PMCHL1 notes (Q16048, Putative pro-MCH-like protein 1)

2026-10-04 Tier 3 over-annotation audit (claude-code)

Does the product exist?

• UniProt: PE5 (Uncertain); CAUTION "Could be the product of a pseudogene"; PMID:9729295 found only antisense PMCHL1 transcripts in brain.
• HGNC (REST, fetched 2026-10-04): name "pro-melanin concentrating hormone like 1 (pseudogene)", locus_type pseudogene, 5p14.3, Entrez 5369.
• Origin: chimeric primate-specific gene. PMID:11181993. Retroposition into an intron of CDH12 30-35 Mya PMID:19068116.
• Truncation: PMID:11070051; PMID:8326825. The 1993 paper nevertheless called it a variant gene "rather than a pseudogene" because RNAs were detected.
• Brain transcripts are antisense: PMID:9729295
• Viale 2000 (PMID:11070051, abstract only): sense unspliced PMCHL1 RNAs carry a novel ORF that "may produce an NLS-containing protein of 8 kDa named VMCH-p8"; translated in vitro and in transfected COS cells only.
• Schmieder 2008 (PMID:19068116, full text): ORF1 = VMCH-p8, NLS KPKKK at N-terminus, 72 aa per the paper (UniProt Q16048 is 86 aa; the N-terminus MLSQKPKKKH matches the NLS, so Q16048 is the VMCH-p8 ORF or a close variant; length difference unresolved). Antiserum against the N-terminal 13 aa detected no protein in human testis, fetal/newborn brain, or macaque brain, nor in HEK293 cells transfected with ORF1-bearing PMCHL1/2 sequences ["This strongly suggests that these putative proteins are not translated in vivo in the human and macaque tissues that we tested."]. Authors propose mRNA-like ncRNA function. Caveat they state: possible expression below detection threshold.
• No proteomics/ribo-seq evidence found in UniProt cross-references (MassIVE listed only as a DR line; no PeptideAtlas/PRIDE). Not further pursued.

Sequence vs parent PMCH (bioinformatics, PMCHL1-bioinformatics/RESULTS.md)

• Q16048 2-86 aligns to PMCH 81-165 (81% identity). PMCH 1-80 (signal peptide 1-21 + N-terminal pro-region) absent.
• No signal peptide: N-terminus is the charged putative NLS. So no secretory-pathway entry, no prohormone-convertase processing, no secreted MCH/NEI.
• MCH-like region: 4 substitutions (M150T, R152S, R160Q, P161S, PMCH numbering); disulfide Cys retained. NEI-like region: I132T and C-terminal amidated I143V.

Propagation routes

• IBA GO:0031777 and GO:0032227: PANTHER PTN002636265 (IBD in IBD.gaf, taxon:117571 Euteleostomi; seed RGD:3358 rat Pmch). PMCHL1 sits in PTHR12091:SF1 (PRO-MCH-LIKE PROTEIN 1-RELATED), a primate-only subfamily derived from PMCH; descends from the node by retroposition, but the copy lacks the secretory signal and is likely non-coding. Recommendation: block SF1 at the PAINT node (NOT annotation / exclude pseudogene subfamily).
• IEA GO:0030354 and GO:0007268: InterPro2GO IPR005456 (Prepro-melanin_conc_hormone) match. GO:0007165 and GO:0045202: GOC inter-ontology inference from those.
• NAS GO:0005576 extracellular region: UniProt from PMID:8326825 (1993 assumption of a secreted prohormone).

Decision

All 7 rows REMOVE. No core function.