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Protein

Rho-associated protein kinase 2

Gene

Rock2

Organism
Mus musculus (Mouse)
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 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

Mg2+By similarity

Activity 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 kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: ARUK-UCL
  • Rho-dependent protein serine/threonine kinase activity Source: MGI
  • Rho GTPase binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:107926 Rock2

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

Disruption phenotypei

Mice exhibit both EOB (eyes open at birth) and omphalocele phenotypes as a result of disorganization of actomyosin cables in the eyelid epithelium and defective actin assembly in the umbilical ring. Mice are impaired in both basal synaptic transmission and hippocampal long-term potentiation (LTP). Embryos manifest extensive thrombus formation in the placenta, resulting in placental dysfunction, intrauterine growth retardation, and fetal death.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866261 – 1388Rho-associated protein kinase 2Add BLAST1388

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei414Phosphothreonine; by ROCK2By similarity1
Modified residuei722Phosphotyrosine; by SRCBy similarity1
Modified residuei1137PhosphoserineCombined sources1
Modified residuei1212PhosphothreonineBy similarity1
Modified residuei1362PhosphoserineBy similarity1
Modified residuei1374PhosphoserineCombined sources1

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.

Sites

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP70336
MaxQBiP70336
PaxDbiP70336
PeptideAtlasiP70336
PRIDEiP70336

PTM databases

iPTMnetiP70336
PhosphoSitePlusiP70336
SwissPalmiP70336

Expressioni

Tissue specificityi

Highly expressed in brain, heart, lung, liver, stomach, spleen, kidney, testis, muscle, embryo and placenta. Isoform 2 is expressed predominantly in the skeletal muscle.2 Publications

Inductioni

Expression oscillates in a circadian manner in the aorta.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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202951, 8 interactors
CORUMiP70336
IntActiP70336, 7 interactors
MINTiP70336
STRINGi10090.ENSMUSP00000020904

Structurei

3D structure databases

ProteinModelPortaliP70336
SMRiP70336
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 354Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini357 – 425AGC-kinase C-terminalAdd BLAST69
Domaini497 – 573REM-1PROSITE-ProRule annotationAdd BLAST77
Domaini979 – 1047RhoBDPROSITE-ProRule annotationAdd BLAST69
Domaini1150 – 1349PHPROSITE-ProRule annotationAdd BLAST200

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni363 – 784Interaction with PPP1R12ABy similarityAdd BLAST422
Regioni373 – 420Interaction with NPM1By similarityAdd BLAST48
Regioni979 – 1047RHOA bindingBy similarityAdd BLAST69

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili439 – 1131Sequence analysisAdd BLAST693

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
HOGENOMiHOG000017259
HOVERGENiHBG053111
InParanoidiP70336
KOiK17388
PhylomeDBiP70336

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
PS51860 REM_1, 1 hit
PS51859 RHO_BD, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P70336-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSRPPPTGKM PGAPEAAPGD 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 GRNGVEEIKQ
360 370 380 390 400
HPFFKNDQWN WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP
410 420 430 440 450
KAFVGNQLPF IGFTYFRENL LLSDSPPCRE NDAIQTRKSE ESQEIQKKLY
460 470 480 490 500
ALEEHLSSEV QAKEELEQKC KSINTRLEKT AKELEEEITL RKSVESTLRQ
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
LEEDLKTGKA 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 LEKQNTELRK
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 LTEKDTTIAS LEETNRTLTS DVANLANEKE ELNNKLKDSQ
1010 1020 1030 1040 1050
EQLSKLKDEE MSAAAIKAQF EKQLLNERTL 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 LECRRCHIKC
1310 1320 1330 1340 1350
HKDHMDKKEE IIAPCKVYYD ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK
1360 1370 1380
KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR QLAPNKPS
Length:1,388
Mass (Da):160,586
Last modified:February 1, 1997 - v1
Checksum:i7A4F331165038161
GO
Isoform 2 (identifier: P70336-2) [UniParc]FASTAAdd to basket
Also known as: ROCK2m

The sequence of this isoform differs from the canonical sequence as follows:
     1149-1149: P → PVHITQSHTMESMSFTYQRSSTSLSIATKPSSSHTLLDFDSEEDSLPYLPSSSEPIST
     1388-1388: Missing.

Show »
Length:1,444
Mass (Da):166,760
Checksum:i42E61D28C806D715
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VPK5F8VPK5_MOUSE
Rho-associated protein kinase
Rock2
1,388Annotation score:
A0A1Y7VMN0A0A1Y7VMN0_MOUSE
Rho-associated protein kinase 2
Rock2
1,444Annotation score:
A0A1Y7VLD1A0A1Y7VLD1_MOUSE
Rho-associated protein kinase 2
Rock2
262Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0418181149P → PVHITQSHTMESMSFTYQRS STSLSIATKPSSSHTLLDFD SEEDSLPYLPSSSEPIST in isoform 2. 1 Publication1
Alternative sequenceiVSP_0418191388Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58513 mRNA Translation: AAC53133.1
DQ864977 mRNA Translation: ABI75318.1
AK045517 mRNA Translation: BAC32403.1
AK035509 mRNA Translation: BAC29084.1
CCDSiCCDS36410.1 [P70336-1]
PIRiS74245
RefSeqiNP_033098.2, NM_009072.2
UniGeneiMm.276024

Genome annotation databases

GeneIDi19878
KEGGimmu:19878
UCSCiuc007ncg.1 mouse [P70336-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58513 mRNA Translation: AAC53133.1
DQ864977 mRNA Translation: ABI75318.1
AK045517 mRNA Translation: BAC32403.1
AK035509 mRNA Translation: BAC29084.1
CCDSiCCDS36410.1 [P70336-1]
PIRiS74245
RefSeqiNP_033098.2, NM_009072.2
UniGeneiMm.276024

3D structure databases

ProteinModelPortaliP70336
SMRiP70336
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202951, 8 interactors
CORUMiP70336
IntActiP70336, 7 interactors
MINTiP70336
STRINGi10090.ENSMUSP00000020904

PTM databases

iPTMnetiP70336
PhosphoSitePlusiP70336
SwissPalmiP70336

Proteomic databases

EPDiP70336
MaxQBiP70336
PaxDbiP70336
PeptideAtlasiP70336
PRIDEiP70336

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi19878
KEGGimmu:19878
UCSCiuc007ncg.1 mouse [P70336-2]

Organism-specific databases

CTDi9475
MGIiMGI:107926 Rock2

Phylogenomic databases

eggNOGiKOG0612 Eukaryota
ENOG410XR1Q LUCA
HOGENOMiHOG000017259
HOVERGENiHBG053111
InParanoidiP70336
KOiK17388
PhylomeDBiP70336

Miscellaneous databases

PROiPR:P70336
SOURCEiSearch...

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
PS51860 REM_1, 1 hit
PS51859 RHO_BD, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiROCK2_MOUSE
AccessioniPrimary (citable) accession number: P70336
Secondary accession number(s): A5XDA7, Q8BR64, Q8CBR0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: February 1, 1997
Last modified: November 7, 2018
This is version 179 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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