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FLASH GENE
Symbol AURKA contributors: shn /mct - updated : 24-09-2017
HGNC name aurora kinase A
HGNC id 11393
Location 20q13.2      Physical location : 54.944.444 - 54.967.351
Synonym name
  • serine/threonine kinase 15
  • aurora-related kinase 1
  • IPL1-related kinase
  • aurora/IPL1-like kinase
  • Aurora 2
  • serine/threonine kinase 6
  • breast tumor-amplified kinase
  • Synonym symbol(s) BTAK, ARK1, STK15, HsPK21, AURA, AURORA2, STK7, STK6, MGC34538, AIK, PPP1R47
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 22.91 kb     11 Exon(s)
    regulatory sequence Promoter
    text structure a region located 96-bp upstream of the transcription initiation site is critical for the activation of the promoter by E2F3
    MAPPING cloned Y linked   status confirmed
    Map cen - D20S832 - D20S100 - AURKA - D20S102 - D20S149 - qter
    RNA
    TRANSCRIPTS type messenger
    text variants 1-6 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 splicing 2554 46 403 - 2007 17634535
    9 splicing 2346 46 403 - 2007 17634535
    10 splicing 2245 46 403 - 2007 17634535
    9 splicing 2135 46 403 - 2007 17634535
    10 splicing 2231 46 403 - 2007 17634535
    9 splicing 2121 46 403 - 2007 17634535
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  lowly
    Reproductivemale systemtestis  highly Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal lowly
    cell lineage
    cell lines cervical cancer cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint, G2M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • catalytic domain alone sufficient to restore spindle bipolarity
  • N-terminal sequences with function in mitotic timing
  • HOMOLOGY
    interspecies ortholog to Aurka, Rattus norvegicus
    ortholog to Aurka, Mus musculus
    ortholog to AURKA, Pan troglodytes
    intraspecies homolog to human STK6
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • Aurora subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • recruited to the spindle pole during mitosis, especially from prophase through anaphase
  • localized to the centrosomes during interphase and at the spindle poles during mitosis, and implicated in promoting mitotic entry and required for centrosome maturation and separation
  • Aurora A and SKI co-localized at the centrosomes
  • localizes to centrosomes and mitotic spindles where it mediates mitotic progression and chromosomal stability (
  • basic FUNCTION
  • serine/threonine kinase, required for segregation process
  • implicated in centrosome amplification, genome instability and cellular transformation
  • involved in the induction of centrosome duplication-distribution abnormalities and aneuploidy in mammalian cells
  • acting downstream of the RanGTPase signaling pathway to stimulate spindle assembly in mitosis
  • playing a role in centrosome amplification, chromosomal instability, and transformation in mammalian cells
  • required for centrosome maturation and accurate chromosome segregation
  • required for G2/M transition and spindle assembly
  • plays key roles in cellular mitosis, being among the downregulated genes along with its related genes, which included AURKB, TPX2 and CENPA
  • centrosome-localized serine/threonine kinase that functions primarily in centrosome maturation and mitotic spindle assembly
  • exerts an effect as a key regulator of microtubule assembly during M phase and therefore of bipolar spindle formation
  • required to be activated by BORA for its role in entrosome maturation, spindle assembly, and asymmetric protein localization during mitosis
  • synergistic action of BORA and the kinase Aurora A (AURKA) controls the G2-M transition
  • involved in the regulation of CKAP5 and KIF2C localization
  • activates Polo-like kinase-1 is to promote checkpoint recovery of the cell division process
  • playing a crucial role for embryonic development and cell cycle progression
  • may act as a haploinsufficient tumor suppressor
  • essential for centrosome separation and bipolar spindle formation
  • required for timely mitotic entry and bipolar spindle formation
  • essential for microtubule dynamics and differentiation of post-mitotic neurons
  • may be involved in establishing cell polarity and axon/dendrite elaboration in young neurons
  • with CDK1 and PLK1, participate in a feedback activation loop and activation of CDK1 initiates the feedback loop activity, leading to rapid and timely entry into mitosis )
  • phosphorylates, activates, and relocalizes the small GTPase RALA
  • through phosphorylation of CENPE at T422, regulates the intrinsic motor properties of CENPE and disrupts the binding of the opposing phosphatase PPP1CC to CENPE, thereby establishing a bistable phosphoswitch for regulation of CENPE
  • having two roles, independent pathways of spindle assembly (mediated by centrosomes and chromosomes) relies on spatial and quantitative control of its kinase activity by two distinct cofactors (CEP192 and TPX2, respectively) that use different organelle-targeting and AURKA-regulation strategies
  • involved in ciliary resorption, cell differentiation, and cell polarity control in interphase cells
  • AURKA modulates likely the microtubule binding activity of HAUS8 in a spatiotemporal manner for proper bipolar spindle assembly
  • via phosphorylating HNRNPK, participates in regulating TP53 activity during DNA damage
  • role for AURKA in epithelial ovarian cancer (EOC) dissemination by regulating migration and adhesion
  • controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis
  • regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner
  • is required for tumor formation
  • AURKA solely functions as a recruitment factor for the TACC3-CKAP5 complex to centrosomes and proximal mitotic spindles
  • centrosome-localized serine/threonine kinase, which plays a critical role in mitotic and meiotic cell division processes
  • promotes the establishment of spindle assembly checkpoint by priming the HASPIN-AURKB feedback loop in late G2 phase
  • control mechanism of microtubule nucleation by AURKA during assembly of the central spindle
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a novel regulatory network composed of RASSF5, the mitotic kinase Aurora A, the small GTPase KRAS, and the microtubule cytoskeleton
  • TPX2/AURKA heterodimer, nominally considered a mitotic kinase complex, is a novel binding partner of TP53BP1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • protein phosphatase 1,PP1 and cell division cycle 20 homolog (S. cerevisiae), CDC20
  • protein phosphatase 1, PP1
  • TP53
  • target of TPX2 to spindle microtubules
  • Aurora-A kinase interacting protein, AIP
  • a putative tumor and metastasis suppressor, NM23-H1
  • ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast), UBE2N
  • transforming, acidic coiled-coil containing protein 1, TACC1 and cytoskeleton associated protein 5, CKAP5
  • breast cancer 1 early onset, BRCA1 (Ouchi et al, 2004)
  • phosphorylates cell division cycle 25 homolog B (S. pombe), CDC25B
  • transforming, acidic coiled-coil containing protein 3, TACC3; baculoviral IAP repeat-containing 5 , survivin; NDC80 homolog, kinetochore complex component (S. cerevisiae), Hec1; and NUF2, NDC80 kinetochore complex component, homolog (S. cerevisiae), Nuf2
  • JUB in mitotic cells
  • regulating MAP9 (phosphorylation MAP9 on Serine 625 by AURKA is required for bipolar spindle assembly and is essential for a correct mitotic progression)
  • direct target of the MAPK pathway and that its overexpression in pancreatic cancer is induced by hyperactivation of the pathway, at least via ETS2
  • SPAG5
  • TPX2 binding with AURKA decreases the size and accessibility of a hydrophobic pocket, adjacent to the ATP site, to inhibitors
  • prometastatic scaffolding protein HEF1/Cas-L/NEDD9 at the basal body of cilia that causes phosphorylation and activation of HDAC6, a tubulin deacetylase, promoting ciliary disassembly
  • BORA/AURKA-dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint-dependent arrest
  • glycogen synthase kinase 3 beta, GSK3B
  • overexpression of AURKA may stabilize CCNB1 through inhibiting its degradation
  • KIF2A is regulated positively by PLK1 and negatively by Aurora A
  • interacts directly with the atypical protein kinase C binding domain of PARD3 and phosphorylates it at serine 962, phosphorylation that contributes to its function in the establishment of neuronal polarity)
  • RASSF1 is a substrate of AURKA
  • interacting with CEP192 (is a cofactor in centrosome-driven spindle assembly)
  • interaction with TPX2 (central role of TPX2 in regulation of Aurora-A)
  • direct downstream target of SMARCB1-mediated repression in rhabdoid tumor cells
  • SKI is a novel target of AURKA and contribute to an understanding of the role of these proteins in the mitotic process
  • binds, phosphorylates, and reduces the activity of PKD2, a Ca(2+)-permeable nonselective cation channel and, thus, limits the amplitude of Ca(2+) release from the endoplasmic reticulum
  • AURKA, specifically binds to and phosphorylates HAUS8
  • PHLDA1 is an Aurora A substrate (AURKA directly phosphorylates PHLDA1 leading to its degradation, and PHLDA1 also negatively regulates Aurora A, thereby triggering a feedback loop)
  • AURKA acts as a substrate of LIMK1, and the function of LIMK1 is important for its specific localization and regulation of spindle morphology
  • physical interaction between AURKA and IQGAP1, through its RGCt domain
  • LIMK2 is a novel AURKA substrate (AURKA regulates LIMK2 kinase activity, subcellular localization and protein levels by direct phosphorylation at S283, T494 and T505)
  • FRY binds to PLK1 and AURKA and promotes AURKA-mediated PLK1 activation
  • one important function of AURKA in mitotic cells is to promote MT nucleation around the chromatin by phosphorylating NEDD1, and thereby to promote functional spindle assembly
  • is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of DCTN1
  • DLGAP5 is a substrate of AURKA, which plays a crucial role in the stabilization of kinetochore fibers
  • UBXN2B/NSFL1C adaptors of VCP regulate mitosis by limiting the centrosomal recruitment of AURKA
  • TACC3 is an AURKA substrate essential in central spindle formation
  • BCL2L11 is regulated during mitosis by the AURKA and protein phosphatase 2A (PPP2CA)
  • PIN1 acts as a negative regulator of the G2/M transition by interacting with the AURKA-BORA complex
  • BRCA1 downregulates the kinase activity of PLK1 by modulating the dynamic interactions of AURKA, BORA, and PLK1
  • INVS, NPHP1 can interfere with ciliary disassembly through interaction with the AURKA module, thereby modulating cell cycle control and cell proliferation
  • STMN1 regulates mitotic entry, partially via MTs, to control localization and activation of both AURKA and PLK1
  • PreLIM domain of AJUBA, an important activator of AURKA, induces the autophosphorylation of the C-terminal kinase domain of AURKA, and is phosphorylated by the C-terminal domain of AURKA
  • CTNNB1 links VHL to AURKA and loss of primary cilia in renal cell carcinoma
  • AURKA-mediated phosphorylation was required for the spindle localization of WDR62 during mitosis
  • FBN1, acts at the downstream of AURKA and BRCA2, promotes ovarian cancer metastasis through the TP53 and SNAI2-associated signaling
  • NAXE functions as a negative regulator to block phosphorylation of NIN mediated by AURKA and PLK1
  • dual molecular mechanism by which the CHEK2-BRCA1 axis restrains oncogenic AURKA activity during mitosis and BRCA1 itself is a target for AURKA relevant for chromosomal instability (CIN)
  • nuclear-accumulated AURKA phosphorylates HASPIN at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex
  • TPX2/AURKA plays a previously unrecognized role in DNA damage repair and replication fork stability by counteracting TP53BP1 function
  • AURKA, phosphorylates DLGAP5 and NEDD1 during assembly of the initial bipolar spindle
  • well-characterised function of TPX2 is the activation, stabilisation and spindle localisation of AURKA
  • cell & other
  • centrosome associated
  • REGULATION
    activated by JUB in mitotic commitment
    TPX2
    chromosome 13 open reading frame 34, C13orf34
    CALM1 (calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis)
    induced by positively regulated by E4TF1 (GABPA, GABPB1, GABPB2
    BCR-ABL inducing expression of AURKA and AURKB at least in part via AKT1
    repressed by CDH1
    SMARCB1 that represses Aurora A transcription in a cell-type-specific manner
    Other regulated by CHFR
    transcriptionally regulated by E2F3 during the cell cycle and that E2F3 is a causal factor for up-regulation of Aurora-A in a subset of ovarian cancer
    down-regulated by Aurora-A kinase interacting protein, AIP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in breast, ovarian, colon, prostate, neuroblastoma and cervical cancer cell lines
    tumoral     --over  
    in breast, ovarian with poor prognosis, colon, prostate, neuroblastoma and cervical cancer cell lines
    tumoral       loss of function
    causes an increased tumor incidence
    constitutional       gain of function
    abnormally expressed and activated in cells lining PKD-associated renal cysts
    constitutional   deletion    
  • in the developing epidermis alters centrosome function of basal keratinocytes and markedly impairs their ability to divide and stratify
  • tumoral     --over  
    simultaneous overexpression of AURKA and CFL1 correlated with lymph node metastasis in thyroid cancer tissue
    Susceptibility to lung cancer
    Variant & Polymorphism other associations between polymorphisms and lung cancer risk
    Candidate gene
  • skin tumor susceptibility gene
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    Aurora kinase inhibitors are currently in clinical trials for cancer treatment
    cancer  
    E2F3-Aurora-A axis could be an important target for cancer intervention
    cancermuscle 
    targeting expression or activity of this gene is a novel therapeutic strategy for rhabdoid tumors
    tumorkidneypolycystic kidney
    may be a relevant new biomarker or target in the therapy of PKD
    cancerskin 
    therapeutic elimination of Aurora-A prevents the progression of skin and mammary gland tumors
    cancerendocrinethyroid
    possibility of targeting AURKA and CFL1 for more effective treatment of thyroid cancer
    cancerdigestivepancreas
    AURKA and TPX2 may serve as promising targets to be explored for KRAS-mutant PDAC therapy
    ANIMAL & CELL MODELS