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

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13, 28, 32, 53, 54, 66...4129, 31, 40, 79333341418, 10, 12, 35, 39...415, 743314, 21, 26, 6414, 1718, 3813, 28, 53, 763313, 28, 53, 76334120, 30, 51, 55, 7013, 28, 53, 67, 761, 15, 3441334123, 26, 374113, 28, 53, 7613, 28, 53, 7613, 28, 53, 7633803313, 28, 53, 7649, 77333, 22, 27, 42, 56...7, 5035, 43, 5241nucleoplasmGolgi lumenendoplasmic reticulum lumencytosolketoaminesNADHADPfactor X heavy chain Metabolism ofvitamin KPPiARSfactor X heavy chain 11xCbxE-3D-F10(32-179) AMPMK4O2pro-factor X,uncarboxylated10xCbxE-F2(44-622)ARSA(448-507) DPH1:DPH2:DPH3ATPMK4 epoxideMK4 epoxideNAD+PROZ(24-400)Hyp-K50-EIF5ADhp-K50-EIF5A ICMT:Zn2+EIF5A 11xCbxE-3D-F10(32-179) 1,3-diaminopropaneNAD+12xCbxE-3D-F9(29-461)EIF5AO2OxA-ARSD PROC(200-461) ATPMK4RibAm3P CO2H2OOxA-ARSE OxA-ARSF factor VIIfactor X light chainpropeptideSUMF1 NADHOxA-ARSJ BGLAP(24-100)OxA-STS H2OPROS1(25-41)DPH2 PsiAm3P 3OHD110-F9(29-461)11xCbxE-GAS6(39-691)TPST1 OxA-ARSI TPST2 PROZ(24-40)PROC(33-42)11xCbxE-PROS1H2OF2(25-622)NAD+F7(21-466)Uptake and functionof diphtheria toxin8xCbxE-3D-PROC(43-197) factor VIIpropeptide13xCbxE-PROZARSD DPH1 NH4+MTADHyp-K50-EIF5A2 13xCbxE-PROZ(24-400)3D-F10(32-179) Metabolism ofvitamin KH2OSTS H2OPAPRibAm3P 10xCbxE-F2(25-622)PROC(200-461) Fe2+ DPH6DPH5Factor VIIIprecursorS-FARN-CMEMetabolism ofvitamin Kfactor X heavy chain ATPPROC(200-461) AdoMetARSF 13xCbxE-PROZ(24-400)PsiAm MK4Metabolism ofvitamin KMK4 epoxideHyp-K50-EIF5A SUMF1pro-protein CMetabolism ofvitamin K3xCbxE-BGLAP(52-100)Ca2+ FruAm3P GAS6(31-691)GAS6(31-38)H2OARSJ PsiAm3P, RibAm3Ppro-protein Cpro-factor VIISUMF1:SUMF2DNAJC24PsiAm, RibAmdiphthine EEF2DPH3 8xCbxE-3D-PROC(33-197) Zn2+ RibAm OxA-ARSB H2Spro-factor XEEF2FruAm ARSA(19-444) O212xCbxE-3D-F9(47-461)8xCbxE-3D-PROC(33-197) TPST1,2ketosamines3-phosphateDPH7RibAm FN3KRP11xCbxE-GAS6(31-691)factor X heavy chain 12xCbxE-3D-F9(29-461)S-FARN-Cysprothrombin (factorII) propeptide11xCbxE-PROS1(25-676)DHPS O2factor X3xCbxE-BGLAP(24-100)ARSB CO2SUMF2 MK4 epoxideGGCXARSG DOHH:Fe++MK4 epoxideOSulf-6Y-FVIIIprecursor3D-PROC(33-197) AdoHcyO2factor IX propeptideactive ARSpro-factor X11xCbxE-PROS1(25-676)nascent EEF2Dhp-K50-EIF5AH+DOHH Dhp-K50-EIF5A2 EIF5A2 ARSK pro-protein C,uncarboxylatedMe-diphthine EEF2PsiAm3P FN3KSPMARSA(448-507) ARSH AdoHcy3xCbxE-BGLAP(24-100)CO2PROS1(25-676)OxA-ARSK MK4AdoMetSUMF2H+aminocarboxypropylEEF2O2ICMT OxA-ARSH ARSE BGLAP(24-51)ADPPROC(200-461) OxA-ARSA(19-444) FURINDHPS tetramer10xCbxE-F7(21-466)PAPSCO210xCbxE-F2(25-622)11xCbxE-GAS6(31-691)protein CMK4PsiAm OxA-ARSG NADHCO211xCbxE-3D-F10(41-179) ARSI 261, 633224, 36, 47, 57, 59...61, 636, 249, 63, 7548, 605044, 46, 7216, 194, 36, 47, 57, 59...11, 25, 6244, 46, 72244, 46, 72329, 7545, 719, 756548, 60239, 63, 7516, 196561, 6361, 638, 3516, 1948, 604, 36, 47, 57, 59...5850654, 36, 47, 57, 59...12, 35, 6816, 199, 759, 63, 759, 63, 7516, 19659, 759, 63, 7561, 6348, 6044, 46, 724, 36, 47, 57, 59...3223244, 46, 7248, 6065


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.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 163841
Reactome-version 
Reactome version: 74
Reactome Author 
Reactome Author: D'Eustachio, Peter

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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-PROC(33-197) ProteinP04070 (Uniprot-TrEMBL)
3OHD110-F9(29-461)ProteinP00740 (Uniprot-TrEMBL)
3xCbxE-BGLAP(24-100)ProteinP02818 (Uniprot-TrEMBL)
3xCbxE-BGLAP(52-100)ProteinP02818 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(33-197) ProteinP04070 (Uniprot-TrEMBL)
8xCbxE-3D-PROC(43-197) ProteinP04070 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
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:30616 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
BGLAP(24-100)ProteinP02818 (Uniprot-TrEMBL)
BGLAP(24-51)ProteinP02818 (Uniprot-TrEMBL)
CO2MetaboliteCHEBI:16526 (ChEBI)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
DHPS ProteinP49366 (Uniprot-TrEMBL)
DHPS tetramerComplexR-HSA-204644 (Reactome)
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-K50-EIF5A ProteinP63241 (Uniprot-TrEMBL)
Dhp-K50-EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
Dhp-K50-EIF5AComplexR-HSA-3149583 (Reactome)
EEF2ProteinP13639 (Uniprot-TrEMBL)
EIF5A ProteinP63241 (Uniprot-TrEMBL)
EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
EIF5AComplexR-HSA-3149585 (Reactome)
F2(25-622)ProteinP00734 (Uniprot-TrEMBL)
F7(21-466)ProteinP08709 (Uniprot-TrEMBL)
FN3KProteinQ9H479 (Uniprot-TrEMBL)
FN3KRPProteinQ9HA64 (Uniprot-TrEMBL)
FURINProteinP09958 (Uniprot-TrEMBL)
Factor VIII precursorProteinP00451 (Uniprot-TrEMBL)
Fe2+ MetaboliteCHEBI:29033 (ChEBI)
FruAm MetaboliteCHEBI:24103 (ChEBI)
FruAm3P MetaboliteCHEBI:87178 (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)
Hyp-K50-EIF5A ProteinP63241 (Uniprot-TrEMBL)
Hyp-K50-EIF5A2 ProteinQ9GZV4 (Uniprot-TrEMBL)
Hyp-K50-EIF5AComplexR-HSA-204658 (Reactome)
ICMT ProteinO60725 (Uniprot-TrEMBL)
ICMT:Zn2+ComplexR-HSA-6788652 (Reactome)
MK4 epoxideMetaboliteCHEBI:90152 (ChEBI)
MK4MetaboliteCHEBI:78277 (ChEBI)
MTADMetaboliteCHEBI:17509 (ChEBI)
Me-diphthine EEF2ProteinP13639 (Uniprot-TrEMBL)
Metabolism of vitamin KPathwayR-HSA-6806664 (Reactome) Vitamin K is a required co-factor in a single metabolic reaction, the gamma-carboxylation of glutamate residues of proteins catalyzed by GGCX (gamma-carboxyglutamyl carboxylase). Substrates of GGCX include blood clotting factors, osteocalcin (OCN), and growth arrest-specific protein 6 (GAS6) (Brenner et al. 1998). Vitamin K is derived from green leafy vegetables as phylloquinone and is synthesized by gut flora as menaquinone-7. These molecules are taken up by intestinal enterocytes with other lipids, packaged into chylomicrons, and delivered via the lymphatic and blood circulation to tissues of the body, notably hepatocytes and osteoblasts, via processes of lipoprotein trafficking (Shearer & Newman 2014; Shearer et al. 2012) described elsewhere in Reactome.

In these tissues, menadiol (reduced vitamin K3) reacts with geranylgeranyl pyrophosphate to form MK4 (vitamin K hydroquinone), the form of the vitamin required as cofactor for gamma-carboxylation of protein glutamate residues (Hirota et al. 2013). The gamma-carboxylation reactions, annotated elsewhere in Reactome as a part of protein metabolism, convert MK4 to its epoxide form, which is inactive as a cofactor. Two related enzymes, VKORC1 and VKORCL1, can each catalyze the reduction of MK4 epoxide to active MK4. VKORC1 activity is essential for normal operation of the blood clotting cascade and for osteocalcin function (Ferron et al. 2015). A physiological function for VKORCL1 has not yet been definitively established (Hammed et al. 2013; Tie et al. 2014).

NAD+MetaboliteCHEBI:57540 (ChEBI)
NADHMetaboliteCHEBI:57945 (ChEBI)
NH4+MetaboliteCHEBI:28938 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OSulf-6Y-FVIII precursorProteinP00451 (Uniprot-TrEMBL)
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)
PAPMetaboliteCHEBI:17985 (ChEBI)
PAPSMetaboliteCHEBI:17980 (ChEBI)
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)
PsiAm MetaboliteCHEBI:87176 (ChEBI)
PsiAm, RibAmComplexR-ALL-6788865 (Reactome)
PsiAm3P MetaboliteCHEBI:87179 (ChEBI)
PsiAm3P, RibAm3PComplexR-ALL-6788858 (Reactome)
RibAm MetaboliteCHEBI:87177 (ChEBI)
RibAm3P MetaboliteCHEBI:87180 (ChEBI)
S-FARN-CMEMetaboliteCHEBI:87167 (ChEBI)
S-FARN-CysMetaboliteCHEBI:86019 (ChEBI)
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)
TPST1 ProteinO60507 (Uniprot-TrEMBL)
TPST1,2ComplexR-HSA-8954265 (Reactome)
TPST2 ProteinO60704 (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).
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
active ARSComplexR-HSA-1614309 (Reactome)
aminocarboxypropyl EEF2ProteinP13639 (Uniprot-TrEMBL)
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)
ketoaminesComplexR-ALL-6788868 (Reactome)
ketosamines 3-phosphateComplexR-ALL-6788848 (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)
protein CComplexR-HSA-159830 (Reactome)
prothrombin (factor II) propeptideProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
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)
3OHD110-F9(29-461)R-HSA-159803 (Reactome)
3xCbxE-BGLAP(24-100)ArrowR-HSA-6807214 (Reactome)
3xCbxE-BGLAP(24-100)ArrowR-HSA-6807229 (Reactome)
3xCbxE-BGLAP(24-100)R-HSA-6807224 (Reactome)
3xCbxE-BGLAP(24-100)R-HSA-6807229 (Reactome)
3xCbxE-BGLAP(52-100)ArrowR-HSA-6807224 (Reactome)
ADPArrowR-HSA-6788855 (Reactome)
ADPArrowR-HSA-6788867 (Reactome)
AMPArrowR-HSA-5358475 (Reactome)
ARSR-HSA-1614362 (Reactome)
ATPR-HSA-5358475 (Reactome)
ATPR-HSA-6788855 (Reactome)
ATPR-HSA-6788867 (Reactome)
AdoHcyArrowR-HSA-5358484 (Reactome)
AdoHcyArrowR-HSA-6788650 (Reactome)
AdoMetR-HSA-5358484 (Reactome)
AdoMetR-HSA-5358494 (Reactome)
AdoMetR-HSA-6788650 (Reactome)
BGLAP(24-100)R-HSA-6807214 (Reactome)
BGLAP(24-51)ArrowR-HSA-6807224 (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)
CO2R-HSA-6807214 (Reactome)
DHPS tetramermim-catalysisR-HSA-204617 (Reactome)
DHPS tetramermim-catalysisR-HSA-204647 (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)
Dhp-K50-EIF5AArrowR-HSA-204647 (Reactome)
Dhp-K50-EIF5AR-HSA-204617 (Reactome)
Dhp-K50-EIF5AR-HSA-204662 (Reactome)
EEF2ArrowR-HSA-5358475 (Reactome)
EIF5AArrowR-HSA-204617 (Reactome)
EIF5AR-HSA-204647 (Reactome)
F2(25-622)R-HSA-159826 (Reactome)
F7(21-466)R-HSA-159761 (Reactome)
FN3KRPmim-catalysisR-HSA-6788855 (Reactome)
FN3Kmim-catalysisR-HSA-6788867 (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)
FURINmim-catalysisR-HSA-6807224 (Reactome)
Factor VIII precursorR-HSA-9668023 (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)
GGCXmim-catalysisR-HSA-6807214 (Reactome)
H+ArrowR-HSA-204647 (Reactome)
H+R-HSA-204617 (Reactome)
H+R-HSA-204662 (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)
H2OArrowR-HSA-204662 (Reactome)
H2OArrowR-HSA-6807214 (Reactome)
H2SArrowR-HSA-1614362 (Reactome)
Hyp-K50-EIF5AArrowR-HSA-204662 (Reactome)
ICMT:Zn2+mim-catalysisR-HSA-6788650 (Reactome)
MK4 epoxideArrowR-HSA-159752 (Reactome)
MK4 epoxideArrowR-HSA-159761 (Reactome)
MK4 epoxideArrowR-HSA-159795 (Reactome)
MK4 epoxideArrowR-HSA-159803 (Reactome)
MK4 epoxideArrowR-HSA-159819 (Reactome)
MK4 epoxideArrowR-HSA-159826 (Reactome)
MK4 epoxideArrowR-HSA-163810 (Reactome)
MK4 epoxideArrowR-HSA-163820 (Reactome)
MK4 epoxideArrowR-HSA-6807214 (Reactome)
MK4R-HSA-159752 (Reactome)
MK4R-HSA-159761 (Reactome)
MK4R-HSA-159795 (Reactome)
MK4R-HSA-159803 (Reactome)
MK4R-HSA-159819 (Reactome)
MK4R-HSA-159826 (Reactome)
MK4R-HSA-163810 (Reactome)
MK4R-HSA-163820 (Reactome)
MK4R-HSA-6807214 (Reactome)
MTADArrowR-HSA-5358494 (Reactome)
Me-diphthine EEF2ArrowR-HSA-5358484 (Reactome)
Me-diphthine EEF2R-HSA-5367022 (Reactome)
NAD+ArrowR-HSA-204617 (Reactome)
NAD+ArrowR-HSA-204662 (Reactome)
NAD+R-HSA-1614362 (Reactome)
NAD+R-HSA-204647 (Reactome)
NADHArrowR-HSA-1614362 (Reactome)
NADHArrowR-HSA-204647 (Reactome)
NADHR-HSA-204617 (Reactome)
NADHR-HSA-204662 (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)
O2R-HSA-6807214 (Reactome)
OSulf-6Y-FVIII precursorArrowR-HSA-9668023 (Reactome)
PAPArrowR-HSA-9668023 (Reactome)
PAPSR-HSA-9668023 (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)
PsiAm, RibAmR-HSA-6788855 (Reactome)
PsiAm3P, RibAm3PArrowR-HSA-6788855 (Reactome)
R-HSA-159728 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-prothrombin to form mature, gamma-carboxylated prothrombin (Wasley et al. 1993).
R-HSA-159729 (Reactome) Gamma-carboxylated pro-protein S is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159733 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-factor X to form mature, gamma-carboxylated factor X (Wasley et al. 1993).
R-HSA-159752 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates eleven glutamate residues on PROS1(25-676) (pro-protein S). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-159757 (Reactome) Gamma-carboxylated pro-factor X is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159761 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates ten glutamate residues on F7(21-466) (pro-factor VII). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-159762 (Reactome) Gamma-carboxylated pro-protein C is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159771 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-protein C to form mature, gamma-carboxylated protein C (Wasley et al. 1993).
R-HSA-159773 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-protein S to form mature, gamma-carboxylated protein S (Wasley et al. 1993).
R-HSA-159783 (Reactome) Gamma-carboxylated pro-factor VII is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159795 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates eight glutamate residues on 3D-PROC(33-197) (pro-protein C light chain). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-159796 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-factor IX to form mature, gamma-carboxylated factor IX (Wasley et al. 1993).
R-HSA-159803 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates twelve glutamate residues on 3D-F9(29-461) (pro-factor IX). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995; Ware et al. 1989).
R-HSA-159819 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates eleven glutamate residues on 3D-F10(32-179) (pro-factor X light chain). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-159826 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates ten glutamate residues on F2(25-622) (pro-prothrombin). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-159836 (Reactome) Gamma-carboxylated pro-factor IX is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159843 (Reactome) Gamma-carboxylated pro-prothrombin (factor II) is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-159868 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-factor VII to form mature, gamma-carboxylated factor VII (Wasley et al. 1993).
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) Furin, associated with the Golgi membrane, cleaves pro-protein Z to form mature, gamma-carboxylated protein Z (Wasley et al. 1993).
R-HSA-163809 (Reactome) Gamma-carboxylated pro-GA6 is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-163810 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates eleven glutamate residues on GAS6(31-691) (pro-GAS6). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process. 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) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates thirteen glutamate residues on PROZ(24-400) (pro-protein Z). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Furie et al. 1999; Stenina et al. 2001; Morris et al. 1995).
R-HSA-163825 (Reactome) Gamma-carboxylated pro-protein Z is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-163843 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-GAS6 to form mature, gamma-carboxylated GAS6 (Wasley et al. 1993).
R-HSA-204617 (Reactome) Cytosolic deoxyhypusine synthase (DHPS) tetramer catalyzes the reaction of the deoxyhypusine (Dhp) residue in EIF5A protein (Dhp-K50-EIF5A) with 1,3 diaminopropane, NADH and H+ to form EIF5A, spermidine (SPM), and NAD+ (Park et al. 2003; Park 2006). While this reaction is readily observed in vitro, it is probably minimized by the rapid, irreversible conversion of EIF5A Dhp residues to hypusine.
R-HSA-204647 (Reactome) Cytosolic deoxyhypusine synthase (DHPS) tetramer catalyzes the reaction of of EIF5A protein, spermidine (SPM), and NAD+ to convert lysine 50 of EIF5A to deoxyhypusine (Dhp), generating 1,3 diaminopropane, NADH and H+ in the process (Clement et al. 2003; Joe et al. 1995; Park 2006; Wolff et al. 1997). Although the reaction is reversible, the reverse reaction is probably minimized under physiological conditions by the rapid, irreversible conversion of EIF5A Dhp residues to hypusine.
R-HSA-204662 (Reactome) Cytosolic deoxyhypusine hydroxylase (DOHH) complexed with Fe2+ catalyzes the irreversible hydroxylation of peptidyl deoxyhypusine (Dhp-K50-EIF5A) to peptidyl hypusine (Hyp-K50-EIF5A) using molecular oxygen. The only known substrate for this enzyme is the modified lysine at residue 50 of the two isoforms of eIF5A (Clement et al. 2003; 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.
R-HSA-6788650 (Reactome) Protein-S-isoprenylcysteine O-methyltransferase (ICMT) mediates the post-translational methyl esterification of C-terminal CAAX motifs in prenylated proteins such as the oncoprotein RAS and related GTPases, neutralising the negative charge of prenylcysteine species and thereby determining their subcellular localisation and correct biological function (Wright et al. 2009, Yang et al. 2011). ICMT may serve as a therapeutic target in cancer development (Lau et al. 2014, Diver et al. 2014).
R-HSA-6788855 (Reactome) Proteins can undergo chemical modifications such as glycation, which occurs when glucose and other free aldoses spontaneously react with N-terminal and eta-amino groups of proteins to form Schiff bases, which slowly rearrange to ketosamines or, if the sugar was glucose, fructosamines. Fructosamines can further react slowly and become advanced glycation end products, which are thought to play a role in the pathophysiology of several disorders, especially diabetic complications. Ketosamine-3-kinase (FN3K) and ketosamine-3-kinase-related protein (FN3KRP) can phosphorylate protein-bound or free ketosamines on the third carbon of the sugar moiety and the resultant, unstable ketosamine 3-phosphates decompose under physiological conditions (a process called deglycation). Both enzymes can 3-phosphorylate psicosamines (PsiAm) and ribulosamines (RibAm) (Collard et al. 2003, 2004), but only FN3K can 3-phosphorylate fructosamines (FruAm) as well.
R-HSA-6788867 (Reactome) Proteins can undergo chemical modifications such as glycation, which occurs when glucose and other free aldoses spontaneously react with N-terminal and eta-amino groups of proteins to form Schiff bases, which slowly rearrange to ketosamines or, if the sugar is glucose, fructosamines. Fructosamines can further react slowly and become advanced glycation end products, which are thought to play a role in the pathophysiology of several disorders, especially diabetic complications. Ketosamine-3-kinase (FN3K) and ketosamine-3-kinase-related protein (FN3KRP) can phosphorylate protein-bound or free ketosamines on the third carbon of the sugar moiety and the resultant, unstable ketosamine 3-phosphates decompose under physiological conditions (a process called deglycation). Both enzymes can 3-phosphorylate psicosamines (PsiAm) and ribulosamines (RibAm), but only FN3K can 3-phosphorylate fructosamines (FruAm) as well (Delpierre et al. 2000, 2004).
R-HSA-6807214 (Reactome) GGCX (gamma glutamyl carboxylase) in the endoplasmic reticulum gamma-carboxylates three glutamate residues on BGLAP(24-100) (pro-osteocalcin). MK4 (vitamin K hydroquinone) is oxidized to MK4 epoxide in the process (Berkner 2000; Ferron et al. 2015; Furie et al. 1999; Hauschka et al. 1989; Morris et al. 1995; oser et al. 1980; Stenina et al. 2001).
R-HSA-6807224 (Reactome) Furin, associated with the Golgi membrane, cleaves pro-BGLAP to form mature, gamma-carboxylated BGLAP (osteocalcin) (Wasley et al. 1993).
R-HSA-6807229 (Reactome) Gamma-carboxylated pro-BGLAP is transported from the endoplasmic reticulum to the Golgi apparatus (Kirchhausen 2000).
R-HSA-9668023 (Reactome) Post-translational cellular processing of the factor VIII (FVIII or F8) precursor enables O-sulfation of tyrosine residues (Pittman DD et al. 1992; Michnick DA et al. 1994). Biochemical characterization demonstrated that recombinant human FVIII when metabolically labeled with [35S]-sulfate upon expression in Chinese hamster ovary (CHO) cells or monkey kidney tissue COS-1 cells contains six potential tyrosine sulfation sites, ie, four on the heavy chain (at amino acid residues 365, 737, 738, and 742) and two in the a3 subdomain of the light chain (residues 1683 and 1699) (Pittman DD et al. 1992; Michnick DA et al. 1994). The presence of six tyrosine sulfate residues in FVIII was further confirmed by a combination of liquid chromatography and electrospray ionization mass spectrometry (LC/ESI-MS) studies of the recombinant human FVIII protein derived from baby hamster kidney (BHK) cells (Severs JC et al. 1999) or CHO cells (Schmidbauer S et al. 2015). Site-directed mutagenesis of individual or multiple tyrosine residues showed that all the six sulfation sites are required to modulate FVIII activity (Pittman DD et al. 1992; Michnick DA et al. 1994). Further, treatment of CHO cells that express FVIII with sodium chlorate, an inhibitor of ATP sulphurylase involved in the synthesis of PAPS, did not affect FVIII secretion, but reduced the functional activity by 5-fold, indicating that sulfation was not required for FVIII secretion (Pittman DD et al. 1992). In addition, mutagenesis of Tyr1699 to Phe (Y1699F) demonstrated that sulfation at that residue was required for high affinity interaction of FVIII with von Willebrand factor (vWF) (Leyte A et al. 1991). In the absence of tyrosine sulfation at 1699 in FVIII, the affinity for vWF was reduced by 5-fold (Leyte A et al. 1991). The nuclear magnetic resonance (NMR) spectrum studies of the complex between FVIII and vWF showed significantly larger residue-specific chemical shift changes when Y1699 was sulfated further highlighting the importance of FVIII sulfation at Y1699 for the binding affinity to vWF (Dagil L et al. 2019). The significance of FVIII sulfation at Y1699 in vivo is made evident by the presence of a Y1699F mutation that causes a moderate hemophilia A, likely due to reduced interaction with vWF and decreased plasma half-life (Higuchi M et al. 1990; van den Biggelaar M et al. 2011). Sulfation at tyrosine residues 365 and 1683 increased FVIII activity by increasing the rate of thrombin cleavage at the adjacent thrombin cleavage sites 391 and 1708, respectively (Michnick DA et al. 1994). Mutation of tyrosine residues 737, 738, and 742 had no effect on the thromhin activation rate, even though the cleavage rate at Arg759 was slightly reduced (Michnick et al. 1994). Further. lower FXa-generation activity (86% of the wild-type activity) and lower clotting activity (51% of the wild-type activity) was observed for the FVIII triple point mutant at Tyr residues 737, 738, and 742 (Michnick et al. 1994). This result is in contrast to other study in which no functional differences were found between full-length FVIIl lacking sulfation at one or more of these three residues (Y737, Y738, and Y742) and the fully sulfated form of FVIII (Mikkelsen J et al. 1991).

Protein tyrosine O-sulfation is a common post-translational modification that is catalyzed by a tyrosyl protein sulfotransferase (TPST) (Moore KL 2003; Yang YS et al. 2015). In humans, two TPST isoforms, termed TPST1 and TPST2, have been identified (Ouyang Yb et al. 1998; Mishiro E et al. 2006). The enzyme was shown to catalyze the transfer of sulfate from the universal sulfate donor adenosine 3′-phosphate 5′-phosphosulfate (PAPS) to the hydroxyl group of a peptidyltyrosine residue to form a tyrosine O4-sulfate ester and 3′,5′-ADP (Lee RW & Huttner WB 1983). Structural studies showed that human TPSTs share the same catalytic mechanism (Teramoto T et al. 2013; Tanaka S et al. 2017). In mammalian cells, tyrosine O-sulfation of membrane and secretory proteins was found to occur in the trans-Golgi network, and biochemical studies indicated that the enzyme was membrane-bound (Lee RW & Huttner WB 1985; Baeuerle PA & Huttner WB 1987).

S-FARN-CMEArrowR-HSA-6788650 (Reactome)
S-FARN-CysR-HSA-6788650 (Reactome)
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)
TPST1,2mim-catalysisR-HSA-9668023 (Reactome)
active ARSArrowR-HSA-1614362 (Reactome)
aminocarboxypropyl EEF2ArrowR-HSA-5358494 (Reactome)
aminocarboxypropyl EEF2R-HSA-5358484 (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)
ketoaminesR-HSA-6788867 (Reactome)
ketosamines 3-phosphateArrowR-HSA-6788867 (Reactome)
nascent EEF2R-HSA-5358494 (Reactome)
pro-factor VIIArrowR-HSA-159783 (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)
protein CArrowR-HSA-159771 (Reactome)
prothrombin (factor II) propeptideArrowR-HSA-159728 (Reactome)
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