Q9BYP7 (WNK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase WNK3
EC=2.7.11.1

Alternative name(s):
Protein kinase lysine-deficient 3
Protein kinase with no lysine 3

Gene names

Name:	WNK3
Synonyms:	KIAA1566, PRKWNK3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1800 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca2+ influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to Ref.12, isoform 1 inhibits the activity of SLC12A3. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9H4A3
Cofactor	Magnesium By similarity. UniProtKB Q9H4A3
Enzyme regulation	Activation requires autophosphorylation of Ser-308. Phosphorylation of Ser-304 also promotes increased activity By similarity. Kinase activity is inhibited by WNK4. Ref.10 UniProtKB Q9JIH7
Subunit structure	Interacts with WNK1 and WNK4. Ref.10
Subcellular location	Cytoplasm Ref.9.
Tissue specificity	Expressed in brain, lung, kidney, liver and pancreas, and in fetal tissues including placenta, fetal brain, lung and kidney. Very low levels of expression were also detected in fetal heart, thymus, liver and spleen. Isoform 1 is brain-specific. Isoform 3 is kidney-specific. Ref.1 Ref.3 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Contains 1 protein kinase domain.
Caution	Cys-176 is present instead of the conserved Lys which is expected to be an active site residue. Lys-159 appears to fulfill the required catalytic function. UniProtKB Q9JIH7

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype Ref.9. Source: UniProtKB positive regulation of calcium ion transport Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of establishment of protein localization to plasma membrane Inferred from direct assay Ref.6. Source: BHF-UCL positive regulation of peptidyl-threonine phosphorylation Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of rubidium ion transmembrane transporter activity Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of rubidium ion transport Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of sodium ion transmembrane transporter activity Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of sodium ion transport Inferred from direct assay Ref.6. Source: BHF-UCL protein autophosphorylation Inferred from direct assay Ref.6. Source: BHF-UCL regulation of ion homeostasis Inferred from mutant phenotype Ref.14. Source: UniProtKB
Cellular_component	adherens junction Inferred from sequence or structural similarity. Source: BHF-UCL cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB tight junction Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP3	P42574	2	EBI-1182602,EBI-524064

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BYP7-1)

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.

Isoform 2 (identifier: Q9BYP7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1614-1624: GKSCLINELEN → D

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9BYP7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1248-1294: Missing.
     1614-1624: GKSCLINELEN → D

Isoform 4 (identifier: Q9BYP7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1248-1294: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1800	1800	Serine/threonine-protein kinase WNK3		PRO_0000086823
Regions
	Domain	147 – 405	259	Protein kinase
	Nucleotide binding	153 – 161	9	ATP By similarity UniProtKB Q8TDX7
Sites
	Active site	275	1	Proton acceptor By similarity UniProtKB Q8TDX7
	Binding site	159	1	ATP By similarity UniProtKB Q9JIH7
Amino acid modifications
	Modified residue	62	1	Phosphoserine Ref.15
	Modified residue	304	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
	Modified residue	308	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
Natural variations
	Alternative sequence	1248 – 1294	47	Missing in isoform 3 and isoform 4.		VSP_041932
	Alternative sequence	1614 – 1624	11	GKSCLINELEN → D in isoform 3 and isoform 2.		VSP_041933
	Natural variant	704	1	Q → H. Ref.16 Corresponds to variant rs56077971 [ dbSNP | Ensembl ].		VAR_041323
	Natural variant	854	1	S → C in a lung squamous cell carcinoma sample; somatic mutation. Ref.16		VAR_041324
	Natural variant	998	1	A → T. Ref.16 Corresponds to variant rs56404148 [ dbSNP | Ensembl ].		VAR_041325
	Natural variant	1169	1	K → E. Ref.16 Corresponds to variant rs55903619 [ dbSNP | Ensembl ].		VAR_041326
	Natural variant	1375	1	T → I. Ref.16 Corresponds to variant rs55879434 [ dbSNP | Ensembl ].		VAR_041327
	Natural variant	1533	1	L → F in a lung large cell carcinoma sample; somatic mutation. Ref.16		VAR_041328
	Natural variant	1634	1	S → P in a renal clear cell carcinoma sample; somatic mutation. Ref.16		VAR_041329
Experimental info
	Mutagenesis	294	1	D → A: Catalytically inactive form. Inhibits sodium-coupled chloride cotransporters and activates potassium-coupled chloride cotransporters. Ref.6 Ref.14
	Sequence conflict	10	1	S → N in AAL99253. Ref.3
	Sequence conflict	431 – 432	2	WV → RD in BAB13392. Ref.5
	Sequence conflict	1211	1	P → S in BAB13392. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 19, 2011. Version 3. Checksum: 1766D6AC8C7DE864	FASTA	1,800	198,416
	10 20 30 40 50 60 MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG ETVERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG GQEVKYEQCS KSTSEISKDC 130 140 150 160 170 180 FKEKNEKEME EEAEMKAVAT SPSGRFLKFD IELGRGAFKT VYKGLDTETW VEVAWCELQD 190 200 210 220 230 240 RKLTKAEQQR FKEEAEMLKG LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK 250 260 270 280 290 300 RFKVMKPKVL RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL 310 320 330 340 350 360 MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE CQNAAQIYRK 370 380 390 400 410 420 VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL NHAFFAEDTG LRVELAEEDD 430 440 450 460 470 480 CSNSSLALRL WVEDPKKLKG KHKDNEAIEF SFNLETDTPE EVAYEMVKSG FFHESDSKAV 490 500 510 520 530 540 AKSIRDRVTP IKKTREKKPA GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE 550 560 570 580 590 600 TEVDQHVRQQ LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV 610 620 630 640 650 660 SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST VLPVHVLGPT 670 680 690 700 710 720 VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR SLNQDVATTK ENVSSPDNPS 730 740 750 760 770 780 GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ VSTSGDNMVE CQLETHNNKM VTFKFDVDGD 790 800 810 820 830 840 APEDIADYMV EDNFVLESEK EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS 850 860 870 880 890 900 QTGSSEQVQI NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR 910 920 930 940 950 960 HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA SVETKQPAIL 970 980 990 1000 1010 1020 YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI FIPVYPCHQT ASQADALMSH 1030 1040 1050 1060 1070 1080 PGESTQTSGN SLTTLAFDQK PQTLSVQQPA MDAEFISQEG ETTVNTEASS PKTVIPTQTP 1090 1100 1110 1120 1130 1140 GLEPTTLQPT TVLESDGERP PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS 1150 1160 1170 1180 1190 1200 IDSPFSSSAE DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF 1210 1220 1230 1240 1250 1260 KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGGGY FGLSFTCPSL 1270 1280 1290 1300 1310 1320 KNPISKKSWT RKLKSWAYRL RQSTSFFKRS KVRQVETEEM RSAIAPDPIP LTRESTADTR 1330 1340 1350 1360 1370 1380 ALNRCKAMSG SFQRGRFQVI TIPQQQSAKM TSFGIEHISV FSETNHSSEE AFIKTAKSQL 1390 1400 1410 1420 1430 1440 VEIEPATQNP KTSFSYEKLQ ALQETCKENK GVPKQGDNFL SFSAACETDV SSVTPEKEFE 1450 1460 1470 1480 1490 1500 ETSATGSSMQ SGSELLLKER EILTAGKQPS SDSEFSASLA GSGKSVAKTG PESNQCLPHH 1510 1520 1530 1540 1550 1560 EEQAYAQTQS SLFYSPSSPM SSDDESEIED EDLKVELQRL REKHIQEVVN LQTQQNKELQ 1570 1580 1590 1600 1610 1620 ELYERLRSIK DSKTQSTEIP LPPASPRRPR SFKSKLRSRP QSLTHVDNGI VATGKSCLIN 1630 1640 1650 1660 1670 1680 ELENPLCVES NAASCQQSPA SKKGMFTDDL HKLVDDWTKE AVGNSLIKPS LNQLKQSQHK 1690 1700 1710 1720 1730 1740 LETENWNKVS ENTPSTMGYT STWISSLSQI RGAVPTSLPQ GLSLPSFPGP LSSYGMPHVC 1750 1760 1770 1780 1790 1800 QYNAVAGAGY PVQWVGISGT TQQSVVIPAQ SGGPFQPGMN MQAFPTSSVQ NPATIPPGPK
	Isoform 2 [UniParc]. Checksum: F49E2D171D308FE3	FASTA	1,790	197,329
	10 20 30 40 50 60 MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG ETVERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG GQEVKYEQCS KSTSEISKDC 130 140 150 160 170 180 FKEKNEKEME EEAEMKAVAT SPSGRFLKFD IELGRGAFKT VYKGLDTETW VEVAWCELQD 190 200 210 220 230 240 RKLTKAEQQR FKEEAEMLKG LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK 250 260 270 280 290 300 RFKVMKPKVL RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL 310 320 330 340 350 360 MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE CQNAAQIYRK 370 380 390 400 410 420 VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL NHAFFAEDTG LRVELAEEDD 430 440 450 460 470 480 CSNSSLALRL WVEDPKKLKG KHKDNEAIEF SFNLETDTPE EVAYEMVKSG FFHESDSKAV 490 500 510 520 530 540 AKSIRDRVTP IKKTREKKPA GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE 550 560 570 580 590 600 TEVDQHVRQQ LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV 610 620 630 640 650 660 SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST VLPVHVLGPT 670 680 690 700 710 720 VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR SLNQDVATTK ENVSSPDNPS 730 740 750 760 770 780 GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ VSTSGDNMVE CQLETHNNKM VTFKFDVDGD 790 800 810 820 830 840 APEDIADYMV EDNFVLESEK EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS 850 860 870 880 890 900 QTGSSEQVQI NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR 910 920 930 940 950 960 HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA SVETKQPAIL 970 980 990 1000 1010 1020 YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI FIPVYPCHQT ASQADALMSH 1030 1040 1050 1060 1070 1080 PGESTQTSGN SLTTLAFDQK PQTLSVQQPA MDAEFISQEG ETTVNTEASS PKTVIPTQTP 1090 1100 1110 1120 1130 1140 GLEPTTLQPT TVLESDGERP PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS 1150 1160 1170 1180 1190 1200 IDSPFSSSAE DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF 1210 1220 1230 1240 1250 1260 KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGGGY FGLSFTCPSL 1270 1280 1290 1300 1310 1320 KNPISKKSWT RKLKSWAYRL RQSTSFFKRS KVRQVETEEM RSAIAPDPIP LTRESTADTR 1330 1340 1350 1360 1370 1380 ALNRCKAMSG SFQRGRFQVI TIPQQQSAKM TSFGIEHISV FSETNHSSEE AFIKTAKSQL 1390 1400 1410 1420 1430 1440 VEIEPATQNP KTSFSYEKLQ ALQETCKENK GVPKQGDNFL SFSAACETDV SSVTPEKEFE 1450 1460 1470 1480 1490 1500 ETSATGSSMQ SGSELLLKER EILTAGKQPS SDSEFSASLA GSGKSVAKTG PESNQCLPHH 1510 1520 1530 1540 1550 1560 EEQAYAQTQS SLFYSPSSPM SSDDESEIED EDLKVELQRL REKHIQEVVN LQTQQNKELQ 1570 1580 1590 1600 1610 1620 ELYERLRSIK DSKTQSTEIP LPPASPRRPR SFKSKLRSRP QSLTHVDNGI VATDPLCVES 1630 1640 1650 1660 1670 1680 NAASCQQSPA SKKGMFTDDL HKLVDDWTKE AVGNSLIKPS LNQLKQSQHK LETENWNKVS 1690 1700 1710 1720 1730 1740 ENTPSTMGYT STWISSLSQI RGAVPTSLPQ GLSLPSFPGP LSSYGMPHVC QYNAVAGAGY 1750 1760 1770 1780 1790 PVQWVGISGT TQQSVVIPAQ SGGPFQPGMN MQAFPTSSVQ NPATIPPGPK
	Isoform 3 [UniParc]. Checksum: 7B06CC8C7E8E4D67	FASTA	1,743	191,789
	10 20 30 40 50 60 MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG ETVERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG GQEVKYEQCS KSTSEISKDC 130 140 150 160 170 180 FKEKNEKEME EEAEMKAVAT SPSGRFLKFD IELGRGAFKT VYKGLDTETW VEVAWCELQD 190 200 210 220 230 240 RKLTKAEQQR FKEEAEMLKG LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK 250 260 270 280 290 300 RFKVMKPKVL RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL 310 320 330 340 350 360 MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE CQNAAQIYRK 370 380 390 400 410 420 VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL NHAFFAEDTG LRVELAEEDD 430 440 450 460 470 480 CSNSSLALRL WVEDPKKLKG KHKDNEAIEF SFNLETDTPE EVAYEMVKSG FFHESDSKAV 490 500 510 520 530 540 AKSIRDRVTP IKKTREKKPA GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE 550 560 570 580 590 600 TEVDQHVRQQ LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV 610 620 630 640 650 660 SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST VLPVHVLGPT 670 680 690 700 710 720 VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR SLNQDVATTK ENVSSPDNPS 730 740 750 760 770 780 GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ VSTSGDNMVE CQLETHNNKM VTFKFDVDGD 790 800 810 820 830 840 APEDIADYMV EDNFVLESEK EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS 850 860 870 880 890 900 QTGSSEQVQI NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR 910 920 930 940 950 960 HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA SVETKQPAIL 970 980 990 1000 1010 1020 YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI FIPVYPCHQT ASQADALMSH 1030 1040 1050 1060 1070 1080 PGESTQTSGN SLTTLAFDQK PQTLSVQQPA MDAEFISQEG ETTVNTEASS PKTVIPTQTP 1090 1100 1110 1120 1130 1140 GLEPTTLQPT TVLESDGERP PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS 1150 1160 1170 1180 1190 1200 IDSPFSSSAE DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF 1210 1220 1230 1240 1250 1260 KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGVET EEMRSAIAPD 1270 1280 1290 1300 1310 1320 PIPLTRESTA DTRALNRCKA MSGSFQRGRF QVITIPQQQS AKMTSFGIEH ISVFSETNHS 1330 1340 1350 1360 1370 1380 SEEAFIKTAK SQLVEIEPAT QNPKTSFSYE KLQALQETCK ENKGVPKQGD NFLSFSAACE 1390 1400 1410 1420 1430 1440 TDVSSVTPEK EFEETSATGS SMQSGSELLL KEREILTAGK QPSSDSEFSA SLAGSGKSVA 1450 1460 1470 1480 1490 1500 KTGPESNQCL PHHEEQAYAQ TQSSLFYSPS SPMSSDDESE IEDEDLKVEL QRLREKHIQE 1510 1520 1530 1540 1550 1560 VVNLQTQQNK ELQELYERLR SIKDSKTQST EIPLPPASPR RPRSFKSKLR SRPQSLTHVD 1570 1580 1590 1600 1610 1620 NGIVATDPLC VESNAASCQQ SPASKKGMFT DDLHKLVDDW TKEAVGNSLI KPSLNQLKQS 1630 1640 1650 1660 1670 1680 QHKLETENWN KVSENTPSTM GYTSTWISSL SQIRGAVPTS LPQGLSLPSF PGPLSSYGMP 1690 1700 1710 1720 1730 1740 HVCQYNAVAG AGYPVQWVGI SGTTQQSVVI PAQSGGPFQP GMNMQAFPTS SVQNPATIPP GPK
	Isoform 4 [UniParc]. Checksum: D08B93F28F01E049	FASTA	1,753	192,875
	10 20 30 40 50 60 MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG ETVERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG GQEVKYEQCS KSTSEISKDC 130 140 150 160 170 180 FKEKNEKEME EEAEMKAVAT SPSGRFLKFD IELGRGAFKT VYKGLDTETW VEVAWCELQD 190 200 210 220 230 240 RKLTKAEQQR FKEEAEMLKG LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK 250 260 270 280 290 300 RFKVMKPKVL RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL 310 320 330 340 350 360 MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE CQNAAQIYRK 370 380 390 400 410 420 VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL NHAFFAEDTG LRVELAEEDD 430 440 450 460 470 480 CSNSSLALRL WVEDPKKLKG KHKDNEAIEF SFNLETDTPE EVAYEMVKSG FFHESDSKAV 490 500 510 520 530 540 AKSIRDRVTP IKKTREKKPA GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE 550 560 570 580 590 600 TEVDQHVRQQ LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV 610 620 630 640 650 660 SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST VLPVHVLGPT 670 680 690 700 710 720 VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR SLNQDVATTK ENVSSPDNPS 730 740 750 760 770 780 GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ VSTSGDNMVE CQLETHNNKM VTFKFDVDGD 790 800 810 820 830 840 APEDIADYMV EDNFVLESEK EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS 850 860 870 880 890 900 QTGSSEQVQI NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR 910 920 930 940 950 960 HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA SVETKQPAIL 970 980 990 1000 1010 1020 YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI FIPVYPCHQT ASQADALMSH 1030 1040 1050 1060 1070 1080 PGESTQTSGN SLTTLAFDQK PQTLSVQQPA MDAEFISQEG ETTVNTEASS PKTVIPTQTP 1090 1100 1110 1120 1130 1140 GLEPTTLQPT TVLESDGERP PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS 1150 1160 1170 1180 1190 1200 IDSPFSSSAE DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF 1210 1220 1230 1240 1250 1260 KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGVET EEMRSAIAPD 1270 1280 1290 1300 1310 1320 PIPLTRESTA DTRALNRCKA MSGSFQRGRF QVITIPQQQS AKMTSFGIEH ISVFSETNHS 1330 1340 1350 1360 1370 1380 SEEAFIKTAK SQLVEIEPAT QNPKTSFSYE KLQALQETCK ENKGVPKQGD NFLSFSAACE 1390 1400 1410 1420 1430 1440 TDVSSVTPEK EFEETSATGS SMQSGSELLL KEREILTAGK QPSSDSEFSA SLAGSGKSVA 1450 1460 1470 1480 1490 1500 KTGPESNQCL PHHEEQAYAQ TQSSLFYSPS SPMSSDDESE IEDEDLKVEL QRLREKHIQE 1510 1520 1530 1540 1550 1560 VVNLQTQQNK ELQELYERLR SIKDSKTQST EIPLPPASPR RPRSFKSKLR SRPQSLTHVD 1570 1580 1590 1600 1610 1620 NGIVATGKSC LINELENPLC VESNAASCQQ SPASKKGMFT DDLHKLVDDW TKEAVGNSLI 1630 1640 1650 1660 1670 1680 KPSLNQLKQS QHKLETENWN KVSENTPSTM GYTSTWISSL SQIRGAVPTS LPQGLSLPSF 1690 1700 1710 1720 1730 1740 PGPLSSYGMP HVCQYNAVAG AGYPVQWVGI SGTTQQSVVI PAQSGGPFQP GMNMQAFPTS 1750 SVQNPATIPP GPK

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION. Tissue: Brain.
[2]	Jordan P. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO N-TERMINUS.
[3]	"Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3)." Holden S., Cox J., Raymond F.L. Gene 335:109-119(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-1800 (ISOFORM 3). Tissue: Brain.
[6]	"WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis." Rinehart J., Kahle K.T., de Los Heros P., Vazquez N., Meade P., Wilson F.H., Hebert S.C., Gimenez I., Gamba G., Lifton R.P. Proc. Natl. Acad. Sci. U.S.A. 102:16777-16782(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-294, TISSUE SPECIFICITY.
[7]	"WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability." Kahle K.T., Rinehart J., de Los Heros P., Louvi A., Meade P., Vazquez N., Hebert S.C., Gamba G., Gimenez I., Lifton R.P. Proc. Natl. Acad. Sci. U.S.A. 102:16783-16788(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)." Leng Q., Kahle K.T., Rinehart J., MacGregor G.G., Wilson F.H., Canessa C.M., Lifton R.P., Hebert S.C. J. Physiol. (Lond.) 571:275-286(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway." Verissimo F., Silva E., Morris J.D., Pepperkok R., Jordan P. Oncogene 25:4172-4182(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex." Yang C.L., Zhu X., Ellison D.H. J. Clin. Invest. 117:3403-3411(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH WNK1 AND WNK4, ENZYME REGULATION.
[11]	"WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway." Zhang W., Na T., Peng J.B. Am. J. Physiol. 295:F1472-F1484(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Renal and brain isoforms of WNK3 have opposite effects on NCCT expression." Glover M., Zuber A.M., O'Shaughnessy K.M. J. Am. Soc. Nephrol. 20:1314-1322(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING.
[13]	"Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members." Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S., Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H. J. Biol. Chem. 285:25161-25167(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Similar Effects of all WNK3 Variants upon SLC12 Cotransporters." Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A., Pasantes-Morales H., Gamba G., Mercado A. Am. J. Physiol. 301:C601-C608(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORM 4), MUTAGENESIS OF ASP-294.
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-704; CYS-854; THR-998; GLU-1169; ILE-1375; PHE-1533 AND PRO-1634.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ409088 mRNA. Translation: CAC32455.2. AY082340 mRNA. Translation: AAL99253.1. AY352048 mRNA. Translation: AAR89465.1. AL591766, AL049793, Z84469 Genomic DNA. Translation: CAI40707.1. Z84469, AL049793, AL591766 Genomic DNA. Translation: CAI42732.1. AL049793, AL591766, Z84469 Genomic DNA. Translation: CAI43128.1. AL591766, AL049793, Z84469 Genomic DNA. Translation: CAI40708.1. Z84469, AL049793, AL591766 Genomic DNA. Translation: CAI42733.1. AL049793, AL591766, Z84469 Genomic DNA. Translation: CAI43129.1. AB046786 mRNA. Translation: BAB13392.1.
IPI	IPI00152474. IPI00387112.
RefSeq	NP_001002838.1. NM_001002838.3. NP_065973.2. NM_020922.4.
UniGene	Hs.92423.
3D structure databases
ProteinModelPortal	Q9BYP7.
SMR	Q9BYP7. Positions 136-498.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BYP7. 2 interactions.
STRING	9606.ENSP00000346667.
PTM databases
PhosphoSite	Q9BYP7.
Polymorphism databases
DMDM	41688792.
Proteomic databases
PaxDb	Q9BYP7.
PRIDE	Q9BYP7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354646; ENSP00000346667; ENSG00000196632. ENST00000375159; ENSP00000364301; ENSG00000196632. ENST00000375169; ENSP00000364312; ENSG00000196632. ENST00000594373; ENSP00000471368; ENSG00000269511. ENST00000598300; ENSP00000472115; ENSG00000269511. ENST00000599955; ENSP00000471833; ENSG00000269511.
GeneID	65267.
KEGG	hsa:65267.
UCSC	uc004dtc.2. human. uc004dtd.2. human.
Organism-specific databases
CTD	65267.
GeneCards	GC0XM054235.
HGNC	HGNC:14543. WNK3.
HPA	HPA031652.
MIM	300358. gene.
neXtProt	NX_Q9BYP7.
PharmGKB	PA33784.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000049042.
HOVERGEN	HBG050346.
KO	K08867.
OMA	KPAGCLE.
OrthoDB	EOG4894KK.
PhylomeDB	Q9BYP7.
Gene expression databases
ArrayExpress	Q9BYP7.
Bgee	Q9BYP7.
CleanEx	HS_WNK3.
Genevestigator	Q9BYP7.
GermOnline	ENSG00000196632. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR024678. Kinase_OSR1/WNK_CCT. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF12202. OSR1_C. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL6055.
GenomeRNAi	65267.
NextBio	67402.
SOURCE	Search...

Entry information

Entry name

WNK3_HUMAN

Accession

Primary (citable) accession number: Q9BYP7
Secondary accession number(s): B1AKG2 , Q5JRC1, Q6JP76, Q8TCX6, Q9HCK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	October 19, 2011
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.