SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000456 
UniProt Accession
Theoretical PI
8.96  
Molecular Weight
35591 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
AURKC 
Gene Synonyms/Alias
AIE2, AIK3, AIRK3, ARK3, STK13 
Protein Name
Aurora kinase C 
Protein Synonyms/Alias
EC=2.7.11.1 Aurora 3; Aurora/IPL1-related kinase 3;ARK-3Aurora-related kinase 3 Aurora/IPL1/Eg2 protein 2; Serine/threonine-protein kinase 13; Serine/threonine-protein kinase aurora-C; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:19;57742377-57746915;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
The absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa. A functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis 
The information of related literatures
1. K. Dieterich, R. Soto Rifo, A. K. Faure, S. Hennebicq, B. Ben Amar, M. Zahi, J. Perrin, D. Martinez, B. Sele, P. S. Jouk, T. Ohlmann, S. Rousseaux, J. Lunardi and P. F. Ray (2007) Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 39(5): 661-5. 

Abstract
The World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa. PMID: [17435757] 

2. K. Dieterich, R. Zouari, R. Harbuz, F. Vialard, D. Martinez, H. Bellayou, N. Prisant, A. Zoghmar, M. R. Guichaoua, I. Koscinski, M. Kharouf, M. Noruzinia, S. Nadifi, A. Sefiani, J. Lornage, M. Zahi, S. Viville, B. Sele, P. S. Jouk, M. C. Jacob, D. Escalier, Y. Nikas, S. Hennebicq, J. Lunardi and P. F. Ray (2009) The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet 18(7): 1301-9. 

Abstract
Infertility concerns a minimum of 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. In a previous study, we demonstrated that a homozygous mutation (c.144delC) in the Aurora Kinase C (AURKC) gene led to the production of large-headed polyploid multi-flagellar spermatozoa, a primary infertility phenotype mainly observed in North Africans. We now want to estimate the prevalence of the defect, to improve our understanding of AURKC physiopathology in spermatogenesis and assess its implication in oogenesis. A carrier frequency of 1/50 was established from individuals from the Maghrebian general population, comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. A total of 62 patients were genotyped, all who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n = 32), whereas no AURKC mutations were detected in the others. Two homozygous females were identified; both were fertile indicating that AURKC is not indispensible in oogenesis. Previous FISH results had showed a great chromosomal heterogeneity in these patient's spermatozoa. We demonstrate here by flow cytometry that all spermatozoa have in fact a homogeneous 4C DNA content and are thus all blocked before the first meiotic division. Our data thus indicate that a functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis. PMID: [19147683] 

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Figures for illustrating the function of this protein/gene
Ref: K. Dieterich, R. Soto Rifo, A. K. Faure, S. Hennebicq, B. Ben Amar, M. Zahi, J. Perrin, D. Martinez, B. Sele, P. S. Jouk, T. Ohlmann, S. Rousseaux, J. Lunardi and P. F. Ray (2007) Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 39(5): 661-5. PMID: [17435757]
Ref: K. Dieterich, R. Zouari, R. Harbuz, F. Vialard, D. Martinez, H. Bellayou, N. Prisant, A. Zoghmar, M. R. Guichaoua, I. Koscinski, M. Kharouf, M. Noruzinia, S. Nadifi, A. Sefiani, J. Lornage, M. Zahi, S. Viville, B. Sele, P. S. Jouk, M. C. Jacob, D. Escalier, Y. Nikas, S. Hennebicq, J. Lunardi and P. F. Ray (2009) The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet 18(7): 1301-9. PMID: [19147683]
Ref: K. Dieterich, R. Zouari, R. Harbuz, F. Vialard, D. Martinez, H. Bellayou, N. Prisant, A. Zoghmar, M. R. Guichaoua, I. Koscinski, M. Kharouf, M. Noruzinia, S. Nadifi, A. Sefiani, J. Lornage, M. Zahi, S. Viville, B. Sele, P. S. Jouk, M. C. Jacob, D. Escalier, Y. Nikas, S. Hennebicq, J. Lunardi and P. F. Ray (2009) The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet 18(7): 1301-9. PMID: [19147683]
Function
Serine/threonine-protein kinase component of thechromosomal passenger complex (CPC), a complex that acts as a keyregulator of mitosis. The CPC complex has essential functions atthe centromere in ensuring correct chromosome alignment andsegregation and is required for chromatin-induced microtubulestabilization and spindle assembly. Plays also a role in meiosisand more particularly in spermatogenesis. Has redundant cellularfunctions with AURKB and can rescue an AURKB knockdown. LikeAURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'.Phosphorylates TACC1, another protein involved in cell division,at 'Ser-228'. 
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Subcellular Location
Nucleus. Chromosome. Chromosome, centromere.Cytoplasm, cytoskeleton, spindle. Note=Distributes in thecondensed chromosomes during prophase to metaphase. After enteringanaphase, there is a dissociation from separated chromosomes and aredistribution to midzone microtubules, and finally remains in themidbody during cytokinesis. 
Tissue Specificity
Isoform 1 and isoform 2 are expressed intestis. Elevated expression levels were seen only in a subset ofcancer cell lines such as Hep-G2, Huh-7 and HeLa. Expression ismaximum at M phase. 
Gene Ontology
GO IDGO termEvidence
GO:0032133 C:chromosome passenger complex TAS:UniProtKB.
GO:0000775 C:chromosome, centromeric region IEA:UniProtKB-SubCell.
GO:0000793 C:condensed chromosome IDA:UniProtKB.
GO:0005737 C:cytoplasm IEA:UniProtKB-KW.
GO:0030496 C:midbody IDA:UniProtKB.
GO:0005634 C:nucleus IEA:UniProtKB-SubCell.
GO:0051233 C:spindle midzone IDA:UniProtKB.
GO:0005524 F:ATP binding IEA:UniProtKB-KW.
GO:0004674 F:protein serine/threonine kinase activity IEA:UniProtKB-KW.
GO:0004712 F:protein serine/threonine/tyrosine kinase activity TAS:UniProtKB.
GO:0008608 P:attachment of spindle microtubules to kinetochore TAS:UniProtKB.
GO:0000910 P:cytokinesis TAS:ProtInc.
GO:0016570 P:histone modification TAS:UniProtKB.
GO:0007126 P:meiosis IEA:UniProtKB-KW.
GO:0071777 P:positive regulation of cell cycle cytokinesis TAS:UniProtKB.
GO:0051256 P:spindle midzone assembly involved in mitosis TAS:UniProtKB.
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Interpro
IPR011009;    Kinase-like_dom.
IPR000719;    Prot_kinase_cat_dom.
IPR017441;    Protein_kinase_ATP_BS.
IPR002290;    Ser/Thr_dual-sp_kinase_dom.
IPR008271;    Ser/Thr_kinase_AS.
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Pfam
PF00069;    Pkinase;    1.
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SMART
SM00220;    S_TKc;    1.
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PROSITE
PS00107;    PROTEIN_KINASE_ATP;    1.
PS50011;    PROTEIN_KINASE_DOM;    1.
PS00108;    PROTEIN_KINASE_ST;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    309       Aurora kinase C.
                             /FTId=PRO_0000085660.
DOMAIN       43    293       Protein kinase.
NP_BIND      49     57       ATP (By similarity).
ACT_SITE    166    166       Proton acceptor (By similarity).
BINDING      72     72       ATP (By similarity).
MOD_RES     198    198       Phosphothreonine; by PKA (By similarity).
VAR_SEQ       1     34       Missing (in isoform 2).
                             /FTId=VSP_004872.
VAR_SEQ       1     20       MSSPRAVVQLGKAQPAGEEL -> M (in isoform 3).
                             /FTId=VSP_041095.
VARIANT      52     52       G -> E (in a lung adenocarcinoma sample;
                             somatic mutation).
                             /FTId=VAR_040385.
VARIANT     148    148       E -> Q (in a lung squamous cell carcinoma
                             sample; somatic mutation).
                             /FTId=VAR_040386.
VARIANT     244    244       H -> Q (in a lung adenocarcinoma sample;
                             somatic mutation).
                             /FTId=VAR_040387.
MUTAGEN      72     72       K->R: Impairs kinase activity.
MUTAGEN     166    166       D->Y: Impairs kinase activity, and keeps
                             AURKC with the chromosomes until the end
                             of mitosis.
MUTAGEN     198    198       T->A: Impairs kinase activity.
CONFLICT    109    109       Y -> H (in Ref. 1; AAC25955).
CONFLICT    150    150       L -> V (in Ref. 2; AAC77369).
CONFLICT    193    195       SLR -> LPE (in Ref. 2; AAC77369).
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Nucleotide Sequence
Length: 1266 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 309 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
TACC2HPRD 
INCENPHPRD 
Other Protein-Protein interaction resources
String database  
View Microarray data
Temporarily unavailable 
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