Reviewed, UniProtKB/Swiss-Prot O00506 (STK25_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase 25
    EC=2.7.11.1
Alternative name(s):
    Sterile 20/oxidant stress-response kinase 1
      Short name=Ste20/oxidant stress response kinase 1
      Short name=SOK-1
    Ste20-like kinase

Gene names

Name:	STK25
Synonyms:	SOK1, YSK1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-174, possibly as a consequence of stabilization of dimer formation. The C-terminal non-catalytic region inhibits the kinase activity. Ref.7
Subunit structure	Homodimer.
Subcellular location	Cytoplasm. Golgi apparatus. Note: Localizes to the Golgi apparatus. Ref.7
Tissue specificity	Ubiquitously expressed. Highest levels are found in testis, large intestine, brain and stomach followed by heart and lung.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.8 Ref.9
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 Golgi apparatus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro response to oxidative stress Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Ref.7 Inferred from physical interaction. Source: IntAct magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-618295,EBI-618295
CCM2	Q9BSQ5	1	EBI-618295,EBI-1573056
GOLGA2	Q08379	2	EBI-618295,EBI-618309
Golga2	Q62839	1	EBI-618295,EBI-618335	From a different organism.
PDCD10	Q9BUL8	1	EBI-618295,EBI-740195
PTPN13	Q12923-4	1	EBI-618295,EBI-355268
STK24	Q5T5B3	1	EBI-618295,EBI-1054809

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 426	426	Serine/threonine-protein kinase 25		PRO_0000086713
Regions
	Domain	20 – 270	251	Protein kinase
	Nucleotide binding	26 – 34	9	ATP By similarity
Sites
	Active site	140	1	Proton acceptor By similarity
	Binding site	49	1	ATP By similarity
Amino acid modifications
	Modified residue	168	1	Phosphothreonine Ref.8 Ref.9
	Modified residue	174	1	Phosphothreonine; by autocatalysis Ref.7
	Modified residue	342	1	Phosphoserine Ref.8
Natural variations
	Natural variant	64	1	Q → H: dbSNP rs34341643.		VAR_051674
Experimental info
	Mutagenesis	49	1	K → R: Loss of kinase activity and autophosphorylation. Ref.7
	Mutagenesis	158	1	D → A: Loss of kinase activity. Ref.7
	Sequence conflict	347 – 348	2	EP → DA in CAA67700. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O00506-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 183CE5700FCEA716	FASTA	426	48,112
	10 20 30 40 50 60 MAHLRGFANQ HSRVDPEELF TKLDRIGKGS FGEVYKGIDN HTKEVVAIKI IDLEEAEDEI 70 80 90 100 110 120 EDIQQEITVL SQCDSPYITR YFGSYLKSTK LWIIMEYLGG GSALDLLKPG PLEETYIATI 130 140 150 160 170 180 LREILKGLDY LHSERKIHRD IKAANVLLSE QGDVKLADFG VAGQLTDTQI KRNTFVGTPF 190 200 210 220 230 240 WMAPEVIKQS AYDFKADIWS LGITAIELAK GEPPNSDLHP MRVLFLIPKN SPPTLEGQHS 250 260 270 280 290 300 KPFKEFVEAC LNKDPRFRPT AKELLKHKFI TRYTKKTSFL TELIDRYKRW KSEGHGEESS 310 320 330 340 350 360 SEDSDIDGEA EDGEQGPIWT FPPTIRPSPH SKLHKGTALH SSQKPAEPVK RQPRSQCLST 370 380 390 400 410 420 LVRPVFGELK EKHKQSGGSV GALEELENAF SLAEESCPGI SDKLMVHLVE RVQRFSHNRN HLTSTR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway." Pombo C.M., Bonventre J.V., Molnar A., Kyriakis J., Force T. EMBO J. 15:4537-4546(1996) [PubMed: 8887545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways." Osada S., Izawa M., Saito R., Mizuno K., Suzuki A., Hirai S., Ohno S. Oncogene 14:2047-2057(1997) [PubMed: 9160885] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	NIEHS SNPs program Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis and Uterus.
[7]	"YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta." Preisinger C., Short B., De Corte V., Bruyneel E., Haas A., Kopajtich R., Gettemans J., Barr F.A. J. Cell Biol. 164:1009-1020(2004) [PubMed: 15037601] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-174, SUBCELLULAR LOCATION, INTERACTION WITH GOLGA2, MUTAGENESIS OF LYS-49 AND ASP-158.
[8]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-168 AND SER-342, MASS SPECTROMETRY.
[9]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-168, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	X99325 mRNA. Translation: CAA67700.1. D63780 mRNA. Translation: BAA20420.1. BT019961 mRNA. Translation: AAV38764.1. AC110299 Genomic DNA. Translation: AAY14683.1. DQ093965 Genomic DNA. Translation: AAY88740.1. BC007852 mRNA. Translation: AAH07852.1. BC091505 mRNA. Translation: AAH91505.1.
IPI	IPI00012093.
PIR	S71886.
RefSeq	NP_006365.2.
UniGene	Hs.516807
3D structure databases
HSSP	HSSP built from PDB template 1F3M based on UniProtKB Q13153.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00506. 7 interactions.
PTM databases
PhosphoSite	O00506.
Proteomic databases
PRIDE	O00506.
Genome annotation databases
Ensembl	ENSG00000115694. Homo sapiens. [Contig view]
GeneID	10494.
KEGG	hsa:10494.
UCSC	uc002wbm.1. human.
Organism-specific databases
GeneCards	GC02M242154.
H-InvDB	HIX0019062.
HGNC	HGNC:11404. STK25.
MIM	602255. gene.
Orphanet	1617. Deletion 2q24.
PharmGKB	PA36211.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00506.
HOVERGEN	O00506.
OMA	O00506. FSHNRNH.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	O00506.
Bgee	O00506.
CleanEx	HS_STK25.
GermOnline	ENSG00000115694. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	39822.
SOURCE	Search...

Entry information

Entry name

STK25_HUMAN

Accession

Primary (citable) accession number: O00506
Secondary accession number(s): Q15522, Q5BJF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 1, 1997
Last modified:	July 7, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)