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Protein

Rho-associated protein kinase 2

Gene

ROCK2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: 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 an important role in generating the circadian rhythm of the aortic myofilament Ca2+ sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+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

Regions

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

GO - Molecular functioni

GO - Biological processi

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
p164 ROCK-2
Gene namesi
Name:ROCK2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13881388Rho-associated protein kinase 2PRO_0000086624Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei414 – 4141Phosphothreonine; by ROCK2By similarity
Modified residuei722 – 7221Phosphotyrosine; by SRCBy similarity
Modified residuei1137 – 11371PhosphoserineBy similarity
Modified residuei1212 – 12121PhosphothreonineBy similarity
Modified residuei1362 – 13621PhosphoserineBy similarity
Modified residuei1374 – 13741PhosphoserineBy 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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1131 – 11322Cleavage; by granzyme BBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ28021.
PRIDEiQ28021.

PTM databases

iPTMnetiQ28021.

Expressioni

Tissue specificityi

Highly expressed in whole brain and in cerebellum, and at lower levels in heart and lung. Detected at low levels in skeletal muscle, spleen, liver, kidney and pancreas.1 Publication

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-29038N.
IntActiQ28021. 1 interaction.
MINTiMINT-1517391.
STRINGi9913.ENSBTAP00000007691.

Chemistry

BindingDBiQ28021.

Structurei

Secondary structure

1
1388
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi30 – 334Combined sources
Helixi43 – 5715Combined sources
Helixi62 – 643Combined sources
Helixi66 – 8217Combined sources
Helixi83 – 853Combined sources
Helixi89 – 913Combined sources
Beta strandi92 – 1009Combined sources
Beta strandi105 – 1117Combined sources
Turni112 – 1143Combined sources
Beta strandi117 – 1248Combined sources
Helixi125 – 1306Combined sources
Beta strandi135 – 1373Combined sources
Helixi138 – 1469Combined sources
Beta strandi155 – 1606Combined sources
Beta strandi162 – 1698Combined sources
Helixi177 – 1837Combined sources
Helixi188 – 20619Combined sources
Turni207 – 2093Combined sources
Helixi217 – 2193Combined sources
Beta strandi220 – 2223Combined sources
Beta strandi228 – 2303Combined sources
Beta strandi241 – 2477Combined sources
Helixi254 – 2563Combined sources
Helixi259 – 2635Combined sources
Helixi264 – 2663Combined sources
Beta strandi269 – 2724Combined sources
Helixi274 – 28916Combined sources
Helixi299 – 3079Combined sources
Helixi309 – 3124Combined sources
Helixi323 – 33210Combined sources
Helixi336 – 3383Combined sources
Turni340 – 3434Combined sources
Helixi346 – 3494Combined sources
Helixi352 – 3543Combined sources
Turni361 – 3633Combined sources
Helixi364 – 3663Combined sources
Helixi408 – 4103Combined sources
Helixi979 – 104365Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UIXX-ray1.80A/B979-1047[»]
2F2UX-ray2.40A/B18-417[»]
2H9VX-ray3.10A18-417[»]
ProteinModelPortaliQ28021.
SMRiQ28021. Positions 27-417, 979-1045, 1151-1351.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ28021.

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 PPP1R12ABy similarityAdd
BLAST
Regioni373 – 42048Interaction with NPM1By similarityAdd
BLAST
Regioni979 – 104769RHOA bindingAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili439 – 1025587Sequence analysisAdd
BLAST
Coiled coili1053 – 113179Sequence analysisAdd
BLAST

Domaini

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

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

eggNOGiKOG0612. Eukaryota.
ENOG410XR1Q. LUCA.
HOGENOMiHOG000017259.
HOVERGENiHBG053111.
InParanoidiQ28021.
KOiK17388.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015008. Rho-bd_dom.
IPR020684. ROCK1/ROCK2.
IPR029878. ROCK2.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22988:SF28. PTHR22988:SF28. 1 hit.
PfamiPF00069. 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]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF56112. 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.

Q28021-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRPPPTGKM PGAPEAVSGD GAGASRQRKL EALIRDPRSP INVESLLDGL
60 70 80 90 100
NPLVLDLDFP ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR
110 120 130 140 150
GAFGEVQLVR HKASQKVYAM KLLSKFEMIK RSDSAFFWEE RDIMAFANSP
160 170 180 190 200
WVVQLFCAFQ DDKYLYMVME 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 NSLCFPEDAE ISKHAKNLIC AFLTDREVRL GRNGVEEIKQ
360 370 380 390 400
HPFFKNDQWN WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP
410 420 430 440 450
KAFVGNQLPF IGFTYYRENL LLSDSPSCKE NDSIQSRKNE ESQEIQKKLY
460 470 480 490 500
TLEEHLSTEI QAKEELEQKC KSVNTRLEKV AKELEEEITL RKNVESTLRQ
510 520 530 540 550
LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL EDLKKRNQNS
560 570 580 590 600
QISTEKVNQL QRQLDETNAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
610 620 630 640 650
DLQDKNCLLE TAKLKLEKEF INLQSVLESE RRDRTHGSEI INDLQGRISG
660 670 680 690 700
LEEDVKNGKI LLAKVELEKR QLQERFTDLE KEKNNMEIDM TYQLKVIQQS
710 720 730 740 750
LEQEETEHKA TKARLADKNK IYESIEEAKS EAMKEMEKKL SEERTLKQKV
760 770 780 790 800
ENLLLEAEKR CSILDCDLKQ SQQKINELLK QKDVLNEDVR NLTLKIEQET
810 820 830 840 850
QKRCLTQNDL KMQTQQVNTL KMSEKQLKQE NNHLLEMKMS LEKQNAELRK
860 870 880 890 900
ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEECEEK TKLCKELQQK
910 920 930 940 950
KQELQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI
960 970 980 990 1000
KEMMARHKQE LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKEAQ
1010 1020 1030 1040 1050
EQLSRLKDEE ISAAAIKAQF EKQLLTERTL KTQAVNKLAE IMNRKEPVKR
1060 1070 1080 1090 1100
GNDTDVRRKE KENRKLHMEL KSEREKLTQQ MIKYQKELNE MQAQIAEESQ
1110 1120 1130 1140 1150
IRIELQMTLD SKDSDIEQLR SQLQALHIGL DSSSIGSGPG DTEADDGFPE
1160 1170 1180 1190 1200
SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
1210 1220 1230 1240 1250
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EQEFPVEPVG
1260 1270 1280 1290 1300
EKSNYICHKG HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECRRCHIKC
1310 1320 1330 1340 1350
HKDHMDKKEE IIAPCKVYYD ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK
1360 1370 1380
KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR QLAPNKPS
Length:1,388
Mass (Da):160,800
Last modified:November 1, 1996 - v1
Checksum:iCA83CE7D3860465D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36909 mRNA. Translation: AAC48567.1.
PIRiS70633.
RefSeqiNP_776877.1. NM_174452.2.
UniGeneiBt.120.

Genome annotation databases

GeneIDi282041.
KEGGibta:282041.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36909 mRNA. Translation: AAC48567.1.
PIRiS70633.
RefSeqiNP_776877.1. NM_174452.2.
UniGeneiBt.120.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UIXX-ray1.80A/B979-1047[»]
2F2UX-ray2.40A/B18-417[»]
2H9VX-ray3.10A18-417[»]
ProteinModelPortaliQ28021.
SMRiQ28021. Positions 27-417, 979-1045, 1151-1351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-29038N.
IntActiQ28021. 1 interaction.
MINTiMINT-1517391.
STRINGi9913.ENSBTAP00000007691.

Chemistry

BindingDBiQ28021.

PTM databases

iPTMnetiQ28021.

Proteomic databases

PaxDbiQ28021.
PRIDEiQ28021.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282041.
KEGGibta:282041.

Organism-specific databases

CTDi9475.

Phylogenomic databases

eggNOGiKOG0612. Eukaryota.
ENOG410XR1Q. LUCA.
HOGENOMiHOG000017259.
HOVERGENiHBG053111.
InParanoidiQ28021.
KOiK17388.

Miscellaneous databases

EvolutionaryTraceiQ28021.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015008. Rho-bd_dom.
IPR020684. ROCK1/ROCK2.
IPR029878. ROCK2.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22988:SF28. PTHR22988:SF28. 1 hit.
PfamiPF00069. 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]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF56112. 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]
ProtoNetiSearch...

Publicationsi

  1. "Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho."
    Matsui T., Amano M., Yamamoto T., Chihara K., Nakafuku M., Ito M., Nakano T., Okawa K., Iwamatsu A., Kaibuchi K.
    EMBO J. 15:2208-2216(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 10-18; 30-44; 58-64; 133-140; 248-252; 291-305; 327-348; 350-360; 366-384; 392-400; 506-511; 527-535; 590-604; 633-652; 670-681; 829-842; 861-872; 913-921; 947-950; 979-988; 1066-1070; 1087-1091; 1114-1120; 1131-1141; 1145-1151; 1158-1166; 1182-1191; 1198-1218 AND 1318-1325, FUNCTION, INTERACTION WITH RHOA, PHOSPHORYLATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  2. "Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)."
    Amano M., Ito M., Kimura K., Fukata Y., Chihara K., Nakano T., Matsuura Y., Kaibuchi K.
    J. Biol. Chem. 271:20246-20249(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal site that is specifically phosphorylated during cytokinesis."
    Goto H., Kosako H., Tanabe K., Yanagida M., Sakurai M., Amano M., Kaibuchi K., Inagaki M.
    J. Biol. Chem. 273:11728-11736(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association."
    Matsui T., Maeda M., Doi Y., Yonemura S., Amano M., Kaibuchi K., Tsukita S., Tsukita S.
    J. Cell Biol. 140:647-657(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility."
    Fukata Y., Oshiro N., Kinoshita N., Kawano Y., Matsuoka Y., Bennett V., Matsuura Y., Kaibuchi K.
    J. Cell Biol. 145:347-361(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: FUNCTION.
  7. "Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse."
    Arimura N., Inagaki N., Chihara K., Menager C., Nakamura N., Amano M., Iwamatsu A., Goshima Y., Kaibuchi K.
    J. Biol. Chem. 275:23973-23980(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Parallel coiled-coil association of the RhoA-binding domain in Rho-kinase."
    Shimizu T., Ihara K., Maesaki R., Amano M., Kaibuchi K., Hakoshima T.
    J. Biol. Chem. 278:46046-46051(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 979-1047 IN COMPLEX WITH RHOA, HOMODIMERIZATION.

Entry informationi

Entry nameiROCK2_BOVIN
AccessioniPrimary (citable) accession number: Q28021
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.