ZNF788P

UniProt ID: Q6ZQV5
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

ZNF788P is a transcribed pseudogene on chromosome 19p13.2 (formerly ZNF788). It is derived from a KRAB-C2H2 zinc-finger gene. The locus contains a KRAB-A exon and a downstream array of about 14-17 C2H2 zinc-finger motifs, but in the known transcripts these two parts are separated by an in-frame stop codon and do not form a single open reading frame. The current UniProt product is a hypothetical 82-residue polypeptide that contains a truncated KRAB-A box with no KRAB-B box and no zinc fingers. A separate zinc-finger-only open reading frame can be translated from an internal start codon. An endogenously YFP-tagged product assigned to this transcript (FLJ46419) was nuclear in a lung carcinoma cell line. Whether any protein from the locus is stably made, and what it does, is unknown.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
HDA
PMID:16791210
Dynamic proteomics in individual human cells uncovers widesp...
UNDECIDED
Summary: This row comes from endogenous CD-tagging (YFP inserted as an internal exon at the chromosomal locus in H1299 cells), not from overexpression. Clone "FLJ46419" (the ZNF788P alias) was one of 20 nuclear proteins tracked. The evidence is real, but it was attached in 2015 to the former 615-aa zinc-finger sequence of this entry, not to the current 82-aa KRAB fragment.
Reason: I read the full text (author-hosted PDF; the publications cache holds only the abstract). Each tagged protein was identified by 3' RACE from YFP to the poly(A) tail, and Fig. 3q lists "uncharacterized protein FLJ46419" as nuclear. A promoterless, ATG-less YFP exon fluoresces only when spliced in frame into a translated mRNA. The observation is therefore direct evidence that some protein encoded by the FLJ46419 transcript is translated and nuclear. Because 3' RACE reads downstream of the insertion, the tagged protein most likely includes the zinc-finger region (the pre-2018 UniProt sequence) and not the current 82-aa KRAB-A fragment, which has no nuclear-targeting zinc fingers. This conflicts with HGNC and Ensembl, which classify the locus as a pseudogene, and with UniProt's PE5 and 2018 remodelling. The 3' RACE read could also have matched a paralogous chr19 zinc-finger gene, and that cannot be checked from the paper. The annotation is neither removed nor accepted. UniProt should reconcile the HDA with the current sequence.
Propagation Review
Root cause: SOURCE STALE OR MISSING
Failure modes: SOURCE EVIDENCE WEAK
Sources checked:
PMID:16791210 SOURCE STALE OR MISSING
HDA assigned by UniProt in 2015 against sequence version 2 (615-aa zinc-finger protein). It was carried over unchanged when the entry was re-modelled to an 82-aa KRAB-A fragment in 2018, so the sequence that was observed is no longer the sequence that is annotated.
Supporting Evidence:
PMID:16791210
each tagged with yellow fluorescent protein (YFP) at its endogenous chromosomal location
file:human/ZNF788P/ZNF788P-bioinformatics/RESULTS.md
Since March 2018, version 3 has been an 82-aa product (PE5) with **0 C2H2 motifs**.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
REMOVE
Summary: InterPro2GO mapping from a truncated KRAB-A box on a pseudogene product. The product has no zinc fingers or any other DNA-binding domain, no KRAB-B box, and a substitution in the KRAB-A MLE motif.
Reason: A KRAB domain represses transcription only when it is tethered to DNA, which in KRAB-zinc-finger proteins is done by the C2H2 array. The annotated 82-aa product lacks any DNA-binding domain. Its KRAB-A box ends at the equivalent of ZNF10 residue 68, so it lacks the end of the A box and the whole B box, and the central leucine of the conserved MLE motif is replaced by glutamine. The locus is classified as a pseudogene by HGNC and Ensembl, and protein existence is PE5. The InterPro signature correctly recognises a KRAB-A remnant, but that does not show participation in transcription regulation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: PSEUDO OR SUBACTIVITY LOSS
Sources checked:
InterPro:IPR001909 Β· KRAB SUPPORTS SOURCE BUT NOT TARGET
The signature matches a truncated KRAB-A remnant. The InterPro2GO mapping assumes the full KRAB-zinc-finger architecture, which is absent here.
InterPro:IPR036051 Β· KRAB_dom_sf SUPPORTS SOURCE BUT NOT TARGET
Same KRAB-A remnant, superfamily-level signature.
Supporting Evidence:
PMID:8183939
the KRAB domain functions as a DNA binding-dependent transcriptional repressor when fused to a heterologous DNA-binding domain from the yeast GAL4 protein
file:human/ZNF788P/ZNF788P-bioinformatics/RESULTS.md
The KRAB exon and the zinc-finger array are therefore in frame with each other but separated by a stop codon.

References

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Suggested Questions for Experts

Q: Was the 3' RACE product of the Sigal et al. FLJ46419 clone unique to ZNF788P, or could it come from a paralogous chr19 KRAB-zinc-finger gene? Should the 2015 HDA nucleus row on Q6ZQV5 be re-evaluated now that the entry describes an 82-aa KRAB-A fragment rather than the zinc-finger protein that was probably observed?

Q: Do the ZNF788P peptides reported in PeptideAtlas/MassIVE map uniquely to this locus, and to which part (KRAB fragment or zinc-finger ORF)?

Suggested Experiments

Experiment: Run ribosome profiling or targeted proteomics with peptides unique to ZNF788P, covering both the 82-aa KRAB-A fragment and the downstream zinc-finger ORF. This would show which, if either, is translated, and could revise PE5 or support retirement of the protein entry.

πŸ“š Additional Documentation

Notes

(ZNF788P-notes.md)

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Bioinformatics Results

(RESULTS.md)

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