Q9H4A3 (WNK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	WNK1
Synonyms:	HSN2, KDP, KIAA0344, PRKWNK1

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	2382 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. 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 By similarity. Ref.4 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.4
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. Interacts with WNK3 and WNK4 By similarity.
Subcellular location	Cytoplasm Ref.4.
Tissue specificity	Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific. Ref.1 Ref.4 Ref.8
Post-translational modification	O-glycosylated. Ref.7
Involvement in disease	Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Hereditary sensory and autonomic neuropathy 2A (HSAN2A) [MIM:201300]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.12 Ref.15
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 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 (Ref.15). It is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5.
Sequence caution	The sequence AAF31483.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part. The sequence AAI30468.1 differs from that shown. Reason: Probable cloning artifact. The sequence AAI30470.1 differs from that shown. Reason: Probable cloning artifact. The sequence DAA04494.1 differs from that shown. Reason: Erroneous gene model prediction. Includes 3' and 3' intronic sequences.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Disease	Neuropathy
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 Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from direct assay Ref.4. Source: UniProtKB ion transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of pancreatic juice secretion Inferred from electronic annotation. Source: Compara negative regulation of phosphatase activity Inferred from direct assay PubMed 19389623. Source: UniProtKB negative regulation of protein kinase activity Inferred from electronic annotation. Source: GOC neuron development Non-traceable author statement Ref.10. Source: UniProtKB positive regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.4. Source: UniProtKB phosphatase binding Inferred from direct assay PubMed 19389623. Source: UniProtKB protein kinase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PPP1CA	P62136	2	EBI-457907,EBI-357253
Syt2	P29101	2	EBI-457907,EBI-458017	From a different organism.

Alternative products

This entry describes 5 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:
     740-740: Missing.
     792-1037: Missing.

Note: No experimental confirmation available.

Isoform 3 Ref.8 (identifier: Q9H4A3-4)

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.

Isoform 4 Ref.8 (identifier: Q9H4A3-5)

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.

Isoform 5 (identifier: Q9H4A3-6)

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.

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.17 Ref.19
	Modified residue	167	1	Phosphoserine By similarity
	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.14 Ref.17 Ref.19
	Modified residue	1978	1	Phosphoserine Ref.18 Ref.19
	Modified residue	2002	1	Phosphoserine Ref.13
	Modified residue	2011	1	Phosphoserine Ref.17
	Modified residue	2012	1	Phosphoserine Ref.17
	Modified residue	2027	1	Phosphoserine Ref.17 Ref.21
	Modified residue	2029	1	Phosphoserine Ref.17 Ref.21
	Modified residue	2032	1	Phosphoserine Ref.13 Ref.17 Ref.19 Ref.21
	Modified residue	2121	1	Phosphoserine Ref.19
Natural variations
	Alternative sequence	1 – 407	407	Missing in isoform 3. Ref.8		VSP_050634
	Alternative sequence	408 – 437	30	FGMCM…RRVTS → MDIKKKDFCSVFVIINSHCC CCPQKDCINE in isoform 3. Ref.8		VSP_050637
	Alternative sequence	713	1	V → VPQSMAHPCGGTPTYPESQI FFPTIHERPVSFSPPPTCPP KVAISQRRKSTSFLEAQTHH FQPLLRTVGQSLLPPGGSPT NWTPEAVVMLGTTASRVTGE SCEIQVHPMFEPSQVYSDYR PGLVLPEEAHYFIPQEAVYV AGVHYQARVAEQYEGIPYNS SVLSSPMKQIPEQKPVQGGP TSSSVFEFPSGQAFLVGHLQ NLRLDSGLGPGSPLSSISAP ISTDATRLKFHPVFVPHSAP AVLTHNNESRSNCVFEFHVH TPSSSSGEGGGILPQRVYRN RQVAVDLNQEELPPQSVGLH GYLQPVTEEKHNYHAPELTV SVVEPIGQNWPIGSPEYSSD SSQITSSDPSDFQSPPPTGG AAAPFGSDVSMPFIHLPQTV LQESPLFFCFPQGTTSQQVL TASFSSGGSALHPQ in isoform 5.		VSP_040267
	Alternative sequence	714 – 1037	324	AQGQS…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.		VSP_040268
	Alternative sequence	740	1	Missing in isoform 2.		VSP_040269
	Alternative sequence	792 – 1037	246	Missing in isoform 2. Ref.5		VSP_050638
	Alternative sequence	792 – 944	153	Missing in isoform 5.		VSP_040270
	Natural variant	141	1	A → T. Ref.23 Corresponds to variant rs11554421 [ dbSNP | Ensembl ].		VAR_041309
	Natural variant	149	1	A → V. Ref.23 Corresponds to variant rs34880640 [ dbSNP | Ensembl ].		VAR_041310
	Natural variant	419	1	E → Q in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.23		VAR_041311
	Natural variant	509	1	I → T. Ref.23 Corresponds to variant rs34728563 [ dbSNP | Ensembl ].		VAR_041312
	Natural variant	527	1	D → G. Ref.23 Corresponds to variant rs34408667 [ dbSNP | Ensembl ].		VAR_041313
	Natural variant	665	1	T → I. Ref.23 Corresponds to variant rs2286007 [ dbSNP | Ensembl ].		VAR_019992
	Natural variant	674	1	T → A. Ref.23 Corresponds to variant rs11833299 [ dbSNP | Ensembl ].		VAR_041314
	Natural variant	823	1	H → R. Ref.23 Corresponds to variant rs56015776 [ dbSNP | Ensembl ].		VAR_041315
	Natural variant	1056	1	T → P. Ref.1 Ref.2 Ref.5 Corresponds to variant rs956868 [ dbSNP | Ensembl ].		VAR_059033
	Natural variant	1199	1	E → G in a colorectal cancer sample; somatic mutation. Ref.22		VAR_035640
	Natural variant	1506	1	C → S. Ref.1 Ref.2 Ref.5 Corresponds to variant rs7955371 [ dbSNP | Ensembl ].		VAR_059034
	Natural variant	1546	1	A → V. Ref.23 Corresponds to variant rs56351358 [ dbSNP | Ensembl ].		VAR_041316
	Natural variant	1799	1	Q → E in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.22 Ref.23		VAR_035641
	Natural variant	1808	1	M → I. Ref.1 Ref.2 Ref.23 Corresponds to variant rs12828016 [ dbSNP | Ensembl ].		VAR_041317
	Natural variant	1823	1	P → L. Ref.23 Corresponds to variant rs17755373 [ dbSNP | Ensembl ].		VAR_041318
	Natural variant	1957	1	R → H. Ref.23 Corresponds to variant rs36083875 [ dbSNP | Ensembl ].		VAR_041319
	Natural variant	2190	1	S → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.23		VAR_041320
	Natural variant	2362	1	F → L in a lung adenocarcinoma sample; somatic mutation. Ref.23		VAR_041321
	Natural variant	2380	1	R → W. Ref.23 Corresponds to variant rs56262445 [ dbSNP | Ensembl ].		VAR_041322
Experimental info
	Sequence conflict	164	1	R → S AA sequence Ref.7
	Sequence conflict	1836	1	Missing in BAA20802. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 426785F98A452A0A	FASTA	2,382	250,794
	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 VAVAQTQATQ 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 TASQLCIQLS 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 RRTLSPEMIT 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 [UniParc]. Checksum: 2961D903C013A22C	FASTA	2,135	225,560
	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 QQGIQQTAPP QQTVQYSLSQ TSTSSEATTA QPVSQPQAPQ 790 800 810 820 830 840 VLPQVSAGKQ STQGVSQVAP AEPVAVAQTQ ATQPTTLASS VDSAHSDVAS GMSDGNENVP 850 860 870 880 890 900 SSSGRHEGRT TKRHYRKSVR SRSRHEKTSR PKLRILNVSN KGDRVVECQL ETHNRKMVTF 910 920 930 940 950 960 KFDLDGDNPE EIATIMVNND FILAIERESF VDQVREIIEK ADEMLSEDVS VEPEGDQGLE 970 980 990 1000 1010 1020 SLQGKDDYGF SGSQKLEGEF KQPIPASSMP QQIGIPTSSL TQVVHSAGRR FIVSPVPESR 1030 1040 1050 1060 1070 1080 LRESKVFPSE ITDTVAASTA QSPGMNLSHS ASSLSLQQAF SELRRAQMTE GPNTAPPNFS 1090 1100 1110 1120 1130 1140 HTGPTFPVVP PFLSSIAGVP TTAAATAPVP ATSSPPNDIS TSVIQSEVTV PTEEGIAGVA 1150 1160 1170 1180 1190 1200 TSTGVVTSGG LPIPPVSESP VLSSVVSSIT IPAVVSISTT SPSLQVPTST SEIVVSSTAL 1210 1220 1230 1240 1250 1260 YPSVTVSATS ASAGGSTATP GPKPPAVVSQ QAAGSTTVGA TLTSVSTTTS FPSTASQLCI 1270 1280 1290 1300 1310 1320 QLSSSTSTPT LAETVVVSAH SLDKTSHSST TGLAFSLSAP SSSSSPGAGV SSYISQPGGL 1330 1340 1350 1360 1370 1380 HPLVIPSVIA STPILPQAAG PTSTPLLPQV PSIPPLVQPV ANVPAVQQTL IHSQPQPALL 1390 1400 1410 1420 1430 1440 PNQPHTHCPE VDSDTQPKAP GIDDIKTLEE KLRSLFSEHS SSGAQHASVS LETSLVIEST 1450 1460 1470 1480 1490 1500 VTPGIPTTAV APSKLLTSTT STCLPPTNLP LGTVALPVTP VVTPGQVSTP VSTTTSGVKP 1510 1520 1530 1540 1550 1560 GTAPSKPPLT KAPVLPVGTE LPAGTLPSEQ LPPFPGPSLT QSQQPLEDLD AQLRRTLSPE 1570 1580 1590 1600 1610 1620 MITVTSAVGP VSMAAPTAIT EAGTQPQKGV SQVKEGPVLA TSSGAGVFKM GRFQVSVAAD 1630 1640 1650 1660 1670 1680 GAQKEGKNKS EDAKSVHFES STSESSVLSS SSPESTLVKP EPNGITIPGI SSDVPESAHK 1690 1700 1710 1720 1730 1740 TTASEAKSDT GQPTKVGRFQ VTTTANKVGR FSVSKTEDKI TDTKKEGPVA SPPFMDLEQA 1750 1760 1770 1780 1790 1800 VLPAVIPKKE KPELSEPSHL NGPSSDPEAA FLSRDVDDGS GSPHSPHQLS SKSLPSQNLS 1810 1820 1830 1840 1850 1860 QSLSNSFNSS YMSSDNESDI EDEDLKLELR RLRDKHLKEI QDLQSRQKHE IESLYTKLGK 1870 1880 1890 1900 1910 1920 VPPAVIIPPA APLSGRRRRP TKSKGSKSSR SSSLGNKSPQ LSGNLSGQSA ASVLHPQQTL 1930 1940 1950 1960 1970 1980 HPPGNIPESG QNQLLQPLKP SPSSDNLYSA FTSDGAISVP SLSAPGQGTS STNTVGATVN 1990 2000 2010 2020 2030 2040 SQAAQAQPPA MTSSRKGTFT DDLHKLVDNW ARDAMNLSGR RGSKGHMNYE GPGMARKFSA 2050 2060 2070 2080 2090 2100 PGQLCISMTS NLGGSAPISA ASATSLGHFT KSMCPPQQYG FPATPFGAQW SGTGGPAPQP 2110 2120 2130 LGQFQPVGTA SLQNFNISNL QKSISNPPGS NLRTT
	Isoform 3 [UniParc]. Checksum: B03B35C0321782D3	FASTA	1,975	206,646
	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 AEPVAVAQTQ 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 FPSTASQLCI 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 MITVTSAVGP 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
	Isoform 4 (Brain and spinal cord variant) [UniParc]. Checksum: 2F95DCDA28619B4C	FASTA	2,634	279,538
	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 SSVPRRGRSM 730 740 750 760 770 780 SVCVPIFLLL PLCPASLPVL FHPTASTVCT SFSFPPPDCP EETFAEKLSK ALESVLPMHS 790 800 810 820 830 840 ASQRKHRRSS LPSLFVSTPQ SMAHPCGGTP TYPESQIFFP TIHERPVSFS PPPTCPPKVA 850 860 870 880 890 900 ISQRRKSTSF LEAQTHHFQP LLRTVGQSLL PPGGSPTNWT PEAVVMLGTT ASRVTGESCE 910 920 930 940 950 960 IQVHPMFEPS QVYSDYRPGL VLPEEAHYFI PQEAVYVAGV HYQARVAEQY EGIPYNSSVL 970 980 990 1000 1010 1020 SSPMKQIPEQ KPVQGGPTSS SVFEFPSGQA FLVGHLQNLR LDSGLGPGSP LSSISAPIST 1030 1040 1050 1060 1070 1080 DATRLKFHPV FVPHSAPAVL THNNESRSNC VFEFHVHTPS SSSGEGGGIL PQRVYRNRQV 1090 1100 1110 1120 1130 1140 AVDLNQEELP PQSVGLHGYL QPVTEEKHNY HAPELTVSVV EPIGQNWPIG SPEYSSDSSQ 1150 1160 1170 1180 1190 1200 ITSSDPSDFQ SPPPTGGAAA PFGSDVSMPF IHLPQTVLQE SPLFFCFPQG TTSQQVLTAS 1210 1220 1230 1240 1250 1260 FSSGGSALHP QAQGQSQGQP SSSSLTGVSS SQPIQHPQQQ QGIQQTAPPQ QTVQYSLSQT 1270 1280 1290 1300 1310 1320 STSSEATTAQ PVSQPQAPQV LPQVSAGKQS TQGVSQVAPA EPVAVAQTQA TQPTTLASSV 1330 1340 1350 1360 1370 1380 DSAHSDVASG MSDGNENVPS SSGRHEGRTT KRHYRKSVRS RSRHEKTSRP KLRILNVSNK 1390 1400 1410 1420 1430 1440 GDRVVECQLE THNRKMVTFK FDLDGDNPEE IATIMVNNDF ILAIERESFV DQVREIIEKA 1450 1460 1470 1480 1490 1500 DEMLSEDVSV EPEGDQGLES LQGKDDYGFS GSQKLEGEFK QPIPASSMPQ QIGIPTSSLT 1510 1520 1530 1540 1550 1560 QVVHSAGRRF IVSPVPESRL RESKVFPSEI TDTVAASTAQ SPGMNLSHSA SSLSLQQAFS 1570 1580 1590 1600 1610 1620 ELRRAQMTEG PNTAPPNFSH TGPTFPVVPP FLSSIAGVPT TAAATAPVPA TSSPPNDIST 1630 1640 1650 1660 1670 1680 SVIQSEVTVP TEEGIAGVAT STGVVTSGGL PIPPVSESPV LSSVVSSITI PAVVSISTTS 1690 1700 1710 1720 1730 1740 PSLQVPTSTS EIVVSSTALY PSVTVSATSA SAGGSTATPG PKPPAVVSQQ AAGSTTVGAT 1750 1760 1770 1780 1790 1800 LTSVSTTTSF PSTASQLCIQ LSSSTSTPTL AETVVVSAHS LDKTSHSSTT GLAFSLSAPS 1810 1820 1830 1840 1850 1860 SSSSPGAGVS SYISQPGGLH PLVIPSVIAS TPILPQAAGP TSTPLLPQVP SIPPLVQPVA 1870 1880 1890 1900 1910 1920 NVPAVQQTLI HSQPQPALLP NQPHTHCPEV DSDTQPKAPG IDDIKTLEEK LRSLFSEHSS 1930 1940 1950 1960 1970 1980 SGAQHASVSL ETSLVIESTV TPGIPTTAVA PSKLLTSTTS TCLPPTNLPL GTVALPVTPV 1990 2000 2010 2020 2030 2040 VTPGQVSTPV STTTSGVKPG TAPSKPPLTK APVLPVGTEL PAGTLPSEQL PPFPGPSLTQ 2050 2060 2070 2080 2090 2100 SQQPLEDLDA QLRRTLSPEM ITVTSAVGPV SMAAPTAITE AGTQPQKGVS QVKEGPVLAT 2110 2120 2130 2140 2150 2160 SSGAGVFKMG RFQVSVAADG AQKEGKNKSE DAKSVHFESS TSESSVLSSS SPESTLVKPE 2170 2180 2190 2200 2210 2220 PNGITIPGIS SDVPESAHKT TASEAKSDTG QPTKVGRFQV TTTANKVGRF SVSKTEDKIT 2230 2240 2250 2260 2270 2280 DTKKEGPVAS PPFMDLEQAV LPAVIPKKEK PELSEPSHLN GPSSDPEAAF LSRDVDDGSG 2290 2300 2310 2320 2330 2340 SPHSPHQLSS KSLPSQNLSQ SLSNSFNSSY MSSDNESDIE DEDLKLELRR LRDKHLKEIQ 2350 2360 2370 2380 2390 2400 DLQSRQKHEI ESLYTKLGKV PPAVIIPPAA PLSGRRRRPT KSKGSKSSRS SSLGNKSPQL 2410 2420 2430 2440 2450 2460 SGNLSGQSAA SVLHPQQTLH PPGNIPESGQ NQLLQPLKPS PSSDNLYSAF TSDGAISVPS 2470 2480 2490 2500 2510 2520 LSAPGQGTSS TNTVGATVNS QAAQAQPPAM TSSRKGTFTD DLHKLVDNWA RDAMNLSGRR 2530 2540 2550 2560 2570 2580 GSKGHMNYEG PGMARKFSAP GQLCISMTSN LGGSAPISAA SATSLGHFTK SMCPPQQYGF 2590 2600 2610 2620 2630 PATPFGAQWS GTGGPAPQPL GQFQPVGTAS LQNFNISNLQ KSISNPPGSN LRTT
	Isoform 5 (Dorsal root ganglia and sciatic nerve variant) (DRG and sciatic nerve variant) [UniParc]. Checksum: D0AB5C95ABFF46A4	FASTA	2,642	279,713
	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 SSVPQSMAHP 730 740 750 760 770 780 CGGTPTYPES QIFFPTIHER PVSFSPPPTC PPKVAISQRR KSTSFLEAQT HHFQPLLRTV 790 800 810 820 830 840 GQSLLPPGGS PTNWTPEAVV MLGTTASRVT GESCEIQVHP MFEPSQVYSD YRPGLVLPEE 850 860 870 880 890 900 AHYFIPQEAV YVAGVHYQAR VAEQYEGIPY NSSVLSSPMK QIPEQKPVQG GPTSSSVFEF 910 920 930 940 950 960 PSGQAFLVGH LQNLRLDSGL GPGSPLSSIS APISTDATRL KFHPVFVPHS APAVLTHNNE 970 980 990 1000 1010 1020 SRSNCVFEFH VHTPSSSSGE GGGILPQRVY RNRQVAVDLN QEELPPQSVG LHGYLQPVTE 1030 1040 1050 1060 1070 1080 EKHNYHAPEL TVSVVEPIGQ NWPIGSPEYS SDSSQITSSD PSDFQSPPPT GGAAAPFGSD 1090 1100 1110 1120 1130 1140 VSMPFIHLPQ TVLQESPLFF CFPQGTTSQQ VLTASFSSGG SALHPQAQGQ SQGQPSSSSL 1150 1160 1170 1180 1190 1200 TGVSSSQPIQ HPQQQQGIQQ TAPPQQTVQY SLSQTSTSSE ATTAQPVSQP QAPQVLPQVS 1210 1220 1230 1240 1250 1260 AGKQGFPPRL PPQYPGDSNI APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE 1270 1280 1290 1300 1310 1320 SNLLVPMGGV GGQVQVSQPG GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP VAVAQTQATQ 1330 1340 1350 1360 1370 1380 PTTLASSVDS AHSDVASGMS DGNENVPSSS GRHEGRTTKR HYRKSVRSRS RHEKTSRPKL 1390 1400 1410 1420 1430 1440 RILNVSNKGD RVVECQLETH NRKMVTFKFD LDGDNPEEIA TIMVNNDFIL AIERESFVDQ 1450 1460 1470 1480 1490 1500 VREIIEKADE MLSEDVSVEP EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI 1510 1520 1530 1540 1550 1560 GIPTSSLTQV VHSAGRRFIV SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS 1570 1580 1590 1600 1610 1620 LSLQQAFSEL RRAQMTEGPN TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA AATAPVPATS 1630 1640 1650 1660 1670 1680 SPPNDISTSV IQSEVTVPTE EGIAGVATST GVVTSGGLPI PPVSESPVLS SVVSSITIPA 1690 1700 1710 1720 1730 1740 VVSISTTSPS LQVPTSTSEI VVSSTALYPS VTVSATSASA GGSTATPGPK PPAVVSQQAA 1750 1760 1770 1780 1790 1800 GSTTVGATLT SVSTTTSFPS TASQLCIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL 1810 1820 1830 1840 1850 1860 AFSLSAPSSS SSPGAGVSSY ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI 1870 1880 1890 1900 1910 1920 PPLVQPVANV PAVQQTLIHS QPQPALLPNQ PHTHCPEVDS DTQPKAPGID DIKTLEEKLR 1930 1940 1950 1960 1970 1980 SLFSEHSSSG AQHASVSLET SLVIESTVTP GIPTTAVAPS KLLTSTTSTC LPPTNLPLGT 1990 2000 2010 2020 2030 2040 VALPVTPVVT PGQVSTPVST TTSGVKPGTA PSKPPLTKAP VLPVGTELPA GTLPSEQLPP 2050 2060 2070 2080 2090 2100 FPGPSLTQSQ QPLEDLDAQL RRTLSPEMIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV 2110 2120 2130 2140 2150 2160 KEGPVLATSS GAGVFKMGRF QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP 2170 2180 2190 2200 2210 2220 ESTLVKPEPN GITIPGISSD VPESAHKTTA SEAKSDTGQP TKVGRFQVTT TANKVGRFSV 2230 2240 2250 2260 2270 2280 SKTEDKITDT KKEGPVASPP FMDLEQAVLP AVIPKKEKPE LSEPSHLNGP SSDPEAAFLS 2290 2300 2310 2320 2330 2340 RDVDDGSGSP HSPHQLSSKS LPSQNLSQSL SNSFNSSYMS SDNESDIEDE DLKLELRRLR 2350 2360 2370 2380 2390 2400 DKHLKEIQDL QSRQKHEIES LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS 2410 2420 2430 2440 2450 2460 LGNKSPQLSG NLSGQSAASV LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS 2470 2480 2490 2500 2510 2520 DGAISVPSLS APGQGTSSTN TVGATVNSQA AQAQPPAMTS SRKGTFTDDL HKLVDNWARD 2530 2540 2550 2560 2570 2580 AMNLSGRRGS KGHMNYEGPG MARKFSAPGQ LCISMTSNLG GSAPISAASA TSLGHFTKSM 2590 2600 2610 2620 2630 2640 CPPQQYGFPA TPFGAQWSGT GGPAPQPLGQ FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT

References

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[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 1), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION, VARIANTS PRO-1056; SER-1506 AND ILE-1808. 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 PRO-1056; SER-1506 AND ILE-1808.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-668 (ISOFORMS 1/2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Mammary carcinoma.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-2382 (ISOFORM 2), VARIANTS PRO-1056 AND SER-1506. 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 163-175, GLYCOSYLATION.
[8]	"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] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (N-TERMINUS OF ISOFORM 3), ALTERNATIVE PROMOTER USAGE, ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Kidney.
[9]	"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: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4/5).
[10]	"Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates." Lafreniere R.G., MacDonald M.L.E., Dube M.-P., MacFarlane J., O'Driscoll M., Brais B., Meilleur S., Brinkman R.R., Dadivas O., Pape T., Platon C., Radomski C., Risler J., Thompson J., Guerra-Escobio A.-M., Davar G., Breakefield X.O., Pimstone S.N. , Green R., Pryse-Phillips W., Goldberg Y.P., Younghusband H.B., Hayden M.R., Sherrington R., Rouleau G.A., Samuels M.E. Am. J. Hum. Genet. 74:1064-1073(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION (ISOFORMS 4/5), FUNCTION, INVOLVEMENT IN HSAN2A.
[11]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHA2C.
[12]	"Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians." Roddier K., Thomas T., Marleau G., Gagnon A.M., Dicaire M.J., St Denis A., Gosselin I., Sarrazin A.M., Larbrisseau A., Lambert M., Vanasse M., Gaudet D., Rouleau G.A., Brais B. Neurology 64:1762-1767(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HSAN2A.
[13]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2002 AND SER-2032, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1261, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II." Shekarabi M., Girard N., Riviere J.B., Dion P., Houle M., Toulouse A., Lafreniere R.G., Vercauteren F., Hince P., Laganiere J., Rochefort D., Faivre L., Samuels M., Rouleau G.A. J. Clin. Invest. 118:2496-2505(2008) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 4 AND 5), INVOLVEMENT IN HSAN2A.
[16]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[17]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-1261; SER-2011; SER-2012; SER-2027; SER-2029 AND SER-2032, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1978, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-1261; SER-1978; SER-2032 AND SER-2121, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"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-2027; SER-2029 AND SER-2032, MASS SPECTROMETRY.
[22]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-1199 AND GLU-1799.
[23]	"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] THR-141; VAL-149; GLN-419; THR-509; GLY-527; ILE-665; ALA-674; ARG-823; VAL-1546; GLU-1799; ILE-1808; LEU-1823; HIS-1957; CYS-2190; LEU-2362 AND TRP-2380.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ296290 mRNA. Translation: CAC15059.1. 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. BC130467 mRNA. Translation: AAI30468.1. Sequence problems. BC130469 mRNA. Translation: AAI30470.1. Sequence problems. BK004108 Genomic DNA. Translation: DAA04494.1. Sequence problems.
IPI	IPI00004472. IPI00397592. IPI00412748. IPI00972952. IPI01013396.
RefSeq	NP_001171914.1. NM_001184985.1. NP_055638.2. NM_014823.2. NP_061852.3. NM_018979.3. NP_998820.3. NM_213655.4.
UniGene	Hs.356604.
3D structure databases
ProteinModelPortal	Q9H4A3.
SMR	Q9H4A3. Positions 210-572.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32648N.
IntAct	Q9H4A3. 49 interactions.
MINT	MINT-2879524.
PTM databases
PhosphoSite	Q9H4A3.
Polymorphism databases
DMDM	74709537.
Proteomic databases
PaxDb	Q9H4A3.
PRIDE	Q9H4A3.
Protocols and materials databases
DNASU	65125.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315939; ENSP00000313059; ENSG00000060237. ENST00000340908; ENSP00000341292; ENSG00000060237. ENST00000537687; ENSP00000444465; ENSG00000060237. ENST00000574564; ENSP00000460651; ENSG00000060237.
GeneID	65125.
KEGG	hsa:65125.
UCSC	uc001qio.4. human. uc001qir.4. human. uc021qss.1. human. uc021qst.1. human.
Organism-specific databases
CTD	65125.
GeneCards	GC12P000862.
H-InvDB	HIX0010312.
HGNC	HGNC:14540. WNK1.
MIM	201300. phenotype. 605232. gene. 614492. phenotype.
neXtProt	NX_Q9H4A3.
Orphanet	970. Hereditary sensory and autonomic neuropathy type 2. 88940. Pseudohypoaldosteronism type 2C.
PharmGKB	PA134944932. PA33782.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG079897.
InParanoid	Q9H4A3.
KO	K08867.
OrthoDB	EOG4C5CKQ.
PhylomeDB	Q9H4A3.
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. IPR024678. Kinase_OSR1/WNK_CCT. IPR000719. Prot_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF12202. OSR1_C. 1 hit. PF00069. Pkinase. 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
BindingDB	Q9H4A3.
ChEMBL	CHEMBL1075173.
ChiTaRS	WNK1. human.
GenomeRNAi	65125.
NextBio	67340.
SOURCE	Search...

Entry information

Entry name

WNK1_HUMAN

Accession

Primary (citable) accession number: Q9H4A3
Secondary accession number(s): A1L4B0 , C5HTZ5, C5HTZ6, C5HTZ7, O15052, P54963, Q4VBX9, Q6IFS5, Q86WL5, Q8N673, Q9P1S9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 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.