ENTRY ko04141 Pathway NAME Protein processing in endoplasmic reticulum DESCRIPTION The endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylated. Correctly folded proteins are packaged into transport vesicles that shuttle them to the Golgi complex. Misfolded proteins are retained within the ER lumen in complex with molecular chaperones. Proteins that are terminally misfolded bind to BiP and are directed toward degradation through the proteasome in a process called ER-associated degradation (ERAD). Accumulation of misfolded proteins in the ER causes ER stress and activates a signaling pathway called the unfolded protein response (UPR). In certain severe situations, however, the protective mechanisms activated by the UPR are not sufficient to restore normal ER function and cells die by apoptosis. CLASS Genetic Information Processing; Folding, sorting and degradation PATHWAY_MAP ko04141 Protein processing in endoplasmic reticulum DBLINKS GO: 0030433 0034976 ORTHOLOGY K10956 protein transport protein SEC61 subunit alpha K09481 protein transport protein SEC61 subunit beta K07342 protein transport protein SEC61 subunit gamma and related proteins K12275 translocation protein SEC62 K09540 translocation protein SEC63 K12666 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit 1 (ribophorin I) K12667 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit 2 (ribophorin II) K12668 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit DAD1/OST2 K12669 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit 3/6 K12670 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit DDOST/WBP1 K00730 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit 4 K12691 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit 5 K07151 dolichyl-diphosphooligosaccharide---protein glycosyltransferase [EC:2.4.99.18] K19478 dolichyl-diphosphooligosaccharide---protein glycosyltransferase subunit MAGT1/TUSC3 K26501 oligosaccharyltransferase complex subunit OSTC K26502 transmembrane protein 258 K01228 mannosyl-oligosaccharide glucosidase [EC:3.2.1.106] K13999 cytoskeleton-associated protein 4 K14000 ribosome-binding protein 1 K14001 nucleotide exchange factor SIL1 K09486 hypoxia up-regulated 1 K09490 endoplasmic reticulum chaperone BiP [EC:3.6.4.10] K09517 DnaJ homolog subfamily B member 11 K09521 DnaJ homolog subfamily C member 1 K09523 DnaJ homolog subfamily C member 3 K09530 DnaJ homolog subfamily C member 10 [EC:1.8.4.-] K14002 DnaJ-related protein SCJ1 K09487 heat shock protein 90kDa beta K05546 mannosyl-oligosaccharide alpha-1,3-glucosidase [EC:3.2.1.207] K08288 protein kinase C substrate 80K-H K08054 calnexin K08056 protein disulfide-isomerase A3 [EC:5.3.4.1] K08057 calreticulin K01230 mannosyl-oligosaccharide alpha-1,2-mannosidase [EC:3.2.1.113] K23741 endoplasmic reticulum Man9GlcNAc2 1,2-alpha-mannosidase [EC:3.2.1.209] K10082 lectin, mannose-binding 2 K10080 lectin, mannose-binding 1 K10081 lectin, mannose-binding 1-like K14003 prolactin regulatory element-binding protein K07953 GTP-binding protein SAR1 [EC:3.6.5.-] K14004 protein transport protein SEC13 K14005 protein transport protein SEC31 K14006 protein transport protein SEC23 K14007 protein transport protein SEC24 K11718 UDP-glucose:glycoprotein glucosyltransferase [EC:2.4.1.-] K10084 ER degradation enhancer, mannosidase alpha-like 1 K10085 ER degradation enhancer, mannosidase alpha-like 2 K10086 ER degradation enhancer, mannosidase alpha-like 3 K09580 protein disulfide-isomerase A1 [EC:5.3.4.1] K09582 protein disulfide-isomerase A4 [EC:5.3.4.1] K09584 protein disulfide-isomerase A6 [EC:5.3.4.1] K13996 protein disulfide-isomerase [EC:5.3.4.1] K09586 endoplasmic reticulum protein 29 K13984 thioredoxin domain-containing protein 5 [EC:5.3.4.1] K10950 ERO1-like protein alpha [EC:1.8.4.-] K10976 ERO1-like protein beta [EC:1.8.4.-] K10088 protein OS-9 K14008 endoplasmic reticulum lectin 1 K13249 translocon-associated protein subunit alpha K13250 translocon-associated protein subunit beta K13251 translocon-associated protein subunit gamma K04571 translocon-associated protein subunit delta K14009 B-cell receptor-associated protein 31 K14010 translocating chain-associated membrane protein 1 K11519 Derlin-1 K13989 Derlin-2/3 K24348 UBX domain-containing protein 1/4 K24349 UBX domain-containing protein 2A K14011 UBX domain-containing protein 6 K24351 UBX domain-containing protein 8 K14012 UBX domain-containing protein 1 K14013 UBX domain-containing protein 2 K14014 small VCP/p97-interacting protein K13525 transitional endoplasmic reticulum ATPase K14015 nuclear protein localization protein 4 K14016 ubiquitin fusion degradation protein 1 K03283 heat shock 70kDa protein 1/6/8 K09502 DnaJ homolog subfamily A member 1 K09503 DnaJ homolog subfamily A member 2 K09507 DnaJ homolog subfamily B member 1 K09508 DnaJ homolog subfamily B member 2 K09518 DnaJ homolog subfamily B member 12 K09525 DnaJ homolog subfamily C member 5 K04079 molecular chaperone HtpG K09485 heat shock protein 110kDa K09555 BCL2-associated athanogene 1 K09556 BCL2-associated athanogene 2 K09562 hsp70-interacting protein K14017 HSP70 co-chaperone SNL1 K09541 crystallin, alpha A K09542 crystallin, alpha B K13993 HSP20 family protein K13719 ubiquitin thioesterase OTU1 [EC:3.1.2.-] K14018 phospholipase A-2-activating protein K10839 UV excision repair protein RAD23 K04523 ubiquilin K01456 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase [EC:3.5.1.52] K11863 Ataxin-3 [EC:3.4.22.-] K10597 ubiquitin conjugation factor E4 B [EC:2.3.2.27] K08860 eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1] K03237 translation initiation factor 2 subunit 1 K05638 nuclear factor erythroid 2-related factor 2 K04374 cyclic AMP-dependent transcription factor ATF-4 K14019 protein phosphatase 1 regulatory subunit 15A K04452 DNA damage-inducible transcript 3 K02161 apoptosis regulator Bcl-2 K09054 cyclic AMP-dependent transcription factor ATF-6 alpha K09049 cyclic AMP-dependent transcription factor ATF-6 beta K14020 wolfamin K08653 membrane-bound transcription factor site-1 protease [EC:3.4.21.112] K07765 S2P endopeptidase [EC:3.4.24.85] K09027 X box-binding protein 1 K08852 serine/threonine-protein kinase/endoribonuclease IRE1 [EC:2.7.11.1 3.1.26.-] K03173 TNF receptor-associated factor 2 [EC:2.3.2.27] K04426 mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25] K04431 mitogen-activated protein kinase kinase 7 [EC:2.7.12.2] K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24] K02159 apoptosis regulator BAX K14021 Bcl-2 homologous antagonist/killer K01367 calpain-1 [EC:3.4.22.52] K03853 calpain-2 [EC:3.4.22.53] K04741 caspase 12 [EC:3.4.22.-] K10661 E3 ubiquitin-protein ligase MARCH6 [EC:2.3.2.27] K10578 ubiquitin-conjugating enzyme E2 J1 [EC:2.3.2.23] K04554 ubiquitin-conjugating enzyme E2 J2 [EC:2.3.2.23] K10575 ubiquitin-conjugating enzyme E2 G1 [EC:2.3.2.23] K04555 ubiquitin-conjugating enzyme E2 G2 [EC:2.3.2.23] K14022 coupling of ubiquitin conjugation to ER degradation protein 1 K14023 ERAD-associated E3 ubiquitin-protein ligase component HRD3 K10601 E3 ubiquitin-protein ligase synoviolin [EC:2.3.2.27] K14024 U1 SNP1-associating protein 1 K10666 E3 ubiquitin-protein ligase RNF5/185 [EC:2.3.2.27] K14025 selenoprotein S K14026 SEL1 protein K14027 homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein K10636 E3 ubiquitin-protein ligase AMFR [EC:2.3.2.36] K09561 STIP1 homology and U-box containing protein 1 [EC:2.3.2.27] K06689 ubiquitin-conjugating enzyme E2 D [EC:2.3.2.23] K04556 parkin [EC:2.3.2.31] K03868 E3 ubiquitin-protein ligase RBX1 [EC:2.3.2.32] K03347 cullin 1 K03094 S-phase kinase-associated protein 1 K10099 F-box protein 2 K10100 F-box protein 6 COMPOUND C00076 Calcium cation G00009 G00010 G00011 G00012 G10694 REFERENCE PMID:19491040 AUTHORS Naidoo N TITLE ER and aging-Protein folding and the ER stress response. JOURNAL Ageing Res Rev 8:150-9 (2009) DOI:10.1016/j.arr.2009.03.001 REFERENCE PMID:18023214 AUTHORS Malhotra JD, Kaufman RJ TITLE The endoplasmic reticulum and the unfolded protein response. JOURNAL Semin Cell Dev Biol 18:716-31 (2007) DOI:10.1016/j.semcdb.2007.09.003 REFERENCE PMID:20347046 AUTHORS Maattanen P, Gehring K, Bergeron JJ, Thomas DY TITLE Protein quality control in the ER: the recognition of misfolded proteins. JOURNAL Semin Cell Dev Biol 21:500-11 (2010) DOI:10.1016/j.semcdb.2010.03.006 REFERENCE PMID:20219571 AUTHORS Stolz A, Wolf DH TITLE Endoplasmic reticulum associated protein degradation: a chaperone assisted journey to hell. JOURNAL Biochim Biophys Acta 1803:694-705 (2010) DOI:10.1016/j.bbamcr.2010.02.005 REFERENCE PMID:20112977 AUTHORS Dejgaard K, Theberge JF, Heath-Engel H, Chevet E, Tremblay ML, Thomas DY TITLE Organization of the Sec61 translocon, studied by high resolution native electrophoresis. JOURNAL J Proteome Res 9:1763-71 (2010) DOI:10.1021/pr900900x REL_PATHWAY ko00510 N-Glycan biosynthesis ko03050 Proteasome ko03060 Protein export ko04210 Apoptosis ko04930 Type II diabetes mellitus ko05010 Alzheimer disease ko05012 Parkinson disease ko05020 Prion disease ///