TECR (Q9NZ01) — gene review notes

Identity

HGNC symbol TECR (HGNC:4551); synonyms GPSN2, SC2. UniProt Q9NZ01 (TECR_HUMAN), 308 aa, chromosome 19p13.
RecName: Very-long-chain enoyl-CoA reductase; EC 1.3.1.93; AltName Trans-2,3-enoyl-CoA reductase (TER); AltName Synaptic glycoprotein SC2 [file:human/TECR/TECR-uniprot.txt "RecName: Full=Very-long-chain enoyl-CoA reductase"; "EC=1.3.1.93"; "AltName: Full=Trans-2,3-enoyl-CoA reductase"].
Belongs to the steroid 5-alpha reductase family [file:human/TECR/TECR-uniprot.txt "Belongs to the steroid 5-alpha reductase family."]. N-terminal ubiquitin-like (Ubl) domain (residues ~1-81, PDB 2DZJ) precedes the multi-pass membrane catalytic region.

Catalyzes the fourth (final) reaction of the microsomal fatty-acid elongation cycle: NADPH-dependent reduction of the trans-2,3-enoyl-CoA intermediate to a fully saturated acyl-CoA, extending the chain by 2 carbons [file:human/TECR/TECR-uniprot.txt "Catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle (PubMed:12482854)."; "This enzyme reduces the trans-2,3-enoyl-CoA fatty acid intermediate to an acyl-CoA that can be further elongated by entering a new cycle of elongation (PubMed:12482854)."].
Canonical catalytic activity (Rhea RHEA:14473, EC 1.3.1.93): a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a very-long-chain (2E)-enoyl-CoA + NADPH + H(+) [file:human/TECR/TECR-uniprot.txt "a very-long-chain (2E)-enoyl-CoA + NADPH + H(+); Xref=Rhea:RHEA:14473"]. Multiple additional Rhea reactions documented (C18 stearoyl-CoA RHEA:35351; the C16 palmitoyl step RHEA:36143; PUFA VLCFA intermediates RHEA:39319/39331/39467).
Identified/characterized as the mammalian trans-2,3-enoyl-CoA reductase (TER) of the elongation cascade by Moon & Horton 2003 PMID:12482854 — abstract-only cache; full text (read by the curators making the IDA annotations) established ER localization and TER activity.

Two-sided involvement in sphingolipids: (1) supplies VLCFAs used as the N-acyl chain of sphingolipids (via elongation), and (2) acts in the sphingosine-1-phosphate (S1P) degradation pathway as the saturation step converting trans-2-hexadecenoyl-CoA to palmitoyl-CoA PMID:25049234. The saturation step (RHEA:36143, (2E)-hexadecenoyl-CoA + NADPH → hexadecanoyl-CoA) is also captured in UniProt [file:human/TECR/TECR-uniprot.txt "Catalyzes the saturation step of the sphingosine 1-phosphate metabolic pathway, the conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA (PubMed:25049234)."].
TER is the previously-"missing gene" for this saturation step PMID:25049234.

ER membrane, multi-pass [file:human/TECR/TECR-uniprot.txt "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"; "Multi-pass membrane protein"]. Topology: cytoplasmic N-terminal Ubl domain (1-86) followed by ~5-6 TM helices (mapped in PMID:38422897). IDA/EXP ER and ER-membrane annotations from PMID:12482854 and PMID:24220030, plus HPA IDA (GO_REF:0000052).
A single large-scale sperm-nucleus proteomics dataset (PMID:21630459, HDA) lists TECR among 403 sperm-nuclear proteins; this is a mass-spec catalog, not evidence of a nuclear function for an ER multi-pass enzyme — treat "nucleus" as non-core.

Part of the VLCFA elongase machinery with ELOVL, KAR (3-ketoacyl-CoA reductase), HACD (3-hydroxyacyl-CoA dehydratase), and TECR PMID:38422897.
Forms a stable complex with HACD2 (and HACD1) for substrate transfer; interaction with HACD1/2 and with ELOVLs is mutually exclusive [PMID:38422897 "we identified a stable complex of human HACD2-TECR based on extensive in vitro characterizations."; "we confirmed the critical interactions between TECR and HACD1/2."]; UniProt: "Interacts with HACD1 and HACD2 (via the third lumenal loop), but not with HACD3 and HACD4"; "interaction with HACD1/2 and that with ELOVLs are mutually exclusive" [file:human/TECR/TECR-uniprot.txt]. Also interacts with ELOVL1 and LASS2/CERS2 [file:human/TECR/TECR-uniprot.txt "Interacts with ELOVL1 and LASS2 (PubMed:20937905)."].
Numerous IntAct/HuRI (PMID:32296183) and single interactome-map (PMID:25416956) and histone-XL-MS (PMID:30021884) entries feed generic protein binding (GO:0005515) IPI annotations. These are the informative functional partners (HACD1/2, ELOVLs) plus many co-membrane/screening hits; the bare "protein binding" term itself is uninformative and is marked over-annotated (functional detail is captured by the complex/interaction description and by MF/BP terms).

Autosomal-recessive nonsyndromic intellectual disability, MRT14 (MIM:614020), caused by the homozygous P182L variant [file:human/TECR/TECR-uniprot.txt "Intellectual developmental disorder, autosomal recessive 14 (MRT14)"; "VARIANT MRT14 LEU-182"]. P182L reduces enzyme activity and protein stability, impairing VLCFA synthesis and shifting the sphingolipid profile (decreased C24 sphingomyelin/ceramide) PMID:24220030. Variant discovery: PMID:21212097 (exome sequencing).

GO:0102758 very-long-chain enoyl-CoA reductase activity — MF, is_a oxidoreductase activity / CH-CH group of donors. Best-supported MF core term (Rhea RHEA:14473 = EC 1.3.1.93; IDA/IMP from PMID:12482854, PMID:24220030).
GO:0019166 trans-2-enoyl-CoA reductase (NADPH) activity — MF, is_a GO:0016627. Parent/sibling MF term also enabled (IEA from Rhea mapping). Both are correct; GO:0102758 is the more specific VLCFA-substrate form.
GO:0070402 NADPH binding — MF (binding). Not currently in GOA but a defensible cofactor MF (NADPH is the physiological reductant; KW:NADP). Included as an additional core function grounded in the catalytic-activity Rhea reactions.
GO:0030497 fatty acid elongation, GO:0042761 very long-chain fatty acid biosynthetic process, GO:0006665 sphingolipid metabolic process — BP core terms (all verified present).
GO:0005789 endoplasmic reticulum membrane — CC core (verified).

Core MF (VLCFA enoyl-CoA reductase / trans-2-enoyl-CoA reductase (NADPH)): ACCEPT the experimental IDA/IMP (PMID:12482854, PMID:24220030) and the Rhea/PANTHER IEA/IBA supporting them.
GO:0016627 (CH-CH oxidoreductase, InterPro IEA) is a correct-but-general parent of GO:0102758 → MARK_AS_OVER_ANNOTATED (redundant with the specific MF).
GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity (Reactome TAS): TECR runs the reductase reaction physiologically (NADPH → saturated acyl-CoA); the Reactome reaction R-HSA-548831 is written as the reverse "dehydrogenate" direction and mapped to a dehydrogenase MF. This is the wrong MF direction/label for the enzyme's biological function → MODIFY to GO:0102758 (do not REMOVE; TAS, and it is the same catalytic activity written backwards).
Core BP: fatty acid elongation, VLCFA biosynthesis, sphingolipid metabolism ACCEPTED (experimental IDA/IMP anchors). General lipid metabolic process / fatty acid biosynthetic process (IEA) kept as non-core or over-annotated (redundant generalizations).
Reactome GO:0035338 long-chain fatty-acyl-CoA biosynthetic process (TAS) — accurate BP for the elongation product; ACCEPT/KEEP_AS_NON_CORE.
CC: ER membrane / ER (IDA/EXP/IBA/HPA) ACCEPT (core). Nucleus (HDA, sperm proteomics) KEEP_AS_NON_CORE (not a functional site).
protein binding (GO:0005515, IPI ×4 references) — MARK_AS_OVER_ANNOTATED per policy (uninformative bare term; functional partners captured elsewhere). Not removed.