Protein & Chemical Interaction Annotation
Please enter your full name (last name, first) in this box:
Please enter the subject(s) of your university studies:
About this procedure
This exercise is both to see if you have (or can develop) the skills we need, and to see if this is the kind of work that you would like to do. The company ultimately aims to provide a complete map of all interactions between chemicals, genes and proteins within living systems in order to make intelligent predictions as to why a particular macroscopic effect is observed. A very important and valuable part of reaching this aim is to identify protein-protein, protein-chemical or other types of interactions.
In all cases you will be asked to find details in abstracts from scientific articles (from PubMed). Please select the
best
answer that you think describes what is written in the abstract. There are always 'Comments' boxes to add additional comments, such as details as to why you chose something, if it is too difficult to say for sure, etc.
There are several hyperlinks given below. When a protein is hyperlinked, e.g.
Protein:
KCNE2
(potassium voltage-gated channel, Isk-related family, member 2)
The link will take you to the NCBI entry for the protein. There you will find various things out about the protein, including (most importantly for this exercise), other names that are used (or were used) to refer to the protein. For example, KCNE2 (above), is also known as MiRP1.
When a chemical is linked (Part 2 only), e.g.
Chemical:
ZD1839
The link will take you to PubChem, where you will see various things about the chemical, including other names for it. For example, the chemical above is also known under the tradenames Iressa or Gefitinib.
For Parts 1 & 2 (below) you will also be given links to one or more references in PubMed, e.g.
Reference(s):
PubMed 10359587 12221085
You will be taken to one or more abstracts at PubMed. If more than one abstract is given, then you will need to select the 'Abstract' option from the 'Display' menu to see them all.
WARNING: it is intended that you do this test once, and in one sitting in roughly 30-60 minutes. DO NOT press reload in the browser, as you will remove any answers already entered, and you will change the random selection of questions.
When finished, please click 'Submit Query' at the bottom of the page.
Part 1: Protein-protein interactions
There are several different ways in which proteins can interact with each other. They may simple bind to each other (stick together) as part of some biological process, one molecule may modify another, for example by attaching a phosphate group to it (or removing one), one protein may activate or block the transcription of another protein, etc.
In the following exercises you will be asked to read an abstract that mentions two proteins (or genes). From this, you will need to select the type of interaction that best describes the relationship between them. In some cases the situation may be ambiguous, or more than one of the descriptors may apply. Note things like this in the optional 'Comments' box for each question. You will need to fill in a 'blank' (marked SELECT initially) betwen the two molecules, for example:
FGF1 DIRECTLY ACTIVATES FGR1
would summarise an abstract speaking about how fibroblast growth factor 1 binds to one of the receptors.
Question 1
The interaction between:
KCNE2
(potassium voltage-gated channel, Isk-related family, member 2) AND
KCNH2
(voltage-gated potassium channel, subfamily H, member 2 isoform a)
Reference(s):
PubMed 10219239
KCNE2
SELECT
IS IN A PROTEIN COMPLEX WITH
ACTIVATES
INHIBITS
PHOSPHORYLATES
CLEAVES/BREAKS-DOWN
BINDS TO
ACTIVATES TRANSCRIPTION OF
BLOCKS TRANSCRIPTION OF
AFFECTS TRANSCRIPTION OF
INDIRECTLY ACTIVATES
INDIRECT INHIBITS
INDIRECTLY AFFECTS (NOT CLEAR)
KCNH2
Comments (optional):
Question 2
The interaction between:
SOD3
(superoxide dismutase 3, extracellular) AND
SHC1
(SHC (Src homology 2 domain containing) transforming protein 1; SHC (Src homology 2 domain-containing) transforming protein 1)
Reference(s):
PubMed 10356288
SOD3
SELECT
IS IN A PROTEIN COMPLEX WITH
ACTIVATES
INHIBITS
PHOSPHORYLATES
CLEAVES/BREAKS-DOWN
BINDS TO
ACTIVATES TRANSCRIPTION OF
BLOCKS TRANSCRIPTION OF
AFFECTS TRANSCRIPTION OF
INDIRECTLY ACTIVATES
INDIRECT INHIBITS
INDIRECTLY AFFECTS (NOT CLEAR)
SHC1
Comments (optional):
Question 3
The interaction between:
MAP3K7 (TAK1)
(mitogen-activated protein kinase kinase kinase 7 isoform A) AND
ATF2
(activating transcription factor 2)
Reference(s):
PubMed 10085140
MAP3K7 (TAK1)
SELECT
IS IN A PROTEIN COMPLEX WITH
ACTIVATES
INHIBITS
PHOSPHORYLATES
CLEAVES/BREAKS-DOWN
BINDS TO
ACTIVATES TRANSCRIPTION OF
BLOCKS TRANSCRIPTION OF
AFFECTS TRANSCRIPTION OF
INDIRECTLY ACTIVATES
INDIRECT INHIBITS
INDIRECTLY AFFECTS (NOT CLEAR)
ATF2
Comments (optional):
Question 4
The interaction between:
IKBKG
(inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) AND
NFKB1
(nuclear factor kappa-B, subunit 1)
Reference(s):
PubMed 10359587 12221085
IKBKG
SELECT
IS IN A PROTEIN COMPLEX WITH
ACTIVATES
INHIBITS
PHOSPHORYLATES
CLEAVES/BREAKS-DOWN
BINDS TO
ACTIVATES TRANSCRIPTION OF
BLOCKS TRANSCRIPTION OF
AFFECTS TRANSCRIPTION OF
INDIRECTLY ACTIVATES
INDIRECT INHIBITS
INDIRECTLY AFFECTS (NOT CLEAR)
NFKB1
Comments (optional):
Question 5
The interaction between:
ATF2
(activating transcription factor 2) AND
SMAD4
(MAD, mothers against decapentaplegic homolog 4)
Reference(s):
PubMed 10085140 11352931
ATF2
SELECT
IS IN A PROTEIN COMPLEX WITH
ACTIVATES
INHIBITS
PHOSPHORYLATES
CLEAVES/BREAKS-DOWN
BINDS TO
ACTIVATES TRANSCRIPTION OF
BLOCKS TRANSCRIPTION OF
AFFECTS TRANSCRIPTION OF
INDIRECTLY ACTIVATES
INDIRECT INHIBITS
INDIRECTLY AFFECTS (NOT CLEAR)
SMAD4
Comments (optional):
Part 2: Protein-chemical interactions
Proteins also bind to, or are influenced by chemicals (i.e. small-molecules). Chemicals can be substrates or products for enzymes, they can be inhibitors, antagonists, agonists, etc. It is also possible that only protein-chemical binding is known without any idea of why this happens, or indeed if binding has any biological effect.
In the following exercises you will be asked to read one or more abstracts that mention a particular protein (or gene) and a chemical. From these, please select the type of interaction that best describes the relationship between them. As above, in some cases the situation may be ambiguous, or more than one of the descriptors may apply. Write things like this in the optional 'Comments' box for each question.
Question 6
The interaction between:
Chemical:
beta-naphthylamine
AND
Protein:
CYP1A2
(cytochrome P450, family 1, subfamily A, polypeptide 2)
Reference(s):
PubMed 2813353
beta-naphthylamine
SELECT
DIRECTLY ACTIVATES
DIRECTLY INHIBITS
DIRECTLY BINDS
IS AN ANTAGONIST OF
IS AN AGONIST OF
IS AN ENZYMATIC SUBSTRATE OF
IS AN ENZYMATIC PRODUCT OF
INDIRECTLY ACTIVATES
INDIRECTLY INHIBITS
INDIRECTLY AFFECTS
CYP1A2
Comments (optional):
Question 7
The interaction between:
Chemical:
di-2-ethylhexylphthalate
AND
Protein:
ESR1
(estrogen receptor 1)
Reference(s):
PubMed 12119130
di-2-ethylhexylphthalate
SELECT
DIRECTLY ACTIVATES
DIRECTLY INHIBITS
DIRECTLY BINDS
IS AN ANTAGONIST OF
IS AN AGONIST OF
IS AN ENZYMATIC SUBSTRATE OF
IS AN ENZYMATIC PRODUCT OF
INDIRECTLY ACTIVATES
INDIRECTLY INHIBITS
INDIRECTLY AFFECTS
ESR1
Comments (optional):
Question 8
The interaction between:
Chemical:
MK801
AND
Protein:
GRIN1
(NMDA receptor 1 isoform NR1-3 precursor)
Reference(s):
PubMed 15567423 12068077 12893641 12753088 9835392 7685113 15338240 16289038 15265015 7679115 14644469 12414113
MK801
SELECT
DIRECTLY ACTIVATES
DIRECTLY INHIBITS
DIRECTLY BINDS
IS AN ANTAGONIST OF
IS AN AGONIST OF
IS AN ENZYMATIC SUBSTRATE OF
IS AN ENZYMATIC PRODUCT OF
INDIRECTLY ACTIVATES
INDIRECTLY INHIBITS
INDIRECTLY AFFECTS
GRIN1
Comments (optional):
Question 9
The interaction between:
Chemical:
ZD1839
AND
Protein:
EGFR
(epidermal growth factor receptor isoform a)
Reference(s):
PubMed 14639003 15239971 12586780 15870435 15967120 15519654 15913841 15447984 15746034 15709185 16322287 16061871 12743604 15623594 15767552 15284455 15118125 15837743 15118073 15665299 15956035 16203769
ZD1839
SELECT
DIRECTLY ACTIVATES
DIRECTLY INHIBITS
DIRECTLY BINDS
IS AN ANTAGONIST OF
IS AN AGONIST OF
IS AN ENZYMATIC SUBSTRATE OF
IS AN ENZYMATIC PRODUCT OF
INDIRECTLY ACTIVATES
INDIRECTLY INHIBITS
INDIRECTLY AFFECTS
EGFR
Comments (optional):
Question 10
The interaction between:
Chemical:
Citrulline
AND
Protein:
NOS3
(nitric oxide synthase 3 (endothelial cell))
Reference(s):
PubMed 15288120 1378832 10681501 14551684 15522324 14561757
Citrulline
SELECT
DIRECTLY ACTIVATES
DIRECTLY INHIBITS
DIRECTLY BINDS
IS AN ANTAGONIST OF
IS AN AGONIST OF
IS AN ENZYMATIC SUBSTRATE OF
IS AN ENZYMATIC PRODUCT OF
INDIRECTLY ACTIVATES
INDIRECTLY INHIBITS
INDIRECTLY AFFECTS
NOS3
Comments (optional):
Part 3: Drug metabolising enzymes
Drug or Xenobiotic metabolism is a critically important process. An important exercise for our company is to catalogue interactions between known chemicals (toxic or otherwise) and drug metabolising enzymes, such as cytochromes P450 (CYPs), UDP-glucuronosyl- (UGTs) or sulfo-transferases (SULTs)
Below we will give you some xenobiotic metabolising enzymes, please use whatever tools (internet) you can to identify at least
three
chemicals that are metabolised by these enzymes. Good starting points for searching are:
Entrez PubMed
,
Wikipedia
or
Google
. Give the names of the chemical in each case, and the source (web page or PubMed identifier) where you got the information.
Question 11 Protein:
SULT2A1
(sulfotransferase family, cytosolic, 2A, dehydroepiandrosterone-preferring, member 1 )
Metabolised chemical 1
(Source 1
)
Metabolised chemical 2
(Source 2
)
Metabolised chemical 3
(Source 3
)
Question 12 Protein:
UGT1A1
(UDP glycosyltransferase 1 family, polypeptide A1 precursor )
Metabolised chemical 1
(Source 1
)
Metabolised chemical 2
(Source 2
)
Metabolised chemical 3
(Source 3
)
Question 13 Protein:
CYP3A4
(cytochrome P450, subfamily IIIA, polypeptide 4 )
Metabolised chemical 1
(Source 1
)
Metabolised chemical 2
(Source 2
)
Metabolised chemical 3
(Source 3
)
Question 14 Protein:
CYP2C9
(cytochrome P450, family 2, subfamily C, polypeptide 9 )
Metabolised chemical 1
(Source 1
)
Metabolised chemical 2
(Source 2
)
Metabolised chemical 3
(Source 3
)
