Bacterial and eukaryotic selenocysteine biosynthesis and co-translational incorporation

A reusable module for the bacterial and eukaryotic synthesis of selenocysteyl-tRNA(Sec) and recoding of UGA as selenocysteine. Selenophosphate synthetase activates selenium, and seryl-tRNA synthetase charges tRNA(Sec) with serine. Bacteria convert Ser-tRNA(Sec) directly with SelA, whereas the represented eukaryotic route first phosphorylates it with PSTK and then uses SepSecS. The completed Sec-tRNA(Sec) is delivered by a lineage-specific elongation system to a UGA codon in a SECIS-dependent translation context.

MODULE:selenocysteine_biosynthesis_incorporationDRAFTCONCRETEBiological Processmodules/selenocysteine_biosynthesis_incorporation.yaml
L-selenocysteine biosynthetic processGO:0016260 selenocysteine incorporationGO:0001514
GO:0016260
L-selenocysteine biosynthetic process
GO:0016260 provides the broad process anchor for activated selenium production and tRNA-dependent selenocysteine biosynthesis.
GO:0001514
selenocysteine incorporation
GO:0001514 captures specialized co-translational insertion of selenocysteine at recoded UGA codons.
file:modules/selenocysteine_biosynthesis_incorporation-deep-research-openscientist.md
OpenScientist review of selenocysteine biosynthesis and incorporation
The reusable-module review supports the ordered tRNA-dependent synthesis route and distinguishes the bacterial SelA/SelB implementation from the represented eukaryotic PSTK-SepSecS and SECISBP2-EEFSEC implementation.
file:projects/P_PUTIDA/deep-research/PSEPK__selenocysteine_biosynthesis_incorporation__ppu00450-deep-research-openscientist.md
OpenScientist PSEPK pathway and taxon review
The taxon-aware review finds the bacterial route satisfiable in KT2440 through selD, serS, selA, and selB, while identifying the KEGG ppu00450 membership as substantially broader than this module boundary.
file:PSEPK/selD/selD-uniprot.txt
UniProtKB entry for PSEPK SelD
P59392 is a reviewed selenophosphate synthetase assigned Rhea 18737.
file:PSEPK/serS/serS-uniprot.txt
UniProtKB entry for PSEPK SerS
Q88FT2 is a reviewed serine-tRNA ligase with the tRNA(Sec)-specific charging reaction Rhea 42580.
file:PSEPK/selA/selA-uniprot.txt
UniProtKB entry for PSEPK SelA
Q88QJ8 is a reviewed bacterial L-seryl-tRNA(Sec) selenium transferase assigned Rhea 22728.
file:PSEPK/selB/selB-uniprot.txt
UniProtKB entry for PSEPK SelB
Q88QJ7 is a selenocysteyl-tRNA-specific translation elongation factor.

This revision generalizes the previous human-only document while preserving its curated eukaryotic route. The shared SerS and selenophosphate steps are modeled once. A single taxonomic EXACTLY_ONE choice couples bacterial SelA/SelB and eukaryotic PSTK/SepSecS/SECISBP2/EEFSEC, preventing hybrid routes. Archaeal Sec-tRNA synthesis overlaps the PSTK-SepSecS chemistry, but archaeal recoding machinery is not represented, so the module title is explicitly limited to bacteria and eukaryotes. tRNA(Sec) and SECIS RNA elements are required non-protein substrates/context, not missing gene parts. Selenium uptake, selenide production, tRNA transcription and maturation, ribosome biogenesis, and downstream selenoprotein function are outside the boundary. CONCRETE is retained because this is a specific, leaf-grounded biological process; cross-lineage reuse does not make it an abstract conformance motif.

12Nodes
9Parts
1Variant Sets
2Variants
9Annotons
6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • selenocysteine_biosynthesis_incorporation-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

9 gene-function check(s) reflected in core functions · 0 conflict(s) · 17 evidence or coverage gap(s) (26 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
seld_sephs_activity SelD (Pseudomonas putida KT2440)
UniProtKB:P59392
Family Representative 		selenide, water dikinase activity
GO:0004756 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
seld_sephs_activity SelD (Escherichia coli K-12)
UniProtKB:P16456
Family Representative 		selenide, water dikinase activity
GO:0004756 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
seld_sephs_activity SEPHS2 (human)
UniProtKB:Q99611
Family Representative 		selenide, water dikinase activity
GO:0004756 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sers_activity SerS (Pseudomonas putida KT2440)
UniProtKB:Q88FT2
Family Representative 		serine-tRNA ligase activity
GO:0004828 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sers_activity SerS (Escherichia coli K-12)
UniProtKB:P0A8L1
Family Representative 		serine-tRNA ligase activity
GO:0004828 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
sers_activity SARS1 (human)
UniProtKB:P49591
Family Representative 		serine-tRNA ligase activity
GO:0004828 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
sela_activity SelA (Pseudomonas putida KT2440)
UniProtKB:Q88QJ8
Family Representative 		L-seryl-tRNA(Sec) selenium transferase activity
GO:0004125 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sela_activity SelA (Escherichia coli K-12)
UniProtKB:P0A821
Family Representative 		L-seryl-tRNA(Sec) selenium transferase activity
GO:0004125 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
selb_secis_binding SelB (Pseudomonas putida KT2440)
UniProtKB:Q88QJ7
Family Representative 		selenocysteine insertion sequence binding
GO:0035368 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
selb_secis_binding SelB (Escherichia coli K-12)
UniProtKB:P14081
Family Representative 		selenocysteine insertion sequence binding
GO:0035368 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
selb_activity SelB (Pseudomonas putida KT2440)
UniProtKB:Q88QJ7
Family Representative 		translation elongation factor activity
GO:0003746 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
selb_activity SelB (Escherichia coli K-12)
UniProtKB:P14081
Family Representative 		translation elongation factor activity
GO:0003746 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
pstk_activity PSTK (human)
UniProtKB:Q8IV42
Family Representative 		L-seryl-tRNA(Sec) kinase activity
GO:0043915 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sepsecs_activity SEPSECS (human)
UniProtKB:Q9HD40
Family Representative 		O-phosphoseryl-tRNA(Sec) selenium transferase activity
GO:0098621 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
secisbp2_activity SECISBP2 (human)
UniProtKB:Q96T21
Family Representative 		selenocysteine insertion sequence binding
GO:0035368 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
eefsec_activity EEFSEC (human)
UniProtKB:P57772
Family Representative 		translation elongation factor activity
GO:0003746 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
seld_sephs_activity selenophosphate synthetase family
PANTHER:PTHR10256
Family 		selenide, water dikinase activity
GO:0004756 		Family Scope Restricted
GO:0004756 requires member-level assessment of residue site catalytic_nucleophile; a family identifier does not establish that condition. Applicability is decided by the nucleophile residue, not by subfamily. The subfamily axis cannot express it here: SF0 contains both the active E. coli SelD (Cys) and the arginine-substituted Drosophila Sps1, so granting the term to SF0 would license it for an inactive protein while denying it would strip it from a canonical active enzyme. Members carrying selenocysteine or cysteine at the site are catalytic (SEPHS2, SelD); members carrying threonine or arginine are not (human SEPHS1, Drosophila Sps1).
sers_activity seryl-tRNA synthetase family
PANTHER:PTHR43697
Family 		serine-tRNA ligase activity
GO:0004828 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43697.
sers_activity seryl-tRNA synthetase family
PANTHER:PTHR11778
Family 		serine-tRNA ligase activity
GO:0004828 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR11778.
sela_activity bacterial SelA family
PANTHER:PTHR32328
Family 		L-seryl-tRNA(Sec) selenium transferase activity
GO:0004125 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR32328.
selb_secis_binding bacterial SelB elongation-factor family
InterPro:IPR004535
Family 		selenocysteine insertion sequence binding
GO:0035368 		Family Review Missing
No supported structured family review is available for InterPro:IPR004535.
selb_activity bacterial SelB elongation-factor family
InterPro:IPR004535
Family 		translation elongation factor activity
GO:0003746 		Family Review Missing
No supported structured family review is available for InterPro:IPR004535.
pstk_activity PSTK family
PANTHER:PTHR20873
Family 		L-seryl-tRNA(Sec) kinase activity
GO:0043915 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR20873.
sepsecs_activity SepSecS family
PANTHER:PTHR12944
Family 		O-phosphoseryl-tRNA(Sec) selenium transferase activity
GO:0098621 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12944.
secisbp2_activity SECISBP2 family
PANTHER:PTHR13284
Family 		selenocysteine insertion sequence binding
GO:0035368 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR13284.
eefsec_activity selenocysteine-specific elongation-factor family
PANTHER:PTHR43721:SF11
Family 		translation elongation factor activity
GO:0003746 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43721:SF11.

Gene-review completeness (9/14 grounded genes reviewed)

9 complete review(s) · 1 with deep research · 5 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
EEFSEC P57772 ✓ ✓ ✗
SelA (Escherichia coli K-12) P0A821 ✗ — —
SerS (Escherichia coli K-12) P0A8L1 ✗ — —
SelB (Escherichia coli K-12) P14081 ✗ — —
SelD (Escherichia coli K-12) P16456 ✗ — —
SARS1 (human) P49591 ✗ — —
PSTK Q8IV42 ✓ ✓ ✗
SECISBP2 Q96T21 ✓ ✓ ✗
selA Q88QJ8 ✓ ✓ ✓
selB Q88QJ7 ✓ ✓ ✗
selD P59392 ✓ ✓ ✗
SEPHS2 Q99611 ✓ ✓ ✗
SEPSECS Q9HD40 ✓ ✓ ✗
serS Q88FT2 ✓ ✓ ✗

Details

Bacterial and eukaryotic selenocysteine biosynthesis and incorporationBiological Processselenocysteine_biosynthesis_incorporation
L-selenocysteine biosynthetic processGO:0016260 selenocysteine incorporationGO:0001514

Connections

Selenophosphate supplies selenium to either taxonomic route.
SerS supplies Ser-tRNA(Sec) to either taxonomic route.
Part 1: activated selenium donor production
Selenophosphate synthesisReactionselenophosphate_synthesis

Annotons

SelD/SEPHS2 selenide, water dikinase activity
seld_sephs_activity
Participant: Family: selenophosphate synthetase family
Family:
selenophosphate synthetase familyPANTHER:PTHR10256
Representative Members: SelD (Pseudomonas putida KT2440)UniProtKB:P59392 SelD (Escherichia coli K-12)UniProtKB:P16456 SEPHS2 (human)UniProtKB:Q99611

Function

selenide, water dikinase activityGO:0004756
Substrates: hydrogenselenide ATP water
Products: selenophosphate AMP phosphate

Processes

L-selenocysteine biosynthetic processGO:0016260

Supplies the activated selenium donor for Sec-tRNA synthesis.

Part 2: tRNA(Sec) aminoacylation with serine
Ser-tRNA(Sec) synthesisReactionser_trna_sec_synthesis

Annotons

SerS/SARS serine-tRNA ligase activity on tRNA(Sec)
sers_activity
Participant: Family: seryl-tRNA synthetase family
Family:
seryl-tRNA synthetase familyPANTHER:PTHR43697 Bacterial SerS proteins and eukaryotic cytoplasmic SARS1 proteins occupy separate PANTHER families but catalyze the shared Ser-tRNA(Sec) synthesis step.
Representative Members: SerS (Pseudomonas putida KT2440)UniProtKB:Q88FT2 SerS (Escherichia coli K-12)UniProtKB:P0A8L1 SARS1 (human)UniProtKB:P49591

Function

serine-tRNA ligase activityGO:0004828
Substrates: tRNA(Sec) L-serine ATP
Products: L-seryl-tRNA(Sec) AMP diphosphate

Processes

L-selenocysteine biosynthetic processGO:0016260

Produces the common Ser-tRNA(Sec) pathway intermediate.

Part 3: lineage-specific Sec-tRNA synthesis and incorporation
Taxonomic selenocysteine synthesis and insertion routesBiological Processlineage_specific_sec_route
Variant set: Coupled synthesis and insertion route by taxonomic implementation (Exactly One)

Synthesis and insertion machinery are selected as one coupled route so bacterial and eukaryotic implementations cannot be mixed.

Bacterial SelA-SelB routeBiological Processbacterial_sec_route
Context
bacteriaNCBITaxon:2
specialized tRNA(Sec) substrate is present in-frame UGA with an adjacent bacterial SECIS element

Connections

SelA-produced Sec-tRNA(Sec) is delivered by SelB.
Part 1: direct Sec-tRNA(Sec) synthesis
SelA-dependent Sec-tRNA(Sec) synthesisReactionbacterial_sela_conversion

Annotons

SelA L-seryl-tRNA(Sec) selenium transferase activity
sela_activity
Participant: Family: bacterial SelA family
Family:
bacterial SelA familyPANTHER:PTHR32328
Representative Members: SelA (Pseudomonas putida KT2440)UniProtKB:Q88QJ8 SelA (Escherichia coli K-12)UniProtKB:P0A821

Function

L-seryl-tRNA(Sec) selenium transferase activityGO:0004125
Substrates: L-seryl-tRNA(Sec) selenophosphate
Products: L-selenocysteinyl-tRNA(Sec) phosphate

Processes

conversion of seryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec)GO:0001717

Performs the one-step bacterial conversion.

Part 2: SECIS recognition and Sec-tRNA delivery
SelB-dependent UGA recodingBiological Processbacterial_selb_delivery

Annotons

SelB bacterial SECIS-binding activity
selb_secis_binding
Participant: Family: bacterial SelB elongation-factor family
Family:
bacterial SelB elongation-factor familyInterPro:IPR004535
Representative Members: SelB (Pseudomonas putida KT2440)UniProtKB:Q88QJ7 SelB (Escherichia coli K-12)UniProtKB:P14081

Function

selenocysteine insertion sequence bindingGO:0035368
Substrates: bacterial SECIS RNA element

Processes

selenocysteine incorporationGO:0001514

Recognizes the bacterial SECIS adjacent to UGA.

SelB selenocysteine-specific elongation factor activity
selb_activity
Participant: Family: bacterial SelB elongation-factor family
Family:
bacterial SelB elongation-factor familyInterPro:IPR004535
Representative Members: SelB (Pseudomonas putida KT2440)UniProtKB:Q88QJ7 SelB (Escherichia coli K-12)UniProtKB:P14081

Function

translation elongation factor activityGO:0003746
Substrates: L-selenocysteinyl-tRNA(Sec) GTP bacterial SECIS-containing UGA codon context
Products: selenocysteine incorporated into nascent protein GDP phosphate

Processes

selenocysteine incorporationGO:0001514

Delivers Sec-tRNA(Sec) at the recoded UGA.

Eukaryotic PSTK-SepSecS-SECISBP2-EEFSEC routeBiological Processeukaryotic_sec_route
Context
eukaryotesNCBITaxon:2759
specialized tRNA(Sec) substrate is present in-frame UGA with a 3-prime UTR SECIS element

Connections

PSTK produces the phosphoseryl-tRNA consumed by SepSecS.
SepSecS-produced Sec-tRNA(Sec) is delivered by EEFSEC.
secisbp2_recognition -> eefsec_delivery Provides Input For
SECISBP2 supplies the RNA recoding context used by EEFSEC.
Part 1: Ser-tRNA(Sec) phosphorylation
PSTK-dependent phosphoseryl-tRNA(Sec) formationReactionpstk_phosphoseryl_trna_formation

Annotons

PSTK L-seryl-tRNA(Sec) kinase activity
pstk_activity
Participant: Family: PSTK family
Family:
PSTK familyPANTHER:PTHR20873
Representative Members: PSTK (human)UniProtKB:Q8IV42

Function

L-seryl-tRNA(Sec) kinase activityGO:0043915
Substrates: L-seryl-tRNA(Sec) ATP
Products: O-phospho-L-seryl-tRNA(Sec) ADP

Produces the SepSecS substrate.

Part 2: phosphoseryl-tRNA(Sec) selenium transfer
SepSecS-dependent Sec-tRNA(Sec) formationReactionsepsecs_sec_trna_formation

Annotons

SepSecS phosphoseryl-tRNA(Sec) selenium transferase activity
sepsecs_activity
Participant: Family: SepSecS family
Family:
SepSecS familyPANTHER:PTHR12944
Representative Members: SEPSECS (human)UniProtKB:Q9HD40

Function

O-phosphoseryl-tRNA(Sec) selenium transferase activityGO:0098621
Substrates: O-phospho-L-seryl-tRNA(Sec) selenophosphate water
Products: L-selenocysteinyl-tRNA(Sec) phosphate

Processes

conversion of seryl-tRNAsec to selenocys-tRNAsecGO:0001717

Produces Sec-tRNA(Sec) from the phosphorylated intermediate.

Part 3: SECIS-element recognition
SECISBP2-dependent SECIS recognitionReactionsecisbp2_recognition

Annotons

SECISBP2 SECIS-binding activity
secisbp2_activity
Participant: Family: SECISBP2 family
Family:
SECISBP2 familyPANTHER:PTHR13284
Representative Members: SECISBP2 (human)UniProtKB:Q96T21

Function

selenocysteine insertion sequence bindingGO:0035368
Substrates: 3-prime UTR SECIS RNA element

Processes

selenocysteine incorporationGO:0001514

Establishes the eukaryotic SECIS-dependent recoding context.

Part 4: Sec-tRNA(Sec) delivery
EEFSEC-dependent Sec-tRNA(Sec) deliveryReactioneefsec_delivery

Annotons

EEFSEC translation elongation factor activity
eefsec_activity
Participant: Family: selenocysteine-specific elongation-factor family
Family:
selenocysteine-specific elongation-factor familyPANTHER:PTHR43721:SF11
Representative Members: EEFSEC (human)UniProtKB:P57772

Function

translation elongation factor activityGO:0003746
Substrates: L-selenocysteinyl-tRNA(Sec) GTP SECIS-recoded ribosome context
Products: selenocysteine incorporated into nascent protein GDP phosphate

Processes

selenocysteine incorporationGO:0001514

Delivers Sec-tRNA(Sec) to the recoded ribosomal A site.