Dolichol phosphate and lipid-linked sugar-donor supply for glycosylation

Assembly of the dolichol-linked oligosaccharide (and of GPI anchors and protein O- and C-mannosylation) depends on a dolichyl-phosphate (Dol-P) lipid carrier, on the cytosolic nucleotide sugars GDP-mannose and UDP-glucose, and on two lipid-linked monosaccharide donors made from them, dolichyl-phosphate-mannose (Dol-P-Man) and dolichyl-phosphate-glucose (Dol-P-Glc). GDP-mannose is made in the cytosol from fructose 6-phosphate by mannose-6-phosphate isomerase, phosphomannomutase and GDP-mannose pyrophosphorylase; UDP-glucose is made from glucose 6-phosphate by phosphoglucomutase and UDP-glucose pyrophosphorylase. Dol-P is made at the endoplasmic-reticulum membrane by a three-step detour from polyprenol: an SDR-family polyprenol dehydrogenase oxidises polyprenol to polyprenal, the steroid-5-alpha-reductase-like polyprenal reductase saturates the alpha-isoprene unit to give dolichal, and the same SDR enzyme reduces dolichal to dolichol, which dolichol kinase phosphorylates with CTP. Dol-P is then charged with mannose from GDP-mannose by Dol-P-Man synthase and with glucose from UDP-glucose by Dol-P-Glc synthase (ALG5). Dol-P-Man synthase exists in two architectures: a single-subunit enzyme with its own C-terminal membrane anchor (budding yeast, Ustilago, trypanosomes) and a soluble catalytic subunit held at the membrane by two small accessory subunits (animals, fission yeast). In mammals a utilisation factor (MPDU1/Lec35) is additionally required for lumenal use of both lipid-linked donors.

MODULE:dolichol_phosphate_sugar_donor_supplyDRAFTMetabolic Pathwaymodules/dolichol_phosphate_sugar_donor_supply.yaml

dolichol-linked oligosaccharide biosynthetic processGO:0006488 dolichyl monophosphate biosynthetic processGO:0043048 GDP-mannose biosynthetic processGO:0009298 dolichol phosphate mannose biosynthetic processGO:0180047

YeastPathways:PWY3O-123

dolichyl phosphate D-mannose biosynthesis (S. cerevisiae, SGD YeastPathways)

YeastCyc lists MANNPISOM-RXN (PMI40), PHOSMANMUT-RXN (SEC53), MANNPGUANYLTRANGDP-RXN (PSA1) and 2.4.1.83-RXN (DPM1). The gene assignments were retained, but the PSA1 reaction is drawn with GDP and phosphate (EC 2.7.7.22); PSA1 is the GTP-dependent mannose-1-phosphate guanylyltransferase (EC 2.7.7.13), modelled here with GO:0004475.

YeastPathways:PWY3O-1565

dolichyl glucosyl phosphate biosynthesis (S. cerevisiae, SGD YeastPathways)

YeastCyc lists PHOSPHOGLUCMUT-RXN (PGM1, PGM2), GLUC1PURIDYLTRANS-RXN (UGP1 and the uncharacterised paralog YHL012W) and 2.4.1.117-RXN (ALG5). PGM1, PGM2, UGP1 and ALG5 were retained; YHL012W was not used as an exemplar because UGP1 is the essential, characterised enzyme.

GO:0006488

dolichol-linked oligosaccharide biosynthetic process

The module supplies the dolichyl-phosphate carrier and the Dol-P-Man/Dol-P-Glc donors consumed by dolichol-linked oligosaccharide biosynthesis (GO:0006488).

GO:0043048

dolichyl monophosphate biosynthetic process

Polyprenol dehydrogenase, polyprenal reductase and dolichol kinase produce the Dol-P carrier.

GO:0009298

GDP-mannose biosynthetic process

Mannose-6-phosphate isomerase, phosphomannomutase and GDP-mannose pyrophosphorylase.

GO:0180047

dolichol phosphate mannose biosynthetic process

Dol-P-Man synthase (single-subunit or three-subunit).

PMID:9878760

The dolichol pathway of N-linked glycosylation.

Review of dolichol as lipid carrier and of the biosynthesis of the sugar donors for LLO assembly.

PMID:23751184

N-linked protein glycosylation in the endoplasmic reticulum.

Review of ER N-glycosylation centred on S. cerevisiae, including the Dol-P-Man and Dol-P-Glc donors.

PMID:1377774

PMI40, an intron-containing gene required for early steps in yeast mannosylation.

A thermolabile pmi40 mutant cannot make GDP-mannose or Dol-P-Man; the deletion requires mannose for growth.

Inactivation of PMI at the restrictive temperature of 37 degrees C prevents synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions and results in cell death.

PMID:3288631

The yeast SEC53 gene encodes phosphomannomutase.

SEC53 encodes the yeast phosphomannomutase needed for ER glycosylation.

PMID:12667607

Overexpression of GDP-mannose pyrophosphorylase in Saccharomyces cerevisiae corrects defects in dolichol-linked saccharide formation and protein glycosylation.

MPG1/PSA1 encodes GDP-mannose pyrophosphorylase; raising GDP-mannose suppresses dpm1, alg1 and alg2 glycosylation defects.

PMID:7588797

Genetic and biochemical characterization of the UGP1 gene encoding the UDP-glucose pyrophosphorylase from Saccharomyces cerevisiae.

UGP1 encodes the essential yeast UDP-glucose pyrophosphorylase.

PMID:9252577

Physiological and morphological effects of genetic alterations leading to a reduced synthesis of UDP-glucose in Saccharomyces cerevisiae.

Deleting both phosphoglucomutase genes in a UGP1-depleted strain further lowers flux to UDP-glucose, showing PGM1/PGM2 feed the UGP1 step.

PMID:38821050

A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis.

Dolichol is made from polyprenol in three steps: DHRSX oxidises polyprenol to polyprenal (NAD+), SRD5A3 or yeast Dfg10 reduces polyprenal to dolichal (NADPH), and DHRSX reduces dolichal to dolichol.

SRD5A3 and its yeast orthologue Dfg10 produce dolichal from polyprenal (reaction 2), but have undetectable activity on polyprenol

PMID:42201967

The revised three-step detour pathway in dolichol biosynthesis is evolutionarily conserved in budding yeast.

TDA5 is the S. cerevisiae functional ortholog of DHRSX; tda5 deletion accumulates polyprenol and reduces dolichol and is rescued by DHRSX but not by DFG10 or SRD5A3. Residual dolichol in tda5 dfg10 cells suggests a bypass route.

These findings show that Tda5 serves the same function as DHRSX in yeast, thereby demonstrating conservation of the three-step detour pathway in yeast and supporting a broader eukaryotic framework for dolichol biosynthesis.

PMID:20637498

SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder.

SRD5A3 (yeast DFG10) is required for dolichol formation from polyprenol; SRD5A3-CDG.

PMID:1323123

Saccharomyces cerevisiae sec59 cells are deficient in dolichol kinase activity.

SEC59 encodes the yeast dolichol kinase that makes Dol-P.

PMID:9223280

Human and Saccharomyces cerevisiae dolichol phosphate mannose synthases represent two classes of the enzyme, but both function in Schizosaccharomyces pombe.

Dol-P-Man synthases fall into a C-terminally anchored class (S. cerevisiae, Ustilago, Trypanosoma) and an unanchored class (human, S. pombe, Caenorhabditis), which are functionally interchangeable in S. pombe.

The two classes of synthase are functionally equivalent, because S. cerevisiae DPM1 and its human counterpart both complement the lethal null mutation in S. pombe dpm1(+).

PMID:10835346

Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.

Human DPM synthase has catalytic DPM1, regulatory DPM2 and stabilising DPM3; S. pombe has orthologs of all three.

Schizosaccharomyces pombe has proteins that resemble three human subunits; S.pombe DPM3 restored biosynthesis of DPM in Lec15 cells, indicating its orthologous relationship to human DPM3.

PMID:16280320

DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3.

DPM3 tethers the catalytic DPM1 subunit to the ER membrane and is essential for activity.

PMID:8076653

Isolation of the ALG5 locus encoding the UDP-glucose:dolichyl-phosphate glucosyltransferase from Saccharomyces cerevisiae.

ALG5 encodes the ER-membrane UDP-glucose:dolichyl-phosphate glucosyltransferase.

Reactome:R-HSA-446199

Synthesis of dolichyl-phosphate

The dolichol -> Dol-P segment (SRD5A3 polyprenol reduction, DOLK phosphorylation) follows the human Reactome "Synthesis of dolichyl-phosphate" sub-pathway.

Reactome:R-HSA-162699

Synthesis of dolichyl-phosphate mannose

The Dol-P-Man branch (DPM1/DPM2/DPM3 complex) follows the human Reactome "Synthesis of dolichyl-phosphate mannose" sub-pathway (reaction R-HSA-162721).

file:human/SRD5A3/SRD5A3-ai-review.yaml

SRD5A3 gene review (human)

The polyprenal reductase step (UniProtKB:Q9H8P0, GO:0160198) matches the completed human SRD5A3 review.

file:human/DOLK/DOLK-ai-review.yaml

DOLK gene review (human)

The dolichol -> Dol-P step (UniProtKB:Q9UPQ8, GO:0004168) matches the completed human DOLK review.

file:human/DPM1/DPM1-ai-review.yaml

DPM1 gene review (human)

The catalytic Dol-P-Man synthase step (UniProtKB:O60762, GO:0004582) matches the completed human DPM1 review.

file:human/DPM2/DPM2-ai-review.yaml

DPM2 gene review (human)

The regulatory DPM-synthase subunit (UniProtKB:O94777, GO:0008047) matches the completed human DPM2 review.

file:human/DPM3/DPM3-ai-review.yaml

DPM3 gene review (human)

The membrane-anchoring DPM-synthase subunit (UniProtKB:Q9P2X0, GO:0043495) matches the completed human DPM3 review.

file:human/ALG5/ALG5-ai-review.yaml

ALG5 gene review (human)

The Dol-P-Glc synthase step (UniProtKB:Q9Y673, GO:0004581) matches the completed human ALG5 review.

file:human/MPDU1/MPDU1-ai-review.yaml

MPDU1 gene review (human)

The Dol-P-Man/Dol-P-Glc utilisation factor (UniProtKB:O75352, GO:0006488) matches the completed human MPDU1 review.

file:yeast/PMI40/PMI40-ai-review.yaml

PMI40 gene review (S. cerevisiae)

PMI40 core function is mannose-6-phosphate isomerase (GO:0004476) in the cytosol, part of GDP-mannose biosynthesis.

file:yeast/PGM2/PGM2-ai-review.yaml

PGM2 gene review (S. cerevisiae)

PGM2 core function is phosphoglucomutase (GO:0004614) in the cytosol.

18Nodes

15Parts

1Variant Sets

2Variants

15Annotons

12Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dolichol_phosphate_sugar_donor_supply deep-research report alongside the module YAML.

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

31 gene-function check(s) reflected in core functions · 0 conflict(s) · 10 evidence or coverage gap(s) (49 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.

Annoton	Participant	Function	Assessment
pmi_activity	PMI40 (Saccharomyces cerevisiae) UniProtKB:P29952 Family Representative	mannose-6-phosphate isomerase activity GO:0004476	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmi_activity	pmi40 (Schizosaccharomyces pombe) UniProtKB:O43014 Family Representative	mannose-6-phosphate isomerase activity GO:0004476	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmi_activity	MPI (human) UniProtKB:P34949 Family Representative	mannose-6-phosphate isomerase activity GO:0004476	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
pmm_activity	SEC53 (Saccharomyces cerevisiae) UniProtKB:P07283 Family Representative	phosphomannomutase activity GO:0004615	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmm_activity	pmm1 (Schizosaccharomyces pombe) UniProtKB:Q9UTJ2 Family Representative	phosphomannomutase activity GO:0004615	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmm_activity	PMM2 (human) UniProtKB:O15305 Family Representative	phosphomannomutase activity GO:0004615	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmpp_activity	PSA1/MPG1 (Saccharomyces cerevisiae) UniProtKB:P41940 Family Representative	mannose-1-phosphate guanylyltransferase (GTP) activity GO:0004475	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmpp_activity	mpg1 (Schizosaccharomyces pombe) UniProtKB:O74484 Family Representative	mannose-1-phosphate guanylyltransferase (GTP) activity GO:0004475	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmpp_activity	GMPPB (human) UniProtKB:Q9Y5P6 Family Representative	mannose-1-phosphate guanylyltransferase (GTP) activity GO:0004475	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
pgm_activity	PGM2 (Saccharomyces cerevisiae; major isoform) UniProtKB:P37012 Family Representative	phosphoglucomutase activity GO:0004614	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm_activity	PGM1 (Saccharomyces cerevisiae; minor isoform) UniProtKB:P33401 Family Representative	phosphoglucomutase activity GO:0004614	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm_activity	pgm1 (Schizosaccharomyces pombe) UniProtKB:O74374 Family Representative	phosphoglucomutase activity GO:0004614	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm_activity	PGM1 (human) UniProtKB:P36871 Family Representative	phosphoglucomutase activity GO:0004614	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ugp_activity	UGP1 (Saccharomyces cerevisiae) UniProtKB:P32861 Family Representative	UTP:glucose-1-phosphate uridylyltransferase activity GO:0003983	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ugp_activity	fyu1 (Schizosaccharomyces pombe) UniProtKB:P78811 Family Representative	UTP:glucose-1-phosphate uridylyltransferase activity GO:0003983	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ugp_activity	UGP2 (human) UniProtKB:Q16851 Family Representative	UTP:glucose-1-phosphate uridylyltransferase activity GO:0003983	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
polyprenol_dehydrogenase_activity	DHRSX (human) UniProtKB:Q8N5I4 Family Representative	polyprenol dehydrogenase (NAD+) activity GO:0160196	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
polyprenol_dehydrogenase_activity	TDA5 (Saccharomyces cerevisiae) UniProtKB:Q06417 Family Representative	polyprenol dehydrogenase (NAD+) activity GO:0160196	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srd5a3_activity	SRD5A3 (human) UniProtKB:Q9H8P0 Family Representative	polyprenal reductase activity GO:0160198	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srd5a3_activity	DFG10 (Saccharomyces cerevisiae) UniProtKB:P40526 Family Representative	polyprenal reductase activity GO:0160198	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srd5a3_activity	dfg10 (Schizosaccharomyces pombe) UniProtKB:O14264 Family Representative	polyprenal reductase activity GO:0160198	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dolichal_reductase_activity	DHRSX (human) UniProtKB:Q8N5I4 Family Representative	dolichal reductase (NADPH) activity GO:0160197	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
dolichal_reductase_activity	TDA5 (Saccharomyces cerevisiae) UniProtKB:Q06417 Family Representative	dolichal reductase (NADPH) activity GO:0160197	Function Unreviewed No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
dolk_activity	DOLK (human) UniProtKB:Q9UPQ8 Family Representative	dolichol kinase activity GO:0004168	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dolk_activity	SEC59 (Saccharomyces cerevisiae) UniProtKB:P20048 Family Representative	dolichol kinase activity GO:0004168	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dolk_activity	sec59 (Schizosaccharomyces pombe) UniProtKB:Q9Y7T6 Family Representative	dolichol kinase activity GO:0004168	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm1_anchored_activity	DPM1 (Saccharomyces cerevisiae) UniProtKB:P14020 Gene	dolichyl-phosphate beta-D-mannosyltransferase activity GO:0004582	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm1_activity	DPM1 (human) UniProtKB:O60762 Family Representative	dolichyl-phosphate beta-D-mannosyltransferase activity GO:0004582	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm1_activity	dpm1 (Schizosaccharomyces pombe) UniProtKB:O14466 Family Representative	dolichyl-phosphate beta-D-mannosyltransferase activity GO:0004582	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm2_activity	DPM2 (human) UniProtKB:O94777 Family Representative	enzyme activator activity GO:0008047	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm2_activity	dpm2 (Schizosaccharomyces pombe) UniProtKB:Q9USW6 Family Representative	enzyme activator activity GO:0008047	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm3_activity	DPM3 (human) UniProtKB:Q9P2X0 Family Representative	protein-membrane adaptor activity GO:0043495	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpm3_activity	dpm3 (Schizosaccharomyces pombe) UniProtKB:O94633 Family Representative	protein-membrane adaptor activity GO:0043495	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg5_activity	ALG5 (human) UniProtKB:Q9Y673 Family Representative	dolichyl-phosphate beta-glucosyltransferase activity GO:0004581	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg5_activity	ALG5 (Saccharomyces cerevisiae) UniProtKB:P40350 Family Representative	dolichyl-phosphate beta-glucosyltransferase activity GO:0004581	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg5_activity	alg5 (Schizosaccharomyces pombe) UniProtKB:O60061 Family Representative	dolichyl-phosphate beta-glucosyltransferase activity GO:0004581	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmi_activity	type I phosphomannose isomerase family PANTHER:PTHR10309 Family	mannose-6-phosphate isomerase activity GO:0004476	Family Supported Family review supports GO:0004476 FAMILY_WIDE. This is the defining activity of every characterized member. Both modules that use the family assert it: dolichol_phosphate_sugar_donor_supply (PMI40, S. pombe SPBC2G2.16, human MPI) and emp_glycolysis (PMI40, S. pombe SPBC2G2.16).
pmm_activity	eukaryotic phosphomannomutase (HAD) family PANTHER:PTHR10466 Family	phosphomannomutase activity GO:0004615	Family Supported Family review supports GO:0004615 FAMILY_WIDE. This is the defining activity. The dolichol_phosphate_sugar_donor_supply module asserts it with representatives SEC53, S. pombe pmm1 and human PMM2, all within scope. PMM1 is in scope too: it is an active phosphomannomutase in vitro whatever its main role in vivo.
gmpp_activity	GDP-mannose pyrophosphorylase catalytic (beta) subfamily PANTHER:PTHR22572:SF15 Family	mannose-1-phosphate guanylyltransferase (GTP) activity GO:0004475	Family Supported Family review supports GO:0004475 for PANTHER:PTHR22572:SF15. Safe for the catalytic GMPPB-type subfamily SF15. This is the subfamily (PANTHER:PTHR22572:SF15) that the dolichol_phosphate_sugar_donor_supply module names for its GMPP annoton, with PSA1, mpg1 and GMPPB as representatives. Not safe for the GMPPA lineage (SF104), nor for prokaryotic members with other nucleotide-sugar specificities (CugP, HddC). Other subfamilies named "MANNOSE-1-PHOSPHATE GUANYLYLTRANSFERASE" (for example SF141, which holds Arabidopsis At4g30570, and SF159, which holds M. tuberculosis ManB) probably also qualify, but their members were not checked here and they are not listed.
pgm_activity	phosphoglucomutase family PANTHER:PTHR22573 Family	phosphoglucomutase activity GO:0004614	Family Supported Family review supports GO:0004614 FAMILY_WIDE. This is the defining activity of the bacterial, fungal, animal and plant PGMs. The five modules that use this family assert it with catalytic representatives (yeast PGM1/PGM2, S. pombe SPBC32F12.10, human PGM1): dolichol_phosphate_sugar_donor_supply, emp_glycolysis, galactose_leloir_pathway, glycogenolysis, and glycogen_metabolism_fungal (as SF2). The vertebrate PGM5 clade (SF27) is the exception, and PAINT already excludes it with an IKR.
ugp_activity	eukaryotic UDP-glucose pyrophosphorylase subfamily PANTHER:PTHR43511:SF4 Family	UTP:glucose-1-phosphate uridylyltransferase activity GO:0003983	Family Supported Family review supports GO:0003983 FAMILY_WIDE. This is the defining activity of the eukaryotic UDPGP type 1 family. All four modules that use the family assert it, with catalytic representatives: dolichol_phosphate_sugar_donor_supply (as SF4, with UGP1, fyu1 and UGP2), glycogen_metabolism_fungal (UGP1, UGP2), and glycogen_biosynthesis (UGP2). The only exception is the S. pombe paralog SPCC794.10, which PAINT records as diverged.
polyprenol_dehydrogenase_activity	DHRSX-type short-chain dehydrogenase/reductase Family	polyprenol dehydrogenase (NAD+) activity GO:0160196	Family Id Missing The family has no identifier linking it to a curated family review.
srd5a3_activity	Steroid 5-alpha reductase family (SRD5A3/DFG10 polyprenal reductase) PANTHER:PTHR14624 Family	polyprenal reductase activity GO:0160198	Family Supported Family review supports GO:0160198 FAMILY_WIDE. Shown for human SRD5A3 and S. cerevisiae Dfg10, which span the family; the family has no divergent paralog group. This is the activity the modules attach to the family.
dolichal_reductase_activity	DHRSX-type short-chain dehydrogenase/reductase Family	dolichal reductase (NADPH) activity GO:0160197	Family Id Missing The family has no identifier linking it to a curated family review.
dolk_activity	Dolichol kinase family (DOLK/SEC59) PANTHER:PTHR13205 Family	dolichol kinase activity GO:0004168	Family Function Unreviewed Family review leaves GO:0004168 UNRESOLVED. Direct yeast and human experiments establish dolichol kinase activity, and curated pombe orthology supports its transfer to Sec59. Other polyprenol kinase branches and substrates must be distinguished rather than inferred from a broad membrane-kinase fold. The complete set of substrate-specific branches is not asserted.
dpm1_activity	Dolichyl-phosphate mannosyltransferase family (DPM1) PANTHER:PTHR43398 Family	dolichyl-phosphate beta-D-mannosyltransferase activity GO:0004582	Family Function Unreviewed Family review leaves GO:0004582 UNRESOLVED. The DPM1 dolichol-phosphate mannose reaction is directly established for intact eukaryotic catalytic proteins. It does not apply to the selected U4PF58 C-terminal peptide, which lacks the glycosyltransferase domain; broader family members may also differ in lipid acceptor. A family-wide activity grant is therefore unsupported. This is an exact-product exclusion, not rejection of DPM1 activity for the worm locus.
dpm2_activity	DPM2 family (regulatory subunit) PANTHER:PTHR15039 Family	enzyme activator activity GO:0008047	Family Supported Family review supports GO:0008047 FAMILY_WIDE. The module asserts this child of the PAINT term GO:0030234. It rests on the tenfold higher synthase activity with DPM2 in mammalian cells; the fission-yeast and plant members are assigned by orthology within a single-function family. Both gene reviews use it as the core activity.
dpm3_activity	DPM3 family (anchoring subunit) PANTHER:PTHR16433 Family	protein-membrane adaptor activity GO:0043495	Family Supported Family review supports GO:0043495 FAMILY_WIDE. The module's activity for this family and the core function in both gene reviews. The tethering of DPM1 by the DPM3 coiled coil was shown in mammalian cells; the activity is assigned to the rest of the family by orthology, supported by the S. pombe complementation. No PAINT node asserts it yet.
alg5_activity	Dolichyl-phosphate glucosyltransferase family (ALG5) PANTHER:PTHR10859 Family	dolichyl-phosphate beta-glucosyltransferase activity GO:0004581	Family Function Unreviewed Family review leaves GO:0004581 UNRESOLVED. Glucose transfer to dolichyl phosphate is experimentally supported for human ALG5 and is distinct from the mannose transfer performed by DPM relatives. The PANTHER vocabulary contains more than one glucosyltransferase-labelled subfamily, so the two benchmark ALG5 representatives do not define an exhaustive list of glucose-transferring branches. Exact substrate specificity and full catalytic architecture must delimit the applicable set; the ALG5 reaction itself is not in doubt.

Gene-review completeness (32/35 grounded genes reviewed)

32 complete review(s) · 14 with deep research · 3 missing review · 18 reviewed but lacking deep research

Gene	Review	Complete	Deep research
alg5 O60061	✓	✓	✗
ALG5 P40350	✓	✓	✓
ALG5 Q9Y673	✓	✓	✓
dfg10 O14264	✓	✓	✗
DFG10 P40526	✓	✓	✓
DOLK Q9UPQ8	✓	✓	✗
dpm1 O14466	✓	✓	✗
DPM1 O60762	✓	✓	✗
DPM1 P14020	✓	✓	✓
DPM2 O94777	✓	✓	✗
dpm2 Q9USW6	✓	✓	✗
dpm3 O94633	✓	✓	✗
DPM3 Q9P2X0	✓	✓	✗
fyu1 P78811	✓	✓	✗
MPDU1 O75352	✓	✓	✗
mpg1 O74484	✓	✓	✗
MPI (human) P34949	✗	—	—
pgm1 O74374	✓	✓	✗
PGM1 P33401	✓	✓	✓
PGM1 P36871	✓	✓	✗
PGM2 P37012	✓	✓	✓
pmi40 O43014	✓	✓	✗
PMI40 P29952	✓	✓	✓
pmm1 Q9UTJ2	✓	✓	✗
PMM2 O15305	✓	✓	✓
PSA1 P41940	✓	✓	✓
DHRSX (human) Q8N5I4	✗	—	—
GMPPB (human) Q9Y5P6	✗	—	—
SEC53 P07283	✓	✓	✓
SEC59 P20048	✓	✓	✓
sec59 Q9Y7T6	✓	✓	✓
SRD5A3 Q9H8P0	✓	✓	✗
TDA5 Q06417	✓	✓	✓
UGP1 P32861	✓	✓	✓
UGP2 Q16851	✓	✓	✗

Tree

Dolichol-P and lipid-linked sugar-donor supplyMetabolic Pathwaydolichol_phosphate_sugar_donor_supply

Parts
1. 1. GDP-mannose supply (cytosol)
2. Fructose 6-phosphate to GDP-mannoseMetabolic Pathwaygdp_mannose_supply
  
  Parts
  1. 1. fructose 6-phosphate to mannose 6-phosphate
  2. Mannose-6-phosphate isomeraseReactionpmi_step
    
    Annotons
    
    Mannose-6-phosphate isomerase Family: type I phosphomannose isomerase family
  3. 2. mannose 6-phosphate to mannose 1-phosphate
  4. PhosphomannomutaseReactionpmm_step
    
    Annotons
    
    Phosphomannomutase Family: eukaryotic phosphomannomutase (HAD) family
  5. 3. mannose 1-phosphate + GTP to GDP-mannose
  6. Mannose-1-phosphate guanylyltransferase (GDP-mannose pyrophosphorylase)Reactiongmpp_step
    
    Annotons
    
    Mannose-1-phosphate guanylyltransferase Family: GDP-mannose pyrophosphorylase catalytic (beta) subfamily
3. 2. UDP-glucose supply (cytosol)
4. Glucose 6-phosphate to UDP-glucoseMetabolic Pathwayudp_glucose_supply
  
  Parts
  1. 1. glucose 6-phosphate to glucose 1-phosphate
  2. PhosphoglucomutaseReactionpgm_step
    
    Annotons
    
    Phosphoglucomutase Family: phosphoglucomutase family
  3. 2. glucose 1-phosphate + UTP to UDP-glucose
  4. UTP-glucose-1-phosphate uridylyltransferaseReactionugp_step
    
    Annotons
    
    UDP-glucose pyrophosphorylase Family: eukaryotic UDP-glucose pyrophosphorylase subfamily
5. 3. dolichyl phosphate synthesis
6. Polyprenol to dolichyl phosphateMetabolic Pathwaydol_p_synthesis
  
  Parts
  1. 1. polyprenol oxidation to polyprenal
  2. Polyprenol dehydrogenaseReactionpolyprenol_oxidation_step
    
    Annotons
    
    SDR polyprenol dehydrogenase (DHRSX/TDA5) Family: DHRSX-type short-chain dehydrogenase/reductase
  3. 2. polyprenal reduction to dolichal
  4. Polyprenal reductaseReactionsrd5a3_step
    
    Annotons
    
    Polyprenal reductase (SRD5A3/DFG10) Family: Steroid 5-alpha reductase family (SRD5A3/DFG10 polyprenal reductase)
  5. 3. dolichal reduction to dolichol
  6. Dolichal reductaseReactiondolichal_reduction_step
    
    Annotons
    
    SDR dolichal reductase (DHRSX/TDA5) Family: DHRSX-type short-chain dehydrogenase/reductase
  7. 4. dolichol phosphorylation to dolichyl phosphate
  8. dolichol to dolichyl phosphate (Dol-P)Reactiondolk_step
    
    Annotons
    
    Dolichol kinase (DOLK/SEC59) Family: Dolichol kinase family (DOLK/SEC59)
7. 4. Dol-P-Man synthesis
8. GDP-mannose + Dol-P to dolichyl-phosphate-mannose (Dol-P-Man)Reactiondpm_complex_step
  
  Variants
  1. Dol-P-Man synthase architecture by enzyme architecture (lineage) (Exactly One)
    
    Single-subunit, C-terminally anchored Dol-P-Man synthase (budding yeast class)Reactiondpm_single_subunit
    
    Annotons
    
    DPM1 (anchored class): Dol-P-Man synthase Gene Product: DPM1 (Saccharomyces cerevisiae)
    
    Three-subunit Dol-P-Man synthase (DPM1/DPM2/DPM3; animals and fission yeast)Protein Complexdpm_three_subunit
    
    Annotons
    
    DPM1: Dol-P-Man synthase catalytic subunit Family: Dolichyl-phosphate mannosyltransferase family (DPM1)
    
    DPM2: DPM synthase regulatory subunit Family: DPM2 family (regulatory subunit)
    
    DPM3: DPM synthase membrane anchor Family: DPM3 family (anchoring subunit)
9. 5. Dol-P-Glc synthesis
10. UDP-glucose + Dol-P to dolichyl-phosphate-glucose (Dol-P-Glc)Reactionalg5_step
  
  Annotons
  - ALG5: dolichyl-phosphate beta-glucosyltransferase Family: Dolichyl-phosphate glucosyltransferase family (ALG5)
11. 6. utilisation of the lipid-linked donors (lineage-dependent) optional
12. presentation/utilisation of Dol-P-Man and Dol-P-GlcReactionmpdu1_step
  
  Annotons
  - MPDU1 (Lec35): Dol-P-Man/Dol-P-Glc utilisation factor Family: MPDU1/Lec35 family

Details

Context

eukaryotesNCBITaxon:2759

Dolichol-P and lipid-linked sugar-donor supplyMetabolic Pathwaydolichol_phosphate_sugar_donor_supply

Context

eukaryotesNCBITaxon:2759

ALIGN (YeastPathways project, 2026-10). Scope widened to the crosswalk boundary "GDP-mannose, Dol-P-Man and Dol-P-Glc supply": the cytosolic GDP-mannose (PMI40/SEC53/PSA1) and UDP-glucose (PGM1/PGM2/UGP1) branches from YeastCyc PWY3O-123 and PWY3O-1565 were added as sub-pathways, the module was made eukaryote-wide, and S. cerevisiae and S. pombe exemplars were added to every role. This module intentionally overlaps dolichyl_phosphate_biosynthesis at the terminal dolichol-synthesis detour and DOLK/SEC59 phosphorylation step: that module follows de novo Dol-P carrier production from cis-PT through the detour to DOLK, while this donor-supply module repeats the detour and kinase because they directly replenish the Dol-P input for Dol-P-Man and Dol-P-Glc synthesis. The revised detour is modeled as three steps (DHRSX/TDA5 polyprenol dehydrogenase, SRD5A3/DFG10 polyprenal reductase, DHRSX/TDA5 dolichal reductase; PMID:38821050, PMID:42201967), matching the GO:0160198 polyprenal reductase term already used. DHRSX and TDA5 fall in different PANTHER families, so that role carries no family id. The cis-prenyltransferase (RER2/SRT1 + NUS1; rer2/nus1) and the polyprenyl-diphosphate dephosphorylation that produce polyprenol are upstream and outside this module, although the PomBase model includes rer2 and nus1. Dol-P-Man synthase is now an EXACTLY_ONE variant set: single-subunit, C-terminally anchored DPM1 (S. cerevisiae) versus the three-subunit DPM1/DPM2/DPM3 complex (human, S. pombe), following PMID:9223280 and PMID:10835346. Both catalytic forms share PANTHER PTHR43398:SF1, so the anchored class is represented by a concrete gene product. MPDU1 is marked optional because neither yeast has a PTHR12226 member. YeastCyc corrections: the PSA1 reaction should be the GTP-dependent EC 2.7.7.13 (GO:0004475), not the GDP/phosphate EC 2.7.7.22 reaction the SGD GO-CAM encodes (GO:0008928); YHL012W is listed beside UGP1 but is uncharacterised. GO-CAM disagreements: both YeastPathways models place the ER-membrane enzymes DPM1 and ALG5 in cytosol and use broad processes (GO:0006013 mannose metabolic process, GO:0016051 carbohydrate biosynthetic process). The cytosolic phosphoglucomutase and UDP-glucose pyrophosphorylase steps are shared with glycogen, trehalose and galactose metabolism; they are included because they are the dedicated route to the Dol-P-Glc donor in the source pathway. This module supplies the Dol-P carrier used by ALG7/DPAGT1 in n_glycan_llo_assembly_cytoplasmic, GDP-mannose for ALG1/ALG2/ALG11 there, and the Dol-P-Man/Dol-P-Glc donors used in n_glycan_llo_assembly_lumenal, GPI-anchor synthesis and O-mannosylation. Disorders: PMM2-CDG, MPI-CDG, GMPPB dystroglycanopathy, SRD5A3-, DHRSX-, DOLK-, DPM1-, DPM2-, DPM3-, MPDU1- and ALG5-CDG.

Connections

gdp_mannose_supply -> dpm_complex_step Provides Input For

GDP-mannose is the mannose donor for Dol-P-Man synthase.

udp_glucose_supply -> alg5_step Provides Input For

UDP-glucose is the glucose donor for ALG5.

dol_p_synthesis -> dpm_complex_step Provides Input For

Dol-P is mannosylated by Dol-P-Man synthase.

dol_p_synthesis -> alg5_step Provides Input For

Dol-P is glucosylated by ALG5.

dpm_complex_step -> mpdu1_step Provides Input For

Dol-P-Man made by the DPM synthase is presented by MPDU1 for lumenal glycosyltransferases.

alg5_step -> mpdu1_step Provides Input For

Dol-P-Glc made by ALG5 is presented by MPDU1 for lumenal glycosyltransferases.

Part 1: GDP-mannose supply (cytosol)

Fructose 6-phosphate to GDP-mannoseMetabolic Pathwaygdp_mannose_supply

Three soluble cytosolic enzymes convert the glycolytic intermediate fructose 6-phosphate to GDP-mannose, the donor for the cytoplasmic LLO mannosyltransferases and for Dol-P-Man synthase.

Connections

pmi_step -> pmm_step Precedes

pmm_step -> gmpp_step Precedes

Part 1: fructose 6-phosphate to mannose 6-phosphate

Mannose-6-phosphate isomeraseReactionpmi_step

Annotons

Mannose-6-phosphate isomerase

pmi_activity

Participant: Family: type I phosphomannose isomerase family

Family:

type I phosphomannose isomerase familyPANTHER:PTHR10309

Representative Members: PMI40 (Saccharomyces cerevisiae)UniProtKB:P29952 pmi40 (Schizosaccharomyces pombe)UniProtKB:O43014 MPI (human)UniProtKB:P34949

Function

mannose-6-phosphate isomerase activityGO:0004476

Substrates: D-fructose 6-phosphate

Products: D-mannose 6-phosphate

Processes

GDP-mannose biosynthetic processGO:0009298

Locations

cytosolGO:0005829

Reversible isomerisation; drawn in the biosynthetic direction (fructose 6-phosphate to mannose 6-phosphate).

Part 2: mannose 6-phosphate to mannose 1-phosphate

PhosphomannomutaseReactionpmm_step

Annotons

Phosphomannomutase

pmm_activity

Participant: Family: eukaryotic phosphomannomutase (HAD) family

Family:

eukaryotic phosphomannomutase (HAD) familyPANTHER:PTHR10466

Representative Members: SEC53 (Saccharomyces cerevisiae)UniProtKB:P07283 pmm1 (Schizosaccharomyces pombe)UniProtKB:Q9UTJ2 PMM2 (human)UniProtKB:O15305

Function

phosphomannomutase activityGO:0004615

Substrates: D-mannose 6-phosphate

Products: alpha-D-mannose 1-phosphate

Processes

GDP-mannose biosynthetic processGO:0009298

Locations

cytosolGO:0005829

Converts mannose 6-phosphate to mannose 1-phosphate.

Part 3: mannose 1-phosphate + GTP to GDP-mannose

Mannose-1-phosphate guanylyltransferase (GDP-mannose pyrophosphorylase)Reactiongmpp_step

Annotons

Mannose-1-phosphate guanylyltransferase

gmpp_activity

Participant: Family: GDP-mannose pyrophosphorylase catalytic (beta) subfamily

Family:

GDP-mannose pyrophosphorylase catalytic (beta) subfamilyPANTHER:PTHR22572:SF15 PANTHER 19.0 per-organism classification files place PSA1 (P41940), mpg1 (O74484) and human GMPPB (Q9Y5P6) in SF15; UniProt and the fetched entries.csv carry only the bare family. The subfamily name BETA comes from the human GMPPB/GMPPA pair; the two yeast exemplars are single catalytic subunits with no GMPPA-like partner in this role.

Representative Members: PSA1/MPG1 (Saccharomyces cerevisiae)UniProtKB:P41940 mpg1 (Schizosaccharomyces pombe)UniProtKB:O74484 GMPPB (human)UniProtKB:Q9Y5P6

Function

mannose-1-phosphate guanylyltransferase (GTP) activityGO:0004475

Substrates: alpha-D-mannose 1-phosphate GTP

Products: GDP-alpha-D-mannose diphosphate

Processes

GDP-mannose biosynthetic processGO:0009298

Locations

cytosolGO:0005829

Forms GDP-mannose from mannose 1-phosphate and GTP.

Part 2: UDP-glucose supply (cytosol)

Glucose 6-phosphate to UDP-glucoseMetabolic Pathwayudp_glucose_supply

Phosphoglucomutase and UDP-glucose pyrophosphorylase make the UDP-glucose used by Dol-P-Glc synthase. Both steps are shared with glycogen, trehalose, galactose and cell-wall glucan metabolism.

Connections

pgm_step -> ugp_step Precedes

Part 1: glucose 6-phosphate to glucose 1-phosphate

PhosphoglucomutaseReactionpgm_step

Annotons

Phosphoglucomutase

pgm_activity

Participant: Family: phosphoglucomutase family

Family:

phosphoglucomutase familyPANTHER:PTHR22573

Representative Members: PGM2 (Saccharomyces cerevisiae; major isoform)UniProtKB:P37012 PGM1 (Saccharomyces cerevisiae; minor isoform)UniProtKB:P33401 pgm1 (Schizosaccharomyces pombe)UniProtKB:O74374 PGM1 (human)UniProtKB:P36871

Function

phosphoglucomutase activityGO:0004614

Substrates: alpha-D-glucose 6-phosphate

Products: alpha-D-glucose 1-phosphate

Locations

cytosolGO:0005829

Reversible; drawn in the glucose 6-phosphate to glucose 1-phosphate direction.

Part 2: glucose 1-phosphate + UTP to UDP-glucose

UTP-glucose-1-phosphate uridylyltransferaseReactionugp_step

Annotons

UDP-glucose pyrophosphorylase

ugp_activity

Participant: Family: eukaryotic UDP-glucose pyrophosphorylase subfamily

Family:

eukaryotic UDP-glucose pyrophosphorylase subfamilyPANTHER:PTHR43511:SF4 PANTHER 19.0 per-organism classification files place UGP1 (P32861), fyu1 (P78811) and human UGP2 (Q16851) in SF4; UniProt and the fetched entries.csv carry only the bare family.

Representative Members: UGP1 (Saccharomyces cerevisiae)UniProtKB:P32861 fyu1 (Schizosaccharomyces pombe)UniProtKB:P78811 UGP2 (human)UniProtKB:Q16851

Function

UTP:glucose-1-phosphate uridylyltransferase activityGO:0003983

Substrates: alpha-D-glucose 1-phosphate UTP

Products: UDP-alpha-D-glucose diphosphate

Locations

cytosolGO:0005829

Forms UDP-glucose, the donor for Dol-P-Glc synthase.

Part 3: dolichyl phosphate synthesis

Polyprenol to dolichyl phosphateMetabolic Pathwaydol_p_synthesis

At the ER membrane polyprenol (from the cis-prenyltransferase product, upstream of this module) is converted to dolichol by a three-step oxidation-reduction-reduction detour, and dolichol is phosphorylated by a CTP-dependent kinase.

Connections

polyprenol_oxidation_step -> srd5a3_step Precedes

srd5a3_step -> dolichal_reduction_step Precedes

dolichal_reduction_step -> dolk_step Precedes

Part 1: polyprenol oxidation to polyprenal

Polyprenol dehydrogenaseReactionpolyprenol_oxidation_step

Annotons

SDR polyprenol dehydrogenase (DHRSX/TDA5)

polyprenol_dehydrogenase_activity

Participant: Family: DHRSX-type short-chain dehydrogenase/reductase

Family:

DHRSX-type short-chain dehydrogenase/reductase Human DHRSX and yeast TDA5 are functional orthologs (PMID:42201967) but are placed in different PANTHER families (PTHR24320 and PTHR24322), so no family id is asserted.

Representative Members: DHRSX (human)UniProtKB:Q8N5I4 TDA5 (Saccharomyces cerevisiae)UniProtKB:Q06417

Function

polyprenol dehydrogenase (NAD+) activityGO:0160196

Substrates: di-trans,poly-cis-polyprenol NAD+

Products: di-trans,poly-cis-polyprenal NADH

Locations

endoplasmic reticulum membraneGO:0005789 lipid dropletGO:0005811

First step of the dolichol detour.

Part 2: polyprenal reduction to dolichal

Polyprenal reductaseReactionsrd5a3_step

Annotons

Polyprenal reductase (SRD5A3/DFG10)

srd5a3_activity

Participant: Family: Steroid 5-alpha reductase family (SRD5A3/DFG10 polyprenal reductase)

Family:

Steroid 5-alpha reductase family (SRD5A3/DFG10 polyprenal reductase)PANTHER:PTHR14624

Representative Members: SRD5A3 (human)UniProtKB:Q9H8P0 DFG10 (Saccharomyces cerevisiae)UniProtKB:P40526 dfg10 (Schizosaccharomyces pombe)UniProtKB:O14264

Function

polyprenal reductase activityGO:0160198

Substrates: di-trans,poly-cis-polyprenal NADPH

Products: di-trans,poly-cis-dolichal NADP+

Locations

endoplasmic reticulum membraneGO:0005789

Saturates the alpha-isoprene unit. Deficiency = SRD5A3-CDG (CDG-Iq; ocular coloboma, cerebellar involvement).

Part 3: dolichal reduction to dolichol

Dolichal reductaseReactiondolichal_reduction_step

Annotons

SDR dolichal reductase (DHRSX/TDA5)

dolichal_reductase_activity

Participant: Family: DHRSX-type short-chain dehydrogenase/reductase

Family:

DHRSX-type short-chain dehydrogenase/reductase Same enzyme as the polyprenol dehydrogenase step.

Representative Members: DHRSX (human)UniProtKB:Q8N5I4 TDA5 (Saccharomyces cerevisiae)UniProtKB:Q06417

Function

dolichal reductase (NADPH) activityGO:0160197

Substrates: di-trans,poly-cis-dolichal NADPH

Products: di-trans,poly-cis-dolichol NADP+

Locations

endoplasmic reticulum membraneGO:0005789 lipid dropletGO:0005811

Last step of the detour; yeast direct evidence is genetic (PMID:42201967).

Part 4: dolichol phosphorylation to dolichyl phosphate

dolichol to dolichyl phosphate (Dol-P)Reactiondolk_step

Annotons

Dolichol kinase (DOLK/SEC59)

dolk_activity

Participant: Family: Dolichol kinase family (DOLK/SEC59)

Family:

Dolichol kinase family (DOLK/SEC59)PANTHER:PTHR13205

Representative Members: DOLK (human)UniProtKB:Q9UPQ8 SEC59 (Saccharomyces cerevisiae)UniProtKB:P20048 sec59 (Schizosaccharomyces pombe)UniProtKB:Q9Y7T6

Function

dolichol kinase activityGO:0004168

Substrates: dolichol CTP

Products: dolichyl phosphate (Dol-P) CDP

Locations

endoplasmic reticulum membraneGO:0005789

Produces the Dol-P carrier used by Dol-P-Man synthase, ALG5, ALG7/DPAGT1 and GPI/O-mannosylation. Deficiency = DOLK-CDG (CDG-Im; dilated cardiomyopathy).

Part 4: Dol-P-Man synthesis

GDP-mannose + Dol-P to dolichyl-phosphate-mannose (Dol-P-Man)Reactiondpm_complex_step

The same mannosyltransfer is carried out by two Dol-P-Man synthase architectures that are functionally interchangeable in S. pombe (PMID:9223280).

Variant set: Dol-P-Man synthase architecture by enzyme architecture (lineage) (Exactly One)

Single-subunit, C-terminally anchored Dol-P-Man synthase (budding yeast class)Reactiondpm_single_subunit

Dpm1 carries its own C-terminal hydrophobic membrane anchor and needs no accessory subunits.

Annotons

DPM1 (anchored class): Dol-P-Man synthase

dpm1_anchored_activity

Participant: Gene Product: DPM1 (Saccharomyces cerevisiae)

Gene Product:

DPM1 (Saccharomyces cerevisiae)UniProtKB:P14020 S. cerevisiae DPM1/SED3/YPR183W; PANTHER PTHR43398:SF1 together with the unanchored class, so the anchored class is not separable by family id.

Function

dolichyl-phosphate beta-D-mannosyltransferase activityGO:0004582

Substrates: GDP-mannose dolichyl phosphate

Products: dolichyl-phosphate-mannose (Dol-P-Man) GDP

Processes

dolichol phosphate mannose biosynthetic processGO:0180047

Locations

endoplasmic reticulum membraneGO:0005789

Single-polypeptide Dol-P-Man synthase.

Three-subunit Dol-P-Man synthase (DPM1/DPM2/DPM3; animals and fission yeast)Protein Complexdpm_three_subunit

Catalytic DPM1 lacks a membrane anchor and is tethered and stabilised by DPM3; DPM2 stabilises DPM3 and enhances activity.

Annotons

DPM1: Dol-P-Man synthase catalytic subunit

dpm1_activity

Participant: Family: Dolichyl-phosphate mannosyltransferase family (DPM1)

Family:

Dolichyl-phosphate mannosyltransferase family (DPM1)PANTHER:PTHR43398

Representative Members: DPM1 (human)UniProtKB:O60762 dpm1 (Schizosaccharomyces pombe)UniProtKB:O14466

Function

dolichyl-phosphate beta-D-mannosyltransferase activityGO:0004582

Substrates: GDP-mannose dolichyl phosphate

Products: dolichyl-phosphate-mannose (Dol-P-Man) GDP

Processes

dolichol phosphate mannose biosynthetic processGO:0180047

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic subunit; deficiency = DPM1-CDG (CDG-Ie).

DPM2: DPM synthase regulatory subunit

dpm2_activity

Participant: Family: DPM2 family (regulatory subunit)

Family:

DPM2 family (regulatory subunit)PANTHER:PTHR15039

Representative Members: DPM2 (human)UniProtKB:O94777 dpm2 (Schizosaccharomyces pombe)UniProtKB:Q9USW6

Function

enzyme activator activityGO:0008047

Locations

endoplasmic reticulum membraneGO:0005789

Regulatory/stabilising subunit; deficiency = DPM2-CDG (dystroglycanopathy).

DPM3: DPM synthase membrane anchor

dpm3_activity

Participant: Family: DPM3 family (anchoring subunit)

Family:

DPM3 family (anchoring subunit)PANTHER:PTHR16433

Representative Members: DPM3 (human)UniProtKB:Q9P2X0 dpm3 (Schizosaccharomyces pombe)UniProtKB:O94633

Function

protein-membrane adaptor activityGO:0043495

Locations

endoplasmic reticulum membraneGO:0005789

Membrane-anchoring subunit; deficiency = DPM3-CDG (dystroglycanopathy).

Part 5: Dol-P-Glc synthesis

UDP-glucose + Dol-P to dolichyl-phosphate-glucose (Dol-P-Glc)Reactionalg5_step

Annotons

ALG5: dolichyl-phosphate beta-glucosyltransferase

alg5_activity

Participant: Family: Dolichyl-phosphate glucosyltransferase family (ALG5)

Family:

Dolichyl-phosphate glucosyltransferase family (ALG5)PANTHER:PTHR10859

Representative Members: ALG5 (human)UniProtKB:Q9Y673 ALG5 (Saccharomyces cerevisiae)UniProtKB:P40350 alg5 (Schizosaccharomyces pombe)UniProtKB:O60061

Function

dolichyl-phosphate beta-glucosyltransferase activityGO:0004581

Substrates: UDP-glucose dolichyl phosphate

Products: dolichyl-phosphate-glucose (Dol-P-Glc) UDP

Locations

endoplasmic reticulum membraneGO:0005789

Makes the Dol-P-Glc glucose donor for the lumenal LLO glucosylation steps. Deficiency = ALG5-CDG.

Part 6: utilisation of the lipid-linked donors (lineage-dependent) (optional)

MPDU1 (PANTHER PTHR12226) has no member in S. cerevisiae or S. pombe, so this factor is not a required part of the eukaryotic module.

presentation/utilisation of Dol-P-Man and Dol-P-GlcReactionmpdu1_step

Annotons

MPDU1 (Lec35): Dol-P-Man/Dol-P-Glc utilisation factor

mpdu1_activity

Participant: Family: MPDU1/Lec35 family

Family:

MPDU1/Lec35 familyPANTHER:PTHR12226

Representative Members: MPDU1 (human)UniProtKB:O75352

Processes

dolichol-linked oligosaccharide biosynthetic processGO:0006488

Locations

endoplasmic reticulum membraneGO:0005789

Non-catalytic utilisation/presentation factor enabling lumenal use of Dol-P-Man and Dol-P-Glc. MPDU1 has no informative molecular-function term (no F-aspect GOA annotation); represented here by its biological-process role.

file:human/MPDU1/MPDU1-ai-review.yaml

non-catalytic ER-membrane factor required for utilisation/presentation of Dol-P-Man and Dol-P-Glc (the lipid-linked donors) to lumenal glycosyltransferases; deficiency = MPDU1-CDG (CDG-If)