Reviewed, UniProtKB/Swiss-Prot O75116 (ROCK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho-associated protein kinase 2
    EC=2.7.11.1
Alternative name(s):
    Rho-associated, coiled-coil-containing protein kinase 2
    p164 ROCK-2
    Rho kinase 2

Gene names

Name:	ROCK2
Synonyms:	KIAA0619

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	1388 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Regulates the assembly of the actin cytoskeleton. Promotes formation of stress fibers and of focal adhesion complexes. Plays a role in smooth muscle contraction By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by RHOA binding.
Subunit structure	Homodimer. Binds RHOA that has been activated by GTP binding. Binds IRS1, RHOB and RHOC By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Peripheral membrane protein By similarity. Note: Cytoplasmic, and associated with actin microfilaments and the plasma membrane By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11
Miscellaneous	Inhibited by Y-27632 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. Contains 1 REM (Hr1) repeat.
Sequence caution	The sequence AAX93049.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cytokinesis Ref.1 Non-traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc structural molecule activity Ref.1 Non-traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKE	Q14164	1	EBI-366288,EBI-307369
STK16	O75716	1	EBI-366288,EBI-749295

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1388	1388	Rho-associated protein kinase 2		PRO_0000086625
Regions
	Domain	92 – 354	263	Protein kinase
	Domain	357 – 425	69	AGC-kinase C-terminal
	Repeat	475 – 559	85	REM
	Domain	1150 – 1349	200	PH
	Nucleotide binding	98 – 106	9	ATP By similarity
	Zinc finger	1260 – 1315	56	Phorbol-ester/DAG-type
	Region	979 – 1047	69	RHOA binding By similarity
	Coiled coil	429 – 1024	596	Potential
	Coiled coil	1053 – 1131	79	Potential
Sites
	Active site	214	1	Proton acceptor By similarity
	Binding site	121	1	ATP By similarity
Amino acid modifications
	Modified residue	425	1	Phosphoserine Ref.8
	Modified residue	1078	1	Phosphothreonine Ref.7
	Modified residue	1133	1	Phosphoserine Ref.9
	Modified residue	1134	1	Phosphoserine Ref.4
	Modified residue	1137	1	Phosphoserine Ref.4 Ref.9 Ref.11
	Modified residue	1362	1	Phosphoserine Ref.5
	Modified residue	1374	1	Phosphoserine Ref.6
Natural variations
	Natural variant	431	1	T → N: dbSNP rs2230774. Ref.1 Ref.2 Ref.12		VAR_041062
	Natural variant	601	1	D → V: dbSNP rs35768389. Ref.12		VAR_041063
	Natural variant	1083	1	K → M: dbSNP rs34945852.		VAR_057110
	Natural variant	1194	1	S → P in a metastatic melanoma sample; somatic mutation. Ref.12		VAR_041064
Experimental info
	Sequence conflict	83	1	R → K in BAA75636. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75116-1 [UniParc]. Last modified November 24, 2009. Version 4. Checksum: 876240F410C2487E	FASTA	1,388	160,900
	10 20 30 40 50 60 MSRPPPTGKM PGAPETAPGD GAGASRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP 70 80 90 100 110 120 ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM 130 140 150 160 170 180 KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFYAFQ DDRYLYMVME YMPGGDLVNL 190 200 210 220 230 240 MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD 250 260 270 280 290 300 ETGMVHCDTA VGTPDYISPE VLKSQGGDGF YGRECDWWSV GVFLYEMLVG DTPFYADSLV 310 320 330 340 350 360 GTYSKIMDHK NSLCFPEDAE ISKHAKNLIC AFLTDREVRL GRNGVEEIRQ HPFFKNDQWH 370 380 390 400 410 420 WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYYRENL 430 440 450 460 470 480 LLSDSPSCRE TDSIQSRKNE ESQEIQKKLY TLEEHLSNEM QAKEELEQKC KSVNTRLEKT 490 500 510 520 530 540 AKELEEEITL RKSVESALRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL 550 560 570 580 590 600 EDLKKRNQNS QISTEKVNQL QRQLDETNAL LRTESDTAAR LRKTQAESSK QIQQLESNNR 610 620 630 640 650 660 DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRICG LEEDLKNGKI 670 680 690 700 710 720 LLAKVELEKR QLQERFTDLE KEKSNMEIDM TYQLKVIQQS LEQEEAEHKA TKARLADKNK 730 740 750 760 770 780 IYESIEEAKS EAMKEMEKKL LEERTLKQKV ENLLLEAEKR CSLLDCDLKQ SQQKINELLK 790 800 810 820 830 840 QKDVLNEDVR NLTLKIEQET QKRCLTQNDL KMQTQQVNTL KMSEKQLKQE NNHLMEMKMN 850 860 870 880 890 900 LEKQNAELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEECEEK TKLGKELQQK 910 920 930 940 950 960 KQELQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE 970 980 990 1000 1010 1020 LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDVQ EQLSRLKDEE ISAAAIKAQF 1030 1040 1050 1060 1070 1080 EKQLLTERTL KTQAVNKLAE IMNRKEPVKR GNDTDVRRKE KENRKLHMEL KSEREKLTQQ 1090 1100 1110 1120 1130 1140 MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGL DSSSIGSGPG 1150 1160 1170 1180 1190 1200 DAEADDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL 1210 1220 1230 1240 1250 1260 DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EQEFPVEPVG EKSNYICHKG 1270 1280 1290 1300 1310 1320 HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECRRCHIKC HKDHMDKKEE IIAPCKVYYD 1330 1340 1350 1360 1370 1380 ISTAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR QLAPNKPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Localization of the gene coding for ROCK II/Rho kinase on human chromosome 2p24." Takahashi N., Tuiki H., Saya H., Kaibuchi K. Genomics 55:235-237(1999) [PubMed: 9933571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-431. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-431. Tissue: Brain.
[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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1134 AND SER-1137, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"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-1362, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1374, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"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-1078, MASS SPECTROMETRY.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, MASS SPECTROMETRY.
[9]	"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-1133 AND SER-1137, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"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] ASN-431; VAL-601 AND PRO-1194.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D87931 mRNA. Translation: BAA75636.1. AB014519 mRNA. Translation: BAA31594.2. Different initiation. AC018463 Genomic DNA. Translation: AAX93049.1. Sequence problems. AC099344 Genomic DNA. Translation: AAY14825.1.
IPI	IPI00307155.
RefSeq	NP_004841.2.
UniGene	Hs.591600
3D structure databases
SMR	O75116. Positions 27-417, 979-1045, 1151-1351.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75116. 6 interactions.
STRING	O75116.
PTM databases
PhosphoSite	O75116.
Proteomic databases
PRIDE	O75116.
Genome annotation databases
Ensembl	ENST00000315872; ENSP00000317985; ENSG00000134318; Homo sapiens. [Genome view]
GeneID	9475.
KEGG	hsa:9475.
Organism-specific databases
CTD	9475.
GeneCards	GC02M011272.
H-InvDB	HIX0001828.
HGNC	HGNC:10252. ROCK2.
HPA	CAB008666. HPA007459.
MIM	604002. gene.
PharmGKB	PA34624.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05561.
HOGENOM	HBG445047.
HOVERGEN	O75116.
PhylomeDB	O75116.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Pathway_Interaction_DB	avb3_opn_pathway. Osteopontin-mediated events. er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
Reactome	REACT_14797. Signaling by GPCR. REACT_18266. Axon guidance.
Gene expression databases
ArrayExpress	O75116.
Bgee	O75116.
CleanEx	HS_ROCK2.
Genevestigator	O75116.
GermOnline	ENSG00000134318. Homo sapiens.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR001849. Pleckstrin_homology. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR020684. Rho-assoc_coiled-coil_kin-like. IPR015751. Rho-assoc_coiled-coil_kinase. IPR015008. Rho_bd. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
Gene3D	G3DSA:1.20.5.730. Rho_bd. 1 hit.
PANTHER	PTHR22988:SF3. Rho_kinase. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. PF08912. Rho_Binding. 1 hit. [Graphical view]
PIRSF	PIRSF037568. Rho_kinase. 1 hit.
SMART	SM00109. C1. 1 hit. SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. False negative. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	35508.
SOURCE	Search...

Entry information

Entry name

ROCK2_HUMAN

Accession

Primary (citable) accession number: O75116
Secondary accession number(s): Q53QZ0, Q53SJ7, Q9UQN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	November 24, 2009
Last modified:	January 19, 2010
This is version 102 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.