Gamma carboxylation, hypusine formation and arylsulfatase activation (Homo sapiens)

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25, 26, 43, 495425, 26, 43, 492, 19, 21-23, 39...4, 25, 26, 43, 491, 6, 725, 26, 43, 493, 16, 5225, 26, 43, 4933, 44, 483, 15, 5025, 26, 43, 4911, 1225, 26, 43, 491, 8, 10, 13, 28...36, 3845, 56cytosolGolgi lumenendoplasmic reticulum lumenO2ARSD factor X light chainpropeptidepro-factor X,uncarboxylatedUptake and functionof diphtheria toxinPROC(33-42)OxA-ARSI VKOARSE aminocarboxypropylEEF2NAD+ARSJ DPH1 CO2OxA-STS DPH6pro-protein C,uncarboxylatedOxA-ARSH 3D-PROC(33-197) DPH5pro-factor VIIPROC(200-461) ARSDHPS Ca2+ 11xCbxE-GAS6(31-691)VKOVKODhp-EIF5A2 DOHH GGCXARSA(448-507) VKHQprotein CSUMF2factor X heavy chain ARSA(19-444) pro-factor XO2SUMF1factor X heavy chain pro-prothrombin(factor II)8xCbxE-3D-PROC(33-197) active ARSOxA-ARSJ EIF5A2 11xCbxE-PROS1STS CO211xCbxE-PROS1(25-676)SUMF1:SUMF2ARSH OxA-ARSG 3D-F9(29-461)H2OMe-diphthine EEF23D-F10(32-179) H+DPH2 FURIN13xCbxE-PROZVKHQGAS6(31-38)OxA-ARSK Fe2+ AdoMetDPH1:DPH2:DPH3pro-protein C12xCbxE-3D-F9(47-461)OxA-ARSF PROZ(24-40)11xCbxE-3D-F10(41-179) 10xCbxE-F2(25-622)10xCbxE-F2(44-622)12xCbxE-3D-F9(29-461)EIF5A(Hyp)H+diphthine EEF2prothrombin (factorII) propeptideAMPfactor X heavy chain NADHDPH711xCbxE-3D-F10(32-179) CO2CO2Dhp-EIF5A 1,3-diaminopropane13xCbxE-PROZ(24-400)H2OCO2PROS1(25-676)VKONAD+11xCbxE-GAS6(39-691)H2SO2ATPPROC(200-461) ARSK factor X heavy chain pro-protein CAdoHcyVKOGAS6(31-691)OxA-ARSE PROC(200-461) factor IX propeptideH2OEIF5Apro-factor X10xCbxE-F2(25-622)ARSI 13xCbxE-PROZ(24-400)CO211xCbxE-GAS6(31-691)factor XO2factor VIISUMF1 NH4+EIF5A(Dhp)SPMPPiDPH3 8xCbxE-3D-PROC(33-197) 12xCbxE-3D-F9(29-461)Hypu-EIF5A2 MTAD10xCbxE-F7(21-466)VKORC1nascent EEF2NADHCO2factor VIIpropeptideVKHQO2ARSA(448-507) SUMF2 ARSF DOHH:Fe++8xCbxE-3D-PROC(43-197) DNAJC24EEF2deoxyhypusinesynthase tetramer11xCbxE-PROS1(25-676)OxA-ARSA(19-444) OxA-ARSB PROZ(24-400)ARSG pro-factor VIIH2OVKHQCO2OxA-ARSD VKHQHypu-EIF5A 11xCbxE-3D-F10(32-179) PROC(200-461) EIF5A PROS1(25-41)ARSB H2O20, 325, 9, 351, 105, 9, 3542, 51, 5330, 4242, 51, 5320, 322430, 4230, 425, 9, 351220, 324020, 32242417, 2730, 4251, 535, 9, 3518, 3117, 2742, 51, 534634, 3720, 32124651, 5317, 2751, 534642, 51, 532417, 271, 13, 2942, 51, 5351, 534630, 425, 9, 3514, 47, 5517, 2724


Description

After translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the body. These modifications include the vitamin K-dependent attachment of carboxyl groups to glutamate residues and the conversion of a lysine residue in eIF5A to hypusine, and the conversion of a histidine residue in EEF to diphthamide. View original pathway at:Reactome.

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
114840view16:34, 25 January 2021ReactomeTeamReactome version 75
113286view11:35, 2 November 2020ReactomeTeamReactome version 74
112497view15:45, 9 October 2020ReactomeTeamReactome version 73
101409view11:29, 1 November 2018ReactomeTeamreactome version 66
100947view21:05, 31 October 2018ReactomeTeamreactome version 65
100484view19:39, 31 October 2018ReactomeTeamreactome version 64
100029view16:23, 31 October 2018ReactomeTeamreactome version 63
99582view14:55, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99204view12:43, 31 October 2018ReactomeTeamreactome version 62
94013view13:51, 16 August 2017ReactomeTeamreactome version 61
93632view11:29, 9 August 2017ReactomeTeamreactome version 61
87451view13:58, 22 July 2016MkutmonOntology Term : 'peptide and protein metabolic process' added !
86744view09:25, 11 July 2016ReactomeTeamreactome version 56
83388view11:04, 18 November 2015ReactomeTeamVersion54
81771view10:19, 26 August 2015ReactomeTeamVersion53
77021view08:31, 17 July 2014ReactomeTeamFixed remaining interactions
76726view12:09, 16 July 2014ReactomeTeamFixed remaining interactions
76052view10:11, 11 June 2014ReactomeTeamRe-fixing comment source
75761view11:26, 10 June 2014ReactomeTeamReactome 48 Update
75111view14:06, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74861view18:44, 2 May 2014KhanspersChanged comment source for description
74758view08:50, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,3-diaminopropaneMetaboliteCHEBI:15725 (ChEBI)
10xCbxE-F2(25-622)ProteinP00734 (Uniprot-TrEMBL)
10xCbxE-F2(44-622)ProteinP00734 (Uniprot-TrEMBL)
10xCbxE-F7(21-466)ProteinP08709 (Uniprot-TrEMBL)
11xCbxE-3D-F10(32-179) ProteinP00742 (Uniprot-TrEMBL)
11xCbxE-3D-F10(41-179) ProteinP00742 (Uniprot-TrEMBL)
11xCbxE-GAS6(31-691)ProteinQ14393 (Uniprot-TrEMBL)
11xCbxE-GAS6(39-691)ProteinQ14393 (Uniprot-TrEMBL)
11xCbxE-PROS1(25-676)ProteinP07225 (Uniprot-TrEMBL)
11xCbxE-PROS1ProteinP07225 (Uniprot-TrEMBL)
12xCbxE-3D-F9(29-461)ProteinP00740 (Uniprot-TrEMBL)
12xCbxE-3D-F9(47-461)ProteinP00740 (Uniprot-TrEMBL)
13xCbxE-PROZ(24-400)ProteinP22891 (Uniprot-TrEMBL)
13xCbxE-PROZProteinP22891 (Uniprot-TrEMBL)
3D-F10(32-179) ProteinP00742 (Uniprot-TrEMBL)
3D-F9(29-461)ProteinP00740 (Uniprot-TrEMBL)
3D-PROC(33-197) ProteinP04070 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(33-197) ProteinP04070 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(43-197) ProteinP04070 (Uniprot-TrEMBL)
AMPMetaboliteCHEBI:16027 (ChEBI)
ARSA(19-444) ProteinP15289 (Uniprot-TrEMBL)
ARSA(448-507) ProteinP15289 (Uniprot-TrEMBL)
ARSB ProteinP15848 (Uniprot-TrEMBL)
ARSD ProteinP51689 (Uniprot-TrEMBL)
ARSE ProteinP51690 (Uniprot-TrEMBL)
ARSF ProteinP54793 (Uniprot-TrEMBL)
ARSG ProteinQ96EG1 (Uniprot-TrEMBL)
ARSH ProteinQ5FYA8 (Uniprot-TrEMBL)
ARSI ProteinQ5FYB1 (Uniprot-TrEMBL)
ARSJ ProteinQ5FYB0 (Uniprot-TrEMBL)
ARSK ProteinQ6UWY0 (Uniprot-TrEMBL)
ARSComplexR-HSA-1614312 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
DHPS ProteinP49366 (Uniprot-TrEMBL)
DNAJC24ProteinQ6P3W2 (Uniprot-TrEMBL)
DOHH ProteinQ9BU89 (Uniprot-TrEMBL)
DOHH:Fe++ComplexR-HSA-204627 (Reactome)
DPH1 ProteinQ9BZG8 (Uniprot-TrEMBL)
DPH1:DPH2:DPH3ComplexR-HSA-5358365 (Reactome)
DPH2 ProteinQ9BQC3 (Uniprot-TrEMBL)
DPH3 ProteinQ96FX2 (Uniprot-TrEMBL)
DPH5ProteinQ9H2P9 (Uniprot-TrEMBL)
DPH6ProteinQ7L8W6 (Uniprot-TrEMBL)
DPH7ProteinQ9BTV6 (Uniprot-TrEMBL)
Dhp-EIF5A ProteinP63241 (Uniprot-TrEMBL)
Dhp-EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
EEF2ProteinP13639 (Uniprot-TrEMBL)
EIF5A ProteinP63241 (Uniprot-TrEMBL)
EIF5A(Dhp)ComplexR-HSA-3149583 (Reactome)
EIF5A(Hyp)ComplexR-HSA-204658 (Reactome)
EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
EIF5AComplexR-HSA-3149585 (Reactome)
FURINProteinP09958 (Uniprot-TrEMBL)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
GAS6(31-38)ProteinQ14393 (Uniprot-TrEMBL)
GAS6(31-691)ProteinQ14393 (Uniprot-TrEMBL)
GGCXProteinP38435 (Uniprot-TrEMBL)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
H2SMetaboliteCHEBI:16136 (ChEBI)
Hypu-EIF5A ProteinP63241 (Uniprot-TrEMBL)
Hypu-EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
MTADMetaboliteCHEBI:17509 (ChEBI)
Me-diphthine EEF2ProteinP13639 (Uniprot-TrEMBL)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NH4+MetaboliteCHEBI:28938 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OxA-ARSA(19-444) ProteinP15289 (Uniprot-TrEMBL)
OxA-ARSB ProteinP15848 (Uniprot-TrEMBL)
OxA-ARSD ProteinP51689 (Uniprot-TrEMBL)
OxA-ARSE ProteinP51690 (Uniprot-TrEMBL)
OxA-ARSF ProteinP54793 (Uniprot-TrEMBL)
OxA-ARSG ProteinQ96EG1 (Uniprot-TrEMBL)
OxA-ARSH ProteinQ5FYA8 (Uniprot-TrEMBL)
OxA-ARSI ProteinQ5FYB1 (Uniprot-TrEMBL)
OxA-ARSJ ProteinQ5FYB0 (Uniprot-TrEMBL)
OxA-ARSK ProteinQ6UWY0 (Uniprot-TrEMBL)
OxA-STS ProteinP08842 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PROC(200-461) ProteinP04070 (Uniprot-TrEMBL)
PROC(33-42)ProteinP04070 (Uniprot-TrEMBL)
PROS1(25-41)ProteinP07225 (Uniprot-TrEMBL)
PROS1(25-676)ProteinP07225 (Uniprot-TrEMBL)
PROZ(24-40)ProteinP22891 (Uniprot-TrEMBL)
PROZ(24-400)ProteinP22891 (Uniprot-TrEMBL)
SPMMetaboliteCHEBI:16610 (ChEBI)
STS ProteinP08842 (Uniprot-TrEMBL)
SUMF1 ProteinQ8NBK3 (Uniprot-TrEMBL)
SUMF1:SUMF2ComplexR-HSA-1614330 (Reactome)
SUMF1ProteinQ8NBK3 (Uniprot-TrEMBL)
SUMF2 ProteinQ8NBJ7 (Uniprot-TrEMBL)
SUMF2ProteinQ8NBJ7 (Uniprot-TrEMBL)
Uptake and function of diphtheria toxinPathwayR-HSA-5336415 (Reactome) Diphtheria is a serious, often fatal human disease associated with damage to many tissues. Bacteria in infected individuals, however, are typically confined to the lining of the throat or to a skin lesion; systemic effects are due to the secretion of an exotoxin encoded by a lysogenic bacteriophage. The toxin is encoded as a single polypeptide but is cleaved by host furin-like proteases to yield an aminoterminal fragment A and a carboxyterminal fragment B, linked by a disulfide bond. Toxin cleavage can occur when it first contacts the target cell surface, as annotated here, or as late as the point at which fragment A is released into the cytosol. Fragment B mediates toxin uptake into target cell endocytic vesicles, where acidification promotes a conformational change enabling fragment B to form a channel in the vesicle membrane through which fragment A is extruded into the target cell cytosol. Cleavage of the inter-fragment disulfide bond frees DT fragment A, which catalyzes ADP ribosylation of the translation elongation factor 2 (EEF2) in a target cell, thereby blocking protein synthesis. Neither fragment is toxic to human cells by itself (Collier 1975; Pappenheim 1977; Murphy 2011).
VKHQMetaboliteCHEBI:28433 (ChEBI)
VKOMetaboliteCHEBI:28371 (ChEBI)
VKORC1ProteinQ9BQB6 (Uniprot-TrEMBL)
active ARSComplexR-HSA-1614309 (Reactome)
aminocarboxypropyl EEF2ProteinP13639 (Uniprot-TrEMBL)
deoxyhypusine synthase tetramerComplexR-HSA-204644 (Reactome)
diphthine EEF2ProteinP13639 (Uniprot-TrEMBL)
factor IX propeptideProteinP00740 (Uniprot-TrEMBL)
factor VII propeptideProteinP08709 (Uniprot-TrEMBL)
factor VIIProteinP08709 (Uniprot-TrEMBL)
factor X heavy chain ProteinP00742 (Uniprot-TrEMBL)
factor X light chain propeptideProteinP00742 (Uniprot-TrEMBL)
factor XComplexR-HSA-159785 (Reactome)
nascent EEF2ProteinP13639 (Uniprot-TrEMBL)
pro-factor VIIProteinP08709 (Uniprot-TrEMBL)
pro-factor X, uncarboxylatedComplexR-HSA-159754 (Reactome)
pro-factor XComplexR-HSA-159734 (Reactome)
pro-factor XComplexR-HSA-159744 (Reactome)
pro-protein C, uncarboxylatedComplexR-HSA-159852 (Reactome)
pro-protein CComplexR-HSA-159731 (Reactome)
pro-protein CComplexR-HSA-159772 (Reactome)
pro-prothrombin (factor II)ProteinP00734 (Uniprot-TrEMBL)
protein CComplexR-HSA-159830 (Reactome)
prothrombin (factor II) propeptideProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
1,3-diaminopropaneArrowR-HSA-204647 (Reactome)
1,3-diaminopropaneR-HSA-204617 (Reactome)
10xCbxE-F2(25-622)ArrowR-HSA-159826 (Reactome)
10xCbxE-F2(25-622)ArrowR-HSA-159843 (Reactome)
10xCbxE-F2(25-622)R-HSA-159728 (Reactome)
10xCbxE-F2(25-622)R-HSA-159843 (Reactome)
10xCbxE-F2(44-622)ArrowR-HSA-159728 (Reactome)
10xCbxE-F7(21-466)ArrowR-HSA-159761 (Reactome)
10xCbxE-F7(21-466)R-HSA-159783 (Reactome)
11xCbxE-GAS6(31-691)ArrowR-HSA-163809 (Reactome)
11xCbxE-GAS6(31-691)ArrowR-HSA-163810 (Reactome)
11xCbxE-GAS6(31-691)R-HSA-163809 (Reactome)
11xCbxE-GAS6(31-691)R-HSA-163843 (Reactome)
11xCbxE-GAS6(39-691)ArrowR-HSA-163843 (Reactome)
11xCbxE-PROS1(25-676)ArrowR-HSA-159729 (Reactome)
11xCbxE-PROS1(25-676)ArrowR-HSA-159752 (Reactome)
11xCbxE-PROS1(25-676)R-HSA-159729 (Reactome)
11xCbxE-PROS1(25-676)R-HSA-159773 (Reactome)
11xCbxE-PROS1ArrowR-HSA-159773 (Reactome)
12xCbxE-3D-F9(29-461)ArrowR-HSA-159803 (Reactome)
12xCbxE-3D-F9(29-461)ArrowR-HSA-159836 (Reactome)
12xCbxE-3D-F9(29-461)R-HSA-159796 (Reactome)
12xCbxE-3D-F9(29-461)R-HSA-159836 (Reactome)
12xCbxE-3D-F9(47-461)ArrowR-HSA-159796 (Reactome)
13xCbxE-PROZ(24-400)ArrowR-HSA-163820 (Reactome)
13xCbxE-PROZ(24-400)ArrowR-HSA-163825 (Reactome)
13xCbxE-PROZ(24-400)R-HSA-163798 (Reactome)
13xCbxE-PROZ(24-400)R-HSA-163825 (Reactome)
13xCbxE-PROZArrowR-HSA-163798 (Reactome)
3D-F9(29-461)R-HSA-159803 (Reactome)
AMPArrowR-HSA-5358475 (Reactome)
ARSR-HSA-1614362 (Reactome)
ATPR-HSA-5358475 (Reactome)
AdoHcyArrowR-HSA-5358484 (Reactome)
AdoMetR-HSA-5358484 (Reactome)
AdoMetR-HSA-5358494 (Reactome)
CO2R-HSA-159752 (Reactome)
CO2R-HSA-159761 (Reactome)
CO2R-HSA-159795 (Reactome)
CO2R-HSA-159803 (Reactome)
CO2R-HSA-159819 (Reactome)
CO2R-HSA-159826 (Reactome)
CO2R-HSA-163810 (Reactome)
CO2R-HSA-163820 (Reactome)
DNAJC24ArrowR-HSA-5358494 (Reactome)
DOHH:Fe++mim-catalysisR-HSA-204662 (Reactome)
DPH1:DPH2:DPH3mim-catalysisR-HSA-5358494 (Reactome)
DPH5mim-catalysisR-HSA-5358484 (Reactome)
DPH6mim-catalysisR-HSA-5358475 (Reactome)
DPH7mim-catalysisR-HSA-5367022 (Reactome)
EEF2ArrowR-HSA-5358475 (Reactome)
EIF5A(Dhp)ArrowR-HSA-204647 (Reactome)
EIF5A(Dhp)R-HSA-204617 (Reactome)
EIF5A(Dhp)R-HSA-204662 (Reactome)
EIF5A(Hyp)ArrowR-HSA-204662 (Reactome)
EIF5AArrowR-HSA-204617 (Reactome)
EIF5AR-HSA-204647 (Reactome)
FURINmim-catalysisR-HSA-159728 (Reactome)
FURINmim-catalysisR-HSA-159733 (Reactome)
FURINmim-catalysisR-HSA-159771 (Reactome)
FURINmim-catalysisR-HSA-159773 (Reactome)
FURINmim-catalysisR-HSA-159796 (Reactome)
FURINmim-catalysisR-HSA-159868 (Reactome)
FURINmim-catalysisR-HSA-163798 (Reactome)
FURINmim-catalysisR-HSA-163843 (Reactome)
GAS6(31-38)ArrowR-HSA-163843 (Reactome)
GAS6(31-691)R-HSA-163810 (Reactome)
GGCXmim-catalysisR-HSA-159752 (Reactome)
GGCXmim-catalysisR-HSA-159761 (Reactome)
GGCXmim-catalysisR-HSA-159795 (Reactome)
GGCXmim-catalysisR-HSA-159803 (Reactome)
GGCXmim-catalysisR-HSA-159819 (Reactome)
GGCXmim-catalysisR-HSA-159826 (Reactome)
GGCXmim-catalysisR-HSA-163810 (Reactome)
GGCXmim-catalysisR-HSA-163820 (Reactome)
H+ArrowR-HSA-204647 (Reactome)
H+R-HSA-159790 (Reactome)
H+R-HSA-204617 (Reactome)
H2OArrowR-HSA-159752 (Reactome)
H2OArrowR-HSA-159761 (Reactome)
H2OArrowR-HSA-159795 (Reactome)
H2OArrowR-HSA-159803 (Reactome)
H2OArrowR-HSA-159819 (Reactome)
H2OArrowR-HSA-159826 (Reactome)
H2OArrowR-HSA-163810 (Reactome)
H2OArrowR-HSA-163820 (Reactome)
H2SArrowR-HSA-1614362 (Reactome)
MTADArrowR-HSA-5358494 (Reactome)
Me-diphthine EEF2ArrowR-HSA-5358484 (Reactome)
Me-diphthine EEF2R-HSA-5367022 (Reactome)
NAD+ArrowR-HSA-204617 (Reactome)
NAD+R-HSA-1614362 (Reactome)
NAD+R-HSA-204647 (Reactome)
NADHArrowR-HSA-1614362 (Reactome)
NADHArrowR-HSA-204647 (Reactome)
NH4+R-HSA-5358475 (Reactome)
O2R-HSA-159752 (Reactome)
O2R-HSA-159761 (Reactome)
O2R-HSA-159795 (Reactome)
O2R-HSA-159803 (Reactome)
O2R-HSA-159819 (Reactome)
O2R-HSA-159826 (Reactome)
O2R-HSA-163810 (Reactome)
O2R-HSA-163820 (Reactome)
O2R-HSA-204662 (Reactome)
PPiArrowR-HSA-5358475 (Reactome)
PROC(33-42)ArrowR-HSA-159771 (Reactome)
PROS1(25-41)ArrowR-HSA-159773 (Reactome)
PROS1(25-676)R-HSA-159752 (Reactome)
PROZ(24-40)ArrowR-HSA-163798 (Reactome)
PROZ(24-400)R-HSA-163820 (Reactome)
R-HSA-159728 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-prothrombin (factor II)' is present. At the end of this reaction, 1 molecule of 'prothrombin (factor II) propeptide', and 1 molecule of 'prothrombin (factor II)' are present.

This reaction takes place in the 'Golgi membrane' and is mediated by the 'furin activity' of 'furin'.

R-HSA-159729 (Reactome) In this reaction, 1 molecule of 'pro-protein S' is translocated from endoplasmic reticulum membrane to Golgi membrane.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159733 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-factor X' is present. At the end of this reaction, 1 molecule of 'factor X light chain propeptide', and 1 molecule of 'factor X' are present.

This reaction takes place in the 'Golgi membrane' and is mediated by the 'furin activity' of 'furin'.

R-HSA-159752 (Reactome) At the beginning of this reaction, 11 molecules of 'Oxygen', 11 molecules of 'vitamin K hydroquinone', 11 molecules of 'CO2', and 1 molecule of 'pro-protein S, uncarboxylated' are present. At the end of this reaction, 1 molecule of 'pro-protein S', 11 molecules of 'H2O', and 11 molecules of 'vitamin K epoxide' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159757 (Reactome) In this reaction, 1 molecule of 'pro-factor X' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159761 (Reactome) At the beginning of this reaction, 10 molecules of 'Oxygen', 10 molecules of 'vitamin K hydroquinone', 10 molecules of 'CO2', and 1 molecule of 'pro-factor VII, uncarboxylated' are present. At the end of this reaction, 1 molecule of 'pro-factor VII', 10 molecules of 'H2O', and 10 molecules of 'vitamin K epoxide' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159762 (Reactome) In this reaction, 1 molecule of 'pro-protein C' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159771 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-protein C' is present. At the end of this reaction, 1 molecule of 'protein C', and 1 molecule of 'protein C light chain propeptide' are present.

This reaction takes place in the 'Golgi lumen' and is mediated by the 'furin activity' of 'furin'.

R-HSA-159773 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-protein S' is present. At the end of this reaction, 1 molecule of 'protein S propeptide', and 1 molecule of 'protein S' are present.

This reaction takes place in the 'Golgi lumen' and is mediated by the 'furin activity' of 'furin'.

R-HSA-159783 (Reactome) In this reaction, 1 molecule of 'pro-factor VII' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159790 (Reactome) The regeneration of reduced vitamin K (vitamin K hydroquinone) from vitamin K epoxide is catalyzed by vitamin K epoxide reductase (VKORC1) (Sadler 2004). This enzyme is the target of the anticoagulant drug warfarin. Two important features of this reaction remain unclear. First, dithiothreitol functions efficiently as a reductant in vitro (Wallin and Martin 1985), but the in vivo reductant remains unknown. Second, while people homozygous for mutations in VKORC1 protein lack epoxide reductase activity (Rost et al. 2004) and cultured insect cells transfected with the cloned human VKORC1 gene express vitamin K epoxide reductase activity (Li et al. 2004), the possibility that the active form of the enzyme is a complex with other proteins cannot be formally excluded.
R-HSA-159795 (Reactome) At the beginning of this reaction, 8 molecules of 'Oxygen', 8 molecules of 'vitamin K hydroquinone', 8 molecules of 'CO2', and 1 molecule of 'pro-protein C, uncarboxylated' are present. At the end of this reaction, 8 molecules of 'H2O', 8 molecules of 'vitamin K epoxide', and 1 molecule of 'pro-protein C' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159796 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-factor IX' is present. At the end of this reaction, 1 molecule of 'factor IX', and 1 molecule of 'factor IX propeptide' are present.

This reaction takes place in the 'Golgi membrane' and is mediated by the 'furin activity' of 'furin'.

R-HSA-159803 (Reactome) At the beginning of this reaction, 12 molecules of 'Oxygen', 12 molecules of 'vitamin K hydroquinone', 12 molecules of 'CO2', and 1 molecule of 'pro-factor IX, uncarboxylated' are present. At the end of this reaction, 12 molecules of 'H2O', 12 molecules of 'vitamin K epoxide', and 1 molecule of 'pro-factor IX' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159819 (Reactome) At the beginning of this reaction, 11 molecules of 'Oxygen', 1 molecule of 'pro-factor X, uncarboxylated', 11 molecules of 'vitamin K hydroquinone', and 11 molecules of 'CO2' are present. At the end of this reaction, 1 molecule of 'pro-factor X', 11 molecules of 'H2O', and 11 molecules of 'vitamin K epoxide' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159826 (Reactome) At the beginning of this reaction, 10 molecules of 'Oxygen', 10 molecules of 'vitamin K hydroquinone', 10 molecules of 'CO2', and 1 molecule of 'pro-prothrombin (factor II), uncarboxylated' are present. At the end of this reaction, 1 molecule of 'pro-prothrombin (factor II)', 10 molecules of 'H2O', and 10 molecules of 'vitamin K epoxide' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-159836 (Reactome) In this reaction, 1 molecule of 'pro-factor IX' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159843 (Reactome) In this reaction, 1 molecule of 'pro-prothrombin (factor II)' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-159868 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-factor VII' is present. At the end of this reaction, 1 molecule of 'factor VII', and 1 molecule of 'factor VII propeptide' are present.

This reaction takes place in the 'Golgi membrane' and is mediated by the 'furin activity' of 'furin'.

R-HSA-1614336 (Reactome) Sulfatase-modifying factor 2 (SUMF2, also called C-alpha-formylglycine-generating enzyme 2, pFGE) is the paralogue of SUMF1. While SUMF1 can modify a critical residue on arylsulfatases to confer activity to them, SUMF2 lacks this ability (Mariappan et al. 2005) and instead, SUMF2 can inhibit the action of SUMF1 by dimerising with it (Zito et al. 2005). SUMF2 can interact with sulfatases with and without SUMF1 (Zito et al. 2005).
R-HSA-1614362 (Reactome) The sulfatase-modifying factor 1 (SUMF1, also called C-alpha-formylglycine-generating enzyme, FGE) (Preusser-Kunze et al. 2005, Cosma et al. 2003, Landgrebe et al. 2003) oxidises the critical cysteine residue in arylsulfatases to an active site 3-oxoalanine residue thus confering sulfatase activity (Roeser et al. 2006). Defects in SUMF1 cause multiple sulfatase deficiency (MSD) (MIM:272200), an impairment of arylsulfatase activity due to defective post-translational modification of the cysteine residue (Cosma et al. 2003, Dierks et al, 2003). This post-translational modification is thought to be highly conserved in eukaryotes (Selmer et al. 1996, von Figura et al. 1998). SUMF1 is active as either a monomer or a homodimer. A monomer is described in this reaction.
R-HSA-163798 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-protein Z' is present. At the end of this reaction, 1 molecule of 'protein Z propeptide', and 1 molecule of 'protein Z' are present.

This reaction takes place in the 'Golgi lumen' and is mediated by the 'furin activity' of 'furin'.

R-HSA-163809 (Reactome) In this reaction, 1 molecule of 'pro-GAS6' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-163810 (Reactome) The details of the gamma-carboxylation of GAS6 have not been determined directly, but are inferred from those worked out for protein S (Manfioletti et al. 1993).
R-HSA-163820 (Reactome) At the beginning of this reaction, 1 molecule of 'pro-protein Z, uncarboxylated', 13 molecules of 'Oxygen', 13 molecules of 'vitamin K hydroquinone', and 13 molecules of 'CO2' are present. At the end of this reaction, 1 molecule of 'pro-protein Z', 13 molecules of 'H2O', and 13 molecules of 'vitamin K epoxide' are present.

This reaction takes place in the 'endoplasmic reticulum membrane' and is mediated by the 'gamma-glutamyl carboxylase activity' of 'vitamin K-dependent gamma-carboxylase'.

R-HSA-163825 (Reactome) In this reaction, 1 molecule of 'pro-protein Z' is translocated from endoplasmic reticulum lumen to Golgi lumen.

This reaction takes place in the 'ER to Golgi transport vesicle'.

R-HSA-163843 (Reactome) The details of the gamma-carboxylation of GAS6 have not been determined directly, but are inferred from those worked out for protein S (Manfioletti et al. 1993).
R-HSA-204617 (Reactome) The reaction of EIF5A, spermidine, and NAD+ to form EIF5A(Dhp), 1,3-diaminopropane, and NADH + H+ is reversible in vitro. Under physiological conditions, the reverse reaction is probably minimized by the rapid, irreversible conversion of FIF5A(Dhp) to EIF5A(Hyp).
R-HSA-204647 (Reactome) Cytosolic deoxyhypusine synthase catalyzes the reaction of EIF5A protein, spermidine, and NAD+ to convert lysine-50 of EIF5A to deoxyhypusine, generating 1,3-diaminopropane and NADH + H+ in the process (Park 2006). Although the reaction is reversible, the reverse reaction is probably minimized under physiological conditions by the rapid, irreversible conversion of EIF5A(Dhp) to EIF5A(Hyp).
R-HSA-204662 (Reactome) Cytosolic deoxyhypusine hydroxylase catalyzes the irreversible conversion of peptidyl-deoxyhypusine to peptidyl-hypusine. The only known substrate for this enzyme is the modified lysine at residue 50 of eIF5A (Kang et al. 2007; Kim et al. 2006).
R-HSA-5358475 (Reactome) Cytosolic diphthamide biosynthesis protein 6 (DPH6) ligates an ammonium ion to diphthine-EEF2 to generate diphthamide-EEF2 in a reaction coupled to the hydrolysis of ATP to yield AMP and PPi (Su et al. 2012; Uthman et al. 2013; Wei et al. 2013).
R-HSA-5358484 (Reactome) Cytosolic diphthamide biosynthesis protein 5 (DPH5) transfers four methyl groups from S-adenosylmethionine (AdoMet) to elongation factor 2 (EEF2) whose histidine residue at position 715 has been conjugated with a 3-amino 3-carboxypropyl group, forming methylated diphthine EEF2 and S-adenosylhomocysteine (AdoHcy). DPH5 activity has been identified in cells of diverse eukaryotic species including humans and has been characterized in detail in budding yeast (Liu et al. 2004; Matteakis et al. 1992; Moehring & Moehring 1988).
R-HSA-5358494 (Reactome) The diphthamide biosynthesis protein 2 (DPH2) subunit of the cytosolic DPH1:DPH2:DPH3 complex catalyzes the transfer of a 3-amino-3-carboxypropyl group from S-adenosylmethionine (AdoMet) to residue 715 of nascent elongation factor 2 (EEF2), forming aminocarboxypropyl EEF2 and S-methylthioadenosine (MTAD). The association of DPH1, 2, and 3 to form a complex is inferred from studies of the homologous yeast proteins (Abdel-Fattah et al. 2013; Bar et al. 2008) and more limited studies of interactions among mouse and human ones (Liu et al. 2004). The identification of DPH2 as the catalytically active subunit of the DPH1:DPH2:DPH3 complex is inferred from the properties of the homologous Pyrococcus horikoshii protein (Zhang et al. 2010). DPH4 (DNAJC24) is needed for the reaction to occur but its exact role is unknown (Liu et al. 2004; Su et al. 2013). DPH3 is an electron donor for DPH1-DPH2 in the first step of diphthamide biosynthesis (Dong et al. 2014).
R-HSA-5367022 (Reactome) By analogy to the activity of its experimentally characterized budding yeast homolog (Lin et al. 2014; Schaffrath et al. 2014), cytosolic DPH7 is inferred to catalyze the removal of a methyl group of Me-diphthine EEF2, yielding diphthine EEF2.
SPMArrowR-HSA-204617 (Reactome)
SPMR-HSA-204647 (Reactome)
SUMF1:SUMF2ArrowR-HSA-1614336 (Reactome)
SUMF1R-HSA-1614336 (Reactome)
SUMF1mim-catalysisR-HSA-1614362 (Reactome)
SUMF2R-HSA-1614336 (Reactome)
SUMF2TBarR-HSA-1614362 (Reactome)
VKHQArrowR-HSA-159790 (Reactome)
VKHQR-HSA-159752 (Reactome)
VKHQR-HSA-159761 (Reactome)
VKHQR-HSA-159795 (Reactome)
VKHQR-HSA-159803 (Reactome)
VKHQR-HSA-159819 (Reactome)
VKHQR-HSA-159826 (Reactome)
VKHQR-HSA-163810 (Reactome)
VKHQR-HSA-163820 (Reactome)
VKOArrowR-HSA-159752 (Reactome)
VKOArrowR-HSA-159761 (Reactome)
VKOArrowR-HSA-159795 (Reactome)
VKOArrowR-HSA-159803 (Reactome)
VKOArrowR-HSA-159819 (Reactome)
VKOArrowR-HSA-159826 (Reactome)
VKOArrowR-HSA-163810 (Reactome)
VKOArrowR-HSA-163820 (Reactome)
VKOR-HSA-159790 (Reactome)
VKORC1mim-catalysisR-HSA-159790 (Reactome)
active ARSArrowR-HSA-1614362 (Reactome)
aminocarboxypropyl EEF2ArrowR-HSA-5358494 (Reactome)
aminocarboxypropyl EEF2R-HSA-5358484 (Reactome)
deoxyhypusine synthase tetramermim-catalysisR-HSA-204617 (Reactome)
deoxyhypusine synthase tetramermim-catalysisR-HSA-204647 (Reactome)
diphthine EEF2ArrowR-HSA-5367022 (Reactome)
diphthine EEF2R-HSA-5358475 (Reactome)
factor IX propeptideArrowR-HSA-159796 (Reactome)
factor VII propeptideArrowR-HSA-159868 (Reactome)
factor VIIArrowR-HSA-159868 (Reactome)
factor X light chain propeptideArrowR-HSA-159733 (Reactome)
factor XArrowR-HSA-159733 (Reactome)
nascent EEF2R-HSA-5358494 (Reactome)
pro-factor VIIArrowR-HSA-159783 (Reactome)
pro-factor VIIR-HSA-159761 (Reactome)
pro-factor VIIR-HSA-159868 (Reactome)
pro-factor X, uncarboxylatedR-HSA-159819 (Reactome)
pro-factor XArrowR-HSA-159757 (Reactome)
pro-factor XArrowR-HSA-159819 (Reactome)
pro-factor XR-HSA-159733 (Reactome)
pro-factor XR-HSA-159757 (Reactome)
pro-protein C, uncarboxylatedR-HSA-159795 (Reactome)
pro-protein CArrowR-HSA-159762 (Reactome)
pro-protein CArrowR-HSA-159795 (Reactome)
pro-protein CR-HSA-159762 (Reactome)
pro-protein CR-HSA-159771 (Reactome)
pro-prothrombin (factor II)R-HSA-159826 (Reactome)
protein CArrowR-HSA-159771 (Reactome)
prothrombin (factor II) propeptideArrowR-HSA-159728 (Reactome)
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