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Protein

Rho-associated protein kinase 1

Gene

Rock1

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 DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. Promotes keratinocyte terminal differentiation (By similarity). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles.By similarity5 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 sitei105ATPPROSITE-ProRule annotation1
Active sitei198Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi82 – 90ATPPROSITE-ProRule annotation9
Zinc fingeri1228 – 1283Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST56

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-111465 Apoptotic cleavage of cellular proteins
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-416572 Sema4D induced cell migration and growth-cone collapse
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-5627117 RHO GTPases Activate ROCKs
R-MMU-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Rho-associated protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Rho-associated, coiled-coil-containing protein kinase 1
Rho-associated, coiled-coil-containing protein kinase I
Short name:
ROCK-I
p160 ROCK-1
Short name:
p160ROCK
Gene namesi
Name:Rock1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:107927 Rock1

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, Cell projection, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000866202 – 1354Rho-associated protein kinase 1Add BLAST1353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei1105PhosphoserineCombined sources1
Modified residuei1108PhosphoserineCombined sources1
Modified residuei1328PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated on serine and threonine residues.
Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1113 – 1114Cleavage; by caspase-3By similarity2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP70335
MaxQBiP70335
PaxDbiP70335
PeptideAtlasiP70335
PRIDEiP70335

PTM databases

iPTMnetiP70335
PhosphoSitePlusiP70335

Expressioni

Tissue specificityi

Highly expressed in brain, heart, lung, liver, stomach, spleen, kidney, testis, muscle, embryo and placenta.1 Publication

Gene expression databases

BgeeiENSMUSG00000024290 Expressed in 294 organ(s), highest expression level in aorta
GenevisibleiP70335 MM

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with RHOA (activated by GTP), RHOB, RHOC, GEM, MYLC2B, RHOE, PPP1R12A, LIMK1, LIMK2, TSG101, CHORDC1, DAPK3, PFN1 and JIP3 (By similarity). Interacts with FHOD1 in a Src-dependent manner (By similarity). Interacts with PTEN. Interacts with ITGB1BP1 (via N-terminus and PTB domain).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rnd3P615887EBI-989293,EBI-6930266

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202950, 30 interactors
DIPiDIP-35521N
IntActiP70335, 30 interactors
MINTiP70335
STRINGi10090.ENSMUSP00000069549

Structurei

3D structure databases

ProteinModelPortaliP70335
SMRiP70335
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 338Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini341 – 409AGC-kinase C-terminalAdd BLAST69
Domaini479 – 556REM-1PROSITE-ProRule annotationAdd BLAST78
Domaini949 – 1015RhoBDPROSITE-ProRule annotationAdd BLAST67
Domaini1118 – 1317PHPROSITE-ProRule annotationAdd BLAST200

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni368 – 727Interaction with FHOD1By similarityAdd BLAST360
Regioni998 – 1010RHOA bindingBy similarityAdd BLAST13
Regioni1115 – 1354Auto-inhibitoryBy similarityAdd BLAST240

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili422 – 692Sequence analysisAdd BLAST271
Coiled coili1011 – 1102Sequence analysisAdd BLAST92

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi636 – 980Glu-richAdd BLAST345

Domaini

The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1228 – 1283Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST56

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG0612 Eukaryota
ENOG410XR1Q LUCA
GeneTreeiENSGT00760000118994
HOGENOMiHOG000017259
HOVERGENiHBG053111
InParanoidiP70335
KOiK04514
OMAiSMLDVDL
OrthoDBiEOG091G0BOR
PhylomeDBiP70335
TreeFamiTF313551

Family and domain databases

CDDicd00029 C1, 1 hit
cd11639 HR1_ROCK1, 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
IPR029876 ROCK1
IPR020684 ROCK1/ROCK2
IPR037310 ROCK1_HR1
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR22988:SF33 PTHR22988:SF33, 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.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P70335-1) [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
MSTGDSFETR FEKIDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK
60 70 80 90 100
NIDNFLSRYK DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK
110 120 130 140 150
VYAMKLLSKF EMIKRSDSAF FWEERDIMAF ANSPWVVQLF YAFQDDRYLY
160 170 180 190 200
MVMEYMPGGD LVNLMSNYDV PEKWARFYTA EVVLALDAIH SMGFIHRDVK
210 220 230 240 250
PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY ISPEVLKSQG
260 270 280 290 300
GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP
310 320 330 340 350
DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD
360 370 380 390 400
TVAPVVPDLS SDIDTSNFDD LEEDKGDEET FPIPKAFVGN QLPFVGFTYY
410 420 430 440 450
SNRRYLPSAN ASENRSSSNV DKSLQESLQK TIYKLEEQLH NEMQLKDEME
460 470 480 490 500
QKCRTSNLKL DKIMKELDEE GNQRRNLESA VSQIEKEKML LQHRINEYQR
510 520 530 540 550
KVEQENEKRR NIENEVSTLK DQLEDLRKAS QTSQLANEKL TQLQKQLEEA
560 570 580 590 600
NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQAD
610 620 630 640 650
KDYYQLQAVL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLERVEG
660 670 680 690 700
ERKEAQDMLN HSEKEKNNLE IDLNYKLKSI QQRLEQEVNE HKVTKARLTD
710 720 730 740 750
KHQSIEEAKS VAMCEMEKKL KEEREAREKA ENRVVETEKQ CSMLDVDLKQ
760 770 780 790 800
SQQKLEHLTE NKERMEDEVK NLALQLEQES NKRLLLQNEL KTQAFEADNL
810 820 830 840 850
KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR ELQDQLEAEQ
860 870 880 890 900
YFSTLYKTQV KELKEEIEEK NRENLRKIQE LQSEKETLST QLDLAETKAE
910 920 930 940 950
SEQLARGILE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEETNSVLTK
960 970 980 990 1000
DIEMLRKENE ELNERMRTAE EEYKLKKEEE INNLKAAFEK NISTERTLKT
1010 1020 1030 1040 1050
QAVNKLAEIM NRKDFKIDRK KANTQDLRKK EKENRKLQLE LNQEREKFNQ
1060 1070 1080 1090 1100
MVVKHQKELN DMQAQLVEEC THRNELQMQL ASKESDIEQL RAKLLDLSDS
1110 1120 1130 1140 1150
TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK QYVVVSSKKI
1160 1170 1180 1190 1200
LFYNDEQDKE QSSPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
1210 1220 1230 1240 1250
ANEGECRKDI EVEPVQQGEK TNFQNHKGHE FIPTLYHFPA NCEACAKPLW
1260 1270 1280 1290 1300
HVFKPPPALE CRRCHVKCHR DHLDKKEDLI SPCKVSYDVT SARDMLLLAC
1310 1320 1330 1340 1350
SQDEQKKWVT HLVKKIPKNP PSGFVRASPR TLSTRSTANQ SFRKVVKNTS

GKTS
Length:1,354
Mass (Da):158,171
Last modified:February 1, 1997 - v1
Checksum:iA1CBD543B831CF96
GO
Isoform 2 (identifier: P70335-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     425-425: Missing.

Note: May be due to a competing donor splice site. No experimental confirmation available.
Show »
Length:1,353
Mass (Da):158,042
Checksum:i209CACFD07E756CF
GO

Sequence cautioni

The sequence AAH57154 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAC34154 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010448425Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58512 mRNA Translation: AAC53132.1
AK050269 mRNA Translation: BAC34154.1 Different initiation.
AK085974 mRNA Translation: BAC39581.1
BC057154 mRNA Translation: AAH57154.1 Sequence problems.
CCDSiCCDS29053.2 [P70335-1]
PIRiS74244
RefSeqiNP_033097.1, NM_009071.2 [P70335-1]
XP_006525788.1, XM_006525725.1 [P70335-2]
UniGeneiMm.6710

Genome annotation databases

EnsembliENSMUST00000067947; ENSMUSP00000069549; ENSMUSG00000024290 [P70335-1]
GeneIDi19877
KEGGimmu:19877
UCSCiuc008eaq.1 mouse [P70335-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiROCK1_MOUSE
AccessioniPrimary (citable) accession number: P70335
Secondary accession number(s): Q8C3G4, Q8C7H0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: February 1, 1997
Last modified: September 12, 2018
This is version 182 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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