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Metabolism & Rhea

UniProt cross-references the chemical reactions an enzyme catalyzes to Rhea, and classifies enzymes with EC (Enzyme Commission) numbers. This page shows how to query that from the UniProt side - starting at a protein and reaching into Rhea and the enzyme classification hierarchy - plus how UniProt links a protein to the biological pathway(s) it’s part of.

For queries that start on the Rhea side instead (reactions, chemical participants, cross-species comparisons), see the Rhea metabolism tutorial.

Catalytic activity, with its supporting evidence

A Catalytic_Activity_Annotation links a protein to the Rhea reaction it catalyzes. UniProt also lets you trace why that link is asserted: the statement itself can be described with an RDF reification (a resource describing a rdf:subject/rdf:predicate/rdf:object triple), which is in turn attributed to evidence - here, ECO:0000269, “experimental evidence”.

Example data (Turtle) — edit it, then re-run any query below

base <http://purl.uniprot.org/uniprot/>
prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#>
prefix up: <http://purl.uniprot.org/core/>
prefix rh: <http://rdf.rhea-db.org/>
prefix eco: <http://purl.obolibrary.org/obo/ECO_>

<P00918> up:reviewed true ;
  up:annotation <P00918#CA> ;
  up:attribution <P00918#attribution1> .

<P00918#CA> a up:Catalytic_Activity_Annotation ;
  up:catalyticActivity <P00918#CA_ca> .

<P00918#CA_ca> up:catalyzedReaction rh:10748 .

[] rdf:subject <P00918#CA> ;
   rdf:predicate up:catalyticActivity ;
   rdf:object <P00918#CA_ca> ;
   up:attribution <P00918#attribution1> .

<P00918#attribution1> up:evidence eco:0000269 .

Adapted from sparql-examples/UniProt 39

PREFIX rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#>
PREFIX up: <http://purl.uniprot.org/core/>

SELECT
  ?protein
  ?rhea
WHERE {
  # ECO 269 is experimental evidence
  BIND (<http://purl.obolibrary.org/obo/ECO_0000269> as ?evidence)
  ?protein up:reviewed true ;
    up:annotation ?a ;
    up:attribution ?attribution  .

  ?a a up:Catalytic_Activity_Annotation ;
    up:catalyticActivity ?ca .
  ?ca up:catalyzedReaction ?rhea .

  [] rdf:subject ?a ;
    rdf:predicate up:catalyticActivity ;
    rdf:object ?ca ;
    up:attribution ?attribution .

  ?attribution up:evidence ?evidence .
}

Enzyme (EC) classification

Enzymes are classified with EC numbers, organized as a hierarchy of four numbers (e.g. 1.1.1.1); UniProt materializes the top-level classes (ec:1.-.-.- through ec:7.-.-.-) as rdfs:subClassOf targets. An enzyme’s EC number can sit on the protein itself, or on one of its domains or components (for polyproteins that get cleaved into several functional pieces).

Example data (Turtle) — edit it, then re-run any query below

base <http://purl.uniprot.org/uniprot/>
prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
prefix up: <http://purl.uniprot.org/core/>
prefix ec: <http://purl.uniprot.org/enzyme/>

ec:1.1.1.1 rdfs:subClassOf ec:1.-.-.- .
ec:3.1.3.1 rdfs:subClassOf ec:3.-.-.- .

<P00330> up:enzyme ec:1.1.1.1 .

<P05067> up:domain <P05067#domain1> .
<P05067#domain1> up:enzyme ec:3.1.3.1 .

Adapted from sparql-examples/UniProt 18

PREFIX ec: <http://purl.uniprot.org/enzyme/>
PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>
PREFIX up: <http://purl.uniprot.org/core/>

SELECT ?ecClass (COUNT(?protein) as ?size)
WHERE
{
    VALUES (?ecClass) {(ec:1.-.-.-) (ec:2.-.-.-) (ec:3.-.-.-) (ec:4.-.-.-) (ec:5.-.-.-) (ec:6.-.-.-) (ec:7.-.-.-)} .
    ?protein ( up:enzyme | up:domain/up:enzyme | up:component/up:enzyme ) ?enzyme .
    # Enzyme subclasses are materialized, do not use rdfs:subClassOf+
    ?enzyme rdfs:subClassOf ?ecClass .
}
GROUP BY ?ecClass ORDER BY ?ecClass

Rhea reactions, with and without an EC number

Not every Rhea reaction UniProt cites has an EC number attached, some catalytic activities are only described by their Rhea reaction. The up:enzymeClass property links a Catalytic_Activity directly to its EC number, when there is one.

Example data (Turtle) — edit it, then re-run any query below

base <http://purl.uniprot.org/uniprot/>
prefix up: <http://purl.uniprot.org/core/>
prefix rh: <http://rdf.rhea-db.org/>
prefix ec: <http://purl.uniprot.org/enzyme/>

<P00918#CA_ca> up:catalyzedReaction rh:10748 ;
  up:enzymeClass ec:4.2.1.1 .

<P00330#CA_ca> up:catalyzedReaction rh:15561 .

PREFIX up: <http://purl.uniprot.org/core/>

SELECT
  ?rhea
  ?EC
WHERE {
  ?CatalyticActivity  up:catalyzedReaction   ?rhea ;
    up:enzymeClass         ?EC .
}

The MINUS version below finds the reactions with no up:enzymeClass at all - ?EC in the SELECT stays unbound for every row, which is the point: it’s the complement of the query above.

Adapted from sparql-examples/UniProt 83

PREFIX up: <http://purl.uniprot.org/core/>

SELECT
  ?rhea
  ?EC
WHERE {
  ?CatalyticActivity up:catalyzedReaction ?rhea .
  MINUS {
    ?CatalyticActivity up:enzymeClass ?EC .
  }
}

Gene → protein → reaction sets

A common systems-biology need: for a given organism, connect each gene to the protein it encodes and every reaction that protein catalyzes, by following UniProt’s own cross-reference to Ensembl.

Example data (Turtle) — edit it, then re-run any query below

base <http://purl.uniprot.org/uniprot/>
prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
prefix up: <http://purl.uniprot.org/core/>
prefix taxon: <http://purl.uniprot.org/taxonomy/>
prefix rh: <http://rdf.rhea-db.org/>
prefix ensembl: <http://purl.uniprot.org/ensembl/>

<P00918> up:reviewed true ;
  up:organism taxon:9606 ;
  up:annotation <P00918#CA> ;
  rdfs:seeAlso ensembl:ENST00000000233 .

<P00918#CA> up:catalyticActivity <P00918#CA_ca> .
<P00918#CA_ca> up:catalyzedReaction rh:10748 .

ensembl:ENST00000000233 up:database <http://purl.uniprot.org/database/Ensembl> ;
  up:transcribedFrom ensembl:ENSG00000000000 .

Adapted from sparql-examples/UniProt 61

PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>
PREFIX taxon: <http://purl.uniprot.org/taxonomy/>
PREFIX up: <http://purl.uniprot.org/core/>

SELECT
  DISTINCT # Distinct because there might be more than one transcript for a gene leading to duplicates
    ?ensemblGene
    ?protein
    ?rhea
WHERE {
  ?protein up:reviewed true ;
           up:organism taxon:9606 .
  ?protein up:annotation ?caa ;
           rdfs:seeAlso ?ensemblTranscript .
  ?ensemblTranscript up:database <http://purl.uniprot.org/database/Ensembl> .
	?caa up:catalyticActivity ?ca .
  ?ca up:catalyzedReaction ?rhea .
  ?ensemblTranscript up:transcribedFrom ?ensemblGene
}

Pathway cross-references

UniProt cross-references proteins to pathway resources like Reactome; the pathway’s own human-readable name is available right on the cross-reference, as rdfs:comment.

Example data (Turtle) — edit it, then re-run any query below

base <http://purl.uniprot.org/uniprot/>
prefix up: <http://purl.uniprot.org/core/>
prefix taxon: <http://purl.uniprot.org/taxonomy/>
prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
prefix reactome: <http://purl.uniprot.org/reactome/>

<Q96EL1> a up:Protein ;
  up:organism taxon:9606 ;
  up:reviewed true ;
  rdfs:seeAlso reactome:R-HSA-0000001 .

reactome:R-HSA-0000001 up:database <http://purl.uniprot.org/database/Reactome> ;
  rdfs:comment "Signaling by FGFR in Cancer" .

Adapted from sparql-examples/UniProt 217

PREFIX up: <http://purl.uniprot.org/core/>
PREFIX taxon: <http://purl.uniprot.org/taxonomy/>
PREFIX rdfs: <http://www.w3.org/2000/01/rdf-schema#>

SELECT
  ?protein
  ?pathway
  ?pathwayName
WHERE {
  ?protein a up:Protein ;
    up:organism taxon:9606 ;
    up:reviewed true ;
    rdfs:seeAlso ?pathway .
  ?pathway up:database <http://purl.uniprot.org/database/Reactome> ;
    rdfs:comment ?pathwayName .
  FILTER(CONTAINS(?pathwayName, "Cancer"))
}