acrA

id: Q55F68
gene_symbol: acrA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: acrA encodes ACR (also called ACB), the terminal-differentiation
  specific adenylate cyclase of Dictyostelium discoideum. It is a large (2123
  aa) multidomain, multi-pass membrane protein comprising seven transmembrane
  helices, a degenerate histidine kinase region (HisKA plus HATPase-C domains),
  two receiver (response regulator) domains, and a C-terminal class III
  nucleotidyl cyclase catalytic domain that converts ATP to 3',5'-cyclic AMP
  (EC 4.6.1.1), using Mg2+ as cofactor and acting as a homodimer. ACR is
  expressed at low levels in growing cells and strongly induced during
  development, peaking during culmination and in prestalk regions of the
  fruiting body. Unlike the receptor-coupled aggregation adenylate cyclase ACA
  and the osmosensing spore-dormancy adenylate cyclase ACG, ACR provides the
  intracellular cAMP that activates cAMP-dependent protein kinase (PKA) at
  culmination, and is required for spore encapsulation/maturation and for
  formation of robust (non-thin) stalks. Rather than functioning as a
  phosphorelay signaling enzyme, its histidine-kinase-like and receiver domains
  have lost their canonical two-component signaling roles; the dimerizing HisKA
  subdomain instead serves to promote dimerization of the cyclase domain.
  Contrary to the plasma-membrane location of ACA, ACR localizes to the
  endoplasmic reticulum and nuclear envelope. It acts downstream of the
  cytokinin (discadenine) / DhkB signaling pathway that triggers rapid spore
  encapsulation.
existing_annotations:
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Adenylate cyclase activity is the core, experimentally established
      molecular function of ACR. The phylogenetic (IBA) inference is fully
      consistent with direct enzymatic evidence for this protein.
    action: ACCEPT
    reason: ACR is a bona fide class III adenylate cyclase whose ATP-to-cAMP
      activity has been directly demonstrated and dissected. This IBA annotation
      correctly captures the central molecular function.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: we discovered a novel adenylyl cyclase gene, acrA, that
        is expressed at low levels in growing cells and at more than 25-fold
        higher levels during development
    - reference_id: PMID:20966074
      supporting_text: In addition to its cyclase (AC) domain, ACR harbors seven
        transmembrane helices, a histidine kinase domain, and two receiver
        domains
- term:
    id: GO:0006171
    label: cAMP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ACR synthesizes cAMP, and cAMP biosynthesis is a core biological
      process for this enzyme, providing the second messenger that activates PKA
      during terminal differentiation.
    action: ACCEPT
    reason: The IBA inference of cAMP biosynthesis is directly supported by the
      catalytic activity of ACR and by the phenotype of acrA null cells, which
      fail to raise adenylyl cyclase activity after aggregation.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: The increase in activity following aggregation fails to
        occur in acrA(-) cells
    - reference_id: PMID:20966074
      supporting_text: adenylate cyclase R (ACR), is essential for spore
        encapsulation
- term:
    id: GO:0000160
    label: phosphorelay signal transduction system
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: This InterPro2GO annotation is inferred from the receiver
      (response-regulator) domain (IPR001789). However, functional dissection of
      ACR showed that its histidine kinase and receiver domains do NOT act as a
      phosphorelay to regulate the enzyme; the phosphoryl-accepting aspartates
      are largely dispensable and the domains have lost the switch-pair residues
      needed for phosphorylation-induced signaling.
    action: REMOVE
    reason: The receiver/histidine-kinase domains are present by ancestry but
      their canonical phosphorelay function has eroded. Experimental evidence
      directly contradicts a role for ACR in phosphorelay signal transduction,
      so this domain-based electronic annotation is an over-annotation.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: indicating that AC activity is not critically regulated
        by phosphorelay
    - reference_id: PMID:20966074
      supporting_text: This indicates that ACR is not regulated by its
        intramolecular histidine kinase activity
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment of adenylate cyclase activity based on
      RHEA/EC mapping (EC 4.6.1.1). This is correct and redundant with the
      experimentally supported core molecular function.
    action: ACCEPT
    reason: The EC/RHEA-based inference matches the directly demonstrated
      ATP-to-cAMP catalytic activity of ACR.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: we discovered a novel adenylyl cyclase gene, acrA, that
        is expressed at low levels in growing cells and at more than 25-fold
        higher levels during development
- term:
    id: GO:0009190
    label: cyclic nucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO annotation from the cyclase domain (IPR001054). It is
      correct but overly general; ACR specifically synthesizes cAMP, so the more
      specific child term cAMP biosynthetic process is preferable.
    action: MODIFY
    reason: ACR is an adenylate (not general nucleotidyl/guanylyl) cyclase, so
      the specific term cAMP biosynthetic process better represents its function
      than the parent cyclic nucleotide biosynthetic process.
    proposed_replacement_terms:
    - id: GO:0006171
      label: cAMP biosynthetic process
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: adenylate cyclase R (ACR), is essential for spore
        encapsulation
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ACR is a multi-pass membrane protein with seven transmembrane
      helices, so a membrane location is correct. However, the specific
      experimentally determined locations are the endoplasmic reticulum and
      nuclear envelope, making the bare membrane term uninformative as a core
      location.
    action: KEEP_AS_NON_CORE
    reason: The generic membrane annotation is technically accurate for this
      multi-pass membrane protein but is subsumed by the more precise ER and
      nuclear-envelope localizations shown experimentally.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: This strongly suggests that ACR localizes to the
        endoplasmic reticulum and nuclear envelope
    - reference_id: PMID:20966074
      supporting_text: In addition to its cyclase (AC) domain, ACR harbors seven
        transmembrane helices, a histidine kinase domain, and two receiver
        domains
- term:
    id: GO:0016772
    label: transferase activity, transferring phosphorus-containing groups
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: This InterPro2GO annotation derives from the histidine-kinase-like
      C-terminal (HATPase) domain (IPR004358), implying phosphotransferase
      activity. But ACR is a lyase (adenylate cyclase, EC 4.6.1.1), and its
      histidine kinase domain is degenerate and catalytically non-functional,
      lacking the phospho-accepting histidine, and mutation of essential
      ATP-binding residues has no effect on activity.
    action: REMOVE
    reason: ACR has no demonstrated phosphotransferase/kinase activity; the
      histidine-kinase-like domain is a pseudokinase used only for
      dimerization. Assigning transferase activity from this degenerate domain
      is a domain-based over-annotation contradicted by experimental evidence.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: Mutation of three essential ATP-binding residues in the
        histidine kinase domain did not affect the AC activity or phenotypic
        rescue
    - reference_id: PMID:20966074
      supporting_text: the dimerizing histidine phosphoacceptor subdomain, which
        in ACR lacks the canonical histidine for autophosphorylation, was
        essential for AC activity
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: ACR produces intracellular cAMP that acts as a second messenger to
      activate PKA, so participation in intracellular signal transduction is
      correct. It is a broad process term subsumed by the more specific cAMP
      biosynthesis and developmental-differentiation annotations.
    action: KEEP_AS_NON_CORE
    reason: The annotation is biologically accurate (ACR generates a
      second-messenger signal) but too general to represent the specific evolved
      function; retained as non-core context.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: Expression of many of the essential developmental genes
        in Dictyostelium discoideum are known to depend on PKA activity
- term:
    id: GO:0009642
    label: response to light intensity
  evidence_type: HEP
  original_reference_id: PMID:41057014
  qualifier: acts_upstream_of_or_within
  review:
    summary: This high-throughput expression (HEP) annotation reflects that acrA
      is a differentially expressed gene, downregulated in the dark, in a
      transcriptomic study of light-mediated development. It captures
      light-regulated expression of acrA rather than a direct functional role of
      the ACR protein in light responses.
    action: KEEP_AS_NON_CORE
    reason: The evidence is transcriptomic/correlative (acrA is a
      light-responsive DEG). This is peripheral to the core catalytic and
      developmental function and is retained as non-core.
    supported_by:
    - reference_id: PMID:41057014
      supporting_text: Here we also observed that the adenylate cyclase gene
        acrA was downregulated under dark in the unicellular phase
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IC
  original_reference_id: PMID:10556070
  qualifier: enables
  review:
    summary: ATP binding is curator-inferred (IC) from the adenylate cyclase
      activity, since ATP is the substrate of the ATP-to-cAMP reaction. This is
      a correct supporting molecular function.
    action: ACCEPT
    reason: ATP binding is a necessary component of the cyclase catalytic
      mechanism (ATP is converted to cAMP plus diphosphate) and is soundly
      inferred from the enzymatic activity.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: we discovered a novel adenylyl cyclase gene, acrA, that
        is expressed at low levels in growing cells and at more than 25-fold
        higher levels during development
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IDA
  original_reference_id: PMID:10556070
  qualifier: enables
  review:
    summary: Direct experimental demonstration of adenylate cyclase activity for
      ACR, the core molecular function. Adenylyl cyclase activity increases
      through development and this increase is lost in acrA null cells.
    action: ACCEPT
    reason: This IDA annotation is the primary experimental evidence for the
      core catalytic function of ACR.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: The increase in activity following aggregation fails to
        occur in acrA(-) cells
- term:
    id: GO:0004016
    label: adenylate cyclase activity
  evidence_type: IDA
  original_reference_id: PMID:20966074
  qualifier: enables
  review:
    summary: Direct measurement of cAMP production by an ACR-YFP fusion in acr-
      cells confirms adenylate cyclase activity and allowed domain-level
      dissection of the enzyme's catalytic requirements.
    action: ACCEPT
    reason: Independent IDA evidence for the core adenylate cyclase activity of
      ACR; the reconstituted enzyme produces cAMP and rescues the null
      phenotype.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: the dimerizing histidine phosphoacceptor subdomain, which
        in ACR lacks the canonical histidine for autophosphorylation, was
        essential for AC activity
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IDA
  original_reference_id: PMID:20966074
  qualifier: located_in
  review:
    summary: ACR-YFP localizes to the nuclear envelope, shown by confocal
      microscopy and colocalization with the ER marker calnexin around the
      nuclei. This is a well-supported, distinctive localization for ACR.
    action: ACCEPT
    reason: Direct imaging evidence places ACR at the nuclear envelope, an
      unusual localization for a Dictyostelium adenylate cyclase and a core
      cellular-component annotation.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: ACR is associated with the nuclear envelope and
        endoplasmic reticulum
    - reference_id: PMID:20966074
      supporting_text: This strongly suggests that ACR localizes to the
        endoplasmic reticulum and nuclear envelope
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:20966074
  qualifier: located_in
  review:
    summary: ACR-YFP colocalizes with the ER marker calnexin in a vesicular
      network throughout the cell, directly demonstrating endoplasmic reticulum
      localization.
    action: ACCEPT
    reason: Direct immunofluorescence/colocalization evidence supports ER
      localization; this is a core cellular-component annotation for ACR.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: This strongly suggests that ACR localizes to the
        endoplasmic reticulum and nuclear envelope
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: HMP
  original_reference_id: PMID:17659086
  qualifier: acts_upstream_of_or_within
  review:
    summary: High-throughput mutant phenotyping placed acrA among genes whose
      disruption produces phenotypes only at later (slug-to-culmination) stages
      of fruiting body (sorocarp) development. This general developmental term
      is correct but is captured more specifically by the sorocarp morphogenesis
      and spore-cell differentiation annotations.
    action: KEEP_AS_NON_CORE
    reason: The broad sorocarp development term is accurate for acrA but
      subsumed by more specific late-development annotations that better
      represent its role.
    supported_by:
    - reference_id: PMID:17659086
      supporting_text: In contrast, dhkA and acrA show mutant phenotypes only at
        later stages consistent with their specific roles during slug to
        culmination stage
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:10556070
  qualifier: acts_upstream_of_or_within
  review:
    summary: ACR-derived cAMP activates PKA, and many essential developmental
      genes depend on PKA activity, so ACR acts upstream of developmental gene
      expression. This is an indirect, downstream effect mediated by the
      second-messenger/PKA cascade.
    action: KEEP_AS_NON_CORE
    reason: The influence of ACR on gene expression is real but indirect (via
      cAMP/PKA) and general; it is retained as non-core context rather than a
      direct molecular function.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: Expression of many of the essential developmental genes
        in Dictyostelium discoideum are known to depend on PKA activity
- term:
    id: GO:0031288
    label: sorocarp morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:10556070
  qualifier: acts_upstream_of_or_within
  review:
    summary: acrA null cells form unnaturally long, thin stalks, demonstrating a
      requirement for ACR in proper morphogenesis of the fruiting body (stalk)
      during culmination.
    action: ACCEPT
    reason: The stalk-morphogenesis defect of acrA mutants directly supports a
      core role in sorocarp morphogenesis at culmination.
    supported_by:
    - reference_id: PMID:10556070
      supporting_text: Growth and development up to the slug stage are unaffected
        in acrA(-) mutant strains but the cells make almost no viable spores and
        produce unnaturally long stalks
    - reference_id: PMID:10556070
      supporting_text: As long as ACA is fully active, ACR is not required until
        culmination but then plays a critical role in sporulation and
        construction of the stalk
- term:
    id: GO:0009736
    label: cytokinin-activated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18216168
  qualifier: acts_upstream_of_or_within
  review:
    summary: AcrA is required, together with the histidine kinase DhkB, to
      transduce the cytokinin (discadenine/isopentenyladenine) signal that
      triggers rapid spore encapsulation. This annotation captures the
      Dictyostelium cytokinin signaling context in which ACR operates.
    action: ACCEPT
    reason: Genetic evidence shows AcrA is a required component of the cytokinin
      signal transduction pathway leading to sporulation, consistent with its
      role as the cAMP source that activates PKA for encapsulation.
    supported_by:
    - reference_id: PMID:18216168
      supporting_text: DhkB and the adenylyl cyclase of late development, AcrA,
        are members of two component signal transduction families and both are
        required to transduce the cytokinin signal
- term:
    id: GO:0031000
    label: response to caffeine
  evidence_type: IDA
  original_reference_id: PMID:16952277
  qualifier: involved_in
  review:
    summary: Pharmacological profiling showed that caffeine inhibits cAMP
      accumulation by ACB (ACR/acrA) in intact cells (an indirect effect, since
      caffeine does not inhibit basal ACB activity in lysates). This records a
      response of ACR-dependent cAMP output to caffeine.
    action: KEEP_AS_NON_CORE
    reason: The caffeine sensitivity is a pharmacological/experimental property
      of ACR-dependent cAMP accumulation rather than a core evolved function;
      retained as non-core.
    supported_by:
    - reference_id: PMID:16952277
      supporting_text: Caffeine, which was previously used to specifically block
        ACA function, also inhibited cAMP accumulation by ACB and ACG
- term:
    id: GO:0044671
    label: sorocarp spore cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:20966074
  qualifier: acts_upstream_of_or_within
  review:
    summary: ACR is essential for spore encapsulation; acr- cells develop to the
      fruiting body stage but fail to make viable, encapsulated spores, and
      ACR-YFP rescues this defect. This is a core developmental role of ACR.
    action: ACCEPT
    reason: Loss- and rescue-of-function evidence establishes ACR as required
      for spore cell differentiation/encapsulation during culmination.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: adenylate cyclase R (ACR), is essential for spore
        encapsulation
    - reference_id: PMID:10556070
      supporting_text: As long as ACA is fully active, ACR is not required until
        culmination but then plays a critical role in sporulation and
        construction of the stalk
- term:
    id: GO:0031288
    label: sorocarp morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20966074
  qualifier: acts_upstream_of_or_within
  review:
    summary: A second IMP annotation for sorocarp morphogenesis, from the
      functional-dissection study in which acr- cells form
      thinner-than-wild-type stalks that are rescued by ACR-YFP.
    action: ACCEPT
    reason: Independent genetic evidence confirms a core role for ACR in proper
      stalk formation during fruiting-body morphogenesis.
    supported_by:
    - reference_id: PMID:20966074
      supporting_text: adenylate cyclase R (ACR), is essential for spore
        encapsulation
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10556070
  title: An adenylyl cyclase that functions during late development of Dictyostelium.
  findings:
  - statement: acrA encodes a novel adenylyl cyclase expressed at low levels in
      growth and induced more than 25-fold during development.
    supporting_text: we discovered a novel adenylyl cyclase gene, acrA, that is
      expressed at low levels in growing cells and at more than 25-fold higher
      levels during development
  - statement: acrA null cells develop normally to the slug stage but fail to make
      viable spores and produce unnaturally long stalks.
    supporting_text: Growth and development up to the slug stage are unaffected in
      acrA(-) mutant strains but the cells make almost no viable spores and produce
      unnaturally long stalks
  - statement: ACR is dispensable until culmination when it is critical for
      sporulation and stalk construction.
    supporting_text: As long as ACA is fully active, ACR is not required until
      culmination but then plays a critical role in sporulation and construction
      of the stalk
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary discovery/characterization of acrA; abstract-only in
      cache but establishes catalytic activity, developmental expression, and the
      sporulation/stalk phenotype. Verified via PubMed title match.
- id: PMID:15875012
  title: The genome of the social amoeba Dictyostelium discoideum.
  findings: []
- id: PMID:16952277
  title: Pharmacological profiling of the Dictyostelium adenylate cyclases ACA, ACB
    and ACG.
  findings:
  - statement: Caffeine inhibits cAMP accumulation by ACB (acrA) as well as ACA and
      ACG in intact cells.
    supporting_text: Caffeine, which was previously used to specifically block ACA
      function, also inhibited cAMP accumulation by ACB and ACG
  - statement: ACB, encoded by the AcrA gene, is required for spore maturation.
    supporting_text: ACB is required for the maturation of spores
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text available; supports the caffeine-response annotation
      and confirms acrA=ACB identity and its spore-maturation role.
- id: PMID:17659086
  title: High-throughput analysis of spatio-temporal dynamics in Dictyostelium.
  findings:
  - statement: acrA mutants show phenotypes only at later (slug-to-culmination)
      developmental stages, consistent with a late-development role.
    supporting_text: In contrast, dhkA and acrA show mutant phenotypes only at
      later stages consistent with their specific roles during slug to culmination
      stage
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text available; high-throughput phenotyping supporting the
      late/culmination-stage sorocarp development annotation.
- id: PMID:18216168
  title: Cytokinins induce sporulation in Dictyostelium.
  findings:
  - statement: AcrA and the histidine kinase DhkB are both required to transduce
      the cytokinin (discadenine) signal that triggers spore encapsulation.
    supporting_text: DhkB and the adenylyl cyclase of late development, AcrA, are
      members of two component signal transduction families and both are required
      to transduce the cytokinin signal
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only in cache but the abstract explicitly names AcrA as
      required for cytokinin signal transduction leading to sporulation.
- id: PMID:20966074
  title: Functional dissection of adenylate cyclase R, an inducer of spore encapsulation.
  findings:
  - statement: ACR is essential for spore encapsulation and its multidomain
      architecture includes seven TM helices, a histidine kinase domain, and two
      receiver domains.
    supporting_text: In addition to its cyclase (AC) domain, ACR harbors seven
      transmembrane helices, a histidine kinase domain, and two receiver domains
  - statement: ACR localizes to the endoplasmic reticulum and nuclear envelope.
    supporting_text: This strongly suggests that ACR localizes to the endoplasmic
      reticulum and nuclear envelope
  - statement: ACR activity is not critically regulated by phosphorelay, and its
      intramolecular histidine kinase activity is dispensable.
    supporting_text: indicating that AC activity is not critically regulated by
      phosphorelay
  - statement: The degenerate HisKA subdomain lacks the canonical
      autophosphorylation histidine yet is essential for AC activity, promoting
      dimerization of the cyclase domain.
    supporting_text: the dimerizing histidine phosphoacceptor subdomain, which in
      ACR lacks the canonical histidine for autophosphorylation, was essential for
      AC activity
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; the definitive domain-dissection and
      localization study, and the basis for removing the phosphorelay and
      transferase (histidine-kinase) domain-based IEA annotations.
- id: PMID:41057014
  title: Transcriptomic and metabolomic insights into light-mediated unicellular-to-multicellular
    transition in Dictyostelium discoideum.
  findings:
  - statement: acrA is a light-responsive differentially expressed gene,
      downregulated in the dark in the unicellular phase.
    supporting_text: Here we also observed that the adenylate cyclase gene acrA was
      downregulated under dark in the unicellular phase
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Full text available; supports only the expression-level (HEP)
      light-response annotation, not a direct protein function.
core_functions:
- description: ACR is the terminal-differentiation-specific adenylate cyclase
    that synthesizes cAMP (from ATP, EC 4.6.1.1) at the endoplasmic reticulum and
    nuclear envelope during culmination. The cAMP it produces activates PKA to
    drive spore encapsulation/maturation and proper stalk formation. Catalysis
    requires homodimerization mediated by the degenerate histidine-kinase (HisKA)
    domain rather than any phosphorelay or kinase activity.
  molecular_function:
    id: GO:0004016
    label: adenylate cyclase activity
  directly_involved_in:
  - id: GO:0006171
    label: cAMP biosynthetic process
  - id: GO:0044671
    label: sorocarp spore cell differentiation
  - id: GO:0031288
    label: sorocarp morphogenesis
  locations:
  - id: GO:0005783
    label: endoplasmic reticulum
  - id: GO:0005635
    label: nuclear envelope
  supported_by:
  - reference_id: PMID:10556070
    supporting_text: As long as ACA is fully active, ACR is not required until
      culmination but then plays a critical role in sporulation and construction
      of the stalk
  - reference_id: PMID:20966074
    supporting_text: adenylate cyclase R (ACR), is essential for spore
      encapsulation
  - reference_id: PMID:20966074
    supporting_text: This strongly suggests that ACR localizes to the endoplasmic
      reticulum and nuclear envelope