Q80XP9 (WNK3_MOUSE) 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1757 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. Activates SLC12A1, SLC12A2, SLC12A3, SCNN1A, SCNN1B, SCNN1D and SGK1. Inhibits SLC12A4, SLC12A5, SLC12A6 and SLC12A7. Phosphorylates WNK4. Increases Ca2+ influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activation requires autophosphorylation of Ser-307. Phosphorylation of Ser-303 also promotes increased activity. Kinase activity is inhibited by WNK4 By similarity.
Subunit structure	Interacts with WNK1 and WNK4 By similarity.
Subcellular location	Cytoplasm By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Contains 1 protein kinase domain.
Caution	Cys-175 is present instead of the conserved Lys which is expected to be an active site residue. Lys-158 appears to fulfill the required catalytic function.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
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	positive regulation of establishment of protein localization to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-threonine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of rubidium ion transmembrane transporter activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of rubidium ion transport Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of sodium ion transmembrane transporter activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of sodium ion transport Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	adherens junction Inferred from direct assay PubMed 16275913. Source: BHF-UCL cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell tight junction Inferred from direct assay PubMed 16275913. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q80XP9-1)

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: Q80XP9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1217-1263: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1757	1757	Serine/threonine-protein kinase WNK3		PRO_0000278775
Regions
	Domain	146 – 404	259	Protein kinase
	Nucleotide binding	152 – 160	9	ATP By similarity
Sites
	Active site	274	1	Proton acceptor By similarity
	Binding site	158	1	ATP By similarity
Amino acid modifications
	Modified residue	62	1	Phosphoserine By similarity
	Modified residue	303	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	307	1	Phosphoserine; by autocatalysis By similarity
Natural variations
	Alternative sequence	1217 – 1263	47	Missing in isoform 2.		VSP_041934

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 9, 2013. Version 3. Checksum: 3E5B070772BE6725	FASTA	1,757	193,991
	10 20 30 40 50 60 MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG ENIERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG QEVKYEQCSK ATSESSKDCF 130 140 150 160 170 180 KEKTEKEMEE EAEMKAVATS PSGRFLKFDI ELGRGAFKTV YKGLDTETWV EVAWCELQDR 190 200 210 220 230 240 KLTKAEQQRF KEEAEMLKGL QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR 250 260 270 280 290 300 FKVMKPKVLR SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM 310 320 330 340 350 360 RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC QNAAQIYRKV 370 380 390 400 410 420 TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN HAFFAEDTGL RVELAEEDDC 430 440 450 460 470 480 SNSSLALRLW VEDPKKLKGK HKDNEAIEFS FNLEADTPEE VAYEMVKSGF FHESDSKAVA 490 500 510 520 530 540 KSIRDRVTLI KKIREKKPAG CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET 550 560 570 580 590 600 EVDQHVRQQF LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP 610 620 630 640 650 660 KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP IGAEQQATLQ 670 680 690 700 710 720 NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS CPRPEKGTKF QLTVLQVSVS 730 740 750 760 770 780 GDNMVECQLE THNNKMVTFK FDVDGDAPED IADYMVEDNF VLENEKEKFV EELRAIVGQA 790 800 810 820 830 840 QEILHVHSAV EKSIGVDSVA LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC 850 860 870 880 890 900 INQTIKNREA QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS 910 920 930 940 950 960 KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV CPVPGECEAL 970 980 990 1000 1010 1020 TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT SVLVSSDQKP QSLSVQQPTI 1030 1040 1050 1060 1070 1080 DAEFISKEGE TTVNTETSSP KAVIATQTPG FEPAVILPAT ILESDGERPP KMEFADNRIK 1090 1100 1110 1120 1130 1140 TLDEKLRNLL YQEHSISSIC PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS 1150 1160 1170 1180 1190 1200 PAQSPNFQQT GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA 1210 1220 1230 1240 1250 1260 YPAAVSSDGT IHLQTGGGYF GLSFTCPSLK NPISRKSWTR KLKSWAYRLR QSTSFFKRSK 1270 1280 1290 1300 1310 1320 VRQVETEDKR SAIASDPIPL TREFSSDTRA LSRCKAMSGS FQRGRFQVIT VPQQQPVKMM 1330 1340 1350 1360 1370 1380 SFGKDHRPPF NKTTVQSSEQ ALTFAEAAVS QLIEVEPAMP THKASVSSRK LRTLYETFKE 1390 1400 1410 1420 1430 1440 DKGDPEQGDI VSYSTACETS VSSVATEKNV TSTTEVSVQS GSEPLDKEKN ESTPGKQTCT 1450 1460 1470 1480 1490 1500 NEFSATLAGN RKSVTKTRPE GDQYLPLREE QAYAQTQNSL FYSPSSPMSS DNESEIEDED 1510 1520 1530 1540 1550 1560 LKVELQRLRE KHIQEVVSLQ TQQNKELQEL YERLRATKDN KAQSSEVPLS PASPRRPRSF 1570 1580 1590 1600 1610 1620 KSKLRSRPQS MTHSDNLVVK DALGVESNTV SCQQSPASKK GMFTDDLHKL VDDWTRETVG 1630 1640 1650 1660 1670 1680 HFPSKPSLNQ LKQSQQKSEA ENWNKSCEST PSTMGYTSNW ISSLSQIRGA APTSLPQGLP 1690 1700 1710 1720 1730 1740 LPSFHGPLAS YGMPHVCQYN AVGAAGYPVQ WVGISGPAQQ SVVLPTQSGG LFQPGMNLQS 1750 FPAPPVQNPA SIPPGPK
	Isoform 2 [UniParc]. Checksum: D825CA0153EC71F6	FASTA	1,710	188,423
	10 20 30 40 50 60 MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG ENIERKRFFR 70 80 90 100 110 120 KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG QEVKYEQCSK ATSESSKDCF 130 140 150 160 170 180 KEKTEKEMEE EAEMKAVATS PSGRFLKFDI ELGRGAFKTV YKGLDTETWV EVAWCELQDR 190 200 210 220 230 240 KLTKAEQQRF KEEAEMLKGL QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR 250 260 270 280 290 300 FKVMKPKVLR SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM 310 320 330 340 350 360 RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC QNAAQIYRKV 370 380 390 400 410 420 TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN HAFFAEDTGL RVELAEEDDC 430 440 450 460 470 480 SNSSLALRLW VEDPKKLKGK HKDNEAIEFS FNLEADTPEE VAYEMVKSGF FHESDSKAVA 490 500 510 520 530 540 KSIRDRVTLI KKIREKKPAG CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET 550 560 570 580 590 600 EVDQHVRQQF LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP 610 620 630 640 650 660 KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP IGAEQQATLQ 670 680 690 700 710 720 NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS CPRPEKGTKF QLTVLQVSVS 730 740 750 760 770 780 GDNMVECQLE THNNKMVTFK FDVDGDAPED IADYMVEDNF VLENEKEKFV EELRAIVGQA 790 800 810 820 830 840 QEILHVHSAV EKSIGVDSVA LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC 850 860 870 880 890 900 INQTIKNREA QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS 910 920 930 940 950 960 KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV CPVPGECEAL 970 980 990 1000 1010 1020 TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT SVLVSSDQKP QSLSVQQPTI 1030 1040 1050 1060 1070 1080 DAEFISKEGE TTVNTETSSP KAVIATQTPG FEPAVILPAT ILESDGERPP KMEFADNRIK 1090 1100 1110 1120 1130 1140 TLDEKLRNLL YQEHSISSIC PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS 1150 1160 1170 1180 1190 1200 PAQSPNFQQT GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA 1210 1220 1230 1240 1250 1260 YPAAVSSDGT IHLQTGVETE DKRSAIASDP IPLTREFSSD TRALSRCKAM SGSFQRGRFQ 1270 1280 1290 1300 1310 1320 VITVPQQQPV KMMSFGKDHR PPFNKTTVQS SEQALTFAEA AVSQLIEVEP AMPTHKASVS 1330 1340 1350 1360 1370 1380 SRKLRTLYET FKEDKGDPEQ GDIVSYSTAC ETSVSSVATE KNVTSTTEVS VQSGSEPLDK 1390 1400 1410 1420 1430 1440 EKNESTPGKQ TCTNEFSATL AGNRKSVTKT RPEGDQYLPL REEQAYAQTQ NSLFYSPSSP 1450 1460 1470 1480 1490 1500 MSSDNESEIE DEDLKVELQR LREKHIQEVV SLQTQQNKEL QELYERLRAT KDNKAQSSEV 1510 1520 1530 1540 1550 1560 PLSPASPRRP RSFKSKLRSR PQSMTHSDNL VVKDALGVES NTVSCQQSPA SKKGMFTDDL 1570 1580 1590 1600 1610 1620 HKLVDDWTRE TVGHFPSKPS LNQLKQSQQK SEAENWNKSC ESTPSTMGYT SNWISSLSQI 1630 1640 1650 1660 1670 1680 RGAAPTSLPQ GLPLPSFHGP LASYGMPHVC QYNAVGAAGY PVQWVGISGP AQQSVVLPTQ 1690 1700 1710 SGGLFQPGMN LQSFPAPPVQ NPASIPPGPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse Wnk3 gene encodes multiple continuous open reading frames." Shmukler B.E., Alper S.L. Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Brain.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1296-1757. Strain: C57BL/6. Tissue: Embryonic brain.
[4]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	JQ247189 mRNA. Translation: AEZ01402.1. JQ247190 mRNA. Translation: AEZ01403.1. AL732420 Genomic DNA. No translation available. AL807396 Genomic DNA. No translation available. BC043119 mRNA. Translation: AAH43119.1. BC060731 mRNA. Translation: AAH60731.1.
IPI	IPI00750069.
RefSeq	NP_001258607.1. NM_001271678.1. NP_001258608.1. NM_001271679.1.
UniGene	Mm.441474.
3D structure databases
ProteinModelPortal	Q80XP9.
SMR	Q80XP9. Positions 135-497.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000094005.
PTM databases
PhosphoSite	Q80XP9.
Proteomic databases
PaxDb	Q80XP9.
PRIDE	Q80XP9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	279561.
KEGG	mmu:279561.
Organism-specific databases
CTD	65267.
MGI	MGI:2652875. Wnk3.
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG050346.
InParanoid	Q80XP9.
KO	K08867.
OrthoDB	EOG4894KK.
Gene expression databases
CleanEx	MM_WNK3.
Genevestigator	Q80XP9.
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
NextBio	35562242.
SOURCE	Search...

Entry information

Entry name

WNK3_MOUSE

Accession

Primary (citable) accession number: Q80XP9
Secondary accession number(s): H6WJI2, H6WJI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	January 9, 2013
Last modified:	May 1, 2013
This is version 70 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program