Sequence-Based Predictions Hemochromatosis
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Don't google it... but a hint: Caesar would solve it ;)
Short Task Description
Detailed description: Sequence-Based Predictions
|P35462 (3PBL)||TMH 1||TMH 2||TMH 3||TMH 4||TMH 5||TMH 6||TMH 7|
|P47863 (2D57)||TMH 1||TMH 2||TMH 3||TMH 4||TMH 5||TMH 6||TMH 7||TMH 8|
|Q9YDF8 (1ORQ/1ORS)||TMH 1||TMH 2||TMH 3||TMH 4||TMH 5||TMH 6||TMH 7||TMH 8|
TODO: score description
SignalP (Webserver 4.0) predictions were made for HFE (Q30201), Aquaporin-4 (P47863), Lysosome-associated membrane glycoprotein 1 (P11279), and Serum albumin (P02768) in order to find signal peptides within these sequences. The results are shown in <xr id="signalp"/> and were compared to the corresponding entries in UniProt.
According to UniProt all four predictions are 100% precise:
- Q30201: signal peptide 1-22
- P47863: no signal peptide
- P11279: signal peptide 1-28
- P02768: signal peptide 1-18
This makes SignalP an excellent candidate for signal peptide predictions.
For the last part of this task we used GOPET and ProtFun to make a GO term prediction for the HFE protein (Q30201). We did also search for Pfam families. The results were then compared to UniProt and QuickGO.
GOPET predicts only two GO terms for our protein (see <xr id="gopet"/>) and even they are somewhat redundant (both are receptor activity). At least the results are correct in that HFE has kind of a receptor activity in that it binds to transferrin receptor (TFR).
|GO:0004872||F (Molecular Function Ontology)||91%||receptor activity|
|GO:0030106||F (Molecular Function Ontology)||88%||MHC class I receptor activity|
The results for the ProtFun prediction are shown in <xr id="protfun"/>. Predictions with a probability below 0.1 and odds below 1.0 are not shown to decrease the size of the table. ProtFun predicts "cell envelope" for the functional category. This is true as the HFE-TFR complex is located in the membrane. "Transport and binding" also has a high probability which corresponds with HFE's part in the iron transport within the body. HFE is categorized as "Nonenzyme" and no enzyme class was predicted. It is further predicted to be involved in "Immune response" as it is a protein of the major histocompatibility complex (MHC) class I.
|Biosynthesis of cofactors||0.105||1.452|
|Central intermediary metabolism||0.231||3.663|
|Fatty acid metabolism||0.016||1.265|
|Purines and pyrimidines||0.583||2.400|
|Transport and binding||0.732||1.785|
|Gene Ontology category|
Pfam lists two significant results for Q30201:
- MHC_I - Class I Histocompatibility antigen, domains alpha 1 and 2 (E-value 3.5e-43)
- C1-set - Immunoglobulin C1-set domain (E-value 2.8e-18)
MHC class I proteins are strongly involved in immune responses. UniProt also lists HFE in the MHC class I family and its structure (three extracellular domains, transmembrane region, cytoplasmic tail) fits. C1-set domains are associated with MHC class I proteins and HFE indeed contains such a domain (residues 207-298)
Compared to QuickGO which lists 27 unique GO terms for Q30201, GOPET predicts only two. Both of them not included in QuickGO's list. These two also seem to fit the HFE-TFR complex better than HFE alone, but at least the MHC class I tag is shows specificity to HFE.
ProtFun's prediction seems more accurate as it successfully identifies HFE's location within the membrane and lists "Transport and binding" as a good second result. "Immune response" is also in accordance to QuickGO's term.
Pfam's two predicted families were both true positives and it was more informative that the other two methods.
Overall none of them did identify HFE's part in the iron transport.