About Gene List

PF3D7_0207500 (SERA6)

Genome location: Pf3D7_02_v3:298,380..302,820(-)

Genome classification: Core

Function and Localization

Product Description: serine repeat antigen 6

SignalP Peptide: MICPIFFLYIINVLFTQYFIKCEG

# Transmembrane Domains: 0

EC Numbers: 3.4.22.- (Cysteine endopeptidases.)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005615 extracellular space
Component GO:0005764 lysosome
Component GO:0005634 nucleus
Component GO:0020003 symbiont-containing vacuole
Function GO:0004197 cysteine-type endopeptidase activity
Function GO:0008234 cysteine-type peptidase activity
Function GO:0005515 protein binding
Process GO:0035891 exit from host cell
Process GO:0002377 immunoglobulin production
Process GO:0006508 proteolysis
Process GO:0051603 proteolysis involved in cellular protein catabolic process
Process GO:0050776 regulation of immune response

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring not expressed 0.07 0.97
Trophozoite expressed 0.86 0.63
Schizont expressed 1.07 0.57
Gametocyte not expressed 0.04 0.98

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0207500

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.252 | MFS: -2.761 | #Insertions: 0

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0305100)

  • Relative Growth Rate: 1.04 ± 0.17
  • Confidence: 4.93

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0304900)

Modification: Tagged | RMgm-272

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q9TY96

"Best" AlphaFill ligand hit: E64 (n-[n-[1-hydroxycarboxyethyl-carbonyl]leucylamino-butyl]-guanidine, Local RMSD=0.21) with 3BPF (Global RMSD=6.58)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.4.22.- Ex: staphylococcal cysteine proteinase NEME64SpiSDSCysEDTAPCMBEGTAPMSFTLCKTPCKMENT...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_126098

No human ortholog(s)

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 5 44 28 57
disruptive 39 86 46 101
missense 34 79 44 87

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 11 72 40 57
disruptive 59 137 69 154
missense 46 124 61 116

PlasmoDB Total SNPs: 224

Non-coding: 170 | Synonymous: 19 | Nonsynonymous: 35 | Stop Codon: 0

Protein Information

Protein Length: 1031 | Molecular Weight (kDa): 118.836

UniProt ID(s): A0A0E3VL22, A0A0E3VL29, A0A0E4B250, A0A0E4B386, A0A0E4B3C7, A0A0E4B3H8, A0A0E4FHY3, Q26015, Q26017, Q9TY96

PDB ID(s): None

Isoelectric Point: 6.21

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000169 Cysteine peptidase, cysteine active site
InterPro IPR000668 Peptidase C1A, papain C-terminal
InterPro IPR038765 Papain-like cysteine peptidase superfamily
PFam PF00112 Peptidase C1A, papain C-terminal
Superfamily SSF54001 Papain-like cysteine peptidase superfamily

Associated Publications

PMID Title Authors DOI/Link
9804551 Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Tettelin H, ..., Hoffman SL 10.1126/science.282.5391.1126
12228245 A subset of Plasmodium falciparum SERA genes are expressed and appear to play animportant role in the erythrocytic cycle. Miller SK, Good RT, ..., Crabb BS 10.1074/jbc.M206974200
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
22984267 Proteolytic activation of the essential parasitophorous vacuole cysteine proteaseSERA6 accompanies malaria parasite egress from its host erythrocyte. Ruecker A, Shea M, ..., Blackman MJ 10.1074/jbc.M112.400820
29459732 A protease cascade regulates release of the human malaria parasite Plasmodiumfalciparum from host red blood cells. Thomas JA, Tan MSY, ..., Blackman MJ 10.1038/s41564-018-0111-0
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596
33932049 Autocatalytic activation of a malarial egress protease is druggable and requiresa protein cofactor. Tan MSY, Koussis K, ..., Blackman MJ 10.15252/embj.2020107226
17609844 Phylogeny and evolution of the SERA multigene family in the genus Plasmodium Arisue N, Hirai M, ..., Horii T 10.1007/s00239-006-0253-1
1654826 Genetic analysis of yeast iso-1-cytochrome c structural requirements: suppressionof Gly6 replacements by an Asn52----Ile replacement Berroteran RW, Hampsey M 10.1016/0003-9861(91)90193-m
17893128 Evidence for a common role for the serine-type Plasmodium falciparum serinerepeat antigen proteases: implications for vaccine and drug design McCoubrie JE, Miller SK, ..., Crabb BS 10.1128/IAI.00405-07
15306658 The serine repeat antigen (SERA) gene family phylogeny in Plasmodium: the impactof GC content and reconciliation of gene and species trees Bourgon R, Delorenzi M, ..., Speed TP 10.1093/molbev/msh228
21660657 Falcipains and other cysteine proteases of malaria parasites Rosenthal PJ 10.1007/978-1-4419-8414-2_3
13679369 Enzymic, phylogenetic, and structural characterization of the unusual papain-likeprotease domain of Plasmodium falciparum SERA5 Hodder AN, Drew DR, ..., Crabb BS 10.1074/jbc.M306755200
32252804 Characteristic features of the SERA multigene family in the malaria parasite Arisue N, Palacpac NMQ, Tougan T, Horii T 10.1186/s13071-020-04044-y