Reviewed,
UniProtKB/Swiss-Prot Q9H4A3 (WNK1_HUMAN)
Last modified
November 24, 2009.
Version 91.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Serine/threonine-protein kinase WNK1 EC=2.7.11.1 Alternative name(s): Protein kinase with no lysine 1 Short name=hWNK1 Protein kinase, lysine-deficient 1 Short name=Kinase deficient protein Erythrocyte 65 kDa protein Short name=p65 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2382 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Controls sodium and chloride ion transport by inhibiting the activity of WNK4, potentially by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Ref.3 UniProtKB P83741 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. Ref.3 |
| Enzyme regulation | By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity By similarity. UniProtKB Q9JIH7 |
| Subunit structure | Interacts with SYT2 By similarity. |
| Subcellular location | |
| Tissue specificity | Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Ref.3 Ref.1 Ref.4 |
| Post-translational modification | O-glycosylated. Ref.7 Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 |
| Involvement in disease | Defects in WNK1 are a cause of pseudohypoaldosteronism type II (PHAII) [MIM:145260]. PHAII is an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron. Ref.8 |
| Sequence similarities | Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Contains 1 protein kinase domain. |
| Caution | Ref.7 describes a peptide sequence containing a GlcNAc glycosylated Ser in position 164 while it is an Arg residue according to others. Cys-250 is present instead of the conserved Lys which is expected to be an active site residue. Lys-233 appears to fulfill the required catalytic function. UniProtKB Q9JIH7 |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Syt2 | P29101 | 1 | EBI-457907,EBI-458017 | From a different organism. |
Alternative products
| This entry describes 3 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select] | ||||||
| Isoform 1 Ref.1 (identifier: Q9H4A3-1) 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. | ||||||
| Note: Produced by alternative promoter usage. | ||||||
| Isoform 2 Ref.5 (identifier: Q9H4A3-2) The sequence of this isoform differs from the canonical sequence as follows: 792-1037: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 Ref.4 (identifier: Q9H4A3-4) Also known as: Kidney-specific; Kinase-defective; The sequence of this isoform differs from the canonical sequence as follows: 1-407: Missing. 408-437: FGMCMLEMATSEYPYSECQNAAQIYRRVTS → MDIKKKDFCSVFVIINSHCCCCPQKDCINE | ||||||
| Note: Produced by alternative promoter usage. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2382 | 2382 | Serine/threonine-protein kinase WNK1 | PRO_0000086819 | |||||
Regions | |||||||||
| Domain | 221 – 479 | 259 | Protein kinase | ||||||
| Nucleotide binding | 227 – 235 | 9 | ATP By similarity UniProtKB Q8TDX7 | ||||||
Sites | |||||||||
| Active site | 349 | 1 | Proton acceptor By similarity UniProtKB Q8TDX7 | ||||||
| Binding site | 233 | 1 | ATP By similarity UniProtKB Q9JIH7 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 19 | 1 | Phosphoserine Ref.15 | ||||||
| Modified residue | 167 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 174 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 378 | 1 | Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7 | ||||||
| Modified residue | 382 | 1 | Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7 | ||||||
| Modified residue | 1261 | 1 | Phosphoserine Ref.10 Ref.15 | ||||||
| Modified residue | 1297 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 1300 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 1978 | 1 | Phosphoserine Ref.11 Ref.15 | ||||||
| Modified residue | 2002 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 2011 | 1 | Phosphoserine Ref.9 Ref.15 | ||||||
| Modified residue | 2012 | 1 | Phosphoserine Ref.9 Ref.15 | ||||||
| Modified residue | 2027 | 1 | Phosphoserine Ref.15 | ||||||
| Modified residue | 2029 | 1 | Phosphoserine Ref.12 Ref.15 | ||||||
| Modified residue | 2032 | 1 | Phosphoserine Ref.9 Ref.12 Ref.15 | ||||||
| Modified residue | 2038 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 2121 | 1 | Phosphoserine Ref.15 | ||||||
| Modified residue | 2372 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 407 | 407 | Missing in isoform 3. Ref.4 | VSP_050634 | |||||
| Alternative sequence | 408 – 437 | 30 | FGMCM…RRVTS → MDIKKKDFCSVFVIINSHCC CCPQKDCINE in isoform 3. Ref.4 | VSP_050637 | |||||
| Alternative sequence | 792 – 1037 | 246 | Missing in isoform 2. Ref.5 | VSP_050638 | |||||
| Natural variant | 141 | 1 | A → T: dbSNP rs11554421. | VAR_041309 | |||||
| Natural variant | 149 | 1 | A → V: dbSNP rs34880640. | VAR_041310 | |||||
| Natural variant | 419 | 1 | E → Q in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.20 | VAR_041311 | |||||
| Natural variant | 509 | 1 | I → T: dbSNP rs34728563. | VAR_041312 | |||||
| Natural variant | 527 | 1 | D → G: dbSNP rs34408667. Ref.20 | VAR_041313 | |||||
| Natural variant | 665 | 1 | T → I: dbSNP rs2286007. Ref.20 | VAR_019992 | |||||
| Natural variant | 674 | 1 | T → A: dbSNP rs11833299. Ref.20 | VAR_041314 | |||||
| Natural variant | 823 | 1 | H → R: dbSNP rs56015776. | VAR_041315 | |||||
| Natural variant | 1056 | 1 | P → T: dbSNP rs956868. Ref.2 | VAR_059033 | |||||
| Natural variant | 1199 | 1 | E → G in a colorectal cancer sample; somatic mutation. Ref.19 | VAR_035640 | |||||
| Natural variant | 1506 | 1 | S → C: dbSNP rs7955371. Ref.2 | VAR_059034 | |||||
| Natural variant | 1546 | 1 | A → V: dbSNP rs56351358. | VAR_041316 | |||||
| Natural variant | 1799 | 1 | Q → E in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.20 Ref.19 | VAR_035641 | |||||
| Natural variant | 1808 | 1 | I → M: dbSNP rs12828016. | VAR_041317 | |||||
| Natural variant | 1823 | 1 | P → L: dbSNP rs17755373. Ref.20 | VAR_041318 | |||||
| Natural variant | 1957 | 1 | R → H: dbSNP rs36083875. | VAR_041319 | |||||
| Natural variant | 2190 | 1 | S → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.20 | VAR_041320 | |||||
| Natural variant | 2362 | 1 | F → L in a lung adenocarcinoma sample; somatic mutation. Ref.20 | VAR_041321 | |||||
| Natural variant | 2380 | 1 | R → W: dbSNP rs56262445. | VAR_041322 | |||||
Experimental info | |||||||||
| Sequence conflict | 164 | 1 | R → S AA sequence Ref.7 | ||||||
| Sequence conflict | 669 – 670 | 2 | VS → GG in AAF31483. Ref.3 | ||||||
| Sequence conflict | 740 | 1 | Missing in BAA20802. Ref.5 | ||||||
| Sequence conflict | 1836 | 1 | Missing in BAA20802. Ref.5 | ||||||
Sequences
| ||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "WNK kinases, a novel protein kinase subfamily in multi-cellular organisms." Verissimo F., Jordan P. Oncogene 20:5562-5569(2001) [PubMed: 11571656] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION. Tissue: Heart. |
| [2] | NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-1056; CYS-1506 AND MET-1808. |
| [3] | "PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the JNK MAPK pathway and regulates actin cytoskeletal organisation." Moore T.M., Garg R., Johnson C., Coptcoat M.J., Ridley A.J., Morris J.D.H. J. Biol. Chem. 275:4311-4322(2000) [PubMed: 10660600] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-670 (ISOFORMS 1/2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Mammary carcinoma. |
| [4] | "Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform." Delaloy C., Lu J., Houot A.-M., Disse-Nicodeme S., Gasc J.-M., Corvol P., Jeunemaitre X. Mol. Cell. Biol. 23:9208-9221(2003) [PubMed: 14645531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (N-TERMINUS OF ISOFORM 3), ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Kidney. |
| [5] | "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-2382 (ISOFORM 2), VARIANT MET-1808. Tissue: Brain. |
| [6] | "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION TO N-TERMINUS. |
| [7] | "Nucleoplasmic and cytoplasmic glycoproteins." Hart G.W., Haltiwanger R.S., Holt G.D., Kelly W.G. Ciba Found. Symp. 145:102-118(1989) [PubMed: 2507249] [Abstract] Cited for: PROTEIN SEQUENCE OF 163-175, GLYCOSYLATION. |
| [8] | "Human hypertension caused by mutations in WNK kinases." Wilson F.H., Disse-Nicodeme S., Choate K.A., Ishikawa K., Nelson-Williams C., Desitter I., Gunel M., Milford D.V., Lipkin G.W., Achard J.-M., Feely M.P., Dussol B., Berland Y., Unwin R.J., Mayan H., Simon D.B., Farfel Z., Jeunemaitre X., Lifton R.P. Science 293:1107-1112(2001) [PubMed: 11498583] [Abstract] Cited for: DISEASE. |
| [9] | "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-2002; SER-2011; SER-2012; SER-2032 AND SER-2038, MASS SPECTROMETRY. Tissue: Epithelium. |
| [10] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1261, MASS SPECTROMETRY. Tissue: Epithelium. |
| [11] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1978, MASS SPECTROMETRY. Tissue: Epithelium. |
| [12] | "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed: 17693683] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2029 AND SER-2032, MASS SPECTROMETRY. |
| [13] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167 AND SER-174, MASS SPECTROMETRY. |
| [14] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1297 AND SER-1300, MASS SPECTROMETRY. |
| [15] | "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-19; SER-1261; SER-1978; SER-2011; SER-2012; SER-2027; SER-2029; SER-2032 AND SER-2121, MASS SPECTROMETRY. |
| [16] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [17] | "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-19; SER-2012 AND SER-2372, MASS SPECTROMETRY. |
| [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-1978 AND SER-2372, MASS SPECTROMETRY. Tissue: T-cell. |
| [19] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-1199 AND GLU-1799. |
| [20] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-141; VAL-149; GLN-419; THR-509; GLY-527; ILE-665; ALA-674; ARG-823; VAL-1546; GLU-1799; MET-1808; LEU-1823; HIS-1957; CYS-2190; LEU-2362 AND TRP-2380. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AJ296290 mRNA. Translation: CAC15059.1. FJ515833 Genomic DNA. Translation: ACS13726.1. FJ515833 Genomic DNA. Translation: ACS13727.1. FJ515833 Genomic DNA. Translation: ACS13728.1. AF061944 mRNA. Translation: AAF31483.1. AY231477 mRNA. Translation: AAO46160.1. AB002342 mRNA. Translation: BAA20802.2. | |
| IPI | IPI00004472. IPI00397590. IPI00397592. |
| RefSeq | NP_061852.2. |
| UniGene | Hs.356604 Hs.656067 |
3D structure databases | |
| SMR | Q9H4A3. Positions 211-480. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9H4A3. 2 interactions. |
| STRING | Q9H4A3. |
PTM databases | |
| PhosphoSite | Q9H4A3. |
Proteomic databases | |
| PRIDE | Q9H4A3. |
Genome annotation databases | |
| Ensembl | ENST00000252477; ENSP00000252477; ENSG00000060237; Homo sapiens. [Genome view] ENST00000315939; ENSP00000313059; ENSG00000060237; Homo sapiens. [Genome view] ENST00000340908; ENSP00000341292; ENSG00000060237; Homo sapiens. [Genome view] |
| GeneID | 65125. |
| KEGG | hsa:65125. |
| UCSC | uc001qin.2. human. uc001qio.2. human. uc001qip.2. human. |
Organism-specific databases | |
| CTD | 65125. |
| GeneCards | GC12P000733. |
| H-InvDB | HIX0010312. |
| HGNC | HGNC:14540. WNK1. |
| MIM | 145260. phenotype. 605232. gene. |
| Orphanet | 757. Pseudohypoaldosteronism, type 2. 88940. Pseudohypoaldosteronism, type 2C. |
| PharmGKB | PA33782. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q9H4A3. |
| HOVERGEN | Q9H4A3. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 247. |
Gene expression databases | |
| ArrayExpress | Q9H4A3. |
| Bgee | Q9H4A3. |
| CleanEx | HS_WNK1. |
| Genevestigator | Q9H4A3. |
| GermOnline | ENSG00000060237. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view] |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 67340. |
| SOURCE | Search... |
Entry information
| Entry name | WNK1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9H4A3 Secondary accession number(s): C5HTZ5 Q9P1S9 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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 12 Human chromosome 12: 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 |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


