Overview
| Uniprot ID | Q9UEW8 |
|---|
| Protein Name | STE20/SPS1-related proline-alanine-rich protein kinase |
|---|
| Gene Name | STK39 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 404 |
KAAFSQEKSRRVKEE |
Function
Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:21321328). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (By similarity). Phosphorylates RELT (By similarity)
Protein Sequence
10
MAEPSGSPVH
20
VQLPQQAAPV
30
TAAAAAAPAA
40
ATAAPAPAAP
50
AAPAPAPAPA
60
AQAVGWPICR
70
DAYELQEVIG
80
SGATAVVQAA
90
LCKPRQERVA
100
IKRINLEKCQ
110
TSMDELLKEI
120
QAMSQCSHPN
130
VVTYYTSFVV
140
KDELWLVMKL
150
LSGGSMLDII
160
KYIVNRGEHK
170
NGVLEEAIIA
180
TILKEVLEGL
190
DYLHRNGQIH
200
RDLKAGNILL
210
GEDGSVQIAD
220
FGVSAFLATG
230
GDVTRNKVRK
240
TFVGTPCWMA
250
PEVMEQVRGY
260
DFKADMWSFG
270
ITAIELATGA
280
APYHKYPPMK
290
VLMLTLQNDP
300
PTLETGVEDK
310
EMMKKYGKSF
320
RKLLSLCLQK
330
DPSKRPTAAE
340
LLKCKFFQKA
350
KNREYLIEKL
360
LTRTPDIAQR
370
AKKVRRVPGS
380
SGHLHKTEDG
390
DWEWSDDEMD
400
EKSEEGKAAF
410
SQEKSRRVKE
420
ENPEIAVSAS
430
TIPEQIQSLS
440
VHDSQGPPNA
450
NEDYREASSC
460
AVNLVLRLRN
470
SRKELNDIRF
480
EFTPGRDTAD
490
GVSQELFSAG
500
LVDGHDVVIV
510
AANLQKIVDD
520
PKALKTLTFK
530
LASGCDGSEI
540
PDEVKLIGFA
QLSVS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016324 |
apical plasma membrane |
| Cellular Component |
GO:0016323 |
basolateral plasma membrane |
| Cellular Component |
GO:0044297 |
cell body |
| Cellular Component |
GO:0005938 |
cell cortex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0099106 |
ion channel regulator activity |
| Molecular Function |
GO:0016301 |
kinase activity |
| Molecular Function |
GO:0019870 |
potassium channel inhibitor activity |
| Molecular Function |
GO:0019901 |
protein kinase binding |
| Molecular Function |
GO:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0044325 |
transmembrane transporter binding |
| Molecular Function |
GO:0141109 |
transporter activator activity |
| Molecular Function |
GO:0141110 |
transporter inhibitor activity |
| Biological Process |
GO:0006884 |
cell volume homeostasis |
| Biological Process |
GO:0071474 |
cellular hyperosmotic response |
| Biological Process |
GO:0071476 |
cellular hypotonic response |
| Biological Process |
GO:1990869 |
cellular response to chemokine |
| Biological Process |
GO:0035865 |
cellular response to potassium ion |
| Biological Process |
GO:0038146 |
chemokine (C-X-C motif) ligand 12 signaling pathway |
| Biological Process |
GO:0006954 |
inflammatory response |
| Biological Process |
GO:0030644 |
intracellular chloride ion homeostasis |
| Biological Process |
GO:0035556 |
intracellular signal transduction |
| Biological Process |
GO:0042116 |
macrophage activation |
| Biological Process |
GO:0036438 |
maintenance of lens transparency |
| Biological Process |
GO:0090188 |
negative regulation of pancreatic juice secretion |
| Biological Process |
GO:1901380 |
negative regulation of potassium ion transmembrane transport |
| Biological Process |
GO:1902306 |
negative regulation of sodium ion transmembrane transport |
| Biological Process |
GO:0034763 |
negative regulation of transmembrane transport |
| Biological Process |
GO:0018105 |
peptidyl-serine phosphorylation |
| Biological Process |
GO:0018107 |
peptidyl-threonine phosphorylation |
| Biological Process |
GO:1900745 |
positive regulation of p38MAPK cascade |
| Biological Process |
GO:1903288 |
positive regulation of potassium ion import across plasma membrane |
| Biological Process |
GO:1903784 |
positive regulation of sodium ion import across plasma membrane |
| Biological Process |
GO:0010820 |
positive regulation of T cell chemotaxis |
| Biological Process |
GO:0046777 |
protein autophosphorylation |
| Biological Process |
GO:0006468 |
protein phosphorylation |
| Biological Process |
GO:1904062 |
regulation of monoatomic cation transmembrane transport |
| Biological Process |
GO:0070294 |
renal sodium ion absorption |
| Biological Process |
GO:1904044 |
response to aldosterone |
| Biological Process |
GO:0002021 |
response to dietary excess |
| Biological Process |
GO:0007165 |
signal transduction |
| Biological Process |
GO:0035725 |
sodium ion transmembrane transport |
Reference
[1] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.