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GSG2 Gene

protein-coding   GIFtS: 56
GCID: GC17P003627

Germ Cell Associated 2 (Haspin)

  See GSG2-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Germ Cell Associated 2 (Haspin)1 2     HASPIN2
Germ Cell-Specific Gene 2 Protein2 3     Serine/Threonine-Protein Kinase Haspin2
Haploid Germ Cell-Specific Nuclear Protein Kinase2 3     EC 2.7.11.13
H-haspin2 3     

External Ids:    HGNC: 196821   Entrez Gene: 839032   Ensembl: ENSG000001776027   OMIM: 6092405   UniProtKB: Q8TF763   

Export aliases for GSG2 gene to outside databases

Previous GC identifers: GC17P003939 GC17P003578 GC17P003833 GC17P003573 GC17P003517


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for GSG2 Gene:
GSG2 (germ cell associated 2 (haspin)) is a protein-coding gene. Diseases associated with GSG2 include rhinotracheitis. GO annotations related to this gene include protein kinase activity and histone kinase activity (H3-T3 specific).

UniProtKB/Swiss-Prot: HASP_HUMAN, Q8TF76
Function: Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This
positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to
ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle

Gene Wiki entry for GSG2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NC_018928.2  NT_010718.17  
Regulatory elements:
   Search for regulatory transcription factor binding sites for GSG2
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGSG2 promoter sequence
   Search Chromatin IP Primers for GSG2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GSG2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17p13   Ensembl cytogenetic band:  17p13.2   HGNC cytogenetic band: 17p13

GSG2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GSG2 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P003627:  view genomic region     (about GC identifiers)

Start:
3,627,197 bp from pter      End:
3,630,067 bp from pter
Size:
2,871 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: HASP_HUMAN, Q8TF76 (See protein sequence)
Recommended Name: Serine/threonine-protein kinase haspin  
Size: 798 amino acids; 88495 Da
Cofactor: Magnesium
Selected PDB 3D structures from and Proteopedia for GSG2 (see all 7):
2VUW (3D)        2WB8 (3D)        3DLZ (3D)        3E7V (3D)        3F2N (3D)        3FMD (3D)    
Secondary accessions: Q5U5K3 Q96MN1 Q9BXS7
Alternative splicing: 2 isoforms:  Q8TF76-1   Q8TF76-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for GSG2: NX_Q8TF76

Explore proteomics data for GSG2 at MOPED

Post-translational modifications: 

  • Autophosphorylated on both serine and threonine residues (By similarity). Strongly phosphorylated during mitosis
    but this does not appear to significantly affect its intrinsic kinase activity. Phosphorylation by AURKB is
    required for full activity toward histone H3 at 'Ser-3' in mitosis1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See GSG2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_114171.2  
    ENSEMBL proteins: 
     ENSP00000325290  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: germ cell associated 2 (haspin)
    Haspin family

    4 InterPro protein domains:
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR024604 DUF3635
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry Q8TF76

    ProtoNet protein and cluster: Q8TF76

    UniProtKB/Swiss-Prot: HASP_HUMAN, Q8TF76
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Haspin subfamily
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with GSG2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HASP_HUMAN, Q8TF76
    Function: Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This
    positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to
    ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Constitutive activity that does not require phosphorylation. Specifically inhibited by
    3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494)

         Enzyme Number (IUBMB): EC 2.7.11.11

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding IEA--
    GO:0004672protein kinase activity IDA11228240
    GO:0004674protein serine/threonine kinase activity ----
    GO:0005515protein binding IPI--
    GO:0005524ATP binding IDA11228240
         
    Find genes that share ontologies with GSG2           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for GSG2:
     Synthetic lethal with Ras 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for GSG2
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    miRNA
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    miRTarBase miRNAs that target GSG2:
    hsa-mir-192-5p (MIRT026264), hsa-mir-215-5p (MIRT024259), hsa-mir-1301-3p (MIRT036050), hsa-mir-93-3p (MIRT038720), hsa-mir-193b-3p (MIRT016277)

    Block miRNA regulation of human, mouse, rat GSG2 using miScript Target Protectors
    4 qRT-PCR Assays for microRNAs that regulate GSG2:
    hsa-miR-4261 hsa-miR-491-5p hsa-miR-3065-5p hsa-miR-578
    SwitchGear 3'UTR luciferase reporter plasmidGSG2 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HASP_HUMAN, Q8TF76: Nucleus. Chromosome. Cytoplasm, cytoskeleton, spindle. Note=Nuclear during interphase and
    associates with the chromosomes and spindle apparatus during mitosis
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    nucleus5
    cytosol3
    plasma membrane3
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA11228240
    GO:0005694chromosome IEA--
    GO:0005737cytoplasm IEA--
    GO:0005813centrosome IDA11228240
    GO:0005819spindle IDA15681610

    Find genes that share ontologies with GSG2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for GSG2
    Interactions:

        Search GeneGlobe Interaction Network for GSG2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 8)

    Selected Interacting proteins for GSG2 (Q8TF761, 2, 3 ENSP000003252904) via UniProtKB, MINT, STRING, and/or I2D (see all 19)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H3AP684313, ENSP000003502754I2D: score=1 STRING: ENSP00000350275
    HIST1H3BP684313I2D: score=1 
    HIST1H3CP684313I2D: score=1 
    HIST1H3DP684313I2D: score=1 
    HIST1H3EP684313I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation IDA11228240
    GO:0007064mitotic sister chromatid cohesion IMP--
    GO:0035556intracellular signal transduction IDA11228240
    GO:0071459protein localization to chromosome, centromeric region IMP--
    GO:0090231regulation of spindle checkpoint IMP--

    Find genes that share ontologies with GSG2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for GSG2 (HASP)

    1 HMDB Compound for GSG2    About this table
    CompoundSynonyms CAS #PubMed Ids
    MagnesiumMagnesium (see all 2)7439-95-4--

    4 DrugBank Compounds for GSG2    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    (2S)-2-{[3-(3-aminophenyl)imidazo[1,2-b]pyridazin-6-yl]amino}-3-methylbutan-1-ol-- --target--10592235
    3-(3-aminophenyl)-N-(3-chlorophenyl)pyrazolo[1,5-a]pyrimidin-5-amine-- --target--10592235
    5-iodotubercidin-- 24386-93-4target--10592235
    N-[2-(4-BROMOCINNAMYLAMINO)ETHYL]-5-ISOQUINOLINE SULFONAMIDE-- --target--10592235



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for GSG2 gene: 
    NM_031965.2  

    Unigene Cluster for GSG2:

    Germ cell associated 2 (haspin)
    Hs.534059  [show with all ESTs]
    Unigene Representative Sequence: AK292715
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000325418(uc002fwp.3)
    miRNA
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    hsa-miR-4261 hsa-miR-491-5p hsa-miR-3065-5p hsa-miR-578
    SwitchGear 3'UTR luciferase reporter plasmidGSG2 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AB039834.3 AF289865.1 AK292715.1 AK310546.1 AK315247.1 BC016626.1 BC036181.1 BC047457.1 

    3 DOTS entries:

    DT.40272358  DT.95270360  DT.100735073 

    Selected AceView cDNA sequences (see all 29):

    BM458397 BM013960 BC036181 CR615999 AK056691 BC047457 AL530642 AF289865 
    BX103601 BC016626 NM_031965 AB039834 BM838281 AL530641 BG025225 AA504563 
    BG390073 BI562569 AA504486 BI562471 AW405732 BM152111 AA765234 AW752339 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GSG2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAGCAAAAAA
    GSG2 Expression
    About this image


    GSG2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Liver (Hepatobiliary System)
             Mesothelial Cells Hepatic Mesenchyme
    GSG2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GSG2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.534059

    UniProtKB/Swiss-Prot: HASP_HUMAN, Q8TF76
    Tissue specificity: Strongly expressed in testis. Also present in thymus and bone marrow and low levels observed
    in prostate, intestine, lung, spleen and lymph node. Expressed in fetal skin, liver, kidney and small intestine
    and also in proliferating but not non-proliferating cell lines

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for GSG2 gene from Selected species (see all 10)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gsg21 , 5 germ cell-specific gene 21, 5 74.64(n)1
    64.44(a)1
      11 (45.25 cM)5
    148411  NM_010353.21  NP_034483.11 
     731354855 
    zebrafish
    (Danio rerio)
    Actinopterygii GSG26
    germ cell associated 2 (haspin)
    23(a)
    1 ↔ 1
    1(22263363-22280628) ENSDARG00000092290
    fruit fly
    (Drosophila melanogaster)
    Insecta Haspin3 protein serine/threonine kinase 40(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea F22H10.53   -- 37(a)   X(16717006-16717976)   --


    ENSEMBL Gene Tree for GSG2 (if available)
    TreeFam Gene Tree for GSG2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    10 SNPs for GSG2    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs562243011,2,4
    ----see VAR_0405432 mis40--------
    rs72232261,2,4
    ----see VAR_0274082 mis40--------
    rs561346951,2,4
    ----see VAR_0405452 mis40--------
    rs556494771,2,4
    ----see VAR_0405442 mis40--------
    rs2204621,2,4
    ----see VAR_0274052 mis40--------
    rs38098061,2,4
    ----see VAR_0274072 mis40--------
    rs116538891,2,4
    ----see VAR_0405402 mis40--------
    rs99071441,2,4
    ----see VAR_0405412 mis40--------
    rs2204611,2,4
    ----see VAR_0274062 mis40--------
    rs559919031,2,4
    ----see VAR_0405422 mis40--------

    HapMap Linkage Disequilibrium report for GSG2 (3627197 - 3630067 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for GSG2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833342CNV Loss17160897
    nsv907570CNV Gain21882294
    nsv469791CNV Complex16826518

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing GSG2
    DNA2.0 Custom Variant and Variant Library Synthesis for GSG2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 609240    OMIM disorders: --

    1 disease for GSG2:    
    About MalaCards
    rhinotracheitis

    1 disease from the University of Copenhagen DISEASES database for GSG2:
    Rhinotracheitis

    Find genes that share disorders with GSG2           About GenesLikeMe

    Human Genome Epidemiology (HuGE) Navigator: GSG2 (1 document)

    Export disorders for GSG2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GSG2 gene, integrated from 10 sources (see all 34):
    (articles sorted by number of sources associating them with GSG2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning and characterization of human haspin gene encoding haploid germ cell-specific nuclear protein kinase. (PubMed id 11228240)1, 2, 9 Tanaka H....Nishimune Y. (Mol. Hum. Reprod. 2001)
    2. Regulation of mitotic chromosome cohesion by Haspin and Aurora B. (PubMed id 17084365)1, 2, 9 Dai J.... Higgins J.M. (Dev. Cell 2006)
    3. The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. (PubMed id 15681610)1, 2, 9 Dai J.... Higgins J.M.G. (Genes Dev. 2005)
    4. The Haspin gene: location in an intron of the Integrin Alpha-E gene, associated transcription of an Integrin alpha-E-derived RNA and expression in diploid as well as haploid cells. (PubMed id 11311556)1, 2, 9 Higgins J.M.G. (Gene 2001)
    5. A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. (PubMed id 21658950)1, 2 Wang F....Higgins J.M. (Curr. Biol. 2011)
    6. Two histone marks establish the inner centromere and chromosome bi- orientation. (PubMed id 20929775)1, 2 Yamagishi Y.... Watanabe Y. (Science 2010)
    7. Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. (PubMed id 20705812)1, 2 Wang F.... Higgins J.M. (Science 2010)
    8. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    9. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    10. Haspin: a newly discovered regulator of mitotic chromosome behavior. (PubMed id 19997740)1, 9 Higgins J.M. (Chromosoma 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 83903 HGNC: 19682 AceView: GSG2 Ensembl:ENSG00000177602 euGenes: HUgn83903
    ECgene: GSG2 H-InvDB: GSG2

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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for GSG2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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