Stable cohesion between sister chromatids before anaphase and their timely separation during anaphase are critical for chromosome inheritance. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms. The first step involves phosphorylation of STAG1 (MIM 604358) or STAG2 (MIM 300826) in the cohesin complex. The second step involves cleavage of th... See more...

Aliases for ESPL1 Gene

Aliases for ESPL1 Gene

  • Extra Spindle Pole Bodies Like 1, Separase 2 3 5
  • Separin 2 3 4
  • ESP1 2 3 4
  • Extra Spindle Poles-Like 1 Protein 3 4
  • Separin, Cysteine Protease 2 3
  • Caspase-Like Protein ESPL1 3 4
  • Separase 2 4
  • KIAA0165 2 4
  • SEPA 2 3
  • Extra Spindle Pole Bodies Homolog 1 (S. Cerevisiae) 2
  • Extra Spindle Poles Like 1 (S. Cerevisiae) 2
  • Extra Spindle Pole Bodies 1, Separase 3
  • Extra Spindle Pole Bodies Homolog 1 3
  • Extra Spindle Poles Like 1 3
  • EC 3.4.22.49 4
  • ESPL1 5

External Ids for ESPL1 Gene

Previous GeneCards Identifiers for ESPL1 Gene

  • GC12M054021
  • GC12M053817
  • GC12P053378
  • GC12P051948
  • GC12P053662
  • GC12P050703

Summaries for ESPL1 Gene

Entrez Gene Summary for ESPL1 Gene

  • Stable cohesion between sister chromatids before anaphase and their timely separation during anaphase are critical for chromosome inheritance. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms. The first step involves phosphorylation of STAG1 (MIM 604358) or STAG2 (MIM 300826) in the cohesin complex. The second step involves cleavage of the cohesin subunit SCC1 (RAD21; MIM 606462) by ESPL1, or separase, which initiates the final separation of sister chromatids (Sun et al., 2009 [PubMed 19345191]).[supplied by OMIM, Nov 2010]

GeneCards Summary for ESPL1 Gene

ESPL1 (Extra Spindle Pole Bodies Like 1, Separase) is a Protein Coding gene. Diseases associated with ESPL1 include Retinitis Pigmentosa 18 and Cholestasis, Intrahepatic, Of Pregnancy, 1. Among its related pathways are Cell cycle_Spindle assembly and chromosome separation and Human T-cell leukemia virus 1 infection. Gene Ontology (GO) annotations related to this gene include peptidase activity and cysteine-type peptidase activity.

UniProtKB/Swiss-Prot Summary for ESPL1 Gene

  • Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ESPL1 Gene

Genomics for ESPL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ESPL1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ESPL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ESPL1

Top Transcription factor binding sites by QIAGEN in the ESPL1 gene promoter:
  • ATF-2
  • c-Jun
  • PPAR-alpha
  • PPAR-gamma1
  • PPAR-gamma2
  • TBP

Genomic Locations for ESPL1 Gene

Genomic Locations for ESPL1 Gene
chr12:53,268,257-53,293,643
(GRCh38/hg38)
Size:
25,387 bases
Orientation:
Plus strand
chr12:53,662,083-53,687,427
(GRCh37/hg19)
Size:
25,345 bases
Orientation:
Plus strand

Genomic View for ESPL1 Gene

Genes around ESPL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ESPL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ESPL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ESPL1 Gene

Proteins for ESPL1 Gene

  • Protein details for ESPL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14674-ESPL1_HUMAN
    Recommended name:
    Separin
    Protein Accession:
    Q14674

    Protein attributes for ESPL1 Gene

    Size:
    2120 amino acids
    Molecular mass:
    233175 Da
    Quaternary structure:
    • Interacts with PTTG1. Interacts with RAD21.

    Alternative splice isoforms for ESPL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ESPL1 Gene

Post-translational modifications for ESPL1 Gene

  • Autocleaves. This function, which is not essential for its protease activity, is unknown.
  • Phosphorylated by CDK1. There are 8 Ser/Thr phosphorylation sites. Among them, Ser-1126 phosphorylation is the major site, which conducts to the enzyme inactivation.
  • Ubiquitination at Lys64, Lys153, Lys755, Lys760, Lys1336, Lys1803, Lys1832, and Lys2103
  • Modification sites at PhosphoSitePlus

Other Protein References for ESPL1 Gene

No data available for DME Specific Peptides for ESPL1 Gene

Domains & Families for ESPL1 Gene

Gene Families for ESPL1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for ESPL1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ESPL1 Gene

GenScript: Design optimal peptide antigens:
  • Separase (ESPL1_HUMAN)
genes like me logo Genes that share domains with ESPL1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ESPL1 Gene

Function for ESPL1 Gene

Molecular function for ESPL1 Gene

UniProtKB/Swiss-Prot Function:
Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=All bonds known to be hydrolyzed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by a hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage.; EC=3.4.22.49;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Regulated by at least two independent mechanisms. First, it is inactivated via its interaction with securin/PTTG1, which probably covers its active site. The association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent. PTTG1 degradation at anaphase, liberates it and triggers RAD21 cleavage. Second, phosphorylation at Ser-1126 inactivates it. The complete phosphorylation during mitosis, is removed when cells undergo anaphase. Activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin and inhibitory phosphate.

Enzyme Numbers (IUBMB) for ESPL1 Gene

Phenotypes From GWAS Catalog for ESPL1 Gene

Gene Ontology (GO) - Molecular Function for ESPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity NAS 12672959
GO:0004197 cysteine-type endopeptidase activity IBA 21873635
GO:0005515 protein binding IPI 12194817
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity TAS --
genes like me logo Genes that share ontologies with ESPL1: view
genes like me logo Genes that share phenotypes with ESPL1: view

Animal Models for ESPL1 Gene

MGI Knock Outs for ESPL1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ESPL1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ESPL1 Gene

Localization for ESPL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ESPL1 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ESPL1 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 4
plasma membrane 3
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ESPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005634 nucleus IEA,IBA 21873635
GO:0005737 cytoplasm IBA 21873635
GO:0005813 centrosome IBA,IDA 12672959
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with ESPL1: view

Pathways & Interactions for ESPL1 Gene

genes like me logo Genes that share pathways with ESPL1: view

Pathways by source for ESPL1 Gene

1 BioSystems pathway for ESPL1 Gene
1 GeneGo (Thomson Reuters) pathway for ESPL1 Gene
  • Cell cycle_Spindle assembly and chromosome separation
1 Qiagen pathway for ESPL1 Gene
  • Mitotic Roles of Polo Like Kinases

SIGNOR curated interactions for ESPL1 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for ESPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000070 mitotic sister chromatid segregation IEA,IMP 12672959
GO:0000212 meiotic spindle organization IEA --
GO:0000278 mitotic cell cycle IEA --
GO:0000281 mitotic cytokinesis NAS 11509732
GO:0006508 proteolysis IEA --
genes like me logo Genes that share ontologies with ESPL1: view

Drugs & Compounds for ESPL1 Gene

(1) Drugs for ESPL1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with ESPL1: view

Transcripts for ESPL1 Gene

mRNA/cDNA for ESPL1 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ESPL1

Alternative Splicing Database (ASD) splice patterns (SP) for ESPL1 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17a · 17b ^
SP1: - -
SP2: - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8: - -
SP9: -
SP10:

ExUns: 18 ^ 19 ^ 20a · 20b · 20c · 20d ^ 21a · 21b ^ 22a · 22b · 22c ^ 23 ^ 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32a · 32b
SP1: - -
SP2: - -
SP3:
SP4: - - -
SP5: - - -
SP6:
SP7:
SP8:
SP9:
SP10:

Relevant External Links for ESPL1 Gene

GeneLoc Exon Structure for
ESPL1

Expression for ESPL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ESPL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ESPL1 Gene

This gene is overexpressed in Esophagus - Mucosa (x16.1), Vagina (x4.6), and Testis (x4.2).

Protein differential expression in normal tissues from HIPED for ESPL1 Gene

This gene is overexpressed in Breast (13.3), Testis (12.7), Pancreas (11.1), Retina (8.0), Heart (7.7), and Liver (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ESPL1 Gene



Protein tissue co-expression partners for ESPL1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ESPL1

SOURCE GeneReport for Unigene cluster for ESPL1 Gene:

Hs.153479

Evidence on tissue expression from TISSUES for ESPL1 Gene

  • Bone marrow(4.4)
  • Skin(2.7)
  • Intestine(2.6)
  • Blood(2.4)
  • Kidney(2.2)
  • Liver(2.2)
  • Nervous system(2.2)
  • Lung(2)
genes like me logo Genes that share expression patterns with ESPL1: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ESPL1 Gene

Orthologs for ESPL1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ESPL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ESPL1 30 31
  • 99.38 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ESPL1 30 31
  • 87.14 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ESPL1 30 31
  • 85.69 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Espl1 30 17 31
  • 81.25 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Espl1 30
  • 81.19 (n)
Oppossum
(Monodelphis domestica)
Mammalia ESPL1 31
  • 61 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ESPL1 31
  • 46 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ESPL1 30 31
  • 59.13 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ESPL1 31
  • 41 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia espl1 30
  • 52.27 (n)
Str.4227 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.11453 30
Zebrafish
(Danio rerio)
Actinopterygii espl1 30 31
  • 48.28 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Sse 31
  • 20 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea ZK430.5 31
  • 17 (a)
OneToMany
sep-1 31 32
  • 17 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ESP1 31 33
  • 19 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 30 (a)
OneToOne
Species where no ortholog for ESPL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for ESPL1 Gene

ENSEMBL:
Gene Tree for ESPL1 (if available)
TreeFam:
Gene Tree for ESPL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ESPL1: view image

Paralogs for ESPL1 Gene

Pseudogenes.org Pseudogenes for ESPL1 Gene

genes like me logo Genes that share paralogs with ESPL1: view

No data available for Paralogs for ESPL1 Gene

Variants for ESPL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ESPL1 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
713762 Benign: not provided 53,286,746(+) G/T MISSENSE_VARIANT
716990 Likely Benign: not provided 53,293,329(+) C/T MISSENSE_VARIANT
732991 Benign: not provided 53,276,706(+) G/A MISSENSE_VARIANT
732992 Benign: not provided 53,288,230(+) A/G MISSENSE_VARIANT
769823 Benign: not provided 53,288,258(+) T/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for ESPL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for ESPL1 Gene

Variant ID Type Subtype PubMed ID
esv2745904 CNV deletion 23290073
esv2745905 CNV deletion 23290073
esv3310490 CNV novel sequence insertion 20981092
esv9002 CNV gain 19470904
nsv517066 CNV loss 19592680
nsv52713 CNV insertion 16902084
nsv558994 CNV loss 21841781
nsv558996 CNV loss 21841781

Variation tolerance for ESPL1 Gene

Residual Variation Intolerance Score: 76.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.43; 81.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ESPL1 Gene

Human Gene Mutation Database (HGMD)
ESPL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ESPL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ESPL1 Gene

Disorders for ESPL1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for ESPL1 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search ESPL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ESPL1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ESPL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ESPL1 Gene

Publications for ESPL1 Gene

  1. Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer: a Swedish prospective case-control study. (PMID: 19008095) Brendle A … Försti A (European journal of cancer (Oxford, England : 1990) 2009) 3 23 41
  2. Anaphase specific auto-cleavage of separase. (PMID: 12297314) Zou H … Kirschner MW (FEBS letters 2002) 3 4 23
  3. Regulation of human separase by securin binding and autocleavage. (PMID: 12194817) Waizenegger I … Peters JM (Current biology : CB 2002) 3 4 23
  4. Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. (PMID: 11509732) Hauf S … Peters JM (Science (New York, N.Y.) 2001) 3 4 23
  5. Dual inhibition of sister chromatid separation at metaphase. (PMID: 11747808) Stemmann O … Kirschner MW (Cell 2001) 3 4 23

Products for ESPL1 Gene

  • Signalway ELISA kits for ESPL1
  • Signalway Proteins for ESPL1

Sources for ESPL1 Gene