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Identification
HMDB Protein ID HMDBP01325
Secondary Accession Numbers
  • 6621
Name Serine/threonine-protein kinase WNK4
Synonyms
  1. Protein kinase lysine-deficient 4
  2. Protein kinase with no lysine 4
Gene Name WNK4
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific Function Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cell junction
  2. tight junction
Gene Properties
Chromosome Location Chromosome:1
Locus 17q21-q22
SNPs WNK4
Gene Sequence
>3732 bp
ATGTTGGCATCCCCGGCCACGGAGACCACCGTCCTCATGTCCCAGACTGAGGCCGACCTG
GCCCTGCGGCCCCCGCCTCCTCTTGGCACCGCGGGGCAGCCCCGCCTCGGGCCCCCTCCT
CGCCGAGCGCGCCGCTTCTCCGGGAAGGCTGAGCCCCGGCCGCGCTCTTCTCGTCTCAGC
CGCCGTAGCTCAGTCGACTTGGGGCTGCTGAGCTCTTGGTCCCTGCCAGCCTCACCCGCT
CCGGACCCCCCCGATCCTCCGGACTCCGCTGGTCCTGGCCCCGCGAGGAGCCCACCGCCT
AGCTCCAAAGAACCCCCCGAGGGCACGTGGACCGAGGGAGCCCCTGTGAAGGCTGCGGAA
GACTCCGCGCGTCCCGAGCTCCCGGACTCTGCAGTGGGCCCGGGGTCCAGGGAGCCGCTA
AGGGTCCCTGAAGCTGTGGCCCTAGAGCGGCGGCGGGAGCAGGAAGAAAAGGAGGACATG
GAGACCCAGGCTGTGGCAACGTCCCCCGATGGCCGATACCTCAAGTTTGACATCGAGATT
GGACGTGGCTCCTTCAAGACGGTGTATCGAGGGCTAGACACCGACACCACAGTGGAGGTG
GCCTGGTGTGAGCTGCAGACTCGGAAACTGTCTAGAGCTGAGCGGCAGCGCTTCTCAGAG
GAGGTGGAGATGCTCAAGGGGCTGCAGCACCCCAACATCGTCCGCTTCTATGATTCGTGG
AAGTCGGTGCTGAGGGGCCAGGTTTGCATCGTGCTGGTCACCGAACTCATGACCTCGGGC
ACGCTCAAGACGTACCTGAGGCGGTTCCGGGAGATGAAGCCGCGGGTCCTTCAGCGCTGG
AGCCGCCAAATCCTGCGGGGACTTCATTTCCTACACTCCCGGGTTCCTCCCATCCTGCAC
CGGGATCTCAAGTGCGACAATGTCTTTATCACGGGACCTACTGGCTCTGTCAAAATCGGG
GACCTGGGCCTGGCCACGCTCAAGCGCGCCTCCTTTGCCAAGAGTGTCATCGGGACCCCG
GAATTCATGGCCCCCGAGATGTACGAGGAAAAGTACGATGAGGCCGTGGACGTGTACGCG
TTCGGCATGTGCATGCTGGAGATGGCCACCTCTGAGTACCCGTACTCCGAGTGCCAGAAT
GCCGCGCAAATCTACCGCAAGGTCACTTCGGGCAGAAAGCCGAACAGCTTCCACAAGGTG
AAGATACCCGAGGTGAAGGAGATCATTGAAGGCTGCATCCGCACGGATAAGAACGAGAGG
TTCACCATCCAGGACCTCCTGGCCCACGCCTTCTTCCGCGAGGAGCGCGGTGTGCACGTG
GAACTAGCGGAGGAGGACGACGGCGAGAAGCCGGGCCTCAAGCTCTGGCTGCGCATGGAG
GACGCGCGGCGCGGGGGGCGCCCACGGGACAACCAGGCCATCGAGTTCCTGTTCCAGCTG
GGCCGGGACGCGGCCGAGGAGGTGGCACAGGAGATGGTGGCTCTGGGCTTGGTCTGTGAA
GCCGATTACCAGCCAGTGGCCCGTGCAGTACGTGAACGGGTTGCTGCCATCCAGCGAAAG
CGTGAGAAGCTGCGTAAAGCAAGGGAATTGGAGGCACTCCCACCAGAGCCAGGACCTCCA
CCAGCAACTGTGCCCATGGCCCCCGGTCCCCCCAGTGTCTTCCCCCCTGAGCCTGAGGAG
CCAGAGGCAGACCAGCACCAGCCCTTCCTTTTCCGCCACGCCAGCTACTCATCTACCACT
TCGGATTGCGAGACTGATGGCTACCTCAGCTCCTCCGGCTTCCTGGATGCCTCAGACCCT
GCCCTTCAGCCCCCTGGGGGGGTGCCATCCAGCCTGGCTGAGTCCCATCTCTGCCTGCCC
TCGGCTTTTGCCCTATCCATTCCACGTTCTGGCCCTGGAAGTGACTTTTCCCCCGGGGAC
AGCTATGCCTCAGATGCAGCTTCAGGCCTTAGCGATGTGGGAGAAGGGATGGGACAAATG
AGGAGACCCCCAGGGAGGAATCTCCGGCGCAGACCCCGATCCCGGCTGCGGGTCACTAGT
GTCTCAGACCAGAATGACAGAGTGGTTGAGTGCCAGCTACAGACCCATAACAGCAAGATG
GTGACCTTCCGATTTGATCTGGATGGGGACAGCCCGGAAGAGATTGCAGCTGCCATGGTA
TATAACGAGTTCATTCTGCCTTCGGAGCGAGATGGATTTCTCAGACGGATTCGGGAGATT
ATCCAGCGAGTGGAGACCCTGTTGAAGAGAGACACTGGCCCCATGGAGGCTGCTGAAGAC
ACCCTAAGCCCCCAGGAGGAGCCAGCACCATTACCTGCCCTGCCCGTCCCCCTCCCAGAC
CCATCCAATGAAGAGCTCCAGAGCAGCACCTCCCTGGAGCACAGGAGCTGGACAGCCTTC
TCCACCTCCTCATCTTCTCCTGGAACTCCTTTGTCTCCTGGAAACCCATTTTCCCCTGGA
ACCCCCATTTCCCCAGGTCCCATCTTCCCCATCACTTCTCCCCCATGTCATCCCAGCCCC
TCCCCATTCTCCCCCATTTCTTCCCAGGTCTCCTCAAATCCCTCTCCACACCCCACCAGC
TCTCCACTTCCATTCTCCTCCAGCACACCCGAGTTTCCGGTCCCACTCTCTCAGTGTCCC
TGGAGTTCTCTCCCCACGACTTCTCCACCTACGTTCTCTCCCACTTGTTCTCAGGTCACT
CTTAGTTCCCCTTTCTTTCCTCCGTGCCCCTCCACTTCTTCCTTCCCCTCCACCACAGCA
GCCCCTCTCCTTTCTCTGGCTAGTGCCTTCTCACTGGCTGTGATGACTGTGGCCCAGTCC
CTGCTGTCCCCCTCACCTGGGCTCCTTTCCCAGTCTCCTCCAGCCCCTCCTAGTCCCCTC
CCTAGCCTGCCCCTTCCCCCTCCCGTTGCTCCTGGTGGCCAGGAAAGCCCTTCACCCCAC
ACAGCTGAGGTGGAGAGTGAGGCCTCACCACCTCCTGCTCGGCCCCTCCCAGGGGAAGCC
AGGCTGGCGCCCATCTCTGAAGAGGGAAAGCCGCAGCTTGTTGGGCGTTTCCAAGTGACT
TCATCCAAGGAACCGGCTGAGCCTCTTCCCTTGCAGCCAACATCCCCCACTCTCTCTGGT
TCTCCAAAACCTTCAACCCCTCAGCTCACTTCAGAGAGCTCAGATACAGAGGACAGTGCT
GGAGGCGGGCCAGAGACCAGGGAAGCTCTGGCTGAGAGCGACCGTGCAGCTGAGGGTCTG
GGGGCTGGAGTTGAGGAGGAAGGAGATGATGGGAAGGAACCCCAAGTTGGGGGCAGCCCC
CAACCCCTGAGCCATCCCAGCCCAGTGTGGATGAACTACTCCTACAGCAGCCTGTGTTTG
AGCAGCGAGGAGTCAGAAAGCAGTGGGGAAGATGAGGAGTTCTGGGCTGAGCTGCAGAGT
CTTCGGCAGAAGCACTTGTCAGAGGTGGAAACACTACAGACACTACAGAAAAAAGAAATT
GAAGATTTGTACAGCCGGCTGGGGAAGCAGCCCCCACCGGGTATTGTGGCCCCAGCTGCT
ATGCTGTCCAGCCGCCAGCGCCGCCTCTCCAAGGGCAGCTTCCCCACCTCCCGCCGCAAC
AGCCTACAGCGCTCTGAGCCCCCAGGCCCTGGCATCATGCGAAGGAACTCTCTGAGTGGC
AGCAGCACCGGCTCCCAGGAGCAGCGGGCAAGCAAGGGGGTGACATTCGCCGGGGATGTT
GGCAGGATGTGA
Protein Properties
Number of Residues 1243
Molecular Weight 134737.7
Theoretical pI 5.15
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Serine/threonine-protein kinase WNK4
MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRFSGKAEPRPRSSRLS
RRSSVDLGLLSSWSLPASPAPDPPDPPDSAGPGPARSPPPSSKEPPEGTWTEGAPVKAAE
DSARPELPDSAVGPGSREPLRVPEAVALERRREQEEKEDMETQAVATSPDGRYLKFDIEI
GRGSFKTVYRGLDTDTTVEVAWCELQTRKLSRAERQRFSEEVEMLKGLQHPNIVRFYDSW
KSVLRGQVCIVLVTELMTSGTLKTYLRRFREMKPRVLQRWSRQILRGLHFLHSRVPPILH
RDLKCDNVFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDEAVDVYA
FGMCMLEMATSEYPYSECQNAAQIYRKVTSGRKPNSFHKVKIPEVKEIIEGCIRTDKNER
FTIQDLLAHAFFREERGVHVELAEEDDGEKPGLKLWLRMEDARRGGRPRDNQAIEFLFQL
GRDAAEEVAQEMVALGLVCEADYQPVARAVRERVAAIQRKREKLRKARELEALPPEPGPP
PATVPMAPGPPSVFPPEPEEPEADQHQPFLFRHASYSSTTSDCETDGYLSSSGFLDASDP
ALQPPGGVPSSLAESHLCLPSAFALSIPRSGPGSDFSPGDSYASDAASGLSDVGEGMGQM
RRPPGRNLRRRPRSRLRVTSVSDQNDRVVECQLQTHNSKMVTFRFDLDGDSPEEIAAAMV
YNEFILPSERDGFLRRIREIIQRVETLLKRDTGPMEAAEDTLSPQEEPAPLPALPVPLPD
PSNEELQSSTSLEHRSWTAFSTSSSSPGTPLSPGNPFSPGTPISPGPIFPITSPPCHPSP
SPFSPISSQVSSNPSPHPTSSPLPFSSSTPEFPVPLSQCPWSSLPTTSPPTFSPTCSQVT
LSSPFFPPCPSTSSFPSTTAAPLLSLASAFSLAVMTVAQSLLSPSPGLLSQSPPAPPSPL
PSLPLPPPVAPGGQESPSPHTAEVESEASPPPARPLPGEARLAPISEEGKPQLVGRFQVT
SSKEPAEPLPLQPTSPTLSGSPKPSTPQLTSESSDTEDSAGGGPETREALAESDRAAEGL
GAGVEEEGDDGKEPQVGGSPQPLSHPSPVWMNYSYSSLCLSSEESESSGEDEEFWAELQS
LRQKHLSEVETLQTLQKKEIEDLYSRLGKQPPPGIVAPAAMLSSRQRRLSKGSFPTSRRN
SLQRSEPPGPGIMRRNSLSGSSTGSQEQRASKGVTFAGDVGRM
GenBank ID Protein 15212448
UniProtKB/Swiss-Prot ID Q96J92
UniProtKB/Swiss-Prot Entry Name WNK4_HUMAN
PDB IDs Not Available
GenBank Gene ID AF390018
GeneCard ID WNK4
GenAtlas ID WNK4
HGNC ID HGNC:14544
References
General References
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  2. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  3. Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP: Human hypertension caused by mutations in WNK kinases. Science. 2001 Aug 10;293(5532):1107-12. [PubMed:11498583 ]
  4. Verissimo F, Jordan P: WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene. 2001 Sep 6;20(39):5562-9. [PubMed:11571656 ]