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Protein

STE20/SPS1-related proline-alanine-rich protein kinase

Gene

STK39

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei92ATPPROSITE-ProRule annotation1
Active sitei192Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi69 – 77ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activation of MAPK activity Source: UniProtKB
  • activation of protein kinase activity Source: GO_Central
  • cellular hypotonic response Source: ParkinsonsUK-UCL
  • intracellular signal transduction Source: ParkinsonsUK-UCL
  • ion homeostasis Source: Ensembl
  • maintenance of lens transparency Source: ParkinsonsUK-UCL
  • negative regulation of creatine transmembrane transporter activity Source: ParkinsonsUK-UCL
  • negative regulation of pancreatic juice secretion Source: Ensembl
  • negative regulation of potassium ion transmembrane transport Source: ParkinsonsUK-UCL
  • negative regulation of potassium ion transmembrane transporter activity Source: ParkinsonsUK-UCL
  • negative regulation of protein phosphorylation Source: Ensembl
  • negative regulation of sodium ion transmembrane transporter activity Source: ParkinsonsUK-UCL
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of ion transmembrane transporter activity Source: ParkinsonsUK-UCL
  • positive regulation of potassium ion transport Source: Ensembl
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: ParkinsonsUK-UCL
  • regulation of apoptotic process Source: GO_Central
  • regulation of blood pressure Source: Ensembl
  • regulation of inflammatory response Source: Ensembl
  • regulation of mitotic cell cycle Source: GO_Central
  • signal transduction by protein phosphorylation Source: ParkinsonsUK-UCL
  • signal transduction by trans-phosphorylation Source: ParkinsonsUK-UCL
  • stress-activated protein kinase signaling cascade Source: GO_Central

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
SignaLinkiQ9UEW8
SIGNORiQ9UEW8

Names & Taxonomyi

Protein namesi
Recommended name:
STE20/SPS1-related proline-alanine-rich protein kinase (EC:2.7.11.1)
Short name:
Ste-20-related kinase
Alternative name(s):
DCHT
Serine/threonine-protein kinase 39
Gene namesi
Name:STK39
Synonyms:SPAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000198648.10
HGNCiHGNC:17717 STK39
MIMi607648 gene
neXtProtiNX_Q9UEW8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi27347
OpenTargetsiENSG00000198648
PharmGKBiPA38243

Chemistry databases

ChEMBLiCHEMBL1163108
GuidetoPHARMACOLOGYi2224

Polymorphism and mutation databases

BioMutaiSTK39
DMDMi317373508

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867221 – 545STE20/SPS1-related proline-alanine-rich protein kinaseAdd BLAST545

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei309Phosphoserine; by PKC/PRKCQ1 Publication1
Modified residuei349N6-acetyllysineCombined sources1
Modified residuei354PhosphothreonineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei371PhosphoserineCombined sources1
Modified residuei385PhosphoserineCombined sources1
Modified residuei393PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-309 by PRKCQ.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UEW8
PaxDbiQ9UEW8
PeptideAtlasiQ9UEW8
PRIDEiQ9UEW8
ProteomicsDBi84159

PTM databases

iPTMnetiQ9UEW8
PhosphoSitePlusiQ9UEW8

Expressioni

Tissue specificityi

Predominantly expressed in brain and pancreas followed by heart, lung, kidney, skeletal muscle, liver, placenta and testis.

Gene expression databases

BgeeiENSG00000198648
CleanExiHS_STK39
GenevisibleiQ9UEW8 HS

Organism-specific databases

HPAiCAB046022
HPA061803
HPA062802

Interactioni

Subunit structurei

The phosphorylated form forms a complex with WNK2.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CAB39Q9Y3764EBI-2680974,EBI-306905

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118159, 39 interactors
CORUMiQ9UEW8
ELMiQ9UEW8
IntActiQ9UEW8, 8 interactors
MINTiQ9UEW8
STRINGi9606.ENSP00000348278

Chemistry databases

BindingDBiQ9UEW8

Structurei

3D structure databases

ProteinModelPortaliQ9UEW8
SMRiQ9UEW8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 337Protein kinasePROSITE-ProRule annotationAdd BLAST275

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi360 – 366Nuclear localization signalSequence analysis7
Motifi387 – 391Caspase cleavage related site5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi12 – 53Ala/Pro-richAdd BLAST42

Domaini

PAPA box (proline-alanine repeats) may target the kinase to a specific subcellular location by facilitating interaction with intracellular proteins such as actin or actin-like proteins.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0582 Eukaryota
ENOG410XSWS LUCA
GeneTreeiENSGT00920000149013
HOGENOMiHOG000234204
HOVERGENiHBG108518
InParanoidiQ9UEW8
KOiK08835
OMAiLSVHDSQ
OrthoDBiEOG091G0AKO
PhylomeDBiQ9UEW8
TreeFamiTF105339

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024678 Kinase_OSR1/WNK_CCT
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF12202 OSR1_C, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UEW8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEPSGSPVH VQLPQQAAPV TAAAAAAPAA ATAAPAPAAP AAPAPAPAPA
60 70 80 90 100
AQAVGWPICR DAYELQEVIG SGATAVVQAA LCKPRQERVA IKRINLEKCQ
110 120 130 140 150
TSMDELLKEI QAMSQCSHPN VVTYYTSFVV KDELWLVMKL LSGGSMLDII
160 170 180 190 200
KYIVNRGEHK NGVLEEAIIA TILKEVLEGL DYLHRNGQIH RDLKAGNILL
210 220 230 240 250
GEDGSVQIAD FGVSAFLATG GDVTRNKVRK TFVGTPCWMA PEVMEQVRGY
260 270 280 290 300
DFKADMWSFG ITAIELATGA APYHKYPPMK VLMLTLQNDP PTLETGVEDK
310 320 330 340 350
EMMKKYGKSF RKLLSLCLQK DPSKRPTAAE LLKCKFFQKA KNREYLIEKL
360 370 380 390 400
LTRTPDIAQR AKKVRRVPGS SGHLHKTEDG DWEWSDDEMD EKSEEGKAAF
410 420 430 440 450
SQEKSRRVKE ENPEIAVSAS TIPEQIQSLS VHDSQGPPNA NEDYREASSC
460 470 480 490 500
AVNLVLRLRN SRKELNDIRF EFTPGRDTAD GVSQELFSAG LVDGHDVVIV
510 520 530 540
AANLQKIVDD PKALKTLTFK LASGCDGSEI PDEVKLIGFA QLSVS
Length:545
Mass (Da):59,474
Last modified:January 11, 2011 - v3
Checksum:i35E68F400A38A861
GO
Isoform 2 (identifier: Q9UEW8-2) [UniParc]FASTAAdd to basket
Also known as: A

The sequence of this isoform differs from the canonical sequence as follows:
     28-46: Missing.

Show »
Length:526
Mass (Da):57,937
Checksum:iA1DD278DEE7A4334
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41A → AAP in AAC72238 (PubMed:10980603).Curated1
Sequence conflicti41A → AAP in AAD01901 (Ref. 3) Curated1
Sequence conflicti173L → F in AAD01901 (Ref. 3) Curated1
Sequence conflicti416A → V in AHW56588 (PubMed:24722188).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05588928 – 46Missing in isoform 2. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF099989 mRNA Translation: AAC72238.1
KJ534948 mRNA Translation: AHW56588.1
AF030403 mRNA Translation: AAD01901.1
AC016723 Genomic DNA Translation: AAY15003.1
AC017069 Genomic DNA Translation: AAY14897.1
AC067940 Genomic DNA Translation: AAY24032.1
AF017635 mRNA Translation: AAB70552.1
CCDSiCCDS42770.1 [Q9UEW8-1]
RefSeqiNP_037365.2, NM_013233.2 [Q9UEW8-1]
UniGeneiHs.276271

Genome annotation databases

EnsembliENST00000355999; ENSP00000348278; ENSG00000198648 [Q9UEW8-1]
GeneIDi27347
KEGGihsa:27347
UCSCiuc002uea.4 human [Q9UEW8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSTK39_HUMAN
AccessioniPrimary (citable) accession number: Q9UEW8
Secondary accession number(s): O14774
, Q53S90, Q53SL7, Q53SS1, Q9UER4, X5D9C8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: June 20, 2018
This is version 177 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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