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    WNK1 WNK lysine deficient protein kinase 1 [ Homo sapiens ]

    Gene ID: 65125, updated on 11-May-2012
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    Summary

    Official Symbol
    WNK1provided by HGNC
    Official Full Name
    WNK lysine deficient protein kinase 1provided by HGNC
    Primary source
    HGNC:14540
    See related
    Ensembl:ENSG00000060237; HPRD:05570; MIM:605232; Vega:OTTHUMG00000090321
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KDP; PSK; p65; HSN2; HSAN2; PRKWNK1; KIAA0344; MGC163339; MGC163341
    Summary
    This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]
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    Genomic context

    Location :
    12p13.3
    Sequence :
    Chromosome: 12; NC_000012.11 (862089..1020618)
    See WNK1 in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene beta-1,4-N-acetyl-galactosaminyl transferase 3 Neighboring gene ninjurin 2 Neighboring gene uncharacterized LOC100049716 Neighboring gene RAD52 homolog (S. cerevisiae) Neighboring gene uncharacterized LOC100130219

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. WNK1 promotes PIP₂ synthesis to coordinate growth factor and GPCR-Gq signaling. An SW, et al. Curr Biol, 2011 Dec 6. PMID 22119528.
    2. Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response. Han Y, et al. Clin Biochem, 2011 Sep. PMID 21704025.
    3. Hereditary sensory and autonomic neuropathy II due to novel mutation in the HSN2 gene in Mexican families. Pacheco-Cuellar G, et al. J Neurol, 2011 Oct. PMID 21625937.
    4. Association of WNK1 exon 1 polymorphisms with essential hypertension in Hani and Yi minorities of China. Cun Y, et al. J Genet Genomics, 2011 Apr 20. PMID 21530900.
    5. Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans. Putku M, et al. Hum Mutat, 2011 Jul. PMID 21520334.

    See all (81) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. WNK1 stimulates PLC-beta signaling in cells by promoting the synthesis of PIP2 via stimulation of phosphatidylinositol 4-kinase IIIalpha.
      Title: WNK1 promotes PIP₂ synthesis to coordinate growth factor and GPCR-Gq signaling.
    2. hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.
      Title: Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response.
    3. we report a novel mutation in the WNK1/HSN2 gene in HSAN2 disease
      Title: Hereditary sensory and autonomic neuropathy II due to novel mutation in the HSN2 gene in Mexican families.
    4. WNK1 AluYb8 insertion might affect human blood pressure via altering the profile of alternatively spliced transcripts
      Title: Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.
    5. These results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population specificity.
      Title: Association of WNK1 exon 1 polymorphisms with essential hypertension in Hani and Yi minorities of China.
    6. Both IRBIT (inositol 1,4,5-trisphosphate receptor-binding protein) and WNK [with no lysine (K)] kinase have been implicated as additional HCO(3)(-) secretory controllers.
      Title: Primers on molecular pathways: bicarbonate transport by the pancreas.
    7. PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1.
      Title: Activation of PI3-kinase stimulates endocytosis of ROMK via Akt1/SGK1-dependent phosphorylation of WNK1.
    8. Data show that a large percentage of WNK1 knockdown cells fail to complete cell division, displaying defects in mitotic spindles and also in abscission and cell survival.
      Title: WNK1 is required for mitosis and abscission.
    9. IRBIT opposes the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities
      Title: IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
    10. WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex
      Title: Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex.
    Submit: New GeneRIF Correction See all (55)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Neuropathy, hereditary sensory and autonomic, type II

    Summary from GeneReviews: Go to GeneReviews

    Disease Characteristics
    Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease.
    Diagnosis Testing
    Diagnosis is based on clinical findings and molecular genetic testing of WNK1 (previously HSN2) (type HSAN2A), FAM134B (type HSAN2B) and KIF1A (type HSAN2C), the only genes in which mutation is known to cause HSAN2.
    Genetic Counseling
    HSAN2, which includes HSAN2A, HSAN2B, and HSAN2C, is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing of at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.
    References

    Pseudohypoaldosteronism, type IIC

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q6IFS5 P54253 ATXN1    HPRD  PubMed  
    Q9H4A3 P31749 AKT1    HPRD  PubMed  
    Q9H4A3 Q9Y2U5 MAP3K2    HPRD  PubMed  
    Q9H4A3 Q99759 MAP3K3    HPRD  PubMed  
    Q9H4A3 Q8N9I0 SYT2    HPRD  PubMed  
    Q9H4A3 P61981 YWHAG    HPRD  PubMed  
    BioGRID:122403 BioGRID:110613 ATP8    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:114907 BAG3    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:107623 CLTC    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:116183 COPS5    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113583 CSDE1    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:108203 E2F3    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:108607 FLNC    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:124182 GLIS2    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:111590 MAP2K1    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:111559 PRKAR1A    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:111561 PRKAR1B    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:115359 RANBP9    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:112438 SLC9A1    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:118141 TNRC6A    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:114374 TSC22D1    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Reconstituted Complex 
    BioGRID:122403 BioGRID:122403 WNK1    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:122423 WNK2    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113363 YWHAE    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113364 YWHAG    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113366 YWHAZ    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:122154 ZFP106    BioGRID  PubMed Two-hybrid 
    BioGRID:122403 BioGRID:113569 ZYX    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • EGFR1 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      EGFR1 Signaling Pathway, organism-specific biosystemThe androgen receptor is a member of the nuclear receptor family of ligand activated transcription factors. These receptors bind to steroid hormones, thyroid hormone, retinoids and vitamin D among ot...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    phosphatase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein kinase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    intracellular protein kinase cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    neuron development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    regulation of cellular process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    serine/threonine-protein kinase WNK1
    Names
    serine/threonine-protein kinase WNK1
    erythrocyte 65 kDa protein
    protein kinase with no lysine 1
    prostate-derived sterile 20-like kinase
    WNK lysine deficient protein kinase 1 isoform
    NP_001171914.1
    NP_055638.2
    NP_061852.3
    NP_998820.3
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    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_007984.2 RefSeqGene

      Range
      4865..163394
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001184985.1 → NP_001171914.1  serine/threonine-protein kinase WNK1 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has multiple differences in the coding region but maintains the reading frame compared to variant 1. This variant represents the exon combination of the dorsal root ganglia and sciatic nerve variant described in Figure 2F of PubMed ID 18521183. This variant encodes isoform 4, which is longer than isoform 1.
      Source sequence(s)
      AC004765, AC004803
      UniProtKB/Swiss-Prot
      Q9H4A3
      Related
      ENSP00000444465, ENST00000537687
      Conserved Domains (3) summary
      cd00180
      Location:227 – 476
      Blast Score: 582
      PKc; Catalytic domain of Protein Kinases
      smart00220
      Location:226 – 479
      Blast Score: 627
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam12202
      Location:500 – 537
      Blast Score: 192
      OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

    2. NM_014823.2 → NP_055638.2  serine/threonine-protein kinase WNK1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses two alternative splice sites and lacks two exons in the coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.
      Source sequence(s)
      AB002342, AC004765, AC004803, AI074334, AJ296290, BC141881, BX644268, CD629562, DA720959
      Consensus CDS
      CCDS53731.1
      UniProtKB/TrEMBL
      A5D8Z4
      UniProtKB/TrEMBL
      F5GWT4
      UniProtKB/Swiss-Prot
      Q9H4A3
      Related
      ENSP00000441972, OTTHUMP00000237889, ENST00000535572, OTTHUMT00000398086
      Conserved Domains (3) summary
      cd00180
      Location:227 – 476
      Blast Score: 582
      PKc; Catalytic domain of Protein Kinases
      smart00220
      Location:226 – 479
      Blast Score: 628
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam12202
      Location:500 – 537
      Blast Score: 188
      OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

    3. NM_018979.3 → NP_061852.3  serine/threonine-protein kinase WNK1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the most common isoform (1), as indicated in PubMed ID 18521183.
      Source sequence(s)
      AB002342, AC004765, AC004803, AI074334, AJ296290, BC141881, BX644268, CD629562, DA720959
      Consensus CDS
      CCDS8506.1
      UniProtKB/TrEMBL
      A5D8Z4
      UniProtKB/Swiss-Prot
      Q9H4A3
      Related
      ENSP00000313059, OTTHUMP00000115370, ENST00000315939, OTTHUMT00000206683
      Conserved Domains (3) summary
      cd00180
      Location:227 – 476
      Blast Score: 585
      PKc; Catalytic domain of Protein Kinases
      smart00220
      Location:226 – 479
      Blast Score: 630
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam12202
      Location:500 – 537
      Blast Score: 192
      OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

    4. NM_213655.4 → NP_998820.3  serine/threonine-protein kinase WNK1 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences in the coding region but maintains the reading frame compared to variant 1. This variant represents the exon combination of the brain and spinal cord variant described in Figure 2F of PubMed ID 18521183. This variant encodes isoform 3, which is longer than isoform 1.
      Source sequence(s)
      AC004765, AC004803
      UniProtKB/Swiss-Prot
      Q9H4A3
      Conserved Domains (3) summary
      cd00180
      Location:227 – 476
      Blast Score: 581
      PKc; Catalytic domain of Protein Kinases
      smart00220
      Location:226 – 479
      Blast Score: 626
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam12202
      Location:500 – 537
      Blast Score: 191
      OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p5 Primary Assembly

      Range
      862089..1020618
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      714669..871790
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC004765.2 (22356..150803) None
    genomic AC004803.11 (2210..32291) None
    genomic BK004108.1 DAA04494.1
    genomic CH471116.2 EAW88951.1
      EAW88952.1
      EAW88953.1
      EAW88954.1
      EAW88955.1
      EAW88956.1
      EAW88957.1
      EAW88958.1
    genomic FJ515833.1 ACS13726.1
    mRNA AB002342.2 BAA20802.2
    mRNA AF061944.1 AAF31483.1
    mRNA AI074334.1 None
    mRNA AJ296290.1 CAC15059.1
    mRNA AY231477.1 AAO46160.1
    mRNA BC013629.2 AAH13629.2
    mRNA BC021121.1 None
    mRNA BC035146.1 None
    mRNA BC044600.1 None
    mRNA BC071959.1 None
    mRNA BC094862.1 None
    mRNA BC130467.1 AAI30468.1
    mRNA BC130469.1 AAI30470.1
    mRNA BC141881.1 AAI41882.1
    mRNA BJ997509.1 None
    mRNA BM716053.1 None
    mRNA BX644268.1 None
    mRNA CD629562.1 None
    mRNA DA720959.1 None
    mRNA JQ358908.1 AEY99342.1
    mRNA N57692.1 None
    other-genetic BC172444.1 AAI72444.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96CZ6 GenPept UniProtKB/TrEMBL:Q96CZ6
    Q9H4A3.2 GenPept UniProtKB/Swiss-Prot:Q9H4A3
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
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    Tools
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