iron uptake, storage & regulation thereof

[Antonialock]

we had a few tickets and the annotation is a bit messy so checking and improving it.

need to add to this story....

1) TRANSCRIPTIONAL REGULATION

HIGH IRON

Fep1 transcriptionally negatively regulates php4 and iron acquisition genes (e.g. frp1, fio1, fip1, str1,2,3) Tup11/12 are corepressors Grx4 bound to iron sulphur cluster activates fep1

Grx4 bound to iron sulphur cluster binds php4, and promotes its nuclear export

Php2/3/5 transcriptionally positively regulates iron requiring genes

positive regulation of transcription from RNA polymerase II promoter in response to iron Php2 Php3 Php5

negative regulation of transcription from RNA polymerase II promoter in response to iron fep1 tup11 tup12

LOW IRON

when grx4 is not bound to iron php4 is allowed to interact with php2/3/5. Fe using genes are no longer expressed

when grx4 is not bound to iron fep1 can't bind DNA and Fe transport genes are activated

negative regulation of transcription from RNA polymerase II promoter in response to iron ion starvation Php4

What's the GO term for the 'switch'? Grx4 - cellular iron ion homeostasis

2) IRON UPTAKE

REDUCTIVE SYSTEM Frp1 reduces ferric iron to ferrous Fio1/fip1 transports the ferrous iron across PM into cell

Reductive iron assimilation Fio1 fip1 Frp1

NONREDUCTIVE UPTAKE Siderophore uptake: str1 -> add GO:0015344 Ferrixomaine B iron: str2 -> add GO:0015344

heme transporter activity str3

heme import across plasma membrane Shu1 Str3

3) IRON STORAGE, METABOLISM

In high iron, iron is stored in vacuoles (possibly as ferrichromes)

Pcl1: in high iron, pal1 transports Fe from cytosol into vacuole Abc3: In low iron abc3 transports iron from vacuole to cytosol

Siderophore ferrichrome biosynthesis: Sib2-SPBC17G9.06c-sib1

intracellular sequestering of iron ion pcl1

some form of heme import that goes across PM to vacuole https://github.com/pombase/curation/issues/2406 shu1

requested heme export from vacuole abc3

HEME BIOSYNTHESIS We have 13 genes annotated to this, but "In Schizosaccharomyces pombe, these eight enzymes are respectively encoded by the following genes: hem1+, hem2+, hem3+, ups1+, hem12+, hem13+, hem14+, and hem15+. " https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400333/

hemin storage shu1? "Consistent with this observation, results have shown that in response to elevated concentrations of hemin or ZnMP, Shu1 undergoes internalization from the cell surface to the vacuole (8)." Heme assimilation in Schizosaccharomyces pombe requires cell-surface-anchored protein Shu1 and vacuolar transporter Abc3

[Antonialock]

leae out str2 and str3 "In the case of Str2, its physiological role in S. pombe is still unclear, and the ORFeome global analysis of protein localization indicates that Str2 localizes to the membrane vacuole (15). Str3 displays the lowest sequence identity with Str1 and Str2 (11). Although Str3 localizes to the plasma membrane of cells (15), its heterologous expression in an iron uptake–deficient S. cerevisiae strain fails to restore growth in the presence of siderophores, including ferrichrome and ferroxiamine B (11). The biological function of Str3 remains therefore undetermined."

[Antonialock]

aside from the heme transmembrane issue the rest looks fine

[ValWood]

Is that from this paper?

https://www.pombase.org/reference/PMID:29549126 The major facilitator transporter Str3 is required for low-affinity heme acquisition in Schizosaccharomyces pombe .

[ValWood]

This is fine, later "automated modelling" should resolve any outstanding issues.