About Gene List

PF3D7_0213100 (SIS1)

Genome location: Pf3D7_02_v3:537,390..540,199(+)

Genome classification: Core

Function and Localization

Product Description: protein SIS1

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020036 Maurer's cleft
Component GO:0005829 cytosol
Component GO:0005634 nucleus
Function GO:0051087 chaperone binding
Function GO:0051082 unfolded protein binding
Process GO:0051085 chaperone cofactor-dependent protein refolding
Process GO:0006457 protein folding
Process GO:0009408 response to heat
Process GO:0006986 response to unfolded protein

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

Stage LR class MCA mean MCA prop. zeros
Sporozoite expressed N/A N/A
Ring expressed 0.32 0.84
Trophozoite expressed 0.79 0.57
Schizont expressed 0.10 0.93
Gametocyte expressed 0.82 0.56

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0213100

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 1 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.238 | MFS: -2.617 | #Insertions: 0

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0310000)

  • Relative Growth Rate: 0.90 ± 0.13
  • Confidence: 5.53

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0310000)

Modification: Disrupted | RMgm-1788

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: O96212

"Best" AlphaFill ligand hit: No AlphaFill hits

No associated EC numbers

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P31689 DnaJ homolog subfamily A member 1 Homo sapiens OrthoDB CHEMBL52073CHEMBL159171

Orthology Information

Ortholog Group (OrthoMCL): OG6_100302

Most Similar Human Ortholog: H0Y4S1

TM-align score: 0.86 | RMSD: 0.70

Seq Identity: 0.55 | Length: 33 / 328

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000132002 DnaJ heat shock protein family (Hsp40) member B1
ENSG00000137094 DnaJ heat shock protein family (Hsp40) member B5
ENSG00000162616 DnaJ heat shock protein family (Hsp40) member B4
ENSG00000187726 DnaJ heat shock protein family (Hsp40) member B13

Protein Information

Protein Length: 328 | Molecular Weight (kDa): 37.356

UniProt ID(s): O96212

PDB ID(s): None

Isoelectric Point: 9.17

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001623 DnaJ domain
InterPro IPR002939 Chaperone DnaJ, C-terminal
InterPro IPR008971 HSP40/DnaJ peptide-binding
InterPro IPR018253 DnaJ domain, conserved site
InterPro IPR036869 Chaperone J-domain superfamily
PFam PF00226 DnaJ domain
PFam PF01556 Chaperone DnaJ, C-terminal
Superfamily SSF46565 Chaperone J-domain superfamily
Superfamily SSF49493 HSP40/DnaJ peptide-binding

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 1 15 11 24
disruptive 0 3 5 18
missense 0 3 4 16

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 3 36 19 29
disruptive 2 18 15 75
missense 0 12 9 57

PlasmoDB Total SNPs: 112

Non-coding: 103 | Synonymous: 8 | Nonsynonymous: 1 | Stop Codon: 0

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
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
25701168 PFB0595w is a Plasmodium falciparum J protein that co-localizes with PfHsp70-1and can stimulate its in vitro ATP hydrolysis activity. Njunge JM, Mandal P, ..., Blatch GL 10.1016/j.biocel.2015.02.008
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596
31631203 A network-based approach reveals novel invasion and Maurer's clefts-relatedproteins in Plasmodium falciparum. Das D, Krishnan SR, Roy A, Bulusu G 10.1039/c9mo00124g
37589820 Backbone and sidechain NMR assignments of residues 1-81 from yeast Sis1 incomplex with an Hsp70 C-terminal EEVD peptide Matos CO, Pinheiro GMS, Ramos CHI, Almeida FCL 10.1007/s12104-023-10148-0
34849884 Yeast J-protein Sis1 prevents prion toxicity by moderating depletion of prionprotein Kumar J, Reidy M, Masison DC 10.1093/genetics/iyab129
34935410 Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome byTti1, a specialized PIKK chaperone Schilke BA, Craig EA 10.1091/mbc.E21-10-0493
36576197 Identification of subfunctionalized aggregate-remodeling J-domain proteins inArabidopsis thaliana Tak Y, Lal SS, ..., Sahi C 10.1093/jxb/erac514
36298715 Hsp40/JDP Requirements for the Propagation of Synthetic Yeast Prions Miller SC, Wegrzynowicz AK, ..., Hines JK 10.3390/v14102160
37158601 Transcriptional regulation of Sis1 promotes fitness but not feedback in the heatshock response Garde R, Singh A, Ali A, Pincus D 10.7554/eLife.79444
36138748 Anti-Prion Systems Block Prion Transmission, Attenuate Prion Generation, CureMost Prions as They Arise and Limit Prion-Induced Pathology in Saccharomycescerevisiae Wickner RB, Edskes HK, Son M, Wu S 10.3390/biology11091266
35205876 Differential Interactions of Molecular Chaperones and Yeast Prions Barbitoff YA, Matveenko AG, Zhouravleva GA 10.3390/jof8020122
37903258 Human proteins curing yeast prions Wu S, Edskes HK, Wickner RB 10.1073/pnas.2314781120
38331212 Role of J-domain Proteins in Yeast Physiology and Protein Quality Control Ruger-Herreros C, Svoboda L, Mogk A, Bukau B 10.1016/j.jmb.2024.168484
35093637 Elevated constitutive expression of Hsp40 chaperone Sis1 reduces TDP-43aggregation-induced oxidative stress in Ire1 pathway dependent-manner in yeastTDP-43 proteinopathy model of amyotrophic lateral sclerosis Bharathi V, Bajpai A, Parappuram IT, Patel BK 10.1016/j.bbrc.2022.01.073
34873058 Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperonepotentiate disaggregation of misfolded proteins Wyszkowski H, Janta A, ..., Liberek K 10.1073/pnas.2108163118
35177839 Amyloid conformation-dependent disaggregation in a reconstituted yeast prionsystem Nakagawa Y, Shen HC, ..., Tanaka M 10.1038/s41589-021-00951-y
36552355 Human J-Domain Protein DnaJB6 Protects Yeast from [PSI(+)] Prion Toxicity Dolder RE 3rd, Kumar J, Reidy M, Masison DC 10.3390/biology11121846
35931773 Disease-associated mutations within the yeast DNAJB6 homolog Sis1 slowconformer-specific substrate processing and can be corrected by the modulation ofnucleotide exchange factors Bhadra AK, Rau MJ, ..., True HL 10.1038/s41467-022-32318-9