Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q62868 (ROCK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rho-associated protein kinase 2

EC=2.7.11.1
Alternative name(s):
Rho-associated, coiled-coil-containing protein kinase 2
Rho-associated, coiled-coil-containing protein kinase II
Short name=ROCK-II
RhoA-binding kinase 2
p150 ROK-alpha
Short name=ROKalpha
p164 ROCK-2
Gene names
Name:Rock2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1388 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays a role in placental homeostasis during the perinatal period By similarity. Ref.1 Ref.2 Ref.3 Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by RHOA binding. Inhibited by Y-27632.

Subunit structure

Homodimer By similarity. Interacts with CHORDC1, PPP1R12A, SORL1, EP300 and BRCA2 By similarity. Interacts with NPM1 and this interaction enhances its activity By similarity. Interacts with RHOA (activated by GTP), RHOB, RHOC and IRS1. Interacts with RAF1. Ref.1 Ref.2 Ref.4 Ref.5 Ref.8

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Note: Cytoplasmic, and associated with actin microfilaments and the plasma membrane. Ref.1 Ref.8

Tissue specificity

Highly expressed in brain, lung, liver, skeletal muscle, kidney and testis. Ref.2

Domain

An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization. Ref.7

Post-translational modification

Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity By similarity. Ref.1 Ref.2 Ref.7

Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.

Involvement in disease

May play a role in hypertension. ROCK-inhibitors lower the blood pressure in spontaneous hypertensive, renal hypertensive and deoxycorticosterone acetate-induced hypertensive rats, but not in normal rats.

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 AAB37540.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MYL12AP191052EBI-1569209,EBI-354418From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13881388Rho-associated protein kinase 2
PRO_0000086627

Regions

Domain92 – 354263Protein kinase
Domain357 – 42569AGC-kinase C-terminal
Repeat475 – 55985REM
Domain1150 – 1349200PH
Nucleotide binding98 – 1069ATP By similarity
Zinc finger1260 – 131556Phorbol-ester/DAG-type
Region363 – 784422Interaction with PPP1R12A
Region373 – 42048Interaction with NPM1 By similarity
Region979 – 104769RHOA binding By similarity
Coiled coil439 – 1024586 Potential
Coiled coil1052 – 113180 Potential

Sites

Active site2141Proton acceptor By similarity
Binding site1211ATP By similarity
Site1131 – 11322Cleavage; by granzyme B

Amino acid modifications

Modified residue4141Phosphothreonine; by ROCK2 Ref.7
Modified residue7221Phosphotyrosine; by SRC By similarity
Modified residue11371Phosphoserine By similarity

Experimental info

Mutagenesis481D → A: Loss of kinase activity; autophosphorylation and dimerization. Ref.7
Mutagenesis1211K → A: Loss of kinase activity. Ref.2 Ref.7
Mutagenesis1211K → M: Loss of autophosphorylation. Ref.2 Ref.7
Mutagenesis4141T → A: Loss of kinase activity; autophosphorylation and dimerization. Ref.7
Mutagenesis11701W → A: Increased activity and autophosphorylation. Ref.7

Secondary structure

............................................. 1388
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q62868 [UniParc].

Last modified September 21, 2011. Version 2.
Checksum: B23672CA8645067C

FASTA1,388160,387
        10         20         30         40         50         60 
MSRPPPTGKM PGAPEAAAGD GAGAGRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP 

        70         80         90        100        110        120 
ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM 

       130        140        150        160        170        180 
KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFCAFQ DDRYLYMVME YMPGGDLVNL 

       190        200        210        220        230        240 
MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD 

       250        260        270        280        290        300 
ETGMVHCDTA VGTPDYISPE VLKSQGGDGY YGRECDWWSV GVFLFEMLVG DTPFYADSLV 

       310        320        330        340        350        360 
GTYSKIMDHK NSLCFPEDTE ISKHAKNLIC AFLTDREVRL GRNGVEEIKS ASFFKNDQWN 

       370        380        390        400        410        420 
WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYFRENL 

       430        440        450        460        470        480 
LLSDSPPCRE NDAIQTRKSE ESQEIQKKLY ALEEHLSSEV QAKEELEQKC KSINTRLEKT 

       490        500        510        520        530        540 
AKELEEEITF RKNVESTLRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL 

       550        560        570        580        590        600 
EDLKKRNQSS QISTEKVNQL QKQLDEANAL LRTESDTAAR LRKTQAESSK QIQQLESNNR 

       610        620        630        640        650        660 
DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRISG LEEDLKTGKT 

       670        680        690        700        710        720 
LLAKVELEKR QLQEKLTDLE KEKSNMEIDM TYQLKVIQQS LEQEEAEHKT TKARLADKNK 

       730        740        750        760        770        780 
IYESIEEAKS EAMKEMEKKL LEERSLKQKV ENLLLEAEKR CSILDCDLKQ SQQKLNELLK 

       790        800        810        820        830        840 
QKDVLNEDVR NLTLKIEQET QKRCLMQNDL KMQTQQVNTL KMSEKQIKQE NNHLMEMKMN 

       850        860        870        880        890        900 
LEKQNAELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEENEEK TKLCKELQQK 

       910        920        930        940        950        960 
KQDLQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE 

       970        980        990       1000       1010       1020 
LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDTQ EQLSKLKDEE ISAAAIKAQF 

      1030       1040       1050       1060       1070       1080 
EKQLLTERTL KTQAVNKLAE IMNRKEPVKR GSDTDVRRKE KENRKLHMEL KSEREKLTQQ 

      1090       1100       1110       1120       1130       1140 
MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGM DSSSIGSGPG 

      1150       1160       1170       1180       1190       1200 
DAEPDDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL 

      1210       1220       1230       1240       1250       1260 
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EPEFPVEPVG EKSNYICHKG 

      1270       1280       1290       1300       1310       1320 
HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECSRCHIKC HKDHMDKKEE IIAPCKVYYD 

      1330       1340       1350       1360       1370       1380 
ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR 


QLAPNKPS 

« Hide

References

[1]"A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes."
Leung T., Manser E., Tan L., Lim L.
J. Biol. Chem. 270:29051-29054(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH RHOA, SUBCELLULAR LOCATION.
Tissue: Brain.
[2]"The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton."
Leung T., Chen X.-Q., Manser E., Lim L.
Mol. Cell. Biol. 16:5313-5327(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH RHOA; RHOB AND RHOC, MUTAGENESIS OF LYS-121, TISSUE SPECIFICITY.
[3]"Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension."
Uehata M., Ishizaki T., Satoh H., Ono T., Kawahara T., Morishita T., Tamakawa H., Yamagami K., Inui J., Maekawa M., Narumiya S.
Nature 389:990-994(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ROLE IN HYPERTENSION, INHIBITION BY Y-27632.
[4]"Active Rho kinase (ROK-alpha) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells."
Begum N., Sandu O.A., Ito M., Lohmann S.M., Smolenski A.
J. Biol. Chem. 277:6214-6222(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IRS1.
[5]"Raf-1 regulates Rho signaling and cell migration."
Ehrenreiter K., Piazzolla D., Velamoor V., Sobczak I., Small J.V., Takeda J., Leung T., Baccarini M.
J. Cell Biol. 168:955-964(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAF1.
[6]"Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner."
Sebbagh M., Hamelin J., Bertoglio J., Solary E., Breard J.
J. Exp. Med. 201:465-471(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE BY GRANZYME B.
[7]"The hydrophobic motif of ROCK2 requires association with the N-terminal extension for kinase activity."
Couzens A.L., Saridakis V., Scheid M.P.
Biochem. J. 419:141-148(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, PHOSPHORYLATION AT THR-414, MUTAGENESIS OF ASP-48; LYS-121; THR-414 AND TRP-1170.
[8]"ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells."
Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X., Surks H.K.
Circ. Res. 104:531-540(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPP1R12A, SUBCELLULAR LOCATION.
[9]"Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase."
Tan I., Lai J., Yong J., Li S.F., Leung T.
FEBS Lett. 585:1260-1268(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MYL9/MLC2 AND PPP1R12A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U38481 mRNA. Translation: AAB37540.1. Different initiation.
RefSeqNP_037154.2. NM_013022.2.
UniGeneRn.88642.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ROVNMR-A1151-1351[»]
2ROWNMR-A1237-1320[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247569. 1 interaction.
IntActQ62868. 5 interactions.
MINTMINT-4598028.
STRING10116.ENSRNOP00000063773.

Chemistry

BindingDBQ62868.
ChEMBLCHEMBL5490.

PTM databases

PhosphoSiteQ62868.

Proteomic databases

PaxDbQ62868.
PRIDEQ62868.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25537.
KEGGrno:25537.

Organism-specific databases

CTD9475.
RGD3590. Rock2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000017259.
HOVERGENHBG053111.
InParanoidQ62868.
KOK17388.

Gene expression databases

GenevestigatorQ62868.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR000961. AGC-kinase_C.
IPR011072. HR1_rho-bd.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR020684. Rho-assoc_coiled-coil_kin.
IPR015008. Rho-bd_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR22988:SF3. PTHR22988:SF3. 1 hit.
PfamPF02185. HR1. 1 hit.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF08912. Rho_Binding. 1 hit.
[Graphical view]
PIRSFPIRSF037568. Rho_kinase. 1 hit.
SMARTSM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ62868.
NextBio607045.
PROQ62868.

Entry information

Entry nameROCK2_RAT
AccessionPrimary (citable) accession number: Q62868
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: September 21, 2011
Last modified: February 19, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references