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Q62868

- ROCK2_RAT

UniProt

Q62868 - ROCK2_RAT

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Protein

Rho-associated protein kinase 2

Gene

Rock2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca2+ sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.By similarity

Enzyme regulationi

Activated by RHOA binding. Inhibited by Y-27632.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei121 – 1211ATPPROSITE-ProRule annotation
Active sitei214 – 2141Proton acceptorPROSITE-ProRule annotation
Sitei1131 – 11322Cleavage; by granzyme B

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi98 – 1069ATPPROSITE-ProRule annotation
Zinc fingeri1260 – 131556Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. kinase activity Source: RGD
  3. metal ion binding Source: UniProtKB-KW
  4. protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. actin cytoskeleton organization Source: InterPro
  2. chromosome condensation Source: RGD
  3. regulation of circadian rhythm Source: UniProtKB
  4. Rho protein signal transduction Source: MGI
  5. rhythmic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Rock2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3590. Rock2.

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. cytoskeleton Source: UniProtKB-KW
  3. nucleus Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi48 – 481D → A: Loss of kinase activity; autophosphorylation and dimerization. 1 Publication
Mutagenesisi121 – 1211K → A: Loss of kinase activity. 2 Publications
Mutagenesisi121 – 1211K → M: Loss of autophosphorylation. 2 Publications
Mutagenesisi414 – 4141T → A: Loss of kinase activity; autophosphorylation and dimerization. 1 Publication
Mutagenesisi1170 – 11701W → A: Increased activity and autophosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13881388Rho-associated protein kinase 2PRO_0000086627Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei414 – 4141Phosphothreonine; by ROCK21 Publication
Modified residuei722 – 7221Phosphotyrosine; by SRCBy similarity
Modified residuei1137 – 11371PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ62868.
PRIDEiQ62868.

PTM databases

PhosphoSiteiQ62868.

Expressioni

Tissue specificityi

Highly expressed in brain, lung, liver, skeletal muscle, kidney and testis.1 Publication

Gene expression databases

GenevestigatoriQ62868.

Interactioni

Subunit structurei

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.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MYL12AP191052EBI-1569209,EBI-354418From a different organism.

Protein-protein interaction databases

BioGridi247569. 1 interaction.
IntActiQ62868. 5 interactions.
MINTiMINT-4598028.
STRINGi10116.ENSRNOP00000063773.

Structurei

Secondary structure

1
1388
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1153 – 11586
Beta strandi1163 – 11664
Beta strandi1172 – 11787
Beta strandi1181 – 11866
Helixi1188 – 11925
Beta strandi1197 – 12004
Helixi1202 – 12043
Beta strandi1205 – 12106
Turni1213 – 12153
Beta strandi1217 – 12193
Turni1221 – 12233
Helixi1224 – 12263
Beta strandi1227 – 12326
Beta strandi1234 – 12363
Beta strandi1256 – 12583
Beta strandi1261 – 12666
Beta strandi1275 – 12817
Beta strandi1284 – 12863
Beta strandi1290 – 12967
Beta strandi1299 – 13013
Helixi1302 – 13076
Turni1317 – 13193
Beta strandi1325 – 13306
Helixi1334 – 134714

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ROVNMR-A1151-1351[»]
2ROWNMR-A1237-1320[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62868.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 354263Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini357 – 42569AGC-kinase C-terminalAdd
BLAST
Repeati475 – 55985REMAdd
BLAST
Domaini1150 – 1349200PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni363 – 784422Interaction with PPP1R12AAdd
BLAST
Regioni373 – 42048Interaction with NPM1By similarityAdd
BLAST
Regioni979 – 104769RHOA bindingBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili439 – 1024586Sequence AnalysisAdd
BLAST
Coiled coili1052 – 113180Sequence AnalysisAdd
BLAST

Domaini

An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization.1 Publication

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 REM (Hr1) repeat.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1260 – 131556Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000017259.
HOVERGENiHBG053111.
InParanoidiQ62868.
KOiK17388.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR000961. AGC-kinase_C.
IPR011072. HR1_rho-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015008. Rho-bd_dom.
IPR020684. ROCK1/ROCK2.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF02185. HR1. 1 hit.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF08912. Rho_Binding. 1 hit.
[Graphical view]
PIRSFiPIRSF037568. Rho_kinase. 1 hit.
SMARTiSM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

Q62868-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRPPPTGKM PGAPEAAAGD GAGAGRQRKL EALIRDPRSP INVESLLDGL
60 70 80 90 100
NSLVLDLDFP ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR
110 120 130 140 150
GAFGEVQLVR HKASQKVYAM KLLSKFEMIK RSDSAFFWEE RDIMAFANSP
160 170 180 190 200
WVVQLFCAFQ DDRYLYMVME YMPGGDLVNL MSNYDVPEKW AKFYTAEVVL
210 220 230 240 250
ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD ETGMVHCDTA
260 270 280 290 300
VGTPDYISPE VLKSQGGDGY YGRECDWWSV GVFLFEMLVG DTPFYADSLV
310 320 330 340 350
GTYSKIMDHK NSLCFPEDTE ISKHAKNLIC AFLTDREVRL GRNGVEEIKS
360 370 380 390 400
ASFFKNDQWN WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP
410 420 430 440 450
KAFVGNQLPF IGFTYFRENL LLSDSPPCRE NDAIQTRKSE ESQEIQKKLY
460 470 480 490 500
ALEEHLSSEV QAKEELEQKC KSINTRLEKT AKELEEEITF RKNVESTLRQ
510 520 530 540 550
LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL EDLKKRNQSS
560 570 580 590 600
QISTEKVNQL QKQLDEANAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
610 620 630 640 650
DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRISG
660 670 680 690 700
LEEDLKTGKT LLAKVELEKR QLQEKLTDLE KEKSNMEIDM TYQLKVIQQS
710 720 730 740 750
LEQEEAEHKT TKARLADKNK IYESIEEAKS EAMKEMEKKL LEERSLKQKV
760 770 780 790 800
ENLLLEAEKR CSILDCDLKQ SQQKLNELLK QKDVLNEDVR NLTLKIEQET
810 820 830 840 850
QKRCLMQNDL KMQTQQVNTL KMSEKQIKQE NNHLMEMKMN LEKQNAELRK
860 870 880 890 900
ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEENEEK TKLCKELQQK
910 920 930 940 950
KQDLQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI
960 970 980 990 1000
KEMMARHKQE LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDTQ
1010 1020 1030 1040 1050
EQLSKLKDEE ISAAAIKAQF EKQLLTERTL KTQAVNKLAE IMNRKEPVKR
1060 1070 1080 1090 1100
GSDTDVRRKE KENRKLHMEL KSEREKLTQQ MIKYQKELNE MQAQIAEESQ
1110 1120 1130 1140 1150
IRIELQMTLD SKDSDIEQLR SQLQALHIGM DSSSIGSGPG DAEPDDGFPE
1160 1170 1180 1190 1200
SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
1210 1220 1230 1240 1250
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EPEFPVEPVG
1260 1270 1280 1290 1300
EKSNYICHKG HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECSRCHIKC
1310 1320 1330 1340 1350
HKDHMDKKEE IIAPCKVYYD ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK
1360 1370 1380
KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR QLAPNKPS
Length:1,388
Mass (Da):160,387
Last modified:September 21, 2011 - v2
Checksum:iB23672CA8645067C
GO

Sequence cautioni

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U38481 mRNA. Translation: AAB37540.1. Different initiation.
RefSeqiNP_037154.2. NM_013022.2.
UniGeneiRn.88642.

Genome annotation databases

GeneIDi25537.
KEGGirno:25537.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U38481 mRNA. Translation: AAB37540.1 . Different initiation.
RefSeqi NP_037154.2. NM_013022.2.
UniGenei Rn.88642.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2ROV NMR - A 1151-1351 [» ]
2ROW NMR - A 1237-1320 [» ]
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247569. 1 interaction.
IntActi Q62868. 5 interactions.
MINTi MINT-4598028.
STRINGi 10116.ENSRNOP00000063773.

Chemistry

BindingDBi Q62868.
ChEMBLi CHEMBL5490.

PTM databases

PhosphoSitei Q62868.

Proteomic databases

PaxDbi Q62868.
PRIDEi Q62868.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25537.
KEGGi rno:25537.

Organism-specific databases

CTDi 9475.
RGDi 3590. Rock2.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000017259.
HOVERGENi HBG053111.
InParanoidi Q62868.
KOi K17388.

Miscellaneous databases

EvolutionaryTracei Q62868.
NextBioi 607045.
PROi Q62868.

Gene expression databases

Genevestigatori Q62868.

Family and domain databases

Gene3Di 2.30.29.30. 2 hits.
InterProi IPR000961. AGC-kinase_C.
IPR011072. HR1_rho-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015008. Rho-bd_dom.
IPR020684. ROCK1/ROCK2.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF02185. HR1. 1 hit.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF08912. Rho_Binding. 1 hit.
[Graphical view ]
PIRSFi PIRSF037568. Rho_kinase. 1 hit.
SMARTi SM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi 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.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiROCK2_RAT
AccessioniPrimary (citable) accession number: Q62868
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: September 21, 2011
Last modified: October 29, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3