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Protein

Rho-associated protein kinase 2

Gene

ROCK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by RHOA binding. Inhibited by Y-27632 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei121ATPPROSITE-ProRule annotation1
Active sitei214Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi98 – 106ATPPROSITE-ProRule annotation9
Zinc fingeri1260 – 1315Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST56

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rho-dependent protein serine/threonine kinase activity Source: UniProtKB
  • Rho GTPase binding Source: InterPro
  • RNA binding Source: UniProtKB
  • structural molecule activity Source: ProtInc

GO - Biological processi

  • cellular response to testosterone stimulus Source: UniProtKB
  • centrosome duplication Source: UniProtKB
  • cortical actin cytoskeleton organization Source: UniProtKB
  • ephrin receptor signaling pathway Source: Reactome
  • G-protein coupled receptor signaling pathway Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of angiogenesis Source: UniProtKB
  • negative regulation of bicellular tight junction assembly Source: UniProtKB
  • negative regulation of myosin-light-chain-phosphatase activity Source: UniProtKB
  • negative regulation of protein localization to lysosome Source: ARUK-UCL
  • peptidyl-serine phosphorylation Source: ARUK-UCL
  • peptidyl-threonine phosphorylation Source: ARUK-UCL
  • positive regulation of amyloid-beta formation Source: ARUK-UCL
  • positive regulation of amyloid precursor protein catabolic process Source: ARUK-UCL
  • positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: ARUK-UCL
  • positive regulation of centrosome duplication Source: InterPro
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of protein localization to early endosome Source: ARUK-UCL
  • positive regulation of protein phosphorylation Source: UniProtKB
  • protein localization to plasma membrane Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cell adhesion Source: UniProtKB
  • regulation of cell motility Source: UniProtKB
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of establishment of cell polarity Source: UniProtKB
  • regulation of establishment of endothelial barrier Source: UniProtKB
  • regulation of focal adhesion assembly Source: UniProtKB
  • regulation of keratinocyte differentiation Source: UniProtKB
  • regulation of protein metabolic process Source: ARUK-UCL
  • regulation of stress fiber assembly Source: UniProtKB
  • Rho protein signal transduction Source: InterPro
  • rhythmic process Source: UniProtKB-KW
  • smooth muscle contraction Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome
  • viral RNA genome replication Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3928662 EPHB-mediated forward signaling
R-HSA-3928663 EPHA-mediated growth cone collapse
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5627117 RHO GTPases Activate ROCKs
SignaLinkiO75116
SIGNORiO75116

Names & Taxonomyi

Protein namesi
Recommended name:
Rho-associated protein kinase 2 (EC:2.7.11.1)
Alternative name(s):
Rho kinase 2
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
Synonyms:KIAA0619
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000134318.13
HGNCiHGNC:10252 ROCK2
MIMi604002 gene
neXtProtiNX_O75116

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1131D → A: Abolishes cleavage by granzyme B. 1 Publication1

Organism-specific databases

DisGeNETi9475
OpenTargetsiENSG00000134318
PharmGKBiPA34624

Chemistry databases

ChEMBLiCHEMBL2973
DrugBankiDB08756 (R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDE
GuidetoPHARMACOLOGYi1504

Polymorphism and mutation databases

BioMutaiROCK2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866251 – 1388Rho-associated protein kinase 2Add BLAST1388

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei414Phosphothreonine; by ROCK2By similarity1
Modified residuei722Phosphotyrosine; by SRC2 Publications1
Modified residuei1137PhosphoserineCombined sources1
Modified residuei1212PhosphothreonineCombined sources1
Modified residuei1362PhosphoserineCombined sources1
Modified residuei1374PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity.2 Publications
Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1131 – 1132Cleavage; by granzyme B2

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO75116
MaxQBiO75116
PaxDbiO75116
PeptideAtlasiO75116
PRIDEiO75116

PTM databases

iPTMnetiO75116
PhosphoSitePlusiO75116
SwissPalmiO75116

Expressioni

Gene expression databases

BgeeiENSG00000134318
CleanExiHS_ROCK2
ExpressionAtlasiO75116 baseline and differential
GenevisibleiO75116 HS

Organism-specific databases

HPAiCAB008666
HPA007459
HPA044109

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114860, 28 interactors
CORUMiO75116
IntActiO75116, 14 interactors
MINTiO75116
STRINGi9606.ENSP00000317985

Chemistry databases

BindingDBiO75116

Structurei

Secondary structure

11388
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 35Combined sources7
Helixi43 – 57Combined sources15
Helixi60 – 63Combined sources4
Helixi66 – 85Combined sources20
Helixi89 – 91Combined sources3
Beta strandi92 – 100Combined sources9
Beta strandi102 – 111Combined sources10
Turni112 – 114Combined sources3
Beta strandi117 – 124Combined sources8
Helixi125 – 130Combined sources6
Helixi138 – 146Combined sources9
Beta strandi155 – 160Combined sources6
Beta strandi162 – 169Combined sources8
Helixi177 – 183Combined sources7
Helixi188 – 207Combined sources20
Helixi217 – 219Combined sources3
Beta strandi220 – 222Combined sources3
Beta strandi228 – 230Combined sources3
Beta strandi241 – 246Combined sources6
Helixi254 – 256Combined sources3
Helixi259 – 264Combined sources6
Beta strandi270 – 272Combined sources3
Helixi274 – 289Combined sources16
Helixi299 – 307Combined sources9
Helixi309 – 312Combined sources4
Beta strandi317 – 319Combined sources3
Helixi323 – 332Combined sources10
Helixi336 – 338Combined sources3
Turni340 – 343Combined sources4
Helixi346 – 349Combined sources4
Helixi352 – 354Combined sources3
Turni361 – 363Combined sources3
Helixi364 – 366Combined sources3
Helixi408 – 410Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4L6QX-ray2.79A/B19-417[»]
4WOTX-ray2.93A/B/C/D22-417[»]
5U7QX-ray3.15A/B/C/D23-417[»]
5U7RX-ray3.33A/B/C/D23-417[»]
ProteinModelPortaliO75116
SMRiO75116
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 354Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini357 – 425AGC-kinase C-terminalAdd BLAST69
Domaini979 – 1047RhoBDPROSITE-ProRule annotationAdd BLAST69
Domaini1150 – 1349PHPROSITE-ProRule annotationAdd BLAST200

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni363 – 784Interaction with PPP1R12AAdd BLAST422
Regioni373 – 420Interaction with NPM11 PublicationAdd BLAST48
Regioni979 – 1047RHOA bindingBy similarityAdd BLAST69

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili429 – 1024Sequence analysisAdd BLAST596
Coiled coili1053 – 1131Sequence analysisAdd BLAST79

Domaini

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

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1260 – 1315Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST56

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG0612 Eukaryota
ENOG410XR1Q LUCA
GeneTreeiENSGT00760000118994
HOGENOMiHOG000017259
HOVERGENiHBG053111
InParanoidiO75116
KOiK17388
OMAiPNQSIRR
OrthoDBiEOG091G0BOR
PhylomeDBiO75116
TreeFamiTF313551

Family and domain databases

CDDicd00029 C1, 1 hit
cd11638 HR1_ROCK2, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR015008 Rho-bd_dom
IPR020684 ROCK1/ROCK2
IPR029878 ROCK2
IPR037311 ROCK2_HR1
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR22988:SF28 PTHR22988:SF28, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF08912 Rho_Binding, 1 hit
PIRSFiPIRSF037568 Rho_kinase, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00233 PH, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in 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
PS51859 RHO_BD, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequencei

Sequence statusi: Complete.

O75116-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRPPPTGKM PGAPETAPGD GAGASRQRKL 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
WVVQLFYAFQ DDRYLYMVME YMPGGDLVNL MSNYDVPEKW AKFYTAEVVL
210 220 230 240 250
ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD ETGMVHCDTA
260 270 280 290 300
VGTPDYISPE VLKSQGGDGF YGRECDWWSV GVFLYEMLVG DTPFYADSLV
310 320 330 340 350
GTYSKIMDHK NSLCFPEDAE ISKHAKNLIC AFLTDREVRL GRNGVEEIRQ
360 370 380 390 400
HPFFKNDQWH WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP
410 420 430 440 450
KAFVGNQLPF IGFTYYRENL LLSDSPSCRE TDSIQSRKNE ESQEIQKKLY
460 470 480 490 500
TLEEHLSNEM QAKEELEQKC KSVNTRLEKT AKELEEEITL RKSVESALRQ
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 INLQSALESE RRDRTHGSEI INDLQGRICG
660 670 680 690 700
LEEDLKNGKI LLAKVELEKR QLQERFTDLE KEKSNMEIDM TYQLKVIQQS
710 720 730 740 750
LEQEEAEHKA TKARLADKNK IYESIEEAKS EAMKEMEKKL LEERTLKQKV
760 770 780 790 800
ENLLLEAEKR CSLLDCDLKQ SQQKINELLK QKDVLNEDVR NLTLKIEQET
810 820 830 840 850
QKRCLTQNDL KMQTQQVNTL KMSEKQLKQE NNHLMEMKMN LEKQNAELRK
860 870 880 890 900
ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEECEEK TKLGKELQQK
910 920 930 940 950
KQELQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI
960 970 980 990 1000
KEMMARHKQE LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDVQ
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 DAEADDGFPE
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 ISTAKNLLLL ANSTEEQQKW VSRLVKKIPK
1360 1370 1380
KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR QLAPNKPS
Length:1,388
Mass (Da):160,900
Last modified:November 24, 2009 - v4
Checksum:i876240F410C2487E
GO

Sequence cautioni

The sequence AAX93049 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAA31594 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti83R → K in BAA75636 (PubMed:9933571).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041062431T → N3 PublicationsCorresponds to variant dbSNP:rs2230774Ensembl.1
Natural variantiVAR_041063601D → V1 PublicationCorresponds to variant dbSNP:rs35768389Ensembl.1
Natural variantiVAR_0571101083K → M. Corresponds to variant dbSNP:rs34945852Ensembl.1
Natural variantiVAR_0410641194S → P in a metastatic melanoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS42654.1
RefSeqiNP_001308572.1, NM_001321643.1
NP_004841.2, NM_004850.4
UniGeneiHs.681743

Genome annotation databases

EnsembliENST00000315872; ENSP00000317985; ENSG00000134318
GeneIDi9475
KEGGihsa:9475
UCSCiuc002rbd.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiROCK2_HUMAN
AccessioniPrimary (citable) accession number: O75116
Secondary accession number(s): Q53QZ0, Q53SJ7, Q9UQN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: November 24, 2009
Last modified: April 25, 2018
This is version 185 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health