Details for: SPAG5

Gene ID: 10615

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SPAG5

Ensembl ID: ENSG00000076382

Description: sperm associated antigen 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural crest cell CL0011012
    CSI 4.71
    rCSI 3.72%
    PRS 98.28
  • neural progenitor cell CL0011020
    CSI 3.85
    rCSI 16.96%
    PRS 94.32
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.16
    rCSI 3.64%
    PRS 96.99
  • transit amplifying cell of colon CL0009011
    CSI 3.01
    rCSI 3.54%
    PRS 99.27
  • ependymal cell CL0000065
    CSI 2.54
    rCSI 5.16%
    PRS 93.33
  • promyelocyte CL0000836
    CSI 2.37
    rCSI 3.43%
    PRS 98.99
  • promonocyte CL0000559
    CSI 2.27
    rCSI 3.9%
    PRS 99.36
  • large pre-B-II cell CL0000957
    CSI 1.46
    rCSI 4.17%
    PRS 98.37

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SPAG5](/details-gene/10615) (Sperm Associated Antigen 5) is a protein-coding gene located on chromosome 17q11.2. The encoded protein, also known as astrin, is a crucial component of the mitotic apparatus. Functional annotations strongly link [SPAG5](/details-gene/10615) to the regulation of cell division, particularly in the organization and function of the mitotic spindle. Its expression profile reveals high significance in a variety of highly proliferative cell populations, including neural progenitors and hematopoietic precursors, underscoring its fundamental role in cell cycle progression and tissue development. Several studies have identified it as a key mitotic-spindle-associated protein essential for progression through mitosis ([Link](https://doi.org/10.1073/pnas.261371298), [Link](https://doi.org/10.1242/jcs.00088)). ## Cellular Roles and Expression Landscape The expression pattern of [SPAG5](/details-gene/10615) highlights its role as a key regulator in actively dividing cells. **Overall**, the gene shows the highest significance in progenitor and precursor cell populations across different lineages. It is a top marker in cells of the developing nervous system, including [neural crest cell](/details-cell/CL0011012) (CSI: 4.71), [neural progenitor cell](/details-cell/CL0011020) (CSI: 3.85), and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 3.16). This suggests a critical function in neurogenesis. Beyond the nervous system, [SPAG5](/details-gene/10615) is also significantly expressed in other rapidly amplifying populations, such as [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 3.01). Furthermore, its high significance in hematopoietic precursors like [promyelocyte](/details-cell/CL0000836) (CSI: 2.37), [promonocyte](/details-cell/CL0000559) (CSI: 2.27), and [large pre-B-II cell](/details-cell/CL0000957) (CSI: 1.46) indicates a broad, essential role in maintaining progenitor pools during hematopoiesis. The collective expression data robustly position [SPAG5](/details-gene/10615) as a marker of cellular proliferation rather than a lineage-defining marker for a specific terminally differentiated cell type. ## Pathways and Molecular Function The molecular functions of [SPAG5](/details-gene/10615) are tightly centered on the mechanics of mitosis, consistent with its cellular expression profile. It is centrally involved in the biological process of '[Cell division](/details-gene/GO:0051301)' and, more specifically, '[Mitotic sister chromatid segregation](/details-gene/GO:0000070)'. This role is facilitated by its molecular function as a '[Microtubule binding](/details-gene/GO:0008017)' protein. [SPAG5](/details-gene/10615) is integral to the structural integrity and function of the mitotic machinery. It is a known component of the '[Mitotic spindle](/details-gene/GO:0072686)', localizing to the '[Mitotic spindle pole](/details-gene/GO:0097431)', '[Kinetochore](/details-gene/GO:0000776)', and '[Midbody](/details-gene/GO:0030496)'. Its functions include crucial regulatory steps such as '[Positive regulation of spindle assembly](/details-gene/GO:1905832)', '[Regulation of attachment of spindle microtubules to kinetochore](/details-gene/GO:0051988)', and '[Establishment of spindle orientation](/details-gene/GO:0051294)'. Research has confirmed that [SPAG5](/details-gene/10615) is essential for maintaining sister chromatid cohesion and centrosome integrity, further cementing its role as a master regulator of mitotic fidelity ([Link](https://doi.org/10.1083/jcb.200701163)). ## Research Directions Given that [SPAG5](/details-gene/10615) is a fundamental component of the cell division machinery, its dysregulation is a plausible driver of diseases characterized by aberrant proliferation, such as cancer. Its high expression in progenitor cells also suggests a potential role in developmental disorders if its function is compromised. **Testable Hypotheses:** 1. **Role in Oncogenesis:** Overexpression of [SPAG5](/details-gene/10615) in somatic cells could disrupt the precise regulation of chromosome segregation, leading to aneuploidy—a hallmark of many cancers. This suggests that [SPAG5](/details-gene/10615) may act as a proto-oncogene by promoting genomic instability and conferring a proliferative advantage. 2. **Role in Neurodevelopmental Disorders:** Since [SPAG5](/details-gene/10615) is highly significant in [neural progenitor cells](/details-cell/CL0011020), loss-of-function mutations or haploinsufficiency may impair their ability to divide symmetrically. This could lead to a depleted progenitor pool and result in congenital disorders such as microcephaly. **Proposed Experiment:** To test the hypothesis that [SPAG5](/details-gene/10615) overexpression drives aneuploidy, one could transfect a non-transformed, chromosomally stable human cell line (e.g., RPE-1) with a vector for constitutive [SPAG5](/details-gene/10615) expression. Control cells would be transfected with an empty vector. The resulting cell populations could be analyzed using live-cell imaging with fluorescently labeled tubulin and histones to quantify mitotic errors like lagging chromosomes, anaphase bridges, or cytokinesis failure. Subsequent metaphase spreads and spectral karyotyping (SKY) or single-cell whole-genome sequencing would provide a direct measure of the rate and type of aneuploidy induced by [SPAG5](/details-gene/10615) overexpression. **Therapeutic Potential:** As a protein essential for mitosis, [SPAG5](/details-gene/10615) represents a promising target for anti-cancer therapeutics. Its inhibition would be expected to induce mitotic arrest and subsequent apoptosis in rapidly dividing cancer cells. Because it is an intracellular protein involved in protein-protein interactions within the spindle apparatus, it would be most amenable to targeting with small molecule inhibitors rather than biologics like antibodies. A key challenge for this strategy would be achieving a therapeutic window that selectively affects cancer cells over healthy, highly proliferative cells, such as hematopoietic stem cells and gut epithelial cells, to minimize off-target toxicity.

Genular Protein ID: 368267247

Symbol: SPAG5_HUMAN

Name: Sperm-associated antigen 5

UniProtKB Accession Codes:

Q96R06 O95213 Q9BWE8 Q9NT17 Q9UFE6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 22 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 3 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 UniProtKB 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11724960

Title: Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein.

PubMed ID: 11724960

DOI: 10.1073/pnas.261371298

PubMed ID: 11549262

Title: Cloning and characterization of hMAP126, a new member of mitotic spindle-associated proteins.

PubMed ID: 11549262

DOI: 10.1006/bbrc.2001.5554

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 12356910

Title: The mitotic-spindle-associated protein astrin is essential for progression through mitosis.

PubMed ID: 12356910

DOI: 10.1242/jcs.00088

PubMed ID: 16964243

Title: A probability-based approach for high-throughput protein phosphorylation analysis and site localization.

PubMed ID: 16964243

DOI: 10.1038/nbt1240

PubMed ID: 17664331

Title: Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity.

PubMed ID: 17664331

DOI: 10.1083/jcb.200701163

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 18361916

Title: Astrin regulates Aurora-A localization.

PubMed ID: 18361916

DOI: 10.1016/j.bbrc.2008.03.072

PubMed ID: 18055457

Title: Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin.

PubMed ID: 18055457

DOI: 10.1074/jbc.m706794200

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19197158

Title: SNM1B/Apollo interacts with astrin and is required for the prophase cell cycle checkpoint.

PubMed ID: 19197158

DOI: 10.4161/cc.8.4.7791

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21402792

Title: The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment.

PubMed ID: 21402792

DOI: 10.1083/jcb.201008023

PubMed ID: 22965910

Title: Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation.

PubMed ID: 22965910

DOI: 10.1083/jcb.201202112

PubMed ID: 23953116

Title: Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells.

PubMed ID: 23953116

DOI: 10.1016/j.cell.2013.07.031

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24424245

Title: OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle.

PubMed ID: 24424245

DOI: 10.1016/j.yexcr.2014.01.002

PubMed ID: 26297806

Title: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.

PubMed ID: 26297806

DOI: 10.7554/elife.07519

PubMed ID: 27462074

Title: Nuclear mitotic apparatus (NuMA) interacts with and regulates astrin at the mitotic spindle.

PubMed ID: 27462074

DOI: 10.1074/jbc.m116.724831

Sequence Information:

  • Length: 1193
  • Mass: 134422
  • Checksum: A846DB3FE624519C
  • Sequence:
    • MWRVKKLSLS LSPSPQTGKP SMRTPLRELT LQPGALTNSG KRSPACSSLT PSLCKLGLQE 
GSNNSSPVDF VNNKRTDLSS EHFSHSSKWL ETCQHESDEQ PLDPIPQISS TPKTSEEAVD 
PLGNYMVKTI VLVPSPLGQQ QDMIFEARLD TMAETNSISL NGPLRTDDLV REEVAPCMGD 
RFSEVAAVSE KPIFQESPSH LLEESPPNPC SEQLHCSKES LSSRTEAVRE DLVPSESNAF 
LPSSVLWLSP STALAADFRV NHVDPEEEIV EHGAMEEREM RFPTHPKESE TEDQALVSSV 
EDILSTCLTP NLVEMESQEA PGPAVEDVGR ILGSDTESWM SPLAWLEKGV NTSVMLENLR 
QSLSLPSMLR DAAIGTTPFS TCSVGTWFTP SAPQEKSTNT SQTGLVGTKH STSETEQLLC 
GRPPDLTALS RHDLEDNLLS SLVILEVLSR QLRDWKSQLA VPHPETQDSS TQTDTSHSGI 
TNKLQHLKES HEMGQALQQA RNVMQSWVLI SKELISLLHL SLLHLEEDKT TVSQESRRAE 
TLVCCCFDLL KKLRAKLQSL KAEREEARHR EEMALRGKDA AEIVLEAFCA HASQRISQLE 
QDLASMREFR GLLKDAQTQL VGLHAKQEEL VQQTVSLTST LQQDWRSMQL DYTTWTALLS 
RSRQLTEKLT VKSQQALQER DVAIEEKQEV SRVLEQVSAQ LEECKGQTEQ LELENSRLAT 
DLRAQLQILA NMDSQLKELQ SQHTHCAQDL AMKDELLCQL TQSNEEQAAQ WQKEEMALKH 
MQAELQQQQA VLAKEVRDLK ETLEFADQEN QVAHLELGQV ECQLKTTLEV LRERSLQCEN 
LKDTVENLTA KLASTIADNQ EQDLEKTRQY SQKLGLLTEQ LQSLTLFLQT KLKEKTEQET 
LLLSTACPPT QEHPLPNDRT FLGSILTAVA DEEPESTPVP LLGSDKSAFT RVASMVSLQP 
AETPGMEESL AEMSIMTTEL QSLCSLLQES KEEAIRTLQR KICELQARLQ AQEEQHQEVQ 
KAKEADIEKL NQALCLRYKN EKELQEVIQQ QNEKILEQID KSGELISLRE EVTHLTRSLR 
RAETETKVLQ EALAGQLDSN CQPMATNWIQ EKVWLSQEVD KLRVMFLEMK NEKEKLMIKF 
QSHRNILEEN LRRSDKELEK LDDIVQHIYK TLLSIPEVVR GCKELQGLLE FLS