Reviewed, UniProtKB/Swiss-Prot O95747 (OXSR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase OSR1
    EC=2.7.11.1
Alternative name(s):
    Oxidative stress-responsive 1 protein

Gene names

Name:	OXSR1
Synonyms:	KIAA1101, OSR1

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

General annotation (Comments)

Function	Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton. Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.6
Cofactor	Magnesium. Ref.6
Enzyme regulation	By autophosphorylation on threonine. Ref.6
Subunit structure	Binds to and phosphorylates PAK1. Interacts with chloride channel proteins SLC12A6 isoform 2, SLC12A1 and SLC12A2 but not with SLC12A4 and SLC12A7, possibly establishing sensor/signaling modules that initiate the cellular response to environmental stress. Binds to and phosphorylates RELL1, RELL2 AND RELT. Ref.6 Ref.7 UniProtKB Q6P9R2
Tissue specificity	Ubiquitously expressed in all tissue examined. Ref.1
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence BAA83053.2 differs from that shown. Reason: Frameshift at position 63.

Ontologies

Keywords
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
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.1 Ref.6 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.6 Inferred from direct assay. Source: UniProtKB response to oxidative stress Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	ATP binding Ref.6 Inferred from direct assay. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct magnesium ion binding Ref.6 Inferred from direct assay. Source: UniProtKB protein serine/threonine kinase activity Ref.1 Ref.6 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-620853,EBI-620853
Pak1	P35465	1	EBI-620853,EBI-444379	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 527

527

Serine/threonine-protein kinase OSR1

PRO_0000086456

Regions

Domain

17 – 291

275

Protein kinase

Nucleotide binding

23 – 31

9

ATP By similarity UniProtKB Q9Z1W9

Sites

Active site

146

1

Proton acceptor By similarity UniProtKB Q9Z1W9

Binding site

46

1

ATP Ref.6

Amino acid modifications

Modified residue

339

1

Phosphoserine Ref.8 Ref.10 Ref.11

Modified residue

427

1

Phosphoserine Ref.9 Ref.10

Natural variations

Natural variant

304

1

T → I: dbSNP rs6599079. Ref.1 Ref.3 Ref.13

VAR_023232

Natural variant

425

1

S → T Ref.3

VAR_025181

Natural variant

433

1

P → S in a metastatic melanoma sample; somatic mutation. Ref.13

VAR_040969

Experimental info

Mutagenesis

46

1

K → A: Loss of autophosphorylation and kinase activity. Ref.6 Ref.7

Mutagenesis

46

1

K → M: Loss of RELT, RELL1 and RELL2 phosphorylation. Retention of some autophosphorylation activity may be due to complex formation with other endogenous kinases in the assay. Ref.6 Ref.7

Sequence conflict

316

1

K → R in AAP97192. Ref.5

Sequence conflict

325

1

S → G in AAP97192. Ref.5

Sequence conflict

363

1

K → R in AAP97192. Ref.5

Secondary structure

1

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527

Helix Strand Turn

Details...

Beta strand

18 – 24

7

Beta strand

31 – 35

5

Beta strand

42 – 46

5

Beta strand

78 – 86

9

Beta strand

88 – 93

6

Helix

100 – 109

10

Turn

110 – 115

6

Helix

120 – 139

20

Helix

149 – 151

3

Beta strand

152 – 154

3

Beta strand

160 – 162

3

Helix

166 – 170

5

Helix

195 – 202

8

Helix

207 – 222

16

Turn

226 – 229

4

Helix

232 – 234

3

Helix

235 – 240

6

Helix

262 – 271

10

Helix

276 – 278

3

Helix

282 – 286

5

Beta strand

434 – 441

8

Beta strand

447 – 454

8

Turn

456 – 458

3

Helix

461 – 470

10

Helix

476 – 478

3

Helix

479 – 491

13

Turn

493 – 495

3

Beta strand

497 – 502

6

Helix

504 – 506

3

Beta strand

507 – 511

5

Helix

515 – 517

3

Beta strand

519 – 526

8

Sequences

	Sequence		Length	Mass (Da)
	O95747-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: B46EC934E95A3A1F	FASTA	527	58,022
	10 20 30 40 50 60 MSEDSSALPW SINRDDYELQ EVIGSGATAV VQAAYCAPKK EKVAIKRINL EKCQTSMDEL 70 80 90 100 110 120 LKEIQAMSQC HHPNIVSYYT SFVVKDELWL VMKLLSGGSV LDIIKHIVAK GEHKSGVLDE 130 140 150 160 170 180 STIATILREV LEGLEYLHKN GQIHRDVKAG NILLGEDGSV QIADFGVSAF LATGGDITRN 190 200 210 220 230 240 KVRKTFVGTP CWMAPEVMEQ VRGYDFKADI WSFGITAIEL ATGAAPYHKY PPMKVLMLTL 250 260 270 280 290 300 QNDPPSLETG VQDKEMLKKY GKSFRKMISL CLQKDPEKRP TAAELLRHKF FQKAKNKEFL 310 320 330 340 350 360 QEKTLQRAPT ISERAKKVRR VPGSSGRLHK TEDGGWEWSD DEFDEESEEG KAAISQLRSP 370 380 390 400 410 420 RVKESISNSE LFPTTDPVGT LLQVPEQISA HLPQPAGQIA TQPTQVSLPP TAEPAKTAQA 430 440 450 460 470 480 LSSGSGSQET KIPISLVLRL RNSKKELNDI RFEFTPGRDT AEGVSQELIS AGLVDGRDLV 490 500 510 520 IVAANLQKIV EEPQSNRSVT FKLASGVEGS DIPDDGKLIG FAQLSIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a novel serine threonine kinase gene on chromosome 3p22-21.3." Tamari M., Daigo Y., Nakamura Y. J. Hum. Genet. 44:116-120(1999) [PubMed: 10083736] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT ILE-304. Tissue: Skeletal muscle.
[2]	"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed: 10470851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	NIEHS SNPs program Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-304 AND THR-425.
[4]	"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: Brain.
[5]	"Cloning and characterization of a novel human cDNA homologous to human DCHT mRNA." Ding J.B., Yu L., Gong R.M., Mao N.H., Han X.F., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 172-527.
[6]	"Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase subfamily." Chen W., Yazicioglu M., Cobb M.H. J. Biol. Chem. 279:11129-11136(2004) [PubMed: 14707132] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, ENZYME REGULATION, INTERACTION WITH PAK1, MUTAGENESIS OF LYS-46.
[7]	"Identification of RELT homologues that associate with RELT and are phosphorylated by OSR1." Cusick J.K., Xu L.-G., Bin L.-H., Han K.-J., Shu H.-B. Biochem. Biophys. Res. Commun. 340:535-543(2006) [PubMed: 16389068] [Abstract] Cited for: INTERACTION WITH RELL1, RELL2 AND RELT, MUTAGENESIS OF LYS-46.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, MASS SPECTROMETRY. Tissue: Epithelium.
[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 SER-427, MASS SPECTROMETRY.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-427, MASS SPECTROMETRY.
[11]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, MASS SPECTROMETRY. Tissue: Liver.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-304 AND SER-433.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB017642 mRNA. Translation: BAA75674.1.
AB029024 mRNA. Translation: BAA83053.2. Frameshift.
DQ201638 Genomic DNA. Translation: ABA27097.1.
BC008726 mRNA. Translation: AAH08726.1.
AF087893 mRNA. Translation: AAP97192.1. Different initiation.

IPI

IPI00010080.

RefSeq

NP_005100.1.

UniGene

Hs.475970

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V3S	X-ray	1.70	A/B	433-527	[»]
2VWI	X-ray	2.15	A/B/C/D	1-303	[»]
3DAK	X-ray	2.25	A/B/C/D	6-295	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O95747. 4 interactions.

PTM databases

PhosphoSite

O95747.

Proteomic databases

PeptideAtlas

O95747.

PRIDE

O95747.

Genome annotation databases

Ensembl

ENSG00000172939. Homo sapiens. [Contig view]

GeneID

9943.

KEGG

hsa:9943.

Organism-specific databases

GeneCards

GC03P038183.

H-InvDB

HIX0003179.

HGNC

HGNC:8508. OXSR1.

HPA

CAB017181.
HPA008237.

MIM

604046. gene.

PharmGKB

PA134973207.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O95747.

HOVERGEN

O95747.

OMA

O95747. EPTIATI.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Gene expression databases

ArrayExpress

O95747.

Bgee

O95747.

CleanEx

HS_OSR1.
HS_OXSR1.

GermOnline

ENSG00000172939. 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

37516.

SOURCE

Search...

Entry information

Entry name

OXSR1_HUMAN

Accession

Primary (citable) accession number: O95747
Secondary accession number(s): Q3LR53, Q7Z501, Q9UPQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	May 1, 1999
Last modified:	June 16, 2009
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)