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WAPL WAPL cohesin release factor [ Homo sapiens (human) ]

Gene ID: 23063, updated on 3-Nov-2024

Summary

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Official Symbol
WAPLprovided by HGNC
Official Full Name
WAPL cohesin release factorprovided by HGNC
Primary source
HGNC:HGNC:23293
See related
Ensembl:ENSG00000062650 MIM:610754; AllianceGenome:HGNC:23293
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
FOE; WAPAL; KIAA0261
Summary
Enables ATP-dependent protein-DNA unloader activity. Involved in several processes, including mitotic sister chromatid segregation; negative regulation of DNA replication; and negative regulation of sister chromatid cohesion. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in testis (RPKM 17.0), lymph node (RPKM 9.9) and 25 other tissues See more
Orthologs
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Genomic context

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See WAPL in Genome Data Viewer
Location:
10q23.2
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (86435256..86521792, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (87315788..87405903, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (88195013..88281549, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene glutamate ionotropic receptor delta type subunit 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88024064-88024564 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_17795 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88051161-88051975 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88051976-88052790 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88057946-88058446 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88089455-88090419 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88091551-88092052 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88092053-88092552 Neighboring gene Sharpr-MPRA regulatory region 9256 Neighboring gene microRNA 346 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88122633-88123146 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88123147-88123660 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2556 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2560 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2559 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2558 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2557 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88136831-88137373 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2563 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3683 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3684 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88159531-88160524 Neighboring gene uncharacterized LOC124902473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88162319-88162871 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88160525-88161518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3688 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3689 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:88183258-88184012 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_17841 Neighboring gene Sharpr-MPRA regulatory region 10398 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:88221644-88222250 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3691 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88263469-88263969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2569 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2570 Neighboring gene RNA, U6 small nuclear 780, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr10:88288988-88289146 Neighboring gene uncharacterized LOC105378408 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88295813-88296362 Neighboring gene uncharacterized LOC105378407 Neighboring gene WAPL divergent transcript

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion. Benedict B, et al. Dev Cell, 2020 Mar 23. PMID 32084359
  2. Identification and cloning of a novel chromatin-associated protein partner of Epstein-Barr nuclear protein 2. Kwiatkowski BA, et al. Exp Cell Res, 2004 Oct 15. PMID 15383329
  3. Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection. Masamsetti VP, et al. Nat Commun, 2019 Sep 17. PMID 31530811, Free PMC Article
  4. WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7. Kumagai K, et al. Oncogene, 2021 May. PMID 33947962, Free PMC Article
  5. Unscheduled overexpression of human WAPL promotes chromosomal instability. Ohbayashi T, et al. Biochem Biophys Res Commun, 2007 May 11. PMID 17382297

See all (121) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A Mediator-cohesin axis controls heterochromatin domain formation.
    Title: A Mediator-cohesin axis controls heterochromatin domain formation.
  2. WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7.
    Title: WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7.
  3. ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin(STAG1) from WAPL.
    Title: ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin(STAG1) from WAPL.
  4. WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion.
    Title: WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion.
  5. Absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin were measured by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells.
    Title: Absolute quantification of cohesin, CTCF and their regulators in human cells.
  6. In p53-compromised cells we find that lethal replication stress confers WAPL-dependent centromere cohesion defects that maintain spindle assembly checkpoint-dependent mitotic arrest in the same cell cycle.
    Title: Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection.
  7. Rec8-Stag3 cohesin is shown to be susceptible to Wapl-dependent ring opening and sororin-mediated protection.
    Title: Studying meiotic cohesin in somatic cells reveals that Rec8-containing cohesin requires Stag3 to function and is regulated by Wapl and sororin.
  8. We provide evidence that the underlying mechanism involves the viral NS3/4 protease and the cohesin regulator, WAPL
    Title: Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.
  9. The results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.
    Title: A kinase-dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion.
  10. The results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
    Title: Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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

EBI GWAS Catalog

Description
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
EBI GWAS Catalog
Genome-wide association study of periodontal pathogen colonization.
EBI GWAS Catalog
Genome-wide meta-analysis identifies new susceptibility loci for migraine.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP-dependent protein-DNA unloader activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in mitotic sister chromatid segregation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of DNA replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of chromatin binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of sister chromatid cohesion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein localization to chromatin IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in chromatin IDA
Inferred from Direct Assay
more info
 PubMed 
located_in chromosome TAS
Traceable Author Statement
more info
  
located_in chromosome, centromeric region TAS
Traceable Author Statement
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in intercellular bridge IDA
Inferred from Direct Assay
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in mitotic spindle IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
wings apart-like protein homolog
Names
friend of EBNA2 (Epstein-Barr virus nuclear protein 2)
friend of EBNA2 protein

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.

mRNA and Protein(s)

  1. NM_001318328.2 → NP_001305257.1  wings apart-like protein homolog isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate, in-frame splice site in the 5' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AL731569, AL844892
    UniProtKB/TrEMBL
    B2RTX8
    Conserved Domains (1) summary
    pfam07814
    Location:632 → 992
    WAPL; Wings apart-like protein regulation of heterochromatin

  2. NM_015045.5 → NP_055860.1  wings apart-like protein homolog isoform 1

    See identical proteins and their annotated locations for NP_055860.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AL731569, AL844892
    Consensus CDS
    CCDS7375.1
    UniProtKB/Swiss-Prot
    A7E2B5, Q5VSK5, Q7Z5K2, Q8IX10, Q92549
    Related
    ENSP00000298767.4, ENST00000298767.10
    Conserved Domains (1) summary
    pfam07814
    Location:638 → 998
    WAPL; Wings apart-like protein regulation of heterochromatin

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    86435256..86521792 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    87315788..87405903 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q7Z5K2.1 GenPept UniProtKB/Swiss-Prot:Q7Z5K2

Gene LinkOut

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