Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase WNK1

Gene

WNK1

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

Functioni

Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, 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. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity).By similarity2 Publications
Isoform 3: Dominant-negative regulator of the longer isoform 1. Does not have kinase acitivity, does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Downregulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity. In kidney, may play an important role regulating sodium and potassium balance.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+1 Publication

Enzyme regulationi

By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei233ATPPROSITE-ProRule annotationBy similarity1
Active sitei349Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi227 – 235ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • chloride channel inhibitor activity Source: UniProtKB
  • magnesium ion binding Source: Ensembl
  • phosphatase binding Source: UniProtKB
  • potassium channel inhibitor activity Source: Ensembl
  • protein kinase activator activity Source: ParkinsonsUK-UCL
  • protein kinase activity Source: ParkinsonsUK-UCL
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • protein serine/threonine kinase inhibitor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Protein kinase inhibitor, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00741-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiQ9H4A3.
SIGNORiQ9H4A3.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK1 (EC:2.7.11.1)
Alternative name(s):
Erythrocyte 65 kDa protein
Short name:
p65
Kinase deficient protein
Protein kinase lysine-deficient 1
Protein kinase with no lysine 1
Short name:
hWNK1
Gene namesi
Name:WNK1
Synonyms:HSN2, KDP, KIAA0344, PRKWNK1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:14540. WNK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: ParkinsonsUK-UCL
  • membrane Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Pseudohypoaldosteronism 2C (PHA2C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics.
See also OMIM:614492
Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves.
See also OMIM:201300

Keywords - Diseasei

Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi65125.
MalaCardsiWNK1.
MIMi201300. phenotype.
614492. phenotype.
OpenTargetsiENSG00000060237.
Orphaneti970. Hereditary sensory and autonomic neuropathy type 2.
88940. Pseudohypoaldosteronism type 2C.
PharmGKBiPA134944932.
PA33782.

Chemistry databases

ChEMBLiCHEMBL1075173.
GuidetoPHARMACOLOGYi2280.

Polymorphism and mutation databases

BioMutaiWNK1.
DMDMi296453029.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868191 – 2382Serine/threonine-protein kinase WNK1Add BLAST2382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19PhosphoserineCombined sources1
Modified residuei167PhosphoserineCombined sources1
Modified residuei174PhosphoserineCombined sources1
Modified residuei378Phosphoserine; by autocatalysisBy similarity1
Modified residuei382Phosphoserine; by autocatalysisBy similarity1
Modified residuei1261PhosphoserineCombined sources1
Modified residuei1978PhosphoserineCombined sources1
Modified residuei2002PhosphoserineCombined sources1
Modified residuei2011PhosphoserineCombined sources1
Modified residuei2012PhosphoserineCombined sources1
Modified residuei2027PhosphoserineCombined sources1
Modified residuei2029PhosphoserineCombined sources1
Modified residuei2032PhosphoserineCombined sources1
Modified residuei2121PhosphoserineCombined sources1
Modified residuei2270PhosphoserineBy similarity1
Modified residuei2286PhosphoserineBy similarity1
Modified residuei2370PhosphoserineCombined sources1
Modified residuei2372PhosphoserineCombined sources1

Post-translational modificationi

O-glycosylated.1 Publication
Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a BCR(KLHL2) complex, leading to proteasomal degradation.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9H4A3.
MaxQBiQ9H4A3.
PaxDbiQ9H4A3.
PeptideAtlasiQ9H4A3.
PRIDEiQ9H4A3.

PTM databases

iPTMnetiQ9H4A3.
PhosphoSitePlusiQ9H4A3.

Expressioni

Tissue specificityi

Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and connecting tubule (CNT) of the nephron.4 Publications

Gene expression databases

BgeeiENSG00000060237.
CleanExiHS_WNK1.
ExpressionAtlasiQ9H4A3. baseline and differential.
GenevisibleiQ9H4A3. HS.

Organism-specific databases

HPAiHPA046541.
HPA059157.

Interactioni

Subunit structurei

Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity). Interacts with KLHL3 (PubMed:23387299, PubMed:23576762). Isoform 3: Interacts with isoform 1 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
OXSR1O957472EBI-457907,EBI-620853
PPP1CAP621362EBI-457907,EBI-357253
Syt2P291012EBI-457907,EBI-458017From a different organism.

GO - Molecular functioni

  • phosphatase binding Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi122403. 65 interactors.
DIPiDIP-32648N.
IntActiQ9H4A3. 61 interactors.
MINTiMINT-2879524.
STRINGi9606.ENSP00000313059.

Chemistry databases

BindingDBiQ9H4A3.

Structurei

Secondary structure

12382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi211 – 214Combined sources4
Beta strandi216 – 218Combined sources3
Beta strandi220 – 228Combined sources9
Beta strandi231 – 240Combined sources10
Turni241 – 244Combined sources4
Beta strandi245 – 252Combined sources8
Helixi266 – 273Combined sources8
Beta strandi283 – 288Combined sources6
Beta strandi297 – 302Combined sources6
Helixi309 – 316Combined sources8
Helixi321 – 340Combined sources20
Beta strandi341 – 343Combined sources3
Helixi352 – 354Combined sources3
Beta strandi355 – 358Combined sources4
Beta strandi364 – 366Combined sources3
Helixi369 – 371Combined sources3
Helixi392 – 396Combined sources5
Helixi402 – 417Combined sources16
Turni421 – 424Combined sources4
Helixi428 – 435Combined sources8
Turni436 – 438Combined sources3
Helixi442 – 446Combined sources5
Helixi450 – 459Combined sources10
Helixi464 – 466Combined sources3
Helixi470 – 474Combined sources5
Helixi477 – 481Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PWNX-ray1.84A210-482[»]
5TF9X-ray2.50A/B206-483[»]
ProteinModelPortaliQ9H4A3.
SMRiQ9H4A3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini221 – 479Protein kinasePROSITE-ProRule annotationAdd BLAST259

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0584. Eukaryota.
ENOG410XQWZ. LUCA.
GeneTreeiENSGT00800000124049.
HOVERGENiHBG079897.
InParanoidiQ9H4A3.
KOiK08867.
OMAiHERPVSF.
OrthoDBiEOG091G06LL.
PhylomeDBiQ9H4A3.
TreeFamiTF315363.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Note: WNK1 is a complex 33-exons gene, in total 9 WNK1 exons are alternatively spliced, some expressed in a tissue-specific manner. Additional isoforms seems to exist.
Isoform 11 Publication (identifier: Q9H4A3-1) [UniParc]FASTAAdd to basket
Also known as: L-WNK1

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
MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR
60 70 80 90 100
TEEYRRRRHT MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL
110 120 130 140 150
SLPQPSIPAA VPQSAPPEPH REETVTATAT SQVAQQPPAA AAPGEQAVAG
160 170 180 190 200
PAPSTVPSST SKDRPVSQPS LVGSKEEPPP ARSGSGGGSA KEPQEERSQQ
210 220 230 240 250
QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD TETTVEVAWC
260 270 280 290 300
ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV
310 320 330 340 350
TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL
360 370 380 390 400
KCDNIFITGP TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD
410 420 430 440 450
ESVDVYAFGM CMLEMATSEY PYSECQNAAQ IYRRVTSGVK PASFDKVAIP
460 470 480 490 500
EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ EETGVRVELA EEDDGEKIAI
510 520 530 540 550
KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM VESGYVCEGD
560 570 580 590 600
HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ
610 620 630 640 650
TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL
660 670 680 690 700
SDGTVDSGQG SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA
710 720 730 740 750
QSQPHGVYPP SSVAQGQSQG QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP
760 770 780 790 800
PQQTVQYSLS QTSTSSEATT AQPVSQPQAP QVLPQVSAGK QLPVSQPVPT
810 820 830 840 850
IQGEPQIPVA TQPSVVPVHS GAHFLPVGQP LPTPLLPQYP VSQIPISTPH
860 870 880 890 900
VSTAQTGFSS LPITMAAGIT QPLLTLASSA TTAAIPGVST VVPSQLPTLL
910 920 930 940 950
QPVTQLPSQV HPQLLQPAVQ SMGIPANLGQ AAEVPLSSGD VLYQGFPPRL
960 970 980 990 1000
PPQYPGDSNI APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE
1010 1020 1030 1040 1050
SNLLVPMGGV GGQVQVSQPG GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP
1060 1070 1080 1090 1100
VAVAQTQATQ PTTLASSVDS AHSDVASGMS DGNENVPSSS GRHEGRTTKR
1110 1120 1130 1140 1150
HYRKSVRSRS RHEKTSRPKL RILNVSNKGD RVVECQLETH NRKMVTFKFD
1160 1170 1180 1190 1200
LDGDNPEEIA TIMVNNDFIL AIERESFVDQ VREIIEKADE MLSEDVSVEP
1210 1220 1230 1240 1250
EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI GIPTSSLTQV
1260 1270 1280 1290 1300
VHSAGRRFIV SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS
1310 1320 1330 1340 1350
LSLQQAFSEL RRAQMTEGPN TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA
1360 1370 1380 1390 1400
AATAPVPATS SPPNDISTSV IQSEVTVPTE EGIAGVATST GVVTSGGLPI
1410 1420 1430 1440 1450
PPVSESPVLS SVVSSITIPA VVSISTTSPS LQVPTSTSEI VVSSTALYPS
1460 1470 1480 1490 1500
VTVSATSASA GGSTATPGPK PPAVVSQQAA GSTTVGATLT SVSTTTSFPS
1510 1520 1530 1540 1550
TASQLCIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL AFSLSAPSSS
1560 1570 1580 1590 1600
SSPGAGVSSY ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI
1610 1620 1630 1640 1650
PPLVQPVANV PAVQQTLIHS QPQPALLPNQ PHTHCPEVDS DTQPKAPGID
1660 1670 1680 1690 1700
DIKTLEEKLR SLFSEHSSSG AQHASVSLET SLVIESTVTP GIPTTAVAPS
1710 1720 1730 1740 1750
KLLTSTTSTC LPPTNLPLGT VALPVTPVVT PGQVSTPVST TTSGVKPGTA
1760 1770 1780 1790 1800
PSKPPLTKAP VLPVGTELPA GTLPSEQLPP FPGPSLTQSQ QPLEDLDAQL
1810 1820 1830 1840 1850
RRTLSPEMIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV KEGPVLATSS
1860 1870 1880 1890 1900
GAGVFKMGRF QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP
1910 1920 1930 1940 1950
ESTLVKPEPN GITIPGISSD VPESAHKTTA SEAKSDTGQP TKVGRFQVTT
1960 1970 1980 1990 2000
TANKVGRFSV SKTEDKITDT KKEGPVASPP FMDLEQAVLP AVIPKKEKPE
2010 2020 2030 2040 2050
LSEPSHLNGP SSDPEAAFLS RDVDDGSGSP HSPHQLSSKS LPSQNLSQSL
2060 2070 2080 2090 2100
SNSFNSSYMS SDNESDIEDE DLKLELRRLR DKHLKEIQDL QSRQKHEIES
2110 2120 2130 2140 2150
LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS LGNKSPQLSG
2160 2170 2180 2190 2200
NLSGQSAASV LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS
2210 2220 2230 2240 2250
DGAISVPSLS APGQGTSSTN TVGATVNSQA AQAQPPAMTS SRKGTFTDDL
2260 2270 2280 2290 2300
HKLVDNWARD AMNLSGRRGS KGHMNYEGPG MARKFSAPGQ LCISMTSNLG
2310 2320 2330 2340 2350
GSAPISAASA TSLGHFTKSM CPPQQYGFPA TPFGAQWSGT GGPAPQPLGQ
2360 2370 2380
FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT
Note: Strong expression in dorsal root ganglia and spinal cord.
Length:2,382
Mass (Da):250,794
Last modified:May 18, 2010 - v2
Checksum:i426785F98A452A0A
GO
Isoform 21 Publication (identifier: Q9H4A3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     740-740: Missing.
     792-1037: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:2,135
Mass (Da):225,560
Checksum:i2961D903C013A22C
GO
Isoform 3 (identifier: Q9H4A3-4) [UniParc]FASTAAdd to basket
Also known as: KS-WNK1, Kidney-Specific

The sequence of this isoform differs from the canonical sequence as follows:
     1-407: Missing.
     408-437: FGMCMLEMATSEYPYSECQNAAQIYRRVTS → MDIKKKDFCSVFVIINSHCCCCPQKDCINE

Note: Kinase-defective isoform. Produced by alternative promoter usage and alternative splicing.
Show »
Length:1,975
Mass (Da):206,646
Checksum:iB03B35C0321782D3
GO
Isoform 4 (identifier: Q9H4A3-5) [UniParc]FASTAAdd to basket
Also known as: Brain and spinal cord variant

The sequence of this isoform differs from the canonical sequence as follows:
     714-1037: AQGQSQGQPS...TTSSQQAVLE → PRRGRSMSVC...VLPQVSAGKQ

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,634
Mass (Da):279,538
Checksum:i2F95DCDA28619B4C
GO
Isoform 5 (identifier: Q9H4A3-6) [UniParc]FASTAAdd to basket
Also known as: Dorsal root ganglia and sciatic nerve variant, DRG and sciatic nerve variant

The sequence of this isoform differs from the canonical sequence as follows:
     713-713: V → VPQSMAHPCG...SSGGSALHPQ
     792-944: Missing.

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,642
Mass (Da):279,713
Checksum:iD0AB5C95ABFF46A4
GO
Isoform 6 (identifier: Q9H4A3-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     713-713: V → VPQSMAHPCG...SSGGSALHPQ
     2215-2215: G → GCAKFNCASEQVTFKPGGRRTRFLRKMVKKVCPCNQLCR

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,833
Mass (Da):299,725
Checksum:i24CA46FC81669858
GO

Sequence cautioni

The sequence AAF31483 differs from that shown. Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated
The sequence AAI30468 differs from that shown. Probable cloning artifact.Curated
The sequence AAI30470 differs from that shown. Probable cloning artifact.Curated
The sequence DAA04494 differs from that shown. Reason: Erroneous gene model prediction. Includes 3' and 3' intronic sequences.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti164R → S AA sequence (PubMed:2507249).Curated1
Sequence conflicti1836Missing in BAA20802 (PubMed:9205841).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041309141A → T.1 PublicationCorresponds to variant rs11554421dbSNPEnsembl.1
Natural variantiVAR_041310149A → V.1 PublicationCorresponds to variant rs34880640dbSNPEnsembl.1
Natural variantiVAR_041311419E → Q in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041312509I → T.1 PublicationCorresponds to variant rs34728563dbSNPEnsembl.1
Natural variantiVAR_041313527D → G.1 PublicationCorresponds to variant rs34408667dbSNPEnsembl.1
Natural variantiVAR_019992665T → I.1 PublicationCorresponds to variant rs2286007dbSNPEnsembl.1
Natural variantiVAR_041314674T → A.1 PublicationCorresponds to variant rs11833299dbSNPEnsembl.1
Natural variantiVAR_041315823H → R.1 PublicationCorresponds to variant rs56015776dbSNPEnsembl.1
Natural variantiVAR_0590331056T → P.3 PublicationsCorresponds to variant rs956868dbSNPEnsembl.1
Natural variantiVAR_0356401199E → G in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0590341506C → S.3 PublicationsCorresponds to variant rs7955371dbSNPEnsembl.1
Natural variantiVAR_0413161546A → V.1 PublicationCorresponds to variant rs56351358dbSNPEnsembl.1
Natural variantiVAR_0356411799Q → E in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_0413171808M → I.3 PublicationsCorresponds to variant rs12828016dbSNPEnsembl.1
Natural variantiVAR_0413181823P → L.1 PublicationCorresponds to variant rs17755373dbSNPEnsembl.1
Natural variantiVAR_0413191957R → H.1 PublicationCorresponds to variant rs36083875dbSNPEnsembl.1
Natural variantiVAR_0413202190S → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0413212362F → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0413222380R → W.1 PublicationCorresponds to variant rs56262445dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0506341 – 407Missing in isoform 3. CuratedAdd BLAST407
Alternative sequenceiVSP_050637408 – 437FGMCM…RRVTS → MDIKKKDFCSVFVIINSHCC CCPQKDCINE in isoform 3. CuratedAdd BLAST30
Alternative sequenceiVSP_040267713V → VPQSMAHPCGGTPTYPESQI FFPTIHERPVSFSPPPTCPP KVAISQRRKSTSFLEAQTHH FQPLLRTVGQSLLPPGGSPT NWTPEAVVMLGTTASRVTGE SCEIQVHPMFEPSQVYSDYR PGLVLPEEAHYFIPQEAVYV AGVHYQARVAEQYEGIPYNS SVLSSPMKQIPEQKPVQGGP TSSSVFEFPSGQAFLVGHLQ NLRLDSGLGPGSPLSSISAP ISTDATRLKFHPVFVPHSAP AVLTHNNESRSNCVFEFHVH TPSSSSGEGGGILPQRVYRN RQVAVDLNQEELPPQSVGLH GYLQPVTEEKHNYHAPELTV SVVEPIGQNWPIGSPEYSSD SSQITSSDPSDFQSPPPTGG AAAPFGSDVSMPFIHLPQTV LQESPLFFCFPQGTTSQQVL TASFSSGGSALHPQ in isoform 5 and isoform 6. 1 Publication1
Alternative sequenceiVSP_040268714 – 1037AQGQS…QAVLE → PRRGRSMSVCVPIFLLLPLC PASLPVLFHPTASTVCTSFS FPPPDCPEETFAEKLSKALE SVLPMHSASQRKHRRSSLPS LFVSTPQSMAHPCGGTPTYP ESQIFFPTIHERPVSFSPPP TCPPKVAISQRRKSTSFLEA QTHHFQPLLRTVGQSLLPPG GSPTNWTPEAVVMLGTTASR VTGESCEIQVHPMFEPSQVY SDYRPGLVLPEEAHYFIPQE AVYVAGVHYQARVAEQYEGI PYNSSVLSSPMKQIPEQKPV QGGPTSSSVFEFPSGQAFLV GHLQNLRLDSGLGPGSPLSS ISAPISTDATRLKFHPVFVP HSAPAVLTHNNESRSNCVFE FHVHTPSSSSGEGGGILPQR VYRNRQVAVDLNQEELPPQS VGLHGYLQPVTEEKHNYHAP ELTVSVVEPIGQNWPIGSPE YSSDSSQITSSDPSDFQSPP PTGGAAAPFGSDVSMPFIHL PQTVLQESPLFFCFPQGTTS QQVLTASFSSGGSALHPQAQ GQSQGQPSSSSLTGVSSSQP IQHPQQQQGIQQTAPPQQTV QYSLSQTSTSSEATTAQPVS QPQAPQVLPQVSAGKQ in isoform 4. CuratedAdd BLAST324
Alternative sequenceiVSP_040269740Missing in isoform 2. 1 Publication1
Alternative sequenceiVSP_050638792 – 1037Missing in isoform 2. 1 PublicationAdd BLAST246
Alternative sequenceiVSP_040270792 – 944Missing in isoform 5. CuratedAdd BLAST153
Alternative sequenceiVSP_0537672215G → GCAKFNCASEQVTFKPGGRR TRFLRKMVKKVCPCNQLCR in isoform 6. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296290 mRNA. Translation: CAC15059.1.
JQ358908 mRNA. Translation: AEY99342.1.
FJ515833 Genomic DNA. Translation: ACS13726.1.
FJ515833 Genomic DNA. Translation: ACS13727.1.
FJ515833 Genomic DNA. Translation: ACS13728.1.
AC004765 Genomic DNA. No translation available.
AC004803 Genomic DNA. No translation available.
AF061944 mRNA. Translation: AAF31483.1. Sequence problems.
AB002342 mRNA. Translation: BAA20802.2.
AY231477 mRNA. Translation: AAO46160.1.
BC013629 mRNA. Translation: AAH13629.2.
BC130467 mRNA. Translation: AAI30468.1. Sequence problems.
BC130469 mRNA. Translation: AAI30470.1. Sequence problems.
BK004108 Genomic DNA. Translation: DAA04494.1. Sequence problems.
CCDSiCCDS73419.1. [Q9H4A3-5]
CCDS8506.1. [Q9H4A3-1]
RefSeqiNP_001171914.1. NM_001184985.1. [Q9H4A3-6]
NP_055638.2. NM_014823.2.
NP_061852.3. NM_018979.3. [Q9H4A3-1]
NP_998820.3. NM_213655.4. [Q9H4A3-5]
XP_016875326.1. XM_017019837.1.
XP_016875327.1. XM_017019838.1. [Q9H4A3-2]
UniGeneiHs.744906.

Genome annotation databases

EnsembliENST00000315939; ENSP00000313059; ENSG00000060237. [Q9H4A3-1]
ENST00000340908; ENSP00000341292; ENSG00000060237. [Q9H4A3-5]
ENST00000530271; ENSP00000433548; ENSG00000060237. [Q9H4A3-7]
ENST00000537687; ENSP00000444465; ENSG00000060237. [Q9H4A3-6]
GeneIDi65125.
KEGGihsa:65125.
UCSCiuc001qio.4. human. [Q9H4A3-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296290 mRNA. Translation: CAC15059.1.
JQ358908 mRNA. Translation: AEY99342.1.
FJ515833 Genomic DNA. Translation: ACS13726.1.
FJ515833 Genomic DNA. Translation: ACS13727.1.
FJ515833 Genomic DNA. Translation: ACS13728.1.
AC004765 Genomic DNA. No translation available.
AC004803 Genomic DNA. No translation available.
AF061944 mRNA. Translation: AAF31483.1. Sequence problems.
AB002342 mRNA. Translation: BAA20802.2.
AY231477 mRNA. Translation: AAO46160.1.
BC013629 mRNA. Translation: AAH13629.2.
BC130467 mRNA. Translation: AAI30468.1. Sequence problems.
BC130469 mRNA. Translation: AAI30470.1. Sequence problems.
BK004108 Genomic DNA. Translation: DAA04494.1. Sequence problems.
CCDSiCCDS73419.1. [Q9H4A3-5]
CCDS8506.1. [Q9H4A3-1]
RefSeqiNP_001171914.1. NM_001184985.1. [Q9H4A3-6]
NP_055638.2. NM_014823.2.
NP_061852.3. NM_018979.3. [Q9H4A3-1]
NP_998820.3. NM_213655.4. [Q9H4A3-5]
XP_016875326.1. XM_017019837.1.
XP_016875327.1. XM_017019838.1. [Q9H4A3-2]
UniGeneiHs.744906.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PWNX-ray1.84A210-482[»]
5TF9X-ray2.50A/B206-483[»]
ProteinModelPortaliQ9H4A3.
SMRiQ9H4A3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122403. 65 interactors.
DIPiDIP-32648N.
IntActiQ9H4A3. 61 interactors.
MINTiMINT-2879524.
STRINGi9606.ENSP00000313059.

Chemistry databases

BindingDBiQ9H4A3.
ChEMBLiCHEMBL1075173.
GuidetoPHARMACOLOGYi2280.

PTM databases

iPTMnetiQ9H4A3.
PhosphoSitePlusiQ9H4A3.

Polymorphism and mutation databases

BioMutaiWNK1.
DMDMi296453029.

Proteomic databases

EPDiQ9H4A3.
MaxQBiQ9H4A3.
PaxDbiQ9H4A3.
PeptideAtlasiQ9H4A3.
PRIDEiQ9H4A3.

Protocols and materials databases

DNASUi65125.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000315939; ENSP00000313059; ENSG00000060237. [Q9H4A3-1]
ENST00000340908; ENSP00000341292; ENSG00000060237. [Q9H4A3-5]
ENST00000530271; ENSP00000433548; ENSG00000060237. [Q9H4A3-7]
ENST00000537687; ENSP00000444465; ENSG00000060237. [Q9H4A3-6]
GeneIDi65125.
KEGGihsa:65125.
UCSCiuc001qio.4. human. [Q9H4A3-1]

Organism-specific databases

CTDi65125.
DisGeNETi65125.
GeneCardsiWNK1.
GeneReviewsiWNK1.
H-InvDBHIX0010312.
HGNCiHGNC:14540. WNK1.
HPAiHPA046541.
HPA059157.
MalaCardsiWNK1.
MIMi201300. phenotype.
605232. gene.
614492. phenotype.
neXtProtiNX_Q9H4A3.
OpenTargetsiENSG00000060237.
Orphaneti970. Hereditary sensory and autonomic neuropathy type 2.
88940. Pseudohypoaldosteronism type 2C.
PharmGKBiPA134944932.
PA33782.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0584. Eukaryota.
ENOG410XQWZ. LUCA.
GeneTreeiENSGT00800000124049.
HOVERGENiHBG079897.
InParanoidiQ9H4A3.
KOiK08867.
OMAiHERPVSF.
OrthoDBiEOG091G06LL.
PhylomeDBiQ9H4A3.
TreeFamiTF315363.

Enzyme and pathway databases

BioCyciZFISH:HS00741-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiQ9H4A3.
SIGNORiQ9H4A3.

Miscellaneous databases

ChiTaRSiWNK1. human.
GeneWikiiWNK1.
GenomeRNAii65125.
PROiQ9H4A3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000060237.
CleanExiHS_WNK1.
ExpressionAtlasiQ9H4A3. baseline and differential.
GenevisibleiQ9H4A3. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWNK1_HUMAN
AccessioniPrimary (citable) accession number: Q9H4A3
Secondary accession number(s): A1L4B0
, C5HTZ5, C5HTZ6, C5HTZ7, H6WZW3, O15052, P54963, Q4VBX9, Q6IFS5, Q86WL5, Q8N673, Q96CZ6, Q9P1S9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 170 of the entry and version 2 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

Caution

PubMed:2507249 describes a peptide sequence containing a GlcNAc glycosylated Ser in position 164 while it is an Arg residue according to others.Curated
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.By similarity
HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown to be a nervous system-specific exon of WNK1 included in isoform 4 and isoform 5 (PubMed:18521183).1 Publication
It is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.