UniProtKB - Q9NUL5 (SHFL_HUMAN)
Shiftless antiviral inhibitor of ribosomal frameshifting protein
SHFL
Functioni
Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site (PubMed:30682371).
Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371).
Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Interrupts also Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway (PubMed:32150556).
Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532).
Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568).
6 PublicationsIsoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes.
1 PublicationGO - Molecular functioni
- identical protein binding Source: IntAct
- ribosome binding Source: UniProtKB
- RNA binding Source: UniProtKB
- sequence-specific mRNA binding Source: UniProtKB
GO - Biological processi
- defense response to virus Source: UniProtKB
- innate immune response Source: GO_Central
- negative regulation of translational frameshifting Source: UniProtKB
- negative regulation of viral genome replication Source: UniProtKB
- regulation of translational termination Source: UniProtKB
- response to interferon-beta Source: UniProtKB
- response to interferon-gamma Source: UniProtKB
- response to type III interferon Source: UniProtKB
- response to type I interferon Source: UniProtKB
- viral translational frameshifting Source: UniProtKB
Keywordsi
Molecular function | RNA-binding |
Biological process | Antiviral defense |
Enzyme and pathway databases
PathwayCommonsi | Q9NUL5 |
SignaLinki | Q9NUL5 |
Names & Taxonomyi
Protein namesi | Recommended name: Shiftless antiviral inhibitor of ribosomal frameshifting proteinCuratedShort name: SFL1 Publication Short name: SHFLCurated Alternative name(s): Interferon-regulated antiviral protein1 Publication Short name: IRAV1 Publication Repressor of yield of DENV protein1 Publication Short name: RyDEN1 Publication |
Gene namesi | Name:SHFLImported Synonyms:C19orf66, FLJ112861 Publication, IRAV1 Publication, RYDEN1 Publication, SFL1 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:25649, SHFL |
MIMi | 616808, gene |
neXtProti | NX_Q9NUL5 |
VEuPathDBi | HostDB:ENSG00000130813 |
Subcellular locationi
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 121 – 137 | RRVPQ…RKCRK → AAVPQAAEVSACAACAA: Decreased efficiency in the interaction with PABPC1 and reduced inhibitory activity against DENV replication. 1 PublicationAdd BLAST | 17 |
Organism-specific databases
DisGeNETi | 55337 |
OpenTargetsi | ENSG00000130813 |
PharmGKBi | PA162378809 |
Miscellaneous databases
Pharosi | Q9NUL5, Tdark |
Genetic variation databases
BioMutai | C19orf66 |
DMDMi | 172044675 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000318701 | 2 – 291 | Shiftless antiviral inhibitor of ribosomal frameshifting proteinAdd BLAST | 290 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q9NUL5 |
jPOSTi | Q9NUL5 |
MassIVEi | Q9NUL5 |
MaxQBi | Q9NUL5 |
PaxDbi | Q9NUL5 |
PeptideAtlasi | Q9NUL5 |
PRIDEi | Q9NUL5 |
ProteomicsDBi | 82688 [Q9NUL5-1] 82689 [Q9NUL5-2] 82690 [Q9NUL5-3] 82691 [Q9NUL5-4] |
PTM databases
iPTMneti | Q9NUL5 |
PhosphoSitePlusi | Q9NUL5 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000130813, Expressed in right lobe of liver and 230 other tissues |
ExpressionAtlasi | Q9NUL5, baseline and differential |
Genevisiblei | Q9NUL5, HS |
Organism-specific databases
HPAi | ENSG00000130813, Tissue enhanced (liver) |
Interactioni
Subunit structurei
(Microbial infection) Interacts with the human dengue virus DENV proteins NS3 and NS4A.
1 Publication(Microbial infection) Interacts with Zika virus protein NS3; this interaction promotes viral NS3 degradation.
1 PublicationBinary interactionsi
Q9NUL5
Isoform 3 [Q9NUL5-3]
SHFL - isoform 4 [Q9NUL5-4]
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 120618, 88 interactors |
CORUMi | Q9NUL5 |
IntActi | Q9NUL5, 71 interactors |
STRINGi | 9606.ENSP00000253110 |
Miscellaneous databases
RNActi | Q9NUL5, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 51 – 71 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 102 – 150 | Interaction with PABPC11 PublicationAdd BLAST | 49 | |
Regioni | 221 – 250 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 270 – 291 | DisorderedSequence analysisAdd BLAST | 22 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 121 – 137 | Nuclear localization signal1 PublicationAdd BLAST | 17 | |
Motifi | 261 – 269 | Nuclear export signal1 Publication | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 56 – 71 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QVND, Eukaryota |
GeneTreei | ENSGT00390000005065 |
HOGENOMi | CLU_087318_0_0_1 |
InParanoidi | Q9NUL5 |
OMAi | EDCQFAC |
OrthoDBi | 1485595at2759 |
PhylomeDBi | Q9NUL5 |
TreeFami | TF337433 |
Family and domain databases
InterProi | View protein in InterPro IPR026795, SHFL |
PANTHERi | PTHR16135, PTHR16135, 1 hit |
Pfami | View protein in Pfam PF15135, UPF0515, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSQEGVELEK SVRRLREKFH GKVSSKKAGA LMRKFGSDHT GVGRSIVYGV
60 70 80 90 100
KQKDGQELSN DLDAQDPPED MKQDRDIQAV ATSLLPLTEA NLRMFQRAQD
110 120 130 140 150
DLIPAVDRQF ACSSCDHVWW RRVPQRKEVS RCRKCRKRYE PVPADKMWGL
160 170 180 190 200
AEFHCPKCRH NFRGWAQMGS PSPCYGCGFP VYPTRILPPR WDRDPDRRST
210 220 230 240 250
HTHSCSAADC YNRREPHVPG TSCAHPKSRK QNHLPKVLHP SNPHISSGST
260 270 280 290
VATCLSQGGL LEDLDNLILE DLKEEEEEEE EVEDEEGGPR E
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7EML3 | K7EML3_HUMAN | Shiftless antiviral inhibitor of ri... | SHFL | 71 | Annotation score: | ||
K7EMS9 | K7EMS9_HUMAN | Shiftless antiviral inhibitor of ri... | SHFL | 127 | Annotation score: | ||
K7EP02 | K7EP02_HUMAN | Shiftless antiviral inhibitor of ri... | SHFL | 143 | Annotation score: | ||
K7ELT7 | K7ELT7_HUMAN | Shiftless antiviral inhibitor of ri... | SHFL | 77 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 191 | W → R in BAA92109 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 249 | S → P in BAA92109 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_031272 | 1 – 65 | MSQEG…DLDAQ → MSQHQQACGICRQE in isoform 2. 1 PublicationAdd BLAST | 65 | |
Alternative sequenceiVSP_031273 | 164 – 291 | Missing in isoform 3. 1 PublicationAdd BLAST | 128 | |
Alternative sequenceiVSP_031274 | 164 – 199 | Missing in isoform 4. 1 PublicationAdd BLAST | 36 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002148 mRNA Translation: BAA92109.1 AK096142 mRNA Translation: BAC04710.1 AC020931 Genomic DNA No translation available. CH471106 Genomic DNA Translation: EAW84066.1 CH471106 Genomic DNA Translation: EAW84068.1 CH471106 Genomic DNA Translation: EAW84069.1 BC010847 mRNA Translation: AAH10847.1 BC026180 mRNA Translation: AAH26180.1 BC035817 mRNA Translation: AAH35817.1 |
CCDSi | CCDS45957.1 [Q9NUL5-1] CCDS77231.1 [Q9NUL5-4] |
RefSeqi | NP_001295206.1, NM_001308277.1 [Q9NUL5-4] NP_060851.2, NM_018381.3 [Q9NUL5-1] XP_016882423.1, XM_017026934.1 |
Genome annotation databases
Ensembli | ENST00000253110; ENSP00000253110; ENSG00000130813 ENST00000397881; ENSP00000380978; ENSG00000130813 [Q9NUL5-2] ENST00000591813; ENSP00000467182; ENSG00000130813 [Q9NUL5-4] |
GeneIDi | 55337 |
KEGGi | hsa:55337 |
MANE-Selecti | ENST00000253110.16; ENSP00000253110.10; NM_018381.4; NP_060851.2 |
UCSCi | uc002mmu.5, human [Q9NUL5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002148 mRNA Translation: BAA92109.1 AK096142 mRNA Translation: BAC04710.1 AC020931 Genomic DNA No translation available. CH471106 Genomic DNA Translation: EAW84066.1 CH471106 Genomic DNA Translation: EAW84068.1 CH471106 Genomic DNA Translation: EAW84069.1 BC010847 mRNA Translation: AAH10847.1 BC026180 mRNA Translation: AAH26180.1 BC035817 mRNA Translation: AAH35817.1 |
CCDSi | CCDS45957.1 [Q9NUL5-1] CCDS77231.1 [Q9NUL5-4] |
RefSeqi | NP_001295206.1, NM_001308277.1 [Q9NUL5-4] NP_060851.2, NM_018381.3 [Q9NUL5-1] XP_016882423.1, XM_017026934.1 |
3D structure databases
SMRi | Q9NUL5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120618, 88 interactors |
CORUMi | Q9NUL5 |
IntActi | Q9NUL5, 71 interactors |
STRINGi | 9606.ENSP00000253110 |
PTM databases
iPTMneti | Q9NUL5 |
PhosphoSitePlusi | Q9NUL5 |
Genetic variation databases
BioMutai | C19orf66 |
DMDMi | 172044675 |
Proteomic databases
EPDi | Q9NUL5 |
jPOSTi | Q9NUL5 |
MassIVEi | Q9NUL5 |
MaxQBi | Q9NUL5 |
PaxDbi | Q9NUL5 |
PeptideAtlasi | Q9NUL5 |
PRIDEi | Q9NUL5 |
ProteomicsDBi | 82688 [Q9NUL5-1] 82689 [Q9NUL5-2] 82690 [Q9NUL5-3] 82691 [Q9NUL5-4] |
Protocols and materials databases
Antibodypediai | 51349, 36 antibodies from 11 providers |
DNASUi | 55337 |
Genome annotation databases
Ensembli | ENST00000253110; ENSP00000253110; ENSG00000130813 ENST00000397881; ENSP00000380978; ENSG00000130813 [Q9NUL5-2] ENST00000591813; ENSP00000467182; ENSG00000130813 [Q9NUL5-4] |
GeneIDi | 55337 |
KEGGi | hsa:55337 |
MANE-Selecti | ENST00000253110.16; ENSP00000253110.10; NM_018381.4; NP_060851.2 |
UCSCi | uc002mmu.5, human [Q9NUL5-1] |
Organism-specific databases
CTDi | 55337 |
DisGeNETi | 55337 |
GeneCardsi | SHFL |
HGNCi | HGNC:25649, SHFL |
HPAi | ENSG00000130813, Tissue enhanced (liver) |
MIMi | 616808, gene |
neXtProti | NX_Q9NUL5 |
OpenTargetsi | ENSG00000130813 |
PharmGKBi | PA162378809 |
VEuPathDBi | HostDB:ENSG00000130813 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QVND, Eukaryota |
GeneTreei | ENSGT00390000005065 |
HOGENOMi | CLU_087318_0_0_1 |
InParanoidi | Q9NUL5 |
OMAi | EDCQFAC |
OrthoDBi | 1485595at2759 |
PhylomeDBi | Q9NUL5 |
TreeFami | TF337433 |
Enzyme and pathway databases
PathwayCommonsi | Q9NUL5 |
SignaLinki | Q9NUL5 |
Miscellaneous databases
BioGRID-ORCSi | 55337, 13 hits in 1016 CRISPR screens |
ChiTaRSi | C19orf66, human |
GenomeRNAii | 55337 |
Pharosi | Q9NUL5, Tdark |
PROi | PR:Q9NUL5 |
RNActi | Q9NUL5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130813, Expressed in right lobe of liver and 230 other tissues |
ExpressionAtlasi | Q9NUL5, baseline and differential |
Genevisiblei | Q9NUL5, HS |
Family and domain databases
InterProi | View protein in InterPro IPR026795, SHFL |
PANTHERi | PTHR16135, PTHR16135, 1 hit |
Pfami | View protein in Pfam PF15135, UPF0515, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SHFL_HUMAN | |
Accessioni | Q9NUL5Primary (citable) accession number: Q9NUL5 Secondary accession number(s): A8MQT9 Q8N8V1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 26, 2008 |
Last sequence update: | February 26, 2008 | |
Last modified: | February 23, 2022 | |
This is version 132 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Uncharacterized protein families (UPF)
List of uncharacterized protein family (UPF) entries - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families