About Gene List

PF3D7_0207600 (SERA5)

Genome location: Pf3D7_02_v3:303,409..307,376(-)

Genome classification: Core

Function and Localization

Product Description: serine repeat antigen 5

SignalP Peptide: MKSYISLFFILCVIFNKNVIKCTG

# Transmembrane Domains: 0

EC Numbers: 3.4.22.- (Cysteine endopeptidases.)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005615 extracellular space
Component GO:1903561 extracellular vesicle
Component GO:0005764 lysosome
Component GO:0005634 nucleus
Component GO:0020004 symbiont-containing vacuolar space
Component GO:0020003 symbiont-containing vacuole
Function GO:0004197 cysteine-type endopeptidase activity
Function GO:0008234 cysteine-type peptidase activity
Function GO:0019900 kinase binding
Function GO:0008233 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 expressed 0.30 0.86
Trophozoite expressed 1.32 0.59
Schizont expressed 2.72 0.36
Gametocyte expressed 0.13 0.93

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0207600

Resistome Missense Mutations: D434N

Resistome Compounds with Missense Mutations: MMV982556

Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.2 | MFS: -2.737 | #Insertions: 0

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0305100)

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

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q9TY95

"Best" AlphaFill ligand hit: I3C (5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid, Local RMSD=0.42) with 6X42 (Global RMSD=1.82)

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 22 32 15 33
disruptive 109 109 35 122
missense 49 47 18 69

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 29 49 26 40
disruptive 139 149 60 152
missense 55 78 40 77

PlasmoDB Total SNPs: 306

Non-coding: 64 | Synonymous: 90 | Nonsynonymous: 151 | Stop Codon: 1

Protein Information

Protein Length: 997 | Molecular Weight (kDa): 111.768

UniProt ID(s): A0A0E3VL27, A0A0E4B1V1, A0A0E4B234, A0A0E4B242, A0A0E4B3A9, A0A0E4B3K2, A0A0E4FHX1, A0A348AW43, I0IZ29, I0IZF8, Q26016, Q9NIF4, Q9TY95

PDB ID(s): 3CH2, 3CH3

Isoelectric Point: 5.06

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000668 Peptidase C1A, papain C-terminal
InterPro IPR025660 Cysteine peptidase, histidine active site
InterPro IPR025661 Cysteine peptidase, asparagine active site
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
21203490 Compartmentation of redox metabolism in malaria parasites. Kehr S, Sturm N, ..., Becker K 10.1371/journal.ppat.1001242
21630256 Antibodies reactive to Plasmodium falciparum serine repeat antigen in childrenwith Burkitt lymphoma from Ghana. Guech-Ongey M, Yagi M, ..., Mbulaiteye SM 10.1002/ijc.26203
24769454 Synthetic peptides derived from the C-terminal 6kDa region of Plasmodiumfalciparum SERA5 inhibit the enzyme activity and malaria parasite development. Kanodia S, Kumar G, ..., Malhotra P 10.1016/j.bbagen.2014.04.013
25599609 Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexualblood-stage lifecycle. Stallmach R, Kavishwar M, ..., Blackman MJ 10.1111/mmi.12941
28202027 A novel Pfs38 protein complex on the surface of Plasmodium falciparum blood-stagemerozoites. Paul G, Deshmukh A, ..., Malhotra P 10.1186/s12936-017-1716-0
28683142 The Plasmodium falciparum pseudoprotease SERA5 regulates the kinetics andefficiency of malaria parasite egress from host erythrocytes. Collins CR, Hackett F, ..., Blackman MJ 10.1371/journal.ppat.1006453
28944300 Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyanclinical isolate defines a core parasite secretome. Abdi A, Yu L, ..., Rayner J 10.12688/wellcomeopenres.11910.2
29567995 Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of HostVitronectin to P47 Fragment of SERA5. Tougan T, Edula JR, ..., Horii T 10.1038/s41598-018-23194-9
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596
31148576 Plasmodium pseudo-Tyrosine Kinase-like binds PP1 and SERA5 and is exported tohost erythrocytes. Gnangnon B, Freville A, ..., Pierrot C 10.1038/s41598-019-44542-3
32955133 Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen. Smith NA, Clarke OB, ..., Smith BJ 10.1002/pro.3956
28808204 Safety, immunogenicity, and cross-species protection of a plasmid DNA encodingPlasmodium falciparum SERA5 polypeptide, microbial epitopes and chemokine genesin mice and olive baboons Onkoba N, M Mumo R, ..., G Egwang T 10.7555/JBR.31.20160025
37908361 Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabeadults and children: a phase 1b randomised, controlled, double-blinded, agede-escalation trial Ouedraogo A, Bougouma EC, ..., Sirima SB 10.3389/fimmu.2023.1267372
27343834 Immunogenicity and protection from malaria infection in BK-SE36 vaccinatedvolunteers in Uganda is not influenced by HLA-DRB1 alleles Tougan T, Ito K, ..., Horii T 10.1016/j.parint.2016.06.012
29716996 Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen5 triggers merozoite egress Iyer GR, Singh S, ..., Malhotra P 10.1074/jbc.RA117.001540
29760216 Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface andGenerates Antibody Response during Natural Infection Deshmukh A, Chourasia BK, ..., Malhotra P 10.1128/IAI.00067-18
33012605 First-in-human randomised trial and follow-up study of Plasmodium falciparumblood-stage malaria vaccine BK-SE36 with CpG-ODN(K3) Ezoe S, Palacpac NMQ, ..., Horii T 10.1016/j.vaccine.2020.09.056
30483336 Genetic Diversity in C-terminal of SERA5 Gene in the Blood Stage of HumanIsolates of Plasmodium vivax in Sistan and Baluchistan, Iran Abolghazi A, Heidari A, ..., Shojaee S https://pubmed.ncbi.nlm.nih.gov/30483336/
33918470 Assessment of Mixed Plasmodium falciparum sera5 Infection in Endemic BurkittLymphoma: A Case-Control Study in Malawi Arisue N, Chagaluka G, ..., Mbulaiteye SM 10.3390/cancers13071692
26725489 In silico approach to ascertain the calcium dependent role of Plasmodiumfalciparum SERA5 Rahul CN, Shiva Krishna K, Pawar AP, Rajesh V 10.1080/07391102.2015.1129988
33032613 Age-dependent carriage of alleles and haplotypes of Plasmodium falciparum sera5,eba-175, and csp in a region of intense malaria transmission in Uganda Agwang C, Erume J, ..., Egwang TG 10.1186/s12936-020-03432-0
36993981 Plasmodium falciparum infection coinciding with the malaria vaccine candidateBK-SE36 administration interferes with the immune responses in Burkinabechildren Tiono AB, Palacpac NMQ, ..., Sirima SB 10.3389/fimmu.2023.1119820
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
36590593 African-specific polymorphisms in Plasmodium falciparum serine repeat antigen 5in Uganda and Burkina Faso clinical samples do not interfere with antibodyresponse to BK-SE36 vaccination Arisue N, Palacpac NMQ, ..., Horii T 10.3389/fcimb.2022.1058081
28662682 Pooled-DNA sequencing identifies genomic regions of selection in Nigerianisolates of Plasmodium falciparum Oyebola KM, Idowu ET, ..., Amambua-Ngwa A 10.1186/s13071-017-2260-z
30579868 Associations between IgG reactivity to Plasmodium falciparum erythrocyte membraneprotein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-controlstudies Derkach A, Otim I, ..., Mbulaiteye SM 10.1016/j.ebiom.2018.12.020