Q7Z5K2 (WAPL_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 66.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Wings apart-like protein homolog Alternative name(s): Friend of EBNA2 protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1190 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. Ref.1 Ref.7 Ref.8 Ref.15 Ref.17 Ref.20 |
| Subunit structure | 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 SORORIN. Interacts (via FGF motifs) with PDS5B; the interaction is direct. Interacts with SMC3. Isoform 2 interacts with Epstein-Barr virus EBNA2. Ref.2 Ref.7 Ref.8 Ref.15 Ref.17 Ref.20 |
| Subcellular location | Isoform 2: Nucleus Ref.2 Ref.7 Ref.8. 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. Ref.2 Ref.7 Ref.8 |
| Tissue specificity | Isoform 1 is highly expressed in uterine cervix tumor. Isoform 2 is widely expressed with a high level in skeletal muscle and heart. Ref.1 Ref.2 |
| Sequence similarities | Contains 1 WAPL domain. |
| Sequence caution | The sequence BAA13391.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAH73376.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI16708.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| PDS5B | Q9NTI5 | 9 | EBI-1022242,EBI-1175604 | |
| RAD21 | O60216 | 11 | EBI-1022242,EBI-80739 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] Note: Named isoforms=2. | ||||||
| Isoform 1 (identifier: Q7Z5K2-1) 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. | ||||||
| Isoform 2 (identifier: Q7Z5K2-2) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MVQGPVQTPALTIHRRKRRRRRRRRPVAKAPARLRGEYETGVKM 510-515: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: Q7Z5K2-3) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MVQGPVQTPA...RGEYETGVKM | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1190 | 1190 | Wings apart-like protein homolog | PRO_0000245232 | |||||
Regions | |||||||||
| Domain | 626 – 1169 | 544 | WAPL | ||||||
| Region | 1 – 659 | 659 | Mediates interaction with the cohesin complex | ||||||
| Coiled coil | 260 – 286 | 27 | Potential | ||||||
| Coiled coil | 749 – 782 | 34 | Potential | ||||||
| Motif | 73 – 75 | 3 | FGF motif 1 | ||||||
| Motif | 429 – 431 | 3 | FGF motif 2 | ||||||
| Motif | 453 – 455 | 3 | FGF motif 3 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 77 | 1 | Phosphoserine Ref.10 Ref.11 Ref.14 Ref.16 Ref.18 | ||||||
| Modified residue | 168 | 1 | N6-acetyllysine Ref.19 | ||||||
| Modified residue | 221 | 1 | Phosphoserine Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.18 | ||||||
| Modified residue | 223 | 1 | Phosphoserine Ref.11 Ref.12 | ||||||
| Modified residue | 226 | 1 | Phosphoserine Ref.9 Ref.10 Ref.11 Ref.13 Ref.18 | ||||||
| Modified residue | 380 | 1 | Phosphoserine Ref.11 Ref.18 | ||||||
| Modified residue | 459 | 1 | Phosphoserine Ref.11 Ref.13 | ||||||
| Modified residue | 461 | 1 | Phosphoserine Ref.11 Ref.13 | ||||||
| Modified residue | 904 | 1 | Phosphoserine Ref.11 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 | 1 | M → MVQGPVQTPALTIHRRKRRR RRRRRPVAKAPARLRGEYET GVKM in isoform 2. | VSP_019649 | |||||
| Alternative sequence | 1 | 1 | M → MVQGPVQTPALTIHRRKRRR SCPPNRASYLPKAESLASLG SHLPALLSRARVPRPPAGRR ERERRRRPVAKAPARLRGEY ETGVKM in isoform 3. | VSP_019650 | |||||
| Alternative sequence | 510 – 515 | 6 | Missing in isoform 2. | VSP_019651 | |||||
| Natural variant | 124 | 1 | V → I. Corresponds to variant rs10887621 [ dbSNP | Ensembl ]. | VAR_026967 | |||||
Experimental info | |||||||||
| Mutagenesis | 73 – 75 | 3 | FGF → EGE: Loss of interaction with PDS5B; when associated with 429-E--E-431 and 453-E--E-455. | ||||||
| Mutagenesis | 429 – 431 | 3 | FGF → EGE: Loss of interaction with PDS5B; when associated with 73-E--E-75 and 453-E--E-455. Ref.15 | ||||||
| Mutagenesis | 453 – 455 | 3 | FGF → EGE: Loss of interaction with PDS5B; when associated with 73-E--E-75 and 429-E--E-431. Ref.15 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Expression of a novel human gene, human wings apart-like (hWAPL), is associated with cervical carcinogenesis and tumor progression." Oikawa K., Ohbayashi T., Kiyono T., Nishi H., Isaka K., Umezawa A., Kuroda M., Mukai K. Cancer Res. 64:3545-3549(2004) [PubMed: 15150110] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. |
| [2] | "Identification and cloning of a novel chromatin-associated protein partner of Epstein-Barr nuclear protein 2." Kwiatkowski B.A., Ragoczy T., Ehly J., Schubach W.H. Exp. Cell Res. 300:223-233(2004) [PubMed: 15383329] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH EPSTEIN-BARR VIRUS EBNA2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [3] | "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Bone marrow. |
| [4] | "The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J.Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [7] | "Wapl controls the dynamic association of cohesin with chromatin." Kueng S., Hegemann B., Peters B.H., Lipp J.J., Schleiffer A., Mechtler K., Peters J.M. Cell 127:955-967(2006) [PubMed: 17113138] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH THE COHESIN COMPLEX AND PDS5A, SUBCELLULAR LOCATION. |
| [8] | "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase." Gandhi R., Gillespie P.J., Hirano T. Curr. Biol. 16:2406-2417(2006) [PubMed: 17112726] [Abstract] Cited for: FUNCTION, INTERACTION WITH THE COHESIN COMPLEX, SUBCELLULAR LOCATION. |
| [9] | "Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [10] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-221 AND SER-226, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-221; SER-223; SER-226; SER-380; SER-459; SER-461 AND SER-904, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [12] | Carrascal M., Abian J. Submitted (JAN-2008) to UniProtKB Cited for: PHOSPHORYLATION AT SER-223, MASS SPECTROMETRY. Tissue: T-cell. |
| [13] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221; SER-226; SER-459 AND SER-461, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [14] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-221, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [15] | "Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1." Shintomi K., Hirano T. Genes Dev. 23:2224-2236(2009) [PubMed: 19696148] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDS5B AND RAD21, MUTAGENESIS OF 73-PHE--PHE-75; 429-PHE--PHE-431 AND 453-PHE--PHE-455, FGF MOTIFS. |
| [16] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-221, MASS SPECTROMETRY. |
| [17] | "Cohesin acetylation speeds the replication fork." Terret M.E., Sherwood R., Rahman S., Qin J., Jallepalli P.V. Nature 462:231-234(2009) [PubMed: 19907496] [Abstract] Cited for: FUNCTION, INTERACTION WITH SMC3. |
| [18] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-221; SER-226 AND SER-380, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [19] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-168, MASS SPECTROMETRY. |
| [20] | "Sororin mediates sister chromatid cohesion by antagonizing wapl." Nishiyama T., Ladurner R., Schmitz J., Kreidl E., Schleiffer A., Bhaskara V., Bando M., Shirahige K., Hyman A.A., Mechtler K., Peters J.M. Cell 143:737-749(2010) [PubMed: 21111234] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDS5A. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00375330. IPI00412441. IPI00744918. |
| RefSeq | NP_055860.1. NM_015045.2. |
| UniGene | Hs.203099. Hs.714876. |
3D structure databases | |
| ProteinModelPortal | Q7Z5K2. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q7Z5K2. 15 interactions. |
| STRING | Q7Z5K2. |
PTM databases | |
| PhosphoSite | Q7Z5K2. |
Polymorphism databases | |
| DMDM | 74713658. |
Proteomic databases | |
| PRIDE | Q7Z5K2. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000298767; ENSP00000298767; ENSG00000062650. ENST00000342368; ENSP00000345162; ENSG00000062650. ENST00000372076; ENSP00000361146; ENSG00000062650. |
| GeneID | 23063. |
| KEGG | hsa:23063. |
| UCSC | uc001kdn.1. human. uc001kdo.1. human. |
Organism-specific databases | |
| CTD | 23063. |
| GeneCards | GC10M088185. |
| H-InvDB | HIX0008996. |
| HGNC | HGNC:23293. WAPAL. |
| HPA | HPA037874. HPA037875. |
| MIM | 610754. gene. |
| neXtProt | NX_Q7Z5K2. |
| PharmGKB | PA134872402. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG15915. |
| GeneTree | ENSGT00390000015768. |
| HOGENOM | HBG715168. |
| HOVERGEN | HBG088338. |
| InParanoid | Q7Z5K2. |
| OMA | NARHWNQ. |
| OrthoDB | EOG4TXBR6. |
Gene expression databases | |
| ArrayExpress | Q7Z5K2. |
| Bgee | Q7Z5K2. |
| CleanEx | HS_WAPAL. |
| Genevestigator | Q7Z5K2. |
| GermOnline | ENSG00000062650. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016024. ARM-type_fold. IPR012502. WAPL_metazoan_plants. IPR022771. WAPL_prot. [Graphical view] |
| Pfam | PF07814. WAPL. 1 hit. [Graphical view] |
| SUPFAM | SSF48371. ARM-type_fold. 1 hit. |
| PROSITE | PS51271. WAPL. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 44141. |
| SOURCE | Search... |
Entry information
| Entry name | WAPL_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q7Z5K2 Secondary accession number(s): A7E2B5 Q92549 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 10 Human chromosome 10: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with