O00506 (STK25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase 25
EC=2.7.11.1

Alternative name(s):
Ste20-like kinase
Sterile 20/oxidant stress-response kinase 1
Short name=SOK-1
Short name=Ste20/oxidant stress response kinase 1

Gene names

Name:	STK25
Synonyms:	SOK1, YSK1

Organism

Homo sapiens (Human)

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.
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.9
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.9
Subunit structure	Homodimer.
Subcellular location	Cytoplasm. Golgi apparatus. Note: Localizes to the Golgi apparatus. Ref.9
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.9 Ref.10 Ref.11 Ref.12
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	response to oxidative stress Traceable author statement. Source: ProtInc signal transduction 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 metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.9. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Golga2	Q62839	2	EBI-618295,EBI-618335	From a different organism.
PDCD10	Q9BUL8	7	EBI-618295,EBI-740195
STRN	O43815	2	EBI-618295,EBI-1046642
YWHAZ	P63104	2	EBI-618295,EBI-347088

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.10 Ref.11 Ref.12

Modified residue

174

1

Phosphothreonine; by autocatalysis Ref.9 Ref.12

Modified residue

342

1

Phosphoserine Ref.10

Natural variations

Natural variant

64

1

Q → H.
Corresponds to variant rs34341643 [ dbSNP | Ensembl ].

VAR_051674

Experimental info

Mutagenesis

49

1

K → R: Loss of kinase activity and autophosphorylation. Ref.9

Mutagenesis

158

1

D → A: Loss of kinase activity. Ref.9

Sequence conflict

347 – 348

2

EP → DA in CAA67700. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

426

Helix Strand Turn

Details...

Helix

8 – 10

3

Helix

16 – 19

4

Turn

40 – 42

3

Beta strand

46 – 52

7

Turn

53 – 56

4

Helix

60 – 72

13

Beta strand

85 – 87

3

Beta strand

90 – 96

7

Helix

103 – 107

5

Helix

114 – 125

12

Helix

129 – 133

5

Helix

143 – 145

3

Beta strand

146 – 148

3

Beta strand

154 – 156

3

Beta strand

170 – 172

3

Helix

179 – 181

3

Helix

184 – 187

4

Helix

195 – 200

6

Helix

204 – 209

6

Turn

214 – 217

4

Helix

220 – 226

7

Turn

227 – 229

3

Helix

241 – 250

10

Helix

255 – 257

3

Helix

261 – 264

4

Helix

268 – 272

5

Helix

277 – 280

4

Helix

281 – 291

11

Sequences

	Sequence		Length	Mass (Da)
	O00506 [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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.
[9]	"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.
[10]	"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. Tissue: Embryonic kidney.
[11]	"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. Tissue: Embryonic kidney.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-168 AND THR-174, MASS SPECTROMETRY.
[13]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X99325 mRNA. Translation: CAA67700.1.
D63780 mRNA. Translation: BAA20420.1.
AK291947 mRNA. Translation: BAF84636.1.
BT019961 mRNA. Translation: AAV38764.1.
AC110299 Genomic DNA. Translation: AAY14683.1.
DQ093965 Genomic DNA. Translation: AAY88740.1.
CH471063 Genomic DNA. Translation: EAW71265.1.
BC007852 mRNA. Translation: AAH07852.1.
BC091505 mRNA. Translation: AAH91505.1.

IPI

IPI00012093.

PIR

S71886.

RefSeq

NP_006365.2. NM_006374.3.

UniGene

Hs.516807.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XIK	X-ray	1.97	A	1-293	[»]

ProteinModelPortal

O00506.

SMR

O00506. Positions 3-292.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00506. 30 interactions.

STRING

O00506.

PTM databases

PhosphoSite

O00506.

Proteomic databases

PRIDE

O00506.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316586; ENSP00000325748; ENSG00000115694.
ENST00000401869; ENSP00000385687; ENSG00000115694.
ENST00000403346; ENSP00000384162; ENSG00000115694.

GeneID

10494.

KEGG

hsa:10494.

UCSC

uc002wbm.1. human.

Organism-specific databases

CTD

10494.

GeneCards

GC02M242453.

H-InvDB

HIX0019062.

HGNC

HGNC:11404. STK25.

HPA

HPA047147.

MIM

602255. gene.

neXtProt

NX_O00506.

PharmGKB

PA36211.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06715.

HOGENOM

HBG755340.

HOVERGEN

HBG108518.

InParanoid

O00506.

OMA

FSHNRNH.

OrthoDB

EOG4NGGMX.

PhylomeDB

O00506.

Gene expression databases

ArrayExpress

O00506.

Bgee

O00506.

CleanEx

HS_STK25.

Genevestigator

O00506.

GermOnline

ENSG00000115694. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K08839.

Pfam

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

NextBio

39822.

SOURCE

Search...

Entry information

Entry name

STK25_HUMAN

Accession

Primary (citable) accession number: O00506
Secondary accession number(s): A8K7D2, Q15522, Q5BJF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 1, 1997
Last modified:	January 25, 2012
This is version 121 of the entry and version 1 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.