Reviewed, UniProtKB/Swiss-Prot Q9H4A3 (WNK1_HUMAN)

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

Name:	WNK1
Synonyms:	KDP, KIAA0344, PRKWNK1

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	Cytoplasm.
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

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Protein kinase inhibitor Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	ion transport Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid phosphorylation Ref.3 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.3 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.3 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct protein kinase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Ref.3 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: ADDA6C86554B7FCA	FASTA	2,382	250,756
	10 20 30 40 50 60 MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR TEEYRRRRHT 70 80 90 100 110 120 MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL SLPQPSIPAA VPQSAPPEPH 130 140 150 160 170 180 REETVTATAT SQVAQQPPAA AAPGEQAVAG PAPSTVPSST SKDRPVSQPS LVGSKEEPPP 190 200 210 220 230 240 ARSGSGGGSA KEPQEERSQQ QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD 250 260 270 280 290 300 TETTVEVAWC ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV 310 320 330 340 350 360 TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL KCDNIFITGP 370 380 390 400 410 420 TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD ESVDVYAFGM CMLEMATSEY 430 440 450 460 470 480 PYSECQNAAQ IYRRVTSGVK PASFDKVAIP EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ 490 500 510 520 530 540 EETGVRVELA EEDDGEKIAI KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM 550 560 570 580 590 600 VESGYVCEGD HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ 610 620 630 640 650 660 TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL SDGTVDSGQG 670 680 690 700 710 720 SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA QSQPHGVYPP SSVAQGQSQG 730 740 750 760 770 780 QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP PQQTVQYSLS QTSTSSEATT AQPVSQPQAP 790 800 810 820 830 840 QVLPQVSAGK QLPVSQPVPT IQGEPQIPVA TQPSVVPVHS GAHFLPVGQP LPTPLLPQYP 850 860 870 880 890 900 VSQIPISTPH VSTAQTGFSS LPITMAAGIT QPLLTLASSA TTAAIPGVST VVPSQLPTLL 910 920 930 940 950 960 QPVTQLPSQV HPQLLQPAVQ SMGIPANLGQ AAEVPLSSGD VLYQGFPPRL PPQYPGDSNI 970 980 990 1000 1010 1020 APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE SNLLVPMGGV GGQVQVSQPG 1030 1040 1050 1060 1070 1080 GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP VAVAQPQATQ PTTLASSVDS AHSDVASGMS 1090 1100 1110 1120 1130 1140 DGNENVPSSS GRHEGRTTKR HYRKSVRSRS RHEKTSRPKL RILNVSNKGD RVVECQLETH 1150 1160 1170 1180 1190 1200 NRKMVTFKFD LDGDNPEEIA TIMVNNDFIL AIERESFVDQ VREIIEKADE MLSEDVSVEP 1210 1220 1230 1240 1250 1260 EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI GIPTSSLTQV VHSAGRRFIV 1270 1280 1290 1300 1310 1320 SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS LSLQQAFSEL RRAQMTEGPN 1330 1340 1350 1360 1370 1380 TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA AATAPVPATS SPPNDISTSV IQSEVTVPTE 1390 1400 1410 1420 1430 1440 EGIAGVATST GVVTSGGLPI PPVSESPVLS SVVSSITIPA VVSISTTSPS LQVPTSTSEI 1450 1460 1470 1480 1490 1500 VVSSTALYPS VTVSATSASA GGSTATPGPK PPAVVSQQAA GSTTVGATLT SVSTTTSFPS 1510 1520 1530 1540 1550 1560 TASQLSIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL AFSLSAPSSS SSPGAGVSSY 1570 1580 1590 1600 1610 1620 ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI PPLVQPVANV PAVQQTLIHS 1630 1640 1650 1660 1670 1680 QPQPALLPNQ PHTHCPEVDS DTQPKAPGID DIKTLEEKLR SLFSEHSSSG AQHASVSLET 1690 1700 1710 1720 1730 1740 SLVIESTVTP GIPTTAVAPS KLLTSTTSTC LPPTNLPLGT VALPVTPVVT PGQVSTPVST 1750 1760 1770 1780 1790 1800 TTSGVKPGTA PSKPPLTKAP VLPVGTELPA GTLPSEQLPP FPGPSLTQSQ QPLEDLDAQL 1810 1820 1830 1840 1850 1860 RRTLSPEIIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV KEGPVLATSS GAGVFKMGRF 1870 1880 1890 1900 1910 1920 QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP ESTLVKPEPN GITIPGISSD 1930 1940 1950 1960 1970 1980 VPESAHKTTA SEAKSDTGQP TKVGRFQVTT TANKVGRFSV SKTEDKITDT KKEGPVASPP 1990 2000 2010 2020 2030 2040 FMDLEQAVLP AVIPKKEKPE LSEPSHLNGP SSDPEAAFLS RDVDDGSGSP HSPHQLSSKS 2050 2060 2070 2080 2090 2100 LPSQNLSQSL SNSFNSSYMS SDNESDIEDE DLKLELRRLR DKHLKEIQDL QSRQKHEIES 2110 2120 2130 2140 2150 2160 LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS LGNKSPQLSG NLSGQSAASV 2170 2180 2190 2200 2210 2220 LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS DGAISVPSLS APGQGTSSTN 2230 2240 2250 2260 2270 2280 TVGATVNSQA AQAQPPAMTS SRKGTFTDDL HKLVDNWARD AMNLSGRRGS KGHMNYEGPG 2290 2300 2310 2320 2330 2340 MARKFSAPGQ LCISMTSNLG GSAPISAASA TSLGHFTKSM CPPQQYGFPA TPFGAQWSGT 2350 2360 2370 2380 GGPAPQPLGQ FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT
	Isoform 2. Checksum: 23AFF05CC1844947	FASTA	2,136	225,650
	10 20 30 40 50 60 MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR TEEYRRRRHT 70 80 90 100 110 120 MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL SLPQPSIPAA VPQSAPPEPH 130 140 150 160 170 180 REETVTATAT SQVAQQPPAA AAPGEQAVAG PAPSTVPSST SKDRPVSQPS LVGSKEEPPP 190 200 210 220 230 240 ARSGSGGGSA KEPQEERSQQ QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD 250 260 270 280 290 300 TETTVEVAWC ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV 310 320 330 340 350 360 TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL KCDNIFITGP 370 380 390 400 410 420 TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD ESVDVYAFGM CMLEMATSEY 430 440 450 460 470 480 PYSECQNAAQ IYRRVTSGVK PASFDKVAIP EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ 490 500 510 520 530 540 EETGVRVELA EEDDGEKIAI KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM 550 560 570 580 590 600 VESGYVCEGD HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ 610 620 630 640 650 660 TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL SDGTVDSGQG 670 680 690 700 710 720 SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA QSQPHGVYPP SSVAQGQSQG 730 740 750 760 770 780 QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP PQQTVQYSLS QTSTSSEATT AQPVSQPQAP 790 800 810 820 830 840 QVLPQVSAGK QSTQGVSQVA PAEPVAVAQP QATQPTTLAS SVDSAHSDVA SGMSDGNENV 850 860 870 880 890 900 PSSSGRHEGR TTKRHYRKSV RSRSRHEKTS RPKLRILNVS NKGDRVVECQ LETHNRKMVT 910 920 930 940 950 960 FKFDLDGDNP EEIATIMVNN DFILAIERES FVDQVREIIE KADEMLSEDV SVEPEGDQGL 970 980 990 1000 1010 1020 ESLQGKDDYG FSGSQKLEGE FKQPIPASSM PQQIGIPTSS LTQVVHSAGR RFIVSPVPES 1030 1040 1050 1060 1070 1080 RLRESKVFPS EITDTVAAST AQSPGMNLSH SASSLSLQQA FSELRRAQMT EGPNTAPPNF 1090 1100 1110 1120 1130 1140 SHTGPTFPVV PPFLSSIAGV PTTAAATAPV PATSSPPNDI STSVIQSEVT VPTEEGIAGV 1150 1160 1170 1180 1190 1200 ATSTGVVTSG GLPIPPVSES PVLSSVVSSI TIPAVVSIST TSPSLQVPTS TSEIVVSSTA 1210 1220 1230 1240 1250 1260 LYPSVTVSAT SASAGGSTAT PGPKPPAVVS QQAAGSTTVG ATLTSVSTTT SFPSTASQLS 1270 1280 1290 1300 1310 1320 IQLSSSTSTP TLAETVVVSA HSLDKTSHSS TTGLAFSLSA PSSSSSPGAG VSSYISQPGG 1330 1340 1350 1360 1370 1380 LHPLVIPSVI ASTPILPQAA GPTSTPLLPQ VPSIPPLVQP VANVPAVQQT LIHSQPQPAL 1390 1400 1410 1420 1430 1440 LPNQPHTHCP EVDSDTQPKA PGIDDIKTLE EKLRSLFSEH SSSGAQHASV SLETSLVIES 1450 1460 1470 1480 1490 1500 TVTPGIPTTA VAPSKLLTST TSTCLPPTNL PLGTVALPVT PVVTPGQVST PVSTTTSGVK 1510 1520 1530 1540 1550 1560 PGTAPSKPPL TKAPVLPVGT ELPAGTLPSE QLPPFPGPSL TQSQQPLEDL DAQLRRTLSP 1570 1580 1590 1600 1610 1620 EIITVTSAVG PVSMAAPTAI TEAGTQPQKG VSQVKEGPVL ATSSGAGVFK MGRFQVSVAA 1630 1640 1650 1660 1670 1680 DGAQKEGKNK SEDAKSVHFE SSTSESSVLS SSSPESTLVK PEPNGITIPG ISSDVPESAH 1690 1700 1710 1720 1730 1740 KTTASEAKSD TGQPTKVGRF QVTTTANKVG RFSVSKTEDK ITDTKKEGPV ASPPFMDLEQ 1750 1760 1770 1780 1790 1800 AVLPAVIPKK EKPELSEPSH LNGPSSDPEA AFLSRDVDDG SGSPHSPHQL SSKSLPSQNL 1810 1820 1830 1840 1850 1860 SQSLSNSFNS SYMSSDNESD IEDEDLKLEL RRLRDKHLKE IQDLQSRQKH EIESLYTKLG 1870 1880 1890 1900 1910 1920 KVPPAVIIPP AAPLSGRRRR PTKSKGSKSS RSSSLGNKSP QLSGNLSGQS AASVLHPQQT 1930 1940 1950 1960 1970 1980 LHPPGNIPES GQNQLLQPLK PSPSSDNLYS AFTSDGAISV PSLSAPGQGT SSTNTVGATV 1990 2000 2010 2020 2030 2040 NSQAAQAQPP AMTSSRKGTF TDDLHKLVDN WARDAMNLSG RRGSKGHMNY EGPGMARKFS 2050 2060 2070 2080 2090 2100 APGQLCISMT SNLGGSAPIS AASATSLGHF TKSMCPPQQY GFPATPFGAQ WSGTGGPAPQ 2110 2120 2130 PLGQFQPVGT ASLQNFNISN LQKSISNPPG SNLRTT
	Isoform 3 (Kidney-specific) (Kinase-defective). Checksum: 5F86DCBFED19D713	FASTA	1,975	206,608
	10 20 30 40 50 60 MDIKKKDFCS VFVIINSHCC CCPQKDCINE GVKPASFDKV AIPEVKEIIE GCIRQNKDER 70 80 90 100 110 120 YSIKDLLNHA FFQEETGVRV ELAEEDDGEK IAIKLWLRIE DIKKLKGKYK DNEAIEFSFD 130 140 150 160 170 180 LERDVPEDVA QEMVESGYVC EGDHKTMAKA IKDRVSLIKR KREQRQLVRE EQEKKKQEES 190 200 210 220 230 240 SLKQQVEQSS ASQTGIKQLP SASTGIPTAS TTSASVSTQV EPEEPEADQH QQLQYQQPSI 250 260 270 280 290 300 SVLSDGTVDS GQGSSVFTES RVSSQQTVSY GSQHEQAHST GTVPGHIPST VQAQSQPHGV 310 320 330 340 350 360 YPPSSVAQGQ SQGQPSSSSL TGVSSSQPIQ HPQQQQGIQQ TAPPQQTVQY SLSQTSTSSE 370 380 390 400 410 420 ATTAQPVSQP QAPQVLPQVS AGKQLPVSQP VPTIQGEPQI PVATQPSVVP VHSGAHFLPV 430 440 450 460 470 480 GQPLPTPLLP QYPVSQIPIS TPHVSTAQTG FSSLPITMAA GITQPLLTLA SSATTAAIPG 490 500 510 520 530 540 VSTVVPSQLP TLLQPVTQLP SQVHPQLLQP AVQSMGIPAN LGQAAEVPLS SGDVLYQGFP 550 560 570 580 590 600 PRLPPQYPGD SNIAPSSNVA SVCIHSTVLS PPMPTEVLAT PGYFPTVVQP YVESNLLVPM 610 620 630 640 650 660 GGVGGQVQVS QPGGSLAQAP TTSSQQAVLE STQGVSQVAP AEPVAVAQPQ ATQPTTLASS 670 680 690 700 710 720 VDSAHSDVAS GMSDGNENVP SSSGRHEGRT TKRHYRKSVR SRSRHEKTSR PKLRILNVSN 730 740 750 760 770 780 KGDRVVECQL ETHNRKMVTF KFDLDGDNPE EIATIMVNND FILAIERESF VDQVREIIEK 790 800 810 820 830 840 ADEMLSEDVS VEPEGDQGLE SLQGKDDYGF SGSQKLEGEF KQPIPASSMP QQIGIPTSSL 850 860 870 880 890 900 TQVVHSAGRR FIVSPVPESR LRESKVFPSE ITDTVAASTA QSPGMNLSHS ASSLSLQQAF 910 920 930 940 950 960 SELRRAQMTE GPNTAPPNFS HTGPTFPVVP PFLSSIAGVP TTAAATAPVP ATSSPPNDIS 970 980 990 1000 1010 1020 TSVIQSEVTV PTEEGIAGVA TSTGVVTSGG LPIPPVSESP VLSSVVSSIT IPAVVSISTT 1030 1040 1050 1060 1070 1080 SPSLQVPTST SEIVVSSTAL YPSVTVSATS ASAGGSTATP GPKPPAVVSQ QAAGSTTVGA 1090 1100 1110 1120 1130 1140 TLTSVSTTTS FPSTASQLSI QLSSSTSTPT LAETVVVSAH SLDKTSHSST TGLAFSLSAP 1150 1160 1170 1180 1190 1200 SSSSSPGAGV SSYISQPGGL HPLVIPSVIA STPILPQAAG PTSTPLLPQV PSIPPLVQPV 1210 1220 1230 1240 1250 1260 ANVPAVQQTL IHSQPQPALL PNQPHTHCPE VDSDTQPKAP GIDDIKTLEE KLRSLFSEHS 1270 1280 1290 1300 1310 1320 SSGAQHASVS LETSLVIEST VTPGIPTTAV APSKLLTSTT STCLPPTNLP LGTVALPVTP 1330 1340 1350 1360 1370 1380 VVTPGQVSTP VSTTTSGVKP GTAPSKPPLT KAPVLPVGTE LPAGTLPSEQ LPPFPGPSLT 1390 1400 1410 1420 1430 1440 QSQQPLEDLD AQLRRTLSPE IITVTSAVGP VSMAAPTAIT EAGTQPQKGV SQVKEGPVLA 1450 1460 1470 1480 1490 1500 TSSGAGVFKM GRFQVSVAAD GAQKEGKNKS EDAKSVHFES STSESSVLSS SSPESTLVKP 1510 1520 1530 1540 1550 1560 EPNGITIPGI SSDVPESAHK TTASEAKSDT GQPTKVGRFQ VTTTANKVGR FSVSKTEDKI 1570 1580 1590 1600 1610 1620 TDTKKEGPVA SPPFMDLEQA VLPAVIPKKE KPELSEPSHL NGPSSDPEAA FLSRDVDDGS 1630 1640 1650 1660 1670 1680 GSPHSPHQLS SKSLPSQNLS QSLSNSFNSS YMSSDNESDI EDEDLKLELR RLRDKHLKEI 1690 1700 1710 1720 1730 1740 QDLQSRQKHE IESLYTKLGK VPPAVIIPPA APLSGRRRRP TKSKGSKSSR SSSLGNKSPQ 1750 1760 1770 1780 1790 1800 LSGNLSGQSA ASVLHPQQTL HPPGNIPESG QNQLLQPLKP SPSSDNLYSA FTSDGAISVP 1810 1820 1830 1840 1850 1860 SLSAPGQGTS STNTVGATVN SQAAQAQPPA MTSSRKGTFT DDLHKLVDNW ARDAMNLSGR 1870 1880 1890 1900 1910 1920 RGSKGHMNYE GPGMARKFSA PGQLCISMTS NLGGSAPISA ASATSLGHFT KSMCPPQQYG 1930 1940 1950 1960 1970 FPATPFGAQW SGTGGPAPQP LGQFQPVGTA SLQNFNISNL QKSISNPPGS NLRTT

References

	« Hide 'large scale' referencesShow '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. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., 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. , 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., 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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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 , C5HTZ6, C5HTZ7, O15052, P54963, Q4VBX9, Q86WL5, Q8N673, Q9P1S9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	March 1, 2001
Last modified:	November 24, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete 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.