air-2

UniProt ID: O01427
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

AIR-2 is the single Aurora B-type serine/threonine protein kinase of Caenorhabditis elegans and the catalytic subunit of the chromosomal passenger complex (CPC), together with ICP-1 (INCENP), BIR-1 (survivin) and CSC-1. ICP-1 binds and strongly activates AIR-2, and AIR-2 in turn phosphorylates ICP-1 in a positive feedback loop; CSC-1 and BIR-1 target the kinase. AIR-2 sits on meiotic and mitotic chromosomes before anaphase (in meiosis restricted to the mid-bivalent and sister-chromatid interfaces), then moves to the central spindle (spindle midzone) and persists at the midbody. On chromosomes it phosphorylates histone H3 and the meiotic cohesin REC-8, promoting the stepwise release of meiotic cohesion and correct mitotic and meiotic chromosome segregation; it is also needed for condensin loading. At the central spindle it binds and phosphorylates the kinesins ZEN-4/MKLP1 and BMK-1 and recruits them to the spindle, driving spindle midzone assembly and completion of cytokinesis; loss of AIR-2 lets cleavage furrows form and then regress. Its activity is stimulated by TLK-1 and restrained by CDC-48.3, PP1 and LAB-1.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000278 mitotic cell cycle
NAS
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
MODIFY
Summary: ComplexPortal statement for the CPC. True, but mitotic cell cycle only contains the specific mitotic roles that AIR-2 plays: chromosome segregation, central spindle assembly and cytokinesis.
Reason: Correct but too general. Replace with the specific mitotic processes supported by experiment, two of which the gene already carries (midzone assembly, cytokinesis). Same handling as the matching icp-1 row.
Supporting Evidence:
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:9852156
transient cleavage furrows initiate at the proper location, but regress before the division is complete
GO:0000281 mitotic cytokinesis
NAS
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
ACCEPT
Summary: ComplexPortal statement. AIR-2 depletion lets furrows initiate and then regress, and AIR-2 acts in cytokinesis independently of its role in segregation, through ZEN-4 localization and phosphorylation.
Reason: Direct role in completing mitotic cytokinesis is well supported by conditional alleles and substrate phosphorylation.
Supporting Evidence:
PMID:11050384
AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4
PMID:9852156
transient cleavage furrows initiate at the proper location, but regress before the division is complete
PMID:15854913
ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues
GO:0000776 kinetochore
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Kinetochore inherited from the Aurora B node. On C. elegans holocentric chromosomes the CPC occupies the region between the kinetochore cups (mid-bivalent / sister axis) rather than the kinetochore itself.
Reason: Worm-specific localization data place AIR-2 on the chromosome between kinetochores; chromosome/condensed chromosome capture the location.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
PANTHER:PTN000681968 SUPPORTS SOURCE BUT NOT TARGET
Aurora B-containing node; inner-centromere/kinetochore-region localization of monocentric orthologs does not map onto the holocentric worm chromosome, where the CPC lies between kinetochore cups.
Supporting Evidence:
PMID:20729837
is enriched for proteins including the chromosomal passenger complex (CPC; Fig. 2b)
PMID:11940606
AIR-2 localizes to subchromosomal regions corresponding to last points of contact between homologues in metaphase I and between sister chromatids in metaphase II
GO:0000793 condensed chromosome
IDA
PMID:10983970
The survivin-like C. elegans BIR-1 protein acts with the Aur...
ACCEPT
Summary: AIR-2 localizes to condensed meiotic and mitotic chromosomes in a BIR-1-dependent manner.
Reason: Direct localization; site of action for chromosome segregation.
Supporting Evidence:
PMID:10983970
AIR-2 was not present on chromosomes in the absence of BIR-1.
GO:0000794 condensed nuclear chromosome
IDA
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
ACCEPT
Summary: AIR-2 on condensed mitotic chromosomes in the embryo.
Reason: Direct localization; agrees with multiple studies.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0000922 spindle pole
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Spindle pole inherited from a node whose donors are largely Aurora A kinases (including C. elegans AIR-1). AIR-2 is chromosomal and midzone-associated; centrosome/pole association is the AIR-1 property.
Reason: Aurora A-type localization propagated to an Aurora B kinase; not supported by any AIR-2 localization study.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
PANTHER:PTN000681968 SUPPORTS SOURCE BUT NOT TARGET
Node includes both Aurora A and Aurora B lineages; pole association is grounded by Aurora A members.
WB:WBGene00000098 SUPPORTS SOURCE BUT NOT TARGET
air-1, the C. elegans Aurora A paralog, is the centrosome/pole-associated kinase; its localization does not transfer to AIR-2.
UniProtKB:O14965 SUPPORTS SOURCE BUT NOT TARGET
Human AURKA, an Aurora A spindle-pole kinase.
Supporting Evidence:
PMID:9852156
AIR-1, like its relatives Eg2, IAK-1, and AIK-1, was also found to be associated with mitotic centrosomes
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0004672 protein kinase activity
IDA
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
MODIFY
Summary: In vitro kinase assays show AIR-2 activity (MBP, TLK-1, or autophosphorylation), stimulated by ICP-1 and inhibited by CDC-48.3.
Reason: Correct but general; AIR-2 is a protein serine/threonine kinase (Aurora subfamily), already annotated with GO:0004674 by IDA.
Supporting Evidence:
PMID:12707312
ICP-1 dramatically stimulates AIR-2 kinase activity.
GO:0004672 protein kinase activity
IDA
PMID:15916946
The C. elegans Tousled-like kinase contributes to chromosome...
MODIFY
Summary: In vitro kinase assays show AIR-2 activity (MBP, TLK-1, or autophosphorylation), stimulated by ICP-1 and inhibited by CDC-48.3.
Reason: Correct but general; AIR-2 is a protein serine/threonine kinase (Aurora subfamily), already annotated with GO:0004674 by IDA.
Supporting Evidence:
PMID:15916946
TLK-1 is phosphorylated by AIR-2 during prophase/prometaphase
GO:0004672 protein kinase activity
IDA
PMID:18854144
An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the sta...
MODIFY
Summary: In vitro kinase assays show AIR-2 activity (MBP, TLK-1, or autophosphorylation), stimulated by ICP-1 and inhibited by CDC-48.3.
Reason: Correct but general; AIR-2 is a protein serine/threonine kinase (Aurora subfamily), already annotated with GO:0004674 by IDA.
Supporting Evidence:
PMID:18854144
CDC-48.3 binds directly to AIR-2 and inhibits its kinase activity from metaphase through telophase
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
MODIFY
Summary: InterPro kinase-domain mapping.
Reason: Correct but general; refine to protein serine/threonine kinase activity.
Supporting Evidence:
file:worm/air-2/air-2-uniprot.txt
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:11940606
The aurora kinase AIR-2 functions in the release of chromoso...
ACCEPT
Summary: In vitro phosphorylation of a defined substrate by recombinant AIR-2.
Reason: Core catalytic activity; AIR-2 directly phosphorylates REC-8, ICP-1, BMK-1, TLK-1, ZEN-4 and KLP-7.
Supporting Evidence:
PMID:11940606
We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:12048181
Phosphorylation of the carboxyl terminus of inner centromere...
ACCEPT
Summary: In vitro phosphorylation of a defined substrate by recombinant AIR-2.
Reason: Core catalytic activity; AIR-2 directly phosphorylates REC-8, ICP-1, BMK-1, TLK-1, ZEN-4 and KLP-7.
Supporting Evidence:
PMID:12048181
AIR-2 specifically phosphorylated the C. elegans INCENP ICP-1 at two adjacent serines within the carboxyl terminus
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:15548597
The Caenorhabditis elegans Aurora B kinase AIR-2 phosphoryla...
ACCEPT
Summary: In vitro phosphorylation of a defined substrate by recombinant AIR-2.
Reason: Core catalytic activity; AIR-2 directly phosphorylates REC-8, ICP-1, BMK-1, TLK-1, ZEN-4 and KLP-7.
Supporting Evidence:
PMID:15548597
the C-terminal tail domain of BMK-1 is specifically phosphorylated by AIR-2 in vitro
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:15916946
The C. elegans Tousled-like kinase contributes to chromosome...
ACCEPT
Summary: In vitro phosphorylation of a defined substrate by recombinant AIR-2.
Reason: Core catalytic activity; AIR-2 directly phosphorylates REC-8, ICP-1, BMK-1, TLK-1, ZEN-4 and KLP-7.
Supporting Evidence:
PMID:15916946
TLK-1 is phosphorylated by AIR-2 during prophase/prometaphase
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:26168236
The KLP-7 Residue S546 Is a Putative Aurora Kinase Site Requ...
ACCEPT
Summary: In vitro phosphorylation of a defined substrate by recombinant AIR-2.
Reason: Core catalytic activity; AIR-2 directly phosphorylates REC-8, ICP-1, BMK-1, TLK-1, ZEN-4 and KLP-7.
Supporting Evidence:
PMID:26168236
The kinase assays demonstrated that KLP-7 is a direct substrate of AIR-1 and AIR-2 kinases in vitro.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated assignment from EC 2.7.11.1.
Reason: Agrees with multiple IDA rows.
Supporting Evidence:
PMID:12048181
AIR-2 specifically phosphorylated the C. elegans INCENP ICP-1 at two adjacent serines within the carboxyl terminus
GO:0005515 protein binding
IPI
PMID:14704431
A map of the interactome network of the metazoan C. elegans.
REMOVE
Summary: High-throughput yeast two-hybrid interaction with ICP-1.
Reason: Bare protein binding is uninformative; the interaction is not doubted, but it adds no functional information beyond the CPC membership and kinase-substrate annotations.
GO:0005515 protein binding
IPI
PMID:15548597
The Caenorhabditis elegans Aurora B kinase AIR-2 phosphoryla...
MODIFY
Summary: Direct interaction with the BimC kinesin BMK-1 (G5ECF4), which AIR-2 phosphorylates and localizes to spindles.
Reason: Replace bare protein binding with kinesin binding, matching the ZEN-4 row.
Proposed replacements: kinesin binding
Supporting Evidence:
PMID:15548597
AIR-2 and BMK-1 directly interact with one another
GO:0005515 protein binding
IPI
PMID:15916946
The C. elegans Tousled-like kinase contributes to chromosome...
REMOVE
Summary: Interaction with ICP-1 (INCENP), the CPC activator subunit.
Reason: Bare protein binding is uninformative; the interaction is not doubted, but it adds no functional information beyond the CPC membership and kinase-substrate annotations.
GO:0005515 protein binding
IPI
PMID:15916946
The C. elegans Tousled-like kinase contributes to chromosome...
REMOVE
Summary: Interaction with TLK-1, a substrate and activator.
Reason: Bare protein binding is uninformative; the interaction is not doubted, but it adds no functional information beyond the CPC membership and kinase-substrate annotations.
GO:0005515 protein binding
IPI
PMID:18070910
RMD-1, a novel microtubule-associated protein, functions in ...
REMOVE
Summary: GST pull-down of FLAG-AIR-2 expressed in COS-7 cells by RMD-1.
Reason: Bare protein binding is uninformative; the interaction is not doubted, but it adds no functional information beyond the CPC membership and kinase-substrate annotations.
GO:0005515 protein binding
IPI
PMID:21110867
A genome-wide study of PDZ-domain interactions in C. elegans...
REMOVE
Summary: Yeast two-hybrid interaction with the PDZ protein LIN-10 in a genome-wide PDZ screen; no functional follow-up.
Reason: Bare protein binding is uninformative; the interaction is not doubted, but it adds no functional information beyond the CPC membership and kinase-substrate annotations.
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Summary: ATP binding inferred from the protein kinase domain.
Reason: Intrinsic to the catalytic kinase domain.
Supporting Evidence:
file:worm/air-2/air-2-uniprot.txt
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
GO:0005634 nucleus
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Nucleus inherited at the Aurora node. AIR-2 associates with chromosomes inside the nucleus of the prophase-I oocyte, but its functional sites are mitotic chromosomes, midzone and midbody.
Reason: Plausible and consistent with chromosome association, but peripheral.
Supporting Evidence:
PMID:9852156
AIR-2 is initially localized to the chromosomes of the most mature prophase I-arrested oocyte
GO:0005634 nucleus
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA prediction of nuclear location.
Reason: Same claim as the IBA row.
Supporting Evidence:
PMID:9852156
AIR-2 is initially localized to the chromosomes of the most mature prophase I-arrested oocyte
GO:0005694 chromosome
EXP
PMID:18923084
LAB-1 antagonizes the Aurora B kinase in C. elegans.
ACCEPT
Summary: Immunostaining/GFP shows AIR-2 on meiotic and mitotic chromosomes before anaphase.
Reason: Direct localization of the CPC kinase at its site of action.
Supporting Evidence:
PMID:18923084
restricting the localization of the C. elegans Aurora B kinase, AIR-2, to the interface between homologs
GO:0005694 chromosome
EXP
PMID:23684975
Condensin and the spindle midzone prevent cytokinesis failur...
ACCEPT
Summary: Immunostaining/GFP shows AIR-2 on meiotic and mitotic chromosomes before anaphase.
Reason: Direct localization of the CPC kinase at its site of action.
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
GO:0005694 chromosome
EXP
PMID:25475837
Dynamic SUMO modification regulates mitotic chromosome assem...
ACCEPT
Summary: Immunostaining/GFP shows AIR-2 on meiotic and mitotic chromosomes before anaphase.
Reason: Direct localization of the CPC kinase at its site of action.
Supporting Evidence:
PMID:25475837
Analysis of endogenous SUMO and AIR-2 by immunostaining showed that they co-localize perfectly on aligned metaphase chromosomes and at anaphase onset
GO:0005694 chromosome
EXP
PMID:9852156
AIR-2: An Aurora/Ipl1-related protein kinase associated with...
ACCEPT
Summary: Immunostaining/GFP shows AIR-2 on meiotic and mitotic chromosomes before anaphase.
Reason: Direct localization of the CPC kinase at its site of action.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0005694 chromosome
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt subcellular location mapping (Chromosome).
Reason: Agrees with experimental rows.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0005813 centrosome
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Centrosome inherited from a node seeded by Aurora A kinases (AURKA, Aurka, Xenopus aurora A, AIR-1). AIR-2 is not reported at centrosomes.
Reason: Aurora A-type localization propagated to an Aurora B kinase; AIR-2 is not needed for centrosome separation and is not centrosomal.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
PANTHER:PTN001219008 SUPPORTS SOURCE BUT NOT TARGET
Centrosome node seeded by Aurora A members (AURKA, mouse Aurka, rat, Xenopus aurora A, AIR-1).
WB:WBGene00000098 SUPPORTS SOURCE BUT NOT TARGET
air-1 (Aurora A) is centrosomal in C. elegans; AIR-2 is not.
Supporting Evidence:
PMID:9852156
AIR-1, like its relatives Eg2, IAK-1, and AIK-1, was also found to be associated with mitotic centrosomes
PMID:10354474
is required for chromosome segregation though not for centrosome separation or for setting up a bipolar spindle
file:worm/air-2/air-2-deep-research-manual.md
Not centrosomal (contrast with AIR-1) [PMID:9852156].
GO:0005819 spindle
IDA
PMID:10983970
The survivin-like C. elegans BIR-1 protein acts with the Aur...
MODIFY
Summary: AIR-2 observed on the spindle; its spindle localization is the anaphase midzone.
Reason: Correct but general; refine to spindle midzone, which the gene already carries by IDA.
Proposed replacements: spindle midzone
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
GO:0005819 spindle
IEA
GO_REF:0000044
MODIFY
Summary: UniProt subcellular location mapping (Spindle).
Reason: Correct but general; refine to spindle midzone.
Proposed replacements: spindle midzone
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
GO:0005856 cytoskeleton
IEA
GO_REF:0000044
MODIFY
Summary: UniProt subcellular location mapping (Cytoskeleton).
Reason: Correct but very general; the cytoskeletal location is the spindle midzone and midbody microtubules.
Proposed replacements: spindle midzone
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0005876 spindle microtubule
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: AIR-2 associates with midzone (interpolar) spindle microtubules in anaphase and telophase.
Reason: True of AIR-2 (midbody microtubules), but its functionally relevant location is better captured by spindle midzone; the IBA node also includes Aurora A members.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0006338 chromatin remodeling
IEA
GO_REF:0000108
KEEP AS NON CORE
Summary: Inferred from the histone H3 kinase activity annotation by an inter-ontology link.
Reason: Follows logically from the H3 kinase activity; mitotic H3 Ser10 phosphorylation is a real but peripheral output relative to segregation and cytokinesis.
Supporting Evidence:
PMID:10975519
both enzymes are required for H3 phosphorylation and chromosome segregation
GO:0007052 mitotic spindle organization
IBA
GO_REF:0000033
MODIFY
Summary: AIR-2 is not needed to build a bipolar spindle; its spindle role is assembly of the anaphase spindle midzone.
Reason: Too general for AIR-2: refine to mitotic spindle midzone assembly, which the gene already carries by IMP.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN000681967 SUPPORTS TRANSFER
Aurora family node; spindle organization is true for the family, but AIR-2's role is restricted to midzone assembly.
Proposed replacements: mitotic spindle midzone assembly
Supporting Evidence:
PMID:10354474
is required for chromosome segregation though not for centrosome separation or for setting up a bipolar spindle
PMID:11050384
AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4
GO:0007059 chromosome segregation
IMP
PMID:10983970
The survivin-like C. elegans BIR-1 protein acts with the Aur...
MODIFY
Summary: BIR-1 and AIR-2 loss give indistinguishable chromosome behaviour defects in fertilized oocytes (meiosis) and embryos (mitosis).
Reason: Correct but general; the defects cover both mitotic sister chromatid segregation and meiotic chromosome segregation, which are the specific supported processes.
Supporting Evidence:
PMID:10983970
We observed indistinguishable defects in fertilized oocytes and embryos lacking the Aurora-like kinase AIR-2.
PMID:11940606
Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases
GO:0007059 chromosome segregation
IMP
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
MODIFY
Summary: Conditional air-2 alleles show AIR-2 is required at metaphase/early anaphase for normal chromosome segregation in the embryo.
Reason: Same claim as the PMID:10983970 row; refine to the specific mitotic and meiotic segregation processes.
Supporting Evidence:
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:11940606
Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases
GO:0015630 microtubule cytoskeleton
IDA
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
MODIFY
Summary: AIR-2 on central spindle microtubules after anaphase onset.
Reason: Correct but general; refine to spindle midzone.
Proposed replacements: spindle midzone
Supporting Evidence:
PMID:12707312
After anaphase onset, Aurora B kinase localizes to the central spindle
GO:0019894 kinesin binding
IPI
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
KEEP AS NON CORE
Summary: AIR-2 interacts directly with the kinesin-6 ZEN-4 in vitro.
Reason: Direct binding of a kinesin substrate; informative but secondary to the kinase activity it serves.
Supporting Evidence:
PMID:11050384
we found that AIR-2 and ZEN-4 interact directly
GO:0030261 chromosome condensation
IMP
PMID:10983970
The survivin-like C. elegans BIR-1 protein acts with the Aur...
KEEP AS NON CORE
Summary: AIR-2 is required for histone H3 phosphorylation and for loading condensin SMC-4 onto mitotic chromosomes; loss gives poorly organised chromosomes.
Reason: Supported (curator read the full text; abstract reports reduced H3 phosphorylation) and consistent with the condensin-recruitment data, but condensation is a downstream contribution rather than the core segregation/cytokinesis role.
Supporting Evidence:
PMID:10983970
Histone H3 phosphorylation and HCP-1 staining, which marks kinetochores, were reduced in the absence of either BIR-1 or AIR-2.
file:worm/air-2/air-2-uniprot.txt
Also required for the localization of the condensin I complex subunit smc-4 to mitotic chromosomes
GO:0030496 midbody
EXP
PMID:23684975
Condensin and the spindle midzone prevent cytokinesis failur...
ACCEPT
Summary: AIR-2::GFP persists at the midbody, where it is activated by chromatin bridges.
Reason: Direct localization at a site of action.
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
PMID:23684975
Chromatin bridges induce activation of Aurora BAIR-2, which then recruits condensin I to the midzone and midbody.
GO:0030496 midbody
EXP
PMID:9852156
AIR-2: An Aurora/Ipl1-related protein kinase associated with...
ACCEPT
Summary: AIR-2 moves to midbody microtubules and persists at the cytokinesis remnant.
Reason: Direct localization.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0030496 midbody
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt subcellular location mapping (Midbody).
Reason: Agrees with experimental rows.
Supporting Evidence:
PMID:9852156
AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant
GO:0031991 regulation of actomyosin contractile ring contraction
IGI
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
MODIFY
Summary: Genetic interaction with cyk-1 (formin). The paper's model places AIR-2/ZEN-4 in a pathway parallel to the CYK-1 contractile ring pathway, acting at completion of cytokinesis.
Reason: AIR-2 regulates cytokinesis, but the cited abstract argues it acts in parallel to, not within, the contractile ring pathway; regulation of cytokinesis (already carried via IBA) captures the supported claim without asserting control of ring contraction.
Proposed replacements: regulation of cytokinesis
Supporting Evidence:
PMID:11050384
AIR-2 and ZEN-4 may act in parallel to a second pathway that includes CYK-1
PMID:11050384
AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4
GO:0031991 regulation of actomyosin contractile ring contraction
IMP
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
MODIFY
Summary: Conditional air-2 mutants and RNAi: furrows form and regress. Same claim as the IGI row.
Reason: Same reasoning as the IGI row: refine to regulation of cytokinesis.
Proposed replacements: regulation of cytokinesis
Supporting Evidence:
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:11050384
AIR-2 and ZEN-4 may act in parallel to a second pathway that includes CYK-1
GO:0032133 chromosome passenger complex
IBA
GO_REF:0000033
ACCEPT
Summary: CPC membership inherited at the Aurora B node; AIR-2 is the experimentally shown catalytic subunit of the worm CPC.
Reason: Agrees with the IPI row.
Supporting Evidence:
PMID:12707312
AIR-2/ICP-1/CSC-1/BIR-1 form a robust complex
GO:0032133 chromosome passenger complex
IPI
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
ACCEPT
Summary: AIR-2, ICP-1, CSC-1 and BIR-1 copurify as a robust complex; ICP-1 activates AIR-2.
Reason: Core complex membership.
Supporting Evidence:
PMID:12707312
AIR-2/ICP-1/CSC-1/BIR-1 form a robust complex
PMID:12707312
ICP-1 dramatically stimulates AIR-2 kinase activity.
GO:0032465 regulation of cytokinesis
IBA
GO_REF:0000033
ACCEPT
Summary: Aurora B/Ipl1 family role in cytokinesis inherited at the CPC node; supported for AIR-2 by phosphorylation of ZEN-4 and recruitment of midzone proteins.
Reason: Phylogenetic inference consistent with direct C. elegans evidence.
Supporting Evidence:
PMID:15854913
ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues
PMID:11050384
AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4
GO:0045184 establishment of protein localization
IMP
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
MODIFY
Summary: AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle; it also binds and phosphorylates BMK-1 and is required for its spindle localization.
Reason: Establishment of protein localization is uninformative; the supported claim is protein localization to the mitotic spindle (motor recruitment).
Supporting Evidence:
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:15548597
In the absence of AIR-2, BMK-1 localization to meiotic and mitotic spindles is greatly reduced.
GO:0051117 ATPase binding
IPI
PMID:18854144
An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the sta...
KEEP AS NON CORE
Summary: AIR-2 binds the AAA ATPase CDC-48.3, its inhibitor.
Reason: Real direct interaction reflecting regulation of AIR-2, not an AIR-2 function.
Supporting Evidence:
PMID:18854144
CDC-48.3 binds directly to AIR-2 and inhibits its kinase activity from metaphase through telophase
GO:0051233 spindle midzone
IBA
GO_REF:0000033
ACCEPT
Summary: Spindle midzone localization inherited at the CPC node; AIR-2 relocates to the central spindle at anaphase.
Reason: Agrees with the IDA row and with live imaging.
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
GO:0051233 spindle midzone
IDA
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
ACCEPT
Summary: AIR-2 relocates from chromosomes to the spindle midzone at anaphase.
Reason: Direct localization at the site of its cytokinesis role.
Supporting Evidence:
PMID:23684975
In control embryos, AIR-2::GFP moves from the metaphase plate to the central spindle and midbody
GO:0051256 mitotic spindle midzone assembly
IMP
PMID:10983970
The survivin-like C. elegans BIR-1 protein acts with the Aur...
ACCEPT
Summary: Loss of AIR-2 disrupts spindle midzone formation and the midzone localization of ZEN-4 and other midzone proteins.
Reason: Core role of the CPC kinase at the central spindle, supported by mutant analysis and by AIR-2 phosphorylation of midzone motors.
Supporting Evidence:
PMID:10983970
Embryos and fertilized oocytes lacking BIR-1 had defects in chromosome behavior, spindle midzone formation, and cytokinesis.
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:15548597
In the absence of AIR-2, BMK-1 localization to meiotic and mitotic spindles is greatly reduced.
GO:0051256 mitotic spindle midzone assembly
IMP
PMID:11050384
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to th...
ACCEPT
Summary: Loss of AIR-2 disrupts spindle midzone formation and the midzone localization of ZEN-4 and other midzone proteins.
Reason: Core role of the CPC kinase at the central spindle, supported by mutant analysis and by AIR-2 phosphorylation of midzone motors.
Supporting Evidence:
PMID:10983970
Embryos and fertilized oocytes lacking BIR-1 had defects in chromosome behavior, spindle midzone formation, and cytokinesis.
PMID:11050384
AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis
PMID:15548597
In the absence of AIR-2, BMK-1 localization to meiotic and mitotic spindles is greatly reduced.
GO:0051256 mitotic spindle midzone assembly
NAS
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
ACCEPT
Summary: ComplexPortal statement; agrees with experimental rows.
Reason: Same claim as the IMP rows.
Supporting Evidence:
PMID:12707312
After anaphase onset, Aurora B kinase localizes to the central spindle where it promotes the stable localization of the centralspindlin complex
GO:0051257 meiotic spindle midzone assembly
IMP
PMID:20729837
A kinetochore-independent mechanism drives anaphase chromoso...
ACCEPT
Summary: In C. elegans oocytes the CPC recruits the ring-domain proteins (BUB-1 and downstream) and controls microtubule assembly between separating meiotic chromosomes.
Reason: Supported by the full text; meiotic counterpart of the mitotic midzone role.
Supporting Evidence:
PMID:20729837
microtubule assembly/bundling during meiotic segregation is likely to primarily be under control of the CPC
PMID:20729837
The CPC was required to recruit BUB-1
GO:0090267 positive regulation of mitotic cell cycle spindle assembly checkpoint
NAS
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
MARK AS OVER ANNOTATED
Summary: ComplexPortal statement transferred from CPC literature in other organisms. The cited paper does not test the spindle assembly checkpoint, and no cached C. elegans AIR-2 checkpoint data were found.
Reason: Not supported for this gene by the cited reference; plausible by analogy only. Consistent with the icp-1 review.
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
ACCEPT
Summary: Rhea-based serine kinase assignment.
Reason: AIR-2 phosphorylates serines on ICP-1, ZEN-4 and TLK-1; correct.
Supporting Evidence:
PMID:12048181
AIR-2 specifically phosphorylated the C. elegans INCENP ICP-1 at two adjacent serines within the carboxyl terminus
PMID:15854913
ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues
GO:0140996 histone H3 kinase activity
IDA
PMID:14614817
The C. elegans Tousled-like kinase (TLK-1) has an essential ...
ACCEPT
Summary: Histone H3 kinase activity attributed via a TLK-1 study (abstract only in cache). Independent data show AIR-2 is required for mitotic H3 Ser10 phosphorylation in C. elegans.
Reason: Cannot see the full text the curator used, but the activity is well supported for AIR-2 and Aurora B orthologs; deferring to the curator.
Supporting Evidence:
PMID:10975519
both enzymes are required for H3 phosphorylation and chromosome segregation
PMID:10983970
Histone H3 phosphorylation and HCP-1 staining, which marks kinetochores, were reduced in the absence of either BIR-1 or AIR-2.
file:worm/air-2/air-2-uniprot.txt
Required for histone H3 'Ser-10' phosphorylation
GO:0140996 histone H3 kinase activity
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA prediction of histone H3 kinase activity.
Reason: Agrees with experimental rows for the same term.
Supporting Evidence:
PMID:10975519
both enzymes are required for H3 phosphorylation and chromosome segregation
GO:0140996 histone H3 kinase activity
IMP
PMID:14614817
The C. elegans Tousled-like kinase (TLK-1) has an essential ...
ACCEPT
Summary: Histone H3 kinase activity attributed via a TLK-1 study (abstract only in cache). Independent data show AIR-2 is required for mitotic H3 Ser10 phosphorylation in C. elegans.
Reason: Cannot see the full text the curator used, but the activity is well supported for AIR-2 and Aurora B orthologs; deferring to the curator.
Supporting Evidence:
PMID:10975519
both enzymes are required for H3 phosphorylation and chromosome segregation
PMID:10983970
Histone H3 phosphorylation and HCP-1 staining, which marks kinetochores, were reduced in the absence of either BIR-1 or AIR-2.
file:worm/air-2/air-2-uniprot.txt
Required for histone H3 'Ser-10' phosphorylation
GO:1901970 positive regulation of mitotic sister chromatid separation
NAS
PMID:12707312
CSC-1: a subunit of the Aurora B kinase complex that binds t...
MARK AS OVER ANNOTATED
Summary: ComplexPortal statement. AIR-2 drives release of meiotic cohesion by phosphorylating REC-8, but the cited paper does not examine mitotic sister chromatid separation and no cached data show a mitotic separation role.
Reason: Mitosis-specific regulatory claim without supporting C. elegans evidence; the documented cohesion-release role is meiotic. Consistent with the icp-1 review.
Supporting Evidence:
PMID:11940606
We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro.

Core Functions

Catalytic subunit of the chromosomal passenger complex. Activated by ICP-1, AIR-2 phosphorylates chromosomal substrates (histone H3, the meiotic cohesin REC-8) while bound to meiotic and mitotic chromosomes, promoting stepwise release of meiotic cohesion and correct mitotic and meiotic chromosome segregation.

Supporting Evidence:
  • PMID:12707312
    ICP-1 dramatically stimulates AIR-2 kinase activity.
  • PMID:11940606
    We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro.
  • PMID:11940606
    Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases
  • PMID:11050384
    AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis

After anaphase onset the CPC kinase relocates to the central spindle and midbody, where AIR-2 binds and phosphorylates the kinesins ZEN-4/MKLP1 and BMK-1, recruits them to the spindle, drives spindle midzone assembly in mitosis and meiosis, and is required for completion of cytokinesis.

Supporting Evidence:
  • PMID:15854913
    ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues
  • PMID:15548597
    the C-terminal tail domain of BMK-1 is specifically phosphorylated by AIR-2 in vitro
  • PMID:11050384
    AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4
  • PMID:20729837
    microtubule assembly/bundling during meiotic segregation is likely to primarily be under control of the CPC
  • PMID:9852156
    AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant

References

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Suggested Questions for Experts

Q: Does AIR-2 directly phosphorylate histone H3 Ser10 in vitro? The existing histone H3 kinase IDA/IMP rows cite a TLK-1 transcription paper (PMID:14614817) whose abstract does not mention AIR-2; if a Ser10 assay exists, GO:0035175 histone H3S10 kinase activity would be the more precise term.

Q: Does AIR-2 contribute to spindle assembly checkpoint signalling or to mitotic sister chromatid separation in C. elegans, as the ComplexPortal annotations assert by analogy?

Q: Are the centrosome and spindle pole IBA annotations an over-propagation from an Aurora A node to the Aurora B clade, and should the PAINT node placement be revisited?

Suggested Experiments

Experiment: Express a kinase-dead or analog-sensitive AIR-2 from the endogenous locus and inhibit it acutely after anaphase onset, scoring midzone assembly, ZEN-4 phosphorylation and furrow stability.

Hypothesis: AIR-2 kinase activity at the central spindle, separate from its earlier chromosomal role, is required for completion of cytokinesis.

Experiment: Measure mitotic delay after auxin-induced degradation of AIR-2 in a background with unattached kinetochores (for example monopolar spindles).

Hypothesis: AIR-2 is needed for full spindle assembly checkpoint signalling in C. elegans.

Deep Research

Manual

(air-2-deep-research-manual.md)

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WormBase

(air-2-deep-research-wormbase.md)

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πŸ“š Additional Documentation

Notes

(air-2-notes.md)

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πŸ“„ View Raw YAML

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