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Protein

Wings apart-like protein homolog

Gene

WAPL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin. Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair.7 Publications

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • meiotic chromosome segregation Source: GO_Central
  • mitotic sister chromatid cohesion Source: GO_Central
  • negative regulation of chromatin binding Source: UniProtKB
  • negative regulation of DNA replication Source: UniProtKB
  • negative regulation of sister chromatid cohesion Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: Ensembl
  • protein localization to chromatin Source: UniProtKB
  • regulation of chromosome condensation Source: GO_Central
  • regulation of cohesin loading Source: UniProtKB
  • response to toxic substance Source: Ensembl
  • sister chromatid cohesion Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Host-virus interaction, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2468052. Establishment of Sister Chromatid Cohesion.
R-HSA-2470946. Cohesin Loading onto Chromatin.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.

Names & Taxonomyi

Protein namesi
Recommended name:
Wings apart-like protein homolog
Alternative name(s):
Friend of EBNA2 protein
WAPL cohesin release factorImported
Gene namesi
Name:WAPLImported
Synonyms:FOE, KIAA0261, WAPAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:23293. WAPL.

Subcellular locationi

  • Nucleus
  • Chromosome
  • Cytoplasm

  • Note: Associates with chromatin through the cohesin complex during interphase. Released in the cytoplasm from nuclear envelope breakdown until anaphase, it reaccumulates in nucleus at telophase.

GO - Cellular componenti

  • chromatin Source: UniProtKB
  • chromosome Source: Reactome
  • chromosome, centromeric region Source: Reactome
  • cohesin complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • intracellular membrane-bounded organelle Source: HPA
  • microtubule cytoskeleton Source: HPA
  • nuclear cohesin complex Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • synaptonemal complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73 – 75FGF → EGE: Loss of interaction with PDS5B; when associated with 429-E--E-431 and 453-E--E-455. 1 Publication3
Mutagenesisi429 – 431FGF → EGE: Loss of interaction with PDS5B; when associated with 73-E--E-75 and 453-E--E-455. 1 Publication3
Mutagenesisi453 – 455FGF → EGE: Loss of interaction with PDS5B; when associated with 73-E--E-75 and 429-E--E-431. 1 Publication3
Mutagenesisi639 – 640VK → AE: Impaired sister chromatid cohesion and resolution. 1 Publication2
Mutagenesisi656 – 657DD → KK: Impaired sister chromatid cohesion and resolution. 1 Publication2
Mutagenesisi770E → K: No effect. 1 Publication1
Mutagenesisi777E → K: No effect. 1 Publication1
Mutagenesisi787E → K: No effect. 1 Publication1
Mutagenesisi790T → A: No effect. 1 Publication1
Mutagenesisi1116M → A: Impaired sister chromatid cohesion and resolution; when associated with A-1120. 1 Publication1
Mutagenesisi1120I → A: Impaired sister chromatid cohesion and resolution; when associated with A-1116. 1 Publication1

Organism-specific databases

DisGeNETi23063.
OpenTargetsiENSG00000062650.
PharmGKBiPA134872402.

Polymorphism and mutation databases

BioMutaiWAPAL.
DMDMi74713658.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002452321 – 1190Wings apart-like protein homologAdd BLAST1190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei77PhosphoserineCombined sources1
Modified residuei168N6-acetyllysineCombined sources1
Modified residuei221PhosphoserineCombined sources1
Modified residuei223PhosphoserineCombined sources1
Modified residuei226PhosphoserineCombined sources1
Modified residuei347PhosphoserineCombined sources1
Modified residuei380PhosphoserineCombined sources1
Modified residuei443PhosphoserineCombined sources1
Modified residuei459PhosphoserineCombined sources1
Modified residuei461PhosphoserineCombined sources1
Modified residuei904PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ7Z5K2.
MaxQBiQ7Z5K2.
PaxDbiQ7Z5K2.
PeptideAtlasiQ7Z5K2.
PRIDEiQ7Z5K2.

PTM databases

iPTMnetiQ7Z5K2.
PhosphoSitePlusiQ7Z5K2.

Expressioni

Tissue specificityi

Isoform 1 is highly expressed in uterine cervix tumor. Isoform 2 is widely expressed with a high level in skeletal muscle and heart.2 Publications

Gene expression databases

BgeeiENSG00000062650.
CleanExiHS_WAPAL.
ExpressionAtlasiQ7Z5K2. baseline and differential.
GenevisibleiQ7Z5K2. HS.

Organism-specific databases

HPAiHPA037874.
HPA037875.

Interactioni

Subunit structurei

Interacts with the cohesin complex throughout the cell cycle; interacts with both chromatin-bound and soluble pools of the complex. Interacts with RAD21; the interaction is direct. Interacts with PDS5A; the interaction is direct, cohesin-dependent and competitive with CDCA5/SORORIN. Interacts (via FGF motifs) with PDS5B; the interaction is direct. Interacts with a SMC1 protein (SMC1A or SMC1B) and SMC3. Isoform 2 interacts with Epstein-Barr virus EBNA2.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDS5BQ9NTI59EBI-1022242,EBI-1175604
RAD21O6021613EBI-1022242,EBI-80739

Protein-protein interaction databases

BioGridi116698. 52 interactors.
DIPiDIP-31176N.
IntActiQ7Z5K2. 30 interactors.
MINTiMINT-4123122.
STRINGi9606.ENSP00000298767.

Structurei

Secondary structure

11190
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi631 – 640Combined sources10
Helixi652 – 664Combined sources13
Helixi671 – 684Combined sources14
Helixi688 – 696Combined sources9
Helixi700 – 706Combined sources7
Turni707 – 709Combined sources3
Helixi710 – 712Combined sources3
Helixi714 – 727Combined sources14
Turni733 – 735Combined sources3
Helixi738 – 749Combined sources12
Helixi765 – 780Combined sources16
Helixi786 – 788Combined sources3
Helixi791 – 802Combined sources12
Turni805 – 807Combined sources3
Helixi810 – 817Combined sources8
Helixi820 – 836Combined sources17
Helixi841 – 862Combined sources22
Helixi866 – 897Combined sources32
Beta strandi909 – 911Combined sources3
Helixi917 – 941Combined sources25
Helixi945 – 952Combined sources8
Helixi957 – 966Combined sources10
Helixi968 – 971Combined sources4
Helixi974 – 976Combined sources3
Helixi977 – 992Combined sources16
Helixi996 – 1003Combined sources8
Helixi1032 – 1058Combined sources27
Helixi1107 – 1135Combined sources29
Helixi1137 – 1146Combined sources10
Helixi1148 – 1150Combined sources3
Helixi1153 – 1169Combined sources17
Helixi1174 – 1188Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4K6JX-ray2.62A/B631-1190[»]
5HDTX-ray2.71E1-33[»]
ProteinModelPortaliQ7Z5K2.
SMRiQ7Z5K2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini626 – 1169WAPLPROSITE-ProRule annotationAdd BLAST544

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 659Mediates interaction with the cohesin complexAdd BLAST659

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili260 – 286Sequence analysisAdd BLAST27
Coiled coili749 – 782Sequence analysisAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi73 – 75FGF motif 13
Motifi429 – 431FGF motif 23
Motifi453 – 455FGF motif 33

Sequence similaritiesi

Belongs to the WAPL family.Curated
Contains 1 WAPL domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2152. Eukaryota.
ENOG410XSDS. LUCA.
GeneTreeiENSGT00390000015768.
HOGENOMiHOG000001563.
HOVERGENiHBG088338.
InParanoidiQ7Z5K2.
OMAiWNSQFGK.
OrthoDBiEOG091G042I.
PhylomeDBiQ7Z5K2.
TreeFamiTF323477.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012502. WAPL_dom.
IPR022771. WAPL_prot.
[Graphical view]
PfamiPF07814. WAPL. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
PROSITEiPS51271. WAPL. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7Z5K2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTSRFGKTYS RKGGNGSSKF DEVFSNKRTT LSTKWGETTF MAKLGQKRPN
60 70 80 90 100
FKPDIQEIPK KPKVEEESTG DPFGFDSDDE SLPVSSKNLA QVKCSSYSES
110 120 130 140 150
SEAAQLEEVT SVLEANSKIS HVVVEDTVVS DKCFPLEDTL LGKEKSTNRI
160 170 180 190 200
VEDDASISSC NKLITSDKVE NFHEEHEKNS HHIHKNADDS TKKPNAETTV
210 220 230 240 250
ASEIKETNDT WNSQFGKRPE SPSEISPIKG SVRTGLFEWD NDFEDIRSED
260 270 280 290 300
CILSLDSDPL LEMKDDDFKN RLENLNEAIE EDIVQSVLRP TNCRTYCRAN
310 320 330 340 350
KTKSSQGASN FDKLMDGTSQ ALAKANSESS KDGLNQAKKG GVSCGTSFRG
360 370 380 390 400
TVGRTRDYTV LHPSCLSVCN VTIQDTMERS MDEFTASTPA DLGEAGRLRK
410 420 430 440 450
KADIATSKTT TRFRPSNTKS KKDVKLEFFG FEDHETGGDE GGSGSSNYKI
460 470 480 490 500
KYFGFDDLSE SEDDEDDDCQ VERKTSKKRT KTAPSPSLQP PPESNDNSQD
510 520 530 540 550
SQSGTNNAEN LDFTEDLPGV PESVKKPINK QGDKSKENTR KIFSGPKRSP
560 570 580 590 600
TKAVYNARHW NHPDSEELPG PPVVKPQSVT VRLSSKEPNQ KDDGVFKAPA
610 620 630 640 650
PPSKVIKTVT IPTQPYQDIV TALKCRREDK ELYTVVQHVK HFNDVVEFGE
660 670 680 690 700
NQEFTDDIEY LLSGLKSTQP LNTRCLSVIS LATKCAMPSF RMHLRAHGMV
710 720 730 740 750
AMVFKTLDDS QHHQNLSLCT AALMYILSRD RLNMDLDRAS LDLMIRLLEL
760 770 780 790 800
EQDASSAKLL NEKDMNKIKE KIRRLCETVH NKHLDLENIT TGHLAMETLL
810 820 830 840 850
SLTSKRAGDW FKEELRLLGG LDHIVDKVKE CVDHLSRDED EEKLVASLWG
860 870 880 890 900
AERCLRVLES VTVHNPENQS YLIAYKDSQL IVSSAKALQH CEELIQQYNR
910 920 930 940 950
AEDSICLADS KPLPHQNVTN HVGKAVEDCM RAIIGVLLNL TNDNEWGSTK
960 970 980 990 1000
TGEQDGLIGT ALNCVLQVPK YLPQEQRFDI RVLGLGLLIN LVEYSARNRH
1010 1020 1030 1040 1050
CLVNMETSCS FDSSICSGEG DDSLRIGGQV HAVQALVQLF LERERAAQLA
1060 1070 1080 1090 1100
ESKTDELIKD APTTQHDKSG EWQETSGEIQ WVSTEKTDGT EEKHKKEEED
1110 1120 1130 1140 1150
EELDLNKALQ HAGKHMEDCI VASYTALLLG CLCQESPINV TTVREYLPEG
1160 1170 1180 1190
DFSIMTEMLK KFLSFMNLTC AVGTTGQKSI SRVIEYLEHC
Length:1,190
Mass (Da):132,946
Last modified:October 1, 2003 - v1
Checksum:iA01026E520BFAB2F
GO
Isoform 2 (identifier: Q7Z5K2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MVQGPVQTPALTIHRRKRRRRRRRRPVAKAPARLRGEYETGVKM
     510-515: Missing.

Note: No experimental confirmation available.
Show »
Length:1,227
Mass (Da):137,314
Checksum:i5431910072375C05
GO
Isoform 3 (identifier: Q7Z5K2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MVQGPVQTPA...RGEYETGVKM

Note: No experimental confirmation available.
Show »
Length:1,275
Mass (Da):142,525
Checksum:i5588D17DBB5C782F
GO

Sequence cautioni

The sequence BAA13391 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAH73376 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI16708 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026967124V → I.Corresponds to variant rs10887621dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0196491M → MVQGPVQTPALTIHRRKRRR RRRRRPVAKAPARLRGEYET GVKM in isoform 2. 1 Publication1
Alternative sequenceiVSP_0196501M → MVQGPVQTPALTIHRRKRRR SCPPNRASYLPKAESLASLG SHLPALLSRARVPRPPAGRR ERERRRRPVAKAPARLRGEY ETGVKM in isoform 3. 1 Publication1
Alternative sequenceiVSP_019651510 – 515Missing in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB065003 mRNA. Translation: BAC78631.1.
AF479418 mRNA. Translation: AAO14651.1.
D87450 mRNA. Translation: BAA13391.1. Different initiation.
AL844892, AL731569 Genomic DNA. Translation: CAH73376.1. Sequence problems.
AL731569, AL844892 Genomic DNA. Translation: CAI16708.1. Sequence problems.
CH471142 Genomic DNA. Translation: EAW80336.1.
BC150269 mRNA. Translation: AAI50270.1.
CCDSiCCDS7375.1. [Q7Z5K2-1]
RefSeqiNP_001305257.1. NM_001318328.1.
NP_055860.1. NM_015045.3. [Q7Z5K2-1]
UniGeneiHs.203099.
Hs.714876.

Genome annotation databases

EnsembliENST00000298767; ENSP00000298767; ENSG00000062650. [Q7Z5K2-1]
ENST00000618527; ENSP00000481451; ENSG00000062650. [Q7Z5K2-1]
GeneIDi23063.
KEGGihsa:23063.
UCSCiuc001kdo.4. human. [Q7Z5K2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB065003 mRNA. Translation: BAC78631.1.
AF479418 mRNA. Translation: AAO14651.1.
D87450 mRNA. Translation: BAA13391.1. Different initiation.
AL844892, AL731569 Genomic DNA. Translation: CAH73376.1. Sequence problems.
AL731569, AL844892 Genomic DNA. Translation: CAI16708.1. Sequence problems.
CH471142 Genomic DNA. Translation: EAW80336.1.
BC150269 mRNA. Translation: AAI50270.1.
CCDSiCCDS7375.1. [Q7Z5K2-1]
RefSeqiNP_001305257.1. NM_001318328.1.
NP_055860.1. NM_015045.3. [Q7Z5K2-1]
UniGeneiHs.203099.
Hs.714876.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4K6JX-ray2.62A/B631-1190[»]
5HDTX-ray2.71E1-33[»]
ProteinModelPortaliQ7Z5K2.
SMRiQ7Z5K2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116698. 52 interactors.
DIPiDIP-31176N.
IntActiQ7Z5K2. 30 interactors.
MINTiMINT-4123122.
STRINGi9606.ENSP00000298767.

PTM databases

iPTMnetiQ7Z5K2.
PhosphoSitePlusiQ7Z5K2.

Polymorphism and mutation databases

BioMutaiWAPAL.
DMDMi74713658.

Proteomic databases

EPDiQ7Z5K2.
MaxQBiQ7Z5K2.
PaxDbiQ7Z5K2.
PeptideAtlasiQ7Z5K2.
PRIDEiQ7Z5K2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000298767; ENSP00000298767; ENSG00000062650. [Q7Z5K2-1]
ENST00000618527; ENSP00000481451; ENSG00000062650. [Q7Z5K2-1]
GeneIDi23063.
KEGGihsa:23063.
UCSCiuc001kdo.4. human. [Q7Z5K2-1]

Organism-specific databases

CTDi23063.
DisGeNETi23063.
GeneCardsiWAPAL.
HGNCiHGNC:23293. WAPL.
HPAiHPA037874.
HPA037875.
MIMi610754. gene.
neXtProtiNX_Q7Z5K2.
OpenTargetsiENSG00000062650.
PharmGKBiPA134872402.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2152. Eukaryota.
ENOG410XSDS. LUCA.
GeneTreeiENSGT00390000015768.
HOGENOMiHOG000001563.
HOVERGENiHBG088338.
InParanoidiQ7Z5K2.
OMAiWNSQFGK.
OrthoDBiEOG091G042I.
PhylomeDBiQ7Z5K2.
TreeFamiTF323477.

Enzyme and pathway databases

ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2468052. Establishment of Sister Chromatid Cohesion.
R-HSA-2470946. Cohesin Loading onto Chromatin.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.

Miscellaneous databases

ChiTaRSiWAPAL. human.
GeneWikiiWAPAL.
GenomeRNAii23063.
PROiQ7Z5K2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000062650.
CleanExiHS_WAPAL.
ExpressionAtlasiQ7Z5K2. baseline and differential.
GenevisibleiQ7Z5K2. HS.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012502. WAPL_dom.
IPR022771. WAPL_prot.
[Graphical view]
PfamiPF07814. WAPL. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
PROSITEiPS51271. WAPL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWAPL_HUMAN
AccessioniPrimary (citable) accession number: Q7Z5K2
Secondary accession number(s): A7E2B5
, Q5VSK5, Q8IX10, Q92549
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: October 1, 2003
Last modified: November 30, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.