Examples of Reaction Syntax in TRANSPATH
In general, reaction names contain symbols that connect the incoming and outgoing molecules in the reaction and indicate the reaction type, as shown in the following table:
TRANSPATH Reaction Syntax
| Connecting Symbol | Reaction Type |
|---|---|
| <==> | Equilibrium reaction (complex formation and dissocation) |
| --E--> | Mass flow catalyzed by enzyme |
| E--> | Semantic activation or unidirectional mechanistic steop |
| --/ | Semantic inhibition |
The stoichiometry is used like this: 2 A --> (A)2 or 2 A --> A:A. If two identical complexes are binding, the syntax is: 2 (A:B:C) <==> (A:B:C)2. Semantic reactions with two (or more) signal donors are formulated like: A & B --> C.
Examples of the syntax used in TRANSPATH for reaction names are provided below. Reaction types are divided into representative direct and indirect reactions. To access specific examples, either click to the reaction example from the table below or scroll through the list beneath the table. Details about format for species names and modified forms, or states, are provided at the respective links. Definitions for the various effects of reactions are provided here.
TRANSPATH Reaction Name Syntax
Direct Reactions
Acetylation
General Syntax:
ProteinA + AcCoA --EnzymeA--> ProteinA{ace} + CoA
Example:
RIP140(h) + AcCoA --p300(m)--> RIP140(h){aceK446} + CoA
ADP-ribosylation
General Syntax:
ProteinA + NAD --EnzymeC--> ProteinA{drib} + nicotinamide
Example:
G-alpha-i-2(r):G-beta(r):EGFR(r) + NAD -->
G-alpha-i-2(r){drib}:G-beta(r):EGFR(r) + nicotinamide
Binding
Examples:
cyclin B1(h):Cdk1(h) + p73alpha(h) <==> cyclin
B1(h):Cdk1(h):p73alpha(h)
(TGFbeta1(h))2 + 2 TGFbetaR-II(h) <==> (TGFbeta1(h))2:(TGFbetaR-II(h))2
ErbB2(r){pY1227} + CrkII(h) <==> ErbB2(r){pY1227}:CrkII(h)
Cholesterol Modification
Example:
cholesterol + SHH(h) --> Shh-C(h) + Shh-N(h){chol}
Shown here is a combined effect of cholesterol modification and
protein cleavage.
Cleavage
General Syntax:
ProteinA --Enzyme--> ProteinA' (+ ProteinA'' + ...) (+ protein
remnants)
Example:
cTnT(r) --Caspase-3(r)--> cTNTp25(r) + protein remnants
A cleavage reaction yields at least two protein fragments. With
appropriate detection methods it is possible to monitor at least
one of the specific cleavage products. Frequently, the amino acid
sequence of the target site of the cleaving enzyme (or the cleavage
site) are discussed in the paper. Products of a cleavage reaction
may still be functional.
Deacetylation
General Syntax:
ProteinA{ace} --EnzymeB--> ProteinA + acetyl
Degradation
Example:
TGFbetaR-I(v.s.){ub} --> protein remnants + ubiquitin(v.s.)
Here, deubiquitination is coupled with protein degradation. A
degradation yields numerous break-down products that become
smaller as protein degradation progresses. Degradation of
ubiquitinated proteins by proteasomes does not result in
degradation of the ubiquitin, however, and the ubiquitin fragment
are recycled. For an example of deubiquination without protein
degradation, see below.
Demethylimination
General Syntax:
ProteinA{metR} --PAD4--> ProteinA{cit} + methylamine
Here, methylated arginine residue is converted to
citrulline.
Demyristoylation
Example:
Galpha-i-1((m.s.){myr} --enzyme--> G-alpha-i-1(m.s.) +
myristoyl
Depalmitoylation
Example:
H-Ras(m.s.){pal} --PPT(b)--> H-Ras(m.s.) + palmityl
Dephosphorylation
General Syntax:
ProteinA{p} --EnzymeC--> ProteinA + p
Examples:
Jak2(v.s.){pY1007} --SHP-2(v.s.)--> Jak2(v.s.) + p
C-Nap1(h){p} --PP1-gamma1(h):Nek2A(h)--> C-Nap1(h) + p
Here, the enzyme is in a complex.
Pyk2(r){pY402}{pY579}{pY580} --PTP-PEST(h)--> Pyk2(r) + 3p
Cdk2(h){pT160}:KAP(h) --> Cdk2(h):KAP(h) + p
Here, the enzyme is in a stable complex with the substrate and
is therefore not separately linked as enzyme.
Deubiquitination
Examples:
AF-6(h){ub} --Fam(m)--> AF-6(h) + ubiquitin(h)
TRAF2(m.s.){ub} --CYLD(m.s.)--> TRAF2(m.s.) +
ubiquitin(m.s.)
Here, the ubiquitin molecule is removed, and the protein is
otherwise unchanged. An example of ubiquitin removed coupled to
protein degradation is shown above.
Dissociation
Example:
ROS(m):SHP-1(h) <==> ROS(m) + SHP-1(h)
Exchange
Example:
Ras:GDP + GTP --NO--> Ras:GTP + GDP
Shown here is a dissociation of one molecule (GDP) and
concurrent association of another molecule (GTP), catalyzed by
guanine nucleotide exchange factors (GEFs).
Glycosylation
General Syntax:
ProteinA + 2 NDP-Gly --enzyme(transferase)--> ProteinA{gly(n)} +
NMP + NDP
The general syntax for N-glycosylation and O-glycosylation is
the same.
Additional General Syntax Examples:
ProteinA + 2 UDP-GlcNAc --enzyme--> ProteinA{GlcNAc(2)} + UMP +
UDP
ProteinA{GlcNAc(2)} + 5 GDP-Man --enzyme-->
ProteinA{GlcNAc(2)}{man(5)} + 5 GDP
ProteinA{GlcNAc(2)}{man(5)} + 4dolichol-p-Man + 3dolichol-p-Glc
--enzyme--> ProteinA{GlcNAc(2)}{man(9)}{glc(3)} + 3dolichol-p +
4dolichol-p
Hydrolysis
Examples:
RhoA(h):GTP --Graf2(m)--> RhoA(h):GDP + p
Shown here is an example of hydrolysis of GTP to GDP by
GTPase.
PIP2 --PLCbeta3(h)--> DAG + IP3
Shown here is an example of lipid hydrolysis.
Hydroxylation
General Syntax:
ProteinA --enzyme--> ProteinA{hyd}
(direct: direct; reversible: false; effect term: hydroxylation)
Example:
HIF-1(ce) --EGL-9(ce)--> HIF-1(ce){hydP621}
Here, proline residue at position 621 has been modified by
hydroxylation.
Methylation
General Syntax Examples:
ProteinA + S-Adenosylmethionine --enzyme--> ProteinA{met} +
S-Adenosylhomocysteine
ProteinA + S-Adenosylmethionine --enzyme--> ProteinA{metR234}
+ S-Adenosylhomocysteine
Shown here is an example of the format used when the authors
determine the position of methylation.
Myristoylation
Example:
G-alpha-i-1(m.s.) + myristoyl-CoA --> Galpha-i-1(m.s.){myr} +
CoA
Here, information about the enzyme involved in palmitoylation
has not been provided.
Neddylation
General Syntax:
ProteinA + Nedd8 --(E1),(E2),E3--> ProteinA{neddK}
Note that deneddylation, which removes the Nedd8 moiety,
requires the isopeptidase activity of the COP9 signalosome
(CSN).
Nitrosylation (S-nitrosylation)
General Syntax:
ProteinA + NO --enzyme--> ProteinA{no}
Example:
dynamin + NO --NO synthase--> dynamin{noC607}
Here, dynamin is nitrosylated at cysteine residue 607 by an
enzyme, nitric oxide synthase.
Palmitoylation
Example:
Shh-N(h){chol} + palmityl-CoA --> Shh-N(h){chol}{palC1} +
CoA
Here, information about the enzyme involved in palmitoylation
has not been provided.
Phosphorylation
General Syntax:
ProteinA + ATP --EnzymeC--> ProteinA{p} + ADP
Examples:
GATA-4(m) + ATP --ERK2(m)--> GATA-4(m){pS105} + ADP
stathmin(x) + 3ATP --Plk1(x)--> stathmin(x){pS16}{pS25}{pS39}
+ 3ADP
Here, three residues have been phosphorylated and thus there are
three molecules of ATP and three molecules of ADP.
KIF23(h) + ATP --cyclin B1(h):Cdk1(h)--> KIF23(h){p} +
ADP
Here, the enzyme is in a complex.
cyclin A(h):Cdk2(h):Cdc25A(h) + ATP --> cyclin
A(h):Cdk2(h):Cdc25A(h){p} + ADP
Here, the enzyme is in a stable complex with the substrate and
is therefore not separately linked as enzyme.
Prenylation (Farnesylation, Geranyl(geranyl)ation)
Examples:
Rab3A(m.s.) --RabGGTase-alpha(m.s.)--> Rab3A(m.s.){pren}
Here is an example of prenylation in general. Specific examples
of farnesylation, geranylation, and geranylgeranylation are
provided below.
Rab7 + geranyl-PPi + NADPH --> Rab7{ger} + PPi + NADP
Here is an example of geranylation.
Rab7 + 2 geranyl-PPi + 2NADPH --> Rab7{ger(2)} + 2PPi +
2NADP
Here is an example of geranylgeranylation.
ProteinA + farnesyl-PPi + NADPH --> ProteinA{far} + PPi +
NADP
And finally, an example of the general syntax for
farnesylation.
Sulfation
General Syntax:
ProteinA + PAPS --TPST--> ProteinA{sulY} + 3',5'-ADP
In this example, PAPS is adenosine 3'-phosphate
5'-phosphosulfate, a universal sulfate donor. TPST is
tyrosylprotein sulfotransferase (EC 2.8.2.20), which catalyzes the
transfer of sulfate from PAPS to the hydroxyl group of a
peptidyltyrosine residue, forming a tyrosine O4-sulfate ester and
3',5'-ADP.
Sumoylation
Examples:
AP-2alpha(h) + SUMO-1(h) --> AP-2alpha(h){sumo}
AP-2gamma(h) + SUMO-1(h) --> AP-2gamma(h){sumoK10}
Here, the position of sumoylation is not known, and details
about the enzymes involved have not been provided in the
literature. Note that it is also possible to describe binding
reactions for SUMO-1 and other proteins that do not result in the
covalent modification of those other proteins.
Ubiquitination
Examples:
alpha-synuclein(m.s.) + ubiquitin(m.s.) --parkin(m.s.)-->
alpha-synuclein(m.s.){ub}
Here, "{ub}" indicates that the protein is ubiquitinated but
details about the size of ubiquitin chain have not been not
provided in the literature.
alpha-synuclein(h){ub(2)} + n ubiquitin(v.s.) --UCH-L1(h)-->
alpha-synuclein(h){ub(n)}
Here, "{ub(2)}" indicates that the alpha-synclein protein has
two ubiquitin molecules attached.
p53(h) + n ubiquitin(v.s.) --PIRH2(v.s.)--> p53(h){ub(n)}
Mdm2(h) + n ubiquitin(v.s.) --> Mdm2(h){ub(n)}
Rad23A(mo) + n ubiquitin(v.s.) --E6-AP(h)-->
Rad23A(mo){ub(n)}
Here, "{ub(n)}" indicates that the protein is polyubiquitinated,
but that details about how many ubiquitin molecules are attached
have not been provided in the literature.
Indirect Reactions
Activation
General Syntax:
ProteinA --> ProteinB
(direct: indirect; reversible: false; effect term: activation)
This reaction format is most often used to indicate that
reporter gene assay has demonstrated that a transcription co-factor
increases the activity of a transcription factor.
Decrease in Abundance
General Syntax:
ProteinA --/ ProteinB
(direct: indirect; reversible: false; effect term: decrease of
abundance)
Here, the effect of ProteinA on ProteinB levels is demonstrated
by a protein assay (Western blot, for example). Note that a
decrease in mRNA abundance is indicated as shown below.
DNA Binding
General Syntax:
ProteinA --> GeneB
(direct: indirect; reversible: false; effect term: DNA binding)
Here, binding of ProteinA to the promoter/enhancer of GeneB has
been shown by electrophoretic gel mobility-shift assay, for
example. Since "DNA binding" does not imply an effect of the
binding, it may be combined with transactivation or transrepression to indicate the
effect.
Expression
General Syntax Examples:
GeneB --> ProteinB
GeneB --> ProteinB-xbb1
(direct: indirect; reversible: false; effect term: expression)
GeneB gives rise to ProteinB. Since expression is a multi-step
process that involves both transcription and translation,
expression is regarded as an indirect effect.
Increase in Abundance
General Syntax:
ProteinA --> ProteinB
(direct: indirect; reversible: false; effect term: increase of
abundance)
Example:
SMAR1(m) --> p21Cip1(h)
Here, the effect of murine SMAR1 on human p21Cip1 was shown by
Western blot, and the result was an increase in expression of the
human protein. Note that an increase in mRNA abundance is indicated
as shown below.
Increase in Binding
General Syntax:
ProteinA --> ProteinB:ProteinC
Example:
Crk(m.s.) --> p110alpha(h):H-Ras(m.s.)
Here, mammalian Crk increases the binding of human p110alpha to
mammalian H-Ras.
Increase in Phosphorylation
General Syntax:
ProteinA --> ProteinB{p}
Example:
ATR(m.s.) --> WRN(m.s.){p}
Here, mammalian ATR indirectly increases the phosphorylation of
mammalian WRN.
Transactivation
General Syntax:
ProteinA --> GeneB
(direct: indirect; reversible: false; effect term:
transactivation)
Here, ProteinA positively regulates the transcription of GeneB.
The activity of ProteinA is typically demonstrated using a reporter
assay, and sometimes it is the case that only the GeneB promoter or
enhancer sequence is used in the assay. The activity of ProteinA
may also be demonstrated by its effect on mRNA produced by GeneB,
using Northern blots or quantitative RT-PCR. Note that an increase
in protein abundance is indicated as shown above.
Transrepression
General Syntax:
ProteinA --/ GeneB
(direct: indirect; reversible: false; effect term:
transrepression)
Here, ProteinA negatively regulates the transcription of GeneB.
As with transactivation, the activity of ProteinA is typically
demonstrated using a reporter assay, and sometimes it is the case
that only the GeneB promoter or enhancer sequence is used in the
assay. The activity of ProteinA may also be demonstrated by its
effect on mRNA produced by GeneB, using Northern blots or
quantitative RT-PCR. Note that an decrease in protein abundance is
indicated as shown above.