Q9UEW8 (STK39_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
STE20/SPS1-related proline-alanine-rich protein kinase
Short name=Ste-20-related kinase
EC=2.7.11.1

Alternative name(s):
DCHT
Serine/threonine-protein kinase 39

Gene names

Name:	STK39
Synonyms:	SPAK

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	545 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May act as a mediator of stress-activated signals.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	The phosphorylated form forms a complex with WNK2 By similarity.
Subcellular location	Cytoplasm Probable. Nucleus Probable. Note: Nucleus when caspase-cleaved Probable.
Tissue specificity	Predominantly expressed in brain and pancreas followed by heart, lung, kidney, skeletal muscle, liver, placenta and testis.
Domain	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.
Post-translational modification	Phosphorylated at Ser-309 by PRKCQ. Ref.5
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of potassium ion transport Inferred from electronic annotation. Source: Compara regulation of inflammatory response Inferred from electronic annotation. Source: Compara response to stress Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara basolateral plasma membrane Inferred from electronic annotation. Source: Compara cytoplasm Non-traceable author statement Ref.1. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: Compara nucleus Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB receptor signaling protein serine/threonine kinase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 545	545	STE20/SPS1-related proline-alanine-rich protein kinase		PRO_0000086722
Regions
	Domain	63 – 337	275	Protein kinase
	Nucleotide binding	69 – 77	9	ATP By similarity
	Motif	360 – 366	7	Nuclear localization signal Potential
	Motif	387 – 391	5	Caspase cleavage related site
	Compositional bias	12 – 53	42	Ala/Pro-rich
Sites
	Active site	192	1	Proton acceptor By similarity
	Binding site	92	1	ATP By similarity
Amino acid modifications
	Modified residue	309	1	Phosphoserine; by PKC/PRKCQ Ref.5
	Modified residue	349	1	N6-acetyllysine Ref.9
	Modified residue	354	1	Phosphothreonine By similarity
	Modified residue	370	1	Phosphoserine Ref.7
	Modified residue	371	1	Phosphoserine Ref.7
	Modified residue	385	1	Phosphoserine Ref.6 Ref.7 Ref.8 Ref.10 Ref.12
Experimental info
	Sequence conflict	41	1	A → AAP in AAC72238. Ref.1
	Sequence conflict	41	1	A → AAP in AAD01901. Ref.2
	Sequence conflict	173	1	L → F in AAD01901. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UEW8 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 35E68F400A38A861	FASTA	545	59,474
	10 20 30 40 50 60 MAEPSGSPVH VQLPQQAAPV TAAAAAAPAA ATAAPAPAAP AAPAPAPAPA AQAVGWPICR 70 80 90 100 110 120 DAYELQEVIG SGATAVVQAA LCKPRQERVA IKRINLEKCQ TSMDELLKEI QAMSQCSHPN 130 140 150 160 170 180 VVTYYTSFVV KDELWLVMKL LSGGSMLDII KYIVNRGEHK NGVLEEAIIA TILKEVLEGL 190 200 210 220 230 240 DYLHRNGQIH RDLKAGNILL GEDGSVQIAD FGVSAFLATG GDVTRNKVRK TFVGTPCWMA 250 260 270 280 290 300 PEVMEQVRGY DFKADMWSFG ITAIELATGA APYHKYPPMK VLMLTLQNDP PTLETGVEDK 310 320 330 340 350 360 EMMKKYGKSF RKLLSLCLQK DPSKRPTAAE LLKCKFFQKA KNREYLIEKL LTRTPDIAQR 370 380 390 400 410 420 AKKVRRVPGS SGHLHKTEDG DWEWSDDEMD EKSEEGKAAF SQEKSRRVKE ENPEIAVSAS 430 440 450 460 470 480 TIPEQIQSLS VHDSQGPPNA NEDYREASSC AVNLVLRLRN SRKELNDIRF EFTPGRDTAD 490 500 510 520 530 540 GVSQELFSAG LVDGHDVVIV AANLQKIVDD PKALKTLTFK LASGCDGSEI PDEVKLIGFA QLSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SPAK, a STE20/SPS1-related kinase that activates the p38 pathway." Johnston A.M., Naselli G., Gonez L.J., Martin R.M., Harrison L.C., de Aizpurua H.J. Oncogene 19:4290-4297(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"New human member of the Ste20 family." Melnick M.B., Petitt M., Perrimon N., Comb M.J. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Baytel D., Don J. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 279-545. Tissue: Testis.
[5]	"SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-induced AP-1 activation pathway." Li Y., Hu J., Vita R., Sun B., Tabata H., Altman A. EMBO J. 23:1112-1122(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-309.
[6]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, MASS SPECTROMETRY. Tissue: Prostate cancer.
[7]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370; SER-371 AND SER-385, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"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-385, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-349, MASS SPECTROMETRY.
[10]	"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-385, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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].
[12]	"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-385, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF099989 mRNA. Translation: AAC72238.1. 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.
IPI	IPI00004363.
RefSeq	NP_037365.2. NM_013233.2.
UniGene	Hs.276271.
3D structure databases
ProteinModelPortal	Q9UEW8.
SMR	Q9UEW8. Positions 53-389, 452-545.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UEW8. 2 interactions.
STRING	9606.ENSP00000348278.
PTM databases
PhosphoSite	Q9UEW8.
Polymorphism databases
DMDM	12643880.
Proteomic databases
PaxDb	Q9UEW8.
PeptideAtlas	Q9UEW8.
PRIDE	Q9UEW8.
Protocols and materials databases
DNASU	27347.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355999; ENSP00000348278; ENSG00000198648.
GeneID	27347.
KEGG	hsa:27347.
UCSC	uc002uea.3. human.
Organism-specific databases
CTD	27347.
GeneCards	GC02M168774.
H-InvDB	HIX0023910.
HGNC	HGNC:17717. STK39.
HPA	CAB046022.
MIM	607648. gene.
neXtProt	NX_Q9UEW8.
PharmGKB	PA38243.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000234204.
HOVERGEN	HBG108518.
InParanoid	Q9UEW8.
KO	K08835.
OMA	LSVHDSQ.
OrthoDB	EOG42V8HR.
Enzyme and pathway databases
BRENDA	2.7.11.1. 2681.
Pathway_Interaction_DB	tcrpathway. TCR signaling in naive CD4+ T cells.
Gene expression databases
Bgee	Q9UEW8.
CleanEx	HS_STK39.
Genevestigator	Q9UEW8.
GermOnline	ENSG00000198648. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR024678. Kinase_OSR1/WNK_CCT. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. [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. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9UEW8.
ChEMBL	CHEMBL1163108.
GenomeRNAi	27347.
NextBio	50438.
SOURCE	Search...

Entry information

Entry name

STK39_HUMAN

Accession

Primary (citable) accession number: Q9UEW8
Secondary accession number(s): O14774 , Q53S90, Q53SL7, Q53SS1, Q9UER4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 126 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.