ESPL1 extra spindle pole bodies like 1, separase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ESPL1provided by HGNC
Official Full Name: extra spindle pole bodies like 1, separaseprovided by HGNC
Primary source: HGNC:HGNC:16856
See related: Ensembl:ENSG00000135476 MIM:604143
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ESP1; SEPA
Summary: 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]
Expression: Biased expression in esophagus (RPKM 7.6), testis (RPKM 5.7) and 12 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q13.13

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (53268257..53293643)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (53662083..53687427)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the spindle assembly checkpoint
Title: Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2.
human cells that enter mitosis with already active separase rapidly undergo death in mitosis owing to direct cleavage of anti-apoptotic MCL1 and BCL-XL by separase; separase-triggered apoptosis enforces minimal length of mitosis
Title: Separase-triggered apoptosis enforces minimal length of mitosis.
data suggests an association between high separase activity, residual BCR-ABL1 gene expression, and enhanced proliferative capacity in hematopoietic cells within the leukemic niche of TKI-treated chronic phase CML.
Title: Separase activity distribution can be a marker of major molecular response and proliferation of CD34<sup>+</sup> cells in TKI-treated chronic myeloid leukemia patients.
LPE motif on the Scc1 substrate is required for rapid and specific cleavage by separase.
Title: Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.
Thus, tethering of separase to DSBs and confined cohesin cleavage promote DSB repair in G2 cells. Importantly, this conserved interphase function of separase protects mammalian cells from oncogenic transformation.
Title: Local activation of mammalian separase in interphase promotes double-strand break repair and prevents oncogenic transformation.
Separase activity measurement may therefore be useful as a novel additional molecular marker for disease monitoring
Title: Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.
Studies identified and characterized the role of separase in mitosis, meiosis, non-canonical roles, its regulation, as a regulator of centriole disengagement, non proteolytic roles, diverse substrates, structural insights, and association of separase with cancer. [review]
Title: Separase: Function Beyond Cohesion Cleavage and an Emerging Oncogene.
High ESP expression is associated with breast cancer.
Title: Separase is a marker for prognosis and mitotic activity in breast cancer.
Proximity mapping of human separase has been presented.
Title: Proximity mapping of human separase by the BioID approach.
The assay was used to quantify Separase proteolytic activity in leukemic cell lines and peripheral blood samples from leukemia patients.
Title: Measurement of separase proteolytic activity in single living cells by a fluorogenic flow cytometry assay.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH45441 (e-PCR)
- UniSTS:56851

D1S3694 (e-PCR)
- UniSTS:474272

SHGC-105759 (e-PCR)
- UniSTS:169412

G64239 (e-PCR)
- UniSTS:166642

G64240 (e-PCR)
- UniSTS:166644

G64244 (e-PCR)
- UniSTS:166646

Homology

Homologs of the ESPL1 gene: The ESPL1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 295 organisms have orthologs with human gene ESPL1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
catalytic activity	NAS Non-traceable Author Statement more info	PubMed
cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cysteine-type peptidase activity	NAS Non-traceable Author Statement more info	PubMed
cysteine-type peptidase activity	TAS Traceable Author Statement more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	TAS Traceable Author Statement more info	PubMed
establishment of mitotic spindle localization	NAS Non-traceable Author Statement more info	PubMed
homologous chromosome segregation	IEA Inferred from Electronic Annotation more info
meiotic chromosome separation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
meiotic spindle organization	IEA Inferred from Electronic Annotation more info
mitotic cytokinesis	NAS Non-traceable Author Statement more info	PubMed
mitotic sister chromatid segregation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of sister chromatid cohesion	NAS Non-traceable Author Statement more info	PubMed
positive regulation of mitotic metaphase/anaphase transition	NAS Non-traceable Author Statement more info	PubMed
proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
centrosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info
mitotic spindle	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: separin

Names: caspase-like protein ESPL1; extra spindle pole bodies 1, separase; extra spindle pole bodies homolog 1; extra spindle poles like 1; extra spindle poles-like 1 protein; separin, cysteine protease

NP_036423.4

EC 3.4.22.49

XP_006719768.1

EC 3.4.22.49

XP_011537326.1

EC 3.4.22.49

XP_011537327.1

EC 3.4.22.49

XP_016875742.1

EC 3.4.22.49

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.