turn

Details...

Beta strand

32 – 37

6

Beta strand

40 – 46

7

Turn

47 – 49

3

Beta strand

52 – 57

6

Beta strand

73 – 75

3

Turn

77 – 79

3

Beta strand

82 – 84

3

Beta strand

93 – 95

3

Helix

100 – 104

5

Beta strand

120 – 128

9

Beta strand

154 – 164

11

Beta strand

168 – 172

5

Beta strand

176 – 182

7

Beta strand

197 – 201

5

Beta strand

205 – 209

5

Turn

211 – 213

3

Beta strand

216 – 221

6

Beta strand

226 – 231

6

Beta strand

238 – 240

3

Beta strand

243 – 246

4

Helix

247 – 264

18

Helix

273 – 279

7

Beta strand

280 – 284

5

Beta strand

286 – 288

3

Beta strand

297 – 300

4

Turn

359 – 361

3

Beta strand

564 – 566

3

Beta strand

569 – 579

11

Helix

581 – 583

3

Beta strand

585 – 601

17

Turn

603 – 605

3

Beta strand

606 – 608

3

Helix

610 – 618

9

Beta strand

628 – 634

7

Beta strand

637 – 643

7

Beta strand

646 – 648

3

Helix

649 – 654

6

Beta strand

655 – 657

3

Helix

665 – 681

17

Beta strand

693 – 696

4

Beta strand

707 – 709

3

Beta strand

714 – 716

3

Helix

740 – 742

3

Helix

754 – 768

15

Turn

778 – 780

3

Helix

781 – 786

6

Helix

800 – 812

13

Helix

817 – 819

3

Helix

823 – 827

5

Turn

830 – 832

3

Helix

835 – 848

14

Helix

857 – 864

8

Turn

868 – 871

4

Helix

874 – 876

3

Helix

880 – 885

6

Helix

897 – 909

13

Turn

910 – 913

4

Helix

916 – 922

7

Helix

927 – 934

8

Helix

940 – 947

8

Helix

948 – 951

4

Beta strand

952 – 954

3

Helix

955 – 957

3

Turn

958 – 960

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: A2DF808CCE015536	FASTA	977	109,735
	10 20 30 40 50 60 MPARRLLLLL TLLLPGLGIF GSTSTVTLPE TLLFVSTLDG SLHAVSKRTG SIKWTLKEDP 70 80 90 100 110 120 VLQVPTHVEE PAFLPDPNDG SLYTLGSKNN EGLTKLPFTI PELVQASPCR SSDGILYMGK 130 140 150 160 170 180 KQDIWYVIDL LTGEKQQTLS SAFADSLCPS TSLLYLGRTE YTITMYDTKT RELRWNATYF 190 200 210 220 230 240 DYAASLPEDD VDYKMSHFVS NGDGLVVTVD SESGDVLWIQ NYASPVVAFY VWQREGLRKV 250 260 270 280 290 300 MHINVAVETL RYLTFMSGEV GRITKWKYPF PKETEAKSKL TPTLYVGKYS TSLYASPSMV 310 320 330 340 350 360 HEGVAVVPRG STLPLLEGPQ TDGVTIGDKG ECVITPSTDV KFDPGLKSKN KLNYLRNYWL 370 380 390 400 410 420 LIGHHETPLS ASTKMLERFP NNLPKHRENV IPADSEKKSF EEVINLVDQT SENAPTTVSR 430 440 450 460 470 480 DVEEKPAHAP ARPEAPVDSM LKDMATIILS TFLLIGWVAF IITYPLSMHQ QQQLQHQQFQ 490 500 510 520 530 540 KELEKIQLLQ QQQQQLPFHP PGDTAQDGEL LDTSGPYSES SGTSSPSTSP RASNHSLCSG 550 560 570 580 590 600 SSASKAGSSP SLEQDDGDEE TSVVIVGKIS FCPKDVLGHG AEGTIVYRGM FDNRDVAVKR 610 620 630 640 650 660 ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH 670 680 690 700 710 720 LGLEPITLLQ QTTSGLAHLH SLNIVHRDLK PHNILISMPN AHGKIKAMIS DFGLCKKLAV 730 740 750 760 770 780 GRHSFSRRSG VPGTEGWIAP EMLSEDCKEN PTYTVDIFSA GCVFYYVISE GSHPFGKSLQ 790 800 810 820 830 840 RQANILLGAC SLDCLHPEKH EDVIARELIE KMIAMDPQKR PSAKHVLKHP FFWSLEKQLQ 850 860 870 880 890 900 FFQDVSDRIE KESLDGPIVK QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL 910 920 930 940 950 960 LRAMRNKKHH YRELPAEVRE TLGSLPDDFV CYFTSRFPHL LAHTYRAMEL CSHERLFQPY 970 YFHEPPEPQP PVTPDAL
	Isoform 2 [UniParc]. Checksum: C93BA0CB092E6204	FASTA	70	6,649
	10 20 30 40 50 60 MPARRLLLLL TLLLPGLGVS DRGAWGGGQL ATAGSGPGQR RGAGAGVRAG SATAAARCPV 70 SPAVGGSGRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells." Tirasophon W., Welihinda A.A., Kaufman R.J. Genes Dev. 12:1812-1824(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, GLYCOSYLATION, MUTAGENESIS OF LYS-599. Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Testis.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Endothelial cell.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-977 (ISOFORM 2). Tissue: Brain and Leukocyte.
[7]	"Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress." Yoneda T., Imaizumi K., Oono K., Yui D., Gomi F., Katayama T., Tohyama M. J. Biol. Chem. 276:13935-13940(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TAOK3 AND TRAF2.
[8]	"Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress." Iwawaki T., Hosoda A., Okuda T., Kamigori Y., Nomura-Furuwatari C., Kimata Y., Tsuru A., Kohno K. Nat. Cell Biol. 3:158-164(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-599.
[9]	"Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha." Liu C.Y., Xu Z., Kaufman R.J. J. Biol. Chem. 278:17680-17687(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, ENZYME REGULATION, INTERACTION WITH HSPA5, MUTAGENESIS OF CYS-109; CYS-148 AND CYS-332.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-973, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK-and IRE1alpha-mediated unfolded protein response." Jwa M., Chang P. Nat. Cell Biol. 14:1223-1230(2012) [PubMed] [Europe PMC] [Abstract] Cited for: ADP-RIBOSYLATION BY PARP16.
[13]	"The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response." Zhou J., Liu C.Y., Back S.H., Clark R.L., Peisach D., Xu Z., Kaufman R.J. Proc. Natl. Acad. Sci. U.S.A. 103:14343-14348(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 24-390.
[14]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-244; MET-418; ARG-474; TRP-635; SER-700; PHE-769 AND LEU-830.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF059198 mRNA. Translation: AAC25991.1.
AK292403 mRNA. Translation: BAF85092.1.
DA254477 mRNA. No translation available.
AB209869 mRNA. Translation: BAD93106.1.
AC005803 Genomic DNA. No translation available.
AC025362 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94214.1.
BC130405 mRNA. Translation: AAI30406.1.
BC130407 mRNA. Translation: AAI30408.1.
BI912495 mRNA. No translation available.

IPI

IPI00015974.
IPI00873219.

RefSeq

NP_001424.3. NM_001433.3.

UniGene

Hs.133982.
Hs.700027.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HZ6	X-ray	3.10	A	24-390	[»]
3P23	X-ray	2.70	A/B/C/D	547-977	[»]

ProteinModelPortal

O75460.

ModBase

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Protein-protein interaction databases

DIP

DIP-31711N.

IntAct

O75460. 7 interactions.

MINT

MINT-3001268.

STRING

9606.ENSP00000401445.

PTM databases

PhosphoSite

O75460.

Proteomic databases

PaxDb

O75460.

PRIDE

O75460.

Protocols and materials databases

DNASU

2081.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000433197; ENSP00000401445; ENSG00000178607.

GeneID

2081.

KEGG

hsa:2081.

UCSC

uc002jdz.2. human.

Organism-specific databases

CTD

2081.

GeneCards

GC17M062120.

H-InvDB

HIX0014084.

HGNC

HGNC:3449. ERN1.

HPA

CAB009495.
HPA027730.

MIM

604033. gene.

neXtProt

NX_O75460.

PharmGKB

PA27861.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000012929.

HOVERGEN

HBG051506.

InParanoid

O75460.

KO

K08852.

OMA

FRSYKGG.

OrthoDB

EOG42Z4PG.

PhylomeDB

O75460.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

Bgee

O75460.

CleanEx

HS_ERN1.

Genevestigator

O75460.

GermOnline

ENSG00000178607. Homo sapiens.

Family and domain databases

InterPro

IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_cat_dom.
IPR006567. PUG-dom.
IPR011047. Quinonprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

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

SMART

SM00564. PQQ. 5 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

BindingDB

O75460.

ChEMBL

CHEMBL1163101.

ChiTaRS

ERN1. human.

EvolutionaryTrace

O75460.

GenomeRNAi

2081.

NextBio

8459.

SOURCE

Search...

Entry information

Entry name

ERN1_HUMAN

Accession

Primary (citable) accession number: O75460
Secondary accession number(s): A1L457 , A8K8N8, A8MXS7, Q59EE2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	July 1, 2008
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.