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Protein

Rho-associated protein kinase 2

Gene

Rock2

Organism
Mus musculus (Mouse)
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 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

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

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:107926. Rock2.

Subcellular locationi

Isoform 1 :

GO - Cellular componenti

  • centrosome Source: MGI
  • cytoplasmic ribonucleoprotein granule Source: MGI
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
  • spindle pole centrosome Source: MGI
Complete GO annotation...

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

Protein-protein interaction databases

BioGridi202951. 5 interactors.
IntActiP70336. 5 interactors.
MINTiMINT-4132887.
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
Repeati475 – 559REMAdd BLAST85
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

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)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.
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]

Sequences (2)i

Sequence statusi: Complete.

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

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

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

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. 5 interactors.
IntActiP70336. 5 interactors.
MINTiMINT-4132887.
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

PROiP70336.
SOURCEiSearch...

Family and domain databases

CDDicd00029. C1. 1 hit.
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...

Entry informationi

Entry nameiROCK2_MOUSE
AccessioniPrimary (citable) accession number: P70336
Secondary accession number(s): A5XDA7, Q8BR64, Q8CBR0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 161 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

Complete proteome, Reference proteome

Documents

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