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Protein

Rho-associated protein kinase 1

Gene

ROCK1

Organism
Homo sapiens (Human)
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 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. 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. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization.14 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by RHOA binding. Inhibited by Y-27632.

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 – 1281Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST54

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • GTP-Rho binding Source: InterPro
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton organization Source: ProtInc
  • apical constriction Source: Ensembl
  • bleb assembly Source: Ensembl
  • cortical actin cytoskeleton organization Source: UniProtKB
  • ephrin receptor signaling pathway Source: Reactome
  • establishment of protein localization to plasma membrane Source: UniProtKB
  • execution phase of apoptosis Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • leukocyte cell-cell adhesion Source: BHF-UCL
  • leukocyte migration Source: BHF-UCL
  • leukocyte tethering or rolling Source: BHF-UCL
  • membrane to membrane docking Source: BHF-UCL
  • myoblast migration 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 neuron apoptotic process Source: Ensembl
  • negative regulation of protein binding Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • positive regulation of focal adhesion assembly Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cell adhesion Source: UniProtKB
  • regulation of cell motility 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 stress fiber assembly Source: UniProtKB
  • Rho protein signal transduction Source: ProtInc
  • signal transduction Source: ProtInc
  • smooth muscle contraction Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-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.
R-HSA-6798695. Neutrophil degranulation.
SABIO-RKiQ13464.
SignaLinkiQ13464.
SIGNORiQ13464.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho-associated protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Renal carcinoma antigen NY-REN-35
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:10251. ROCK1.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1113D → A: Abolishes cleavage by caspase-3. 1 Publication1

Organism-specific databases

DisGeNETi6093.
OpenTargetsiENSG00000067900.
PharmGKBiPA34623.

Chemistry databases

ChEMBLiCHEMBL3231.
DrugBankiDB08756. (R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDE.
DB07876. (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE.
DB04707. HYDROXYFASUDIL.
GuidetoPHARMACOLOGYi1503.

Polymorphism and mutation databases

BioMutaiROCK1.
DMDMi47605999.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000866192 – 1354Rho-associated protein kinase 1Add BLAST1353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei647N6-acetyllysineCombined sources1
Modified residuei1105PhosphoserineCombined sources1
Modified residuei1108PhosphoserineBy similarity1
Modified residuei1328PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated on serine and threonine residues.1 Publication
Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1113 – 1114Cleavage; by caspase-32

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13464.
MaxQBiQ13464.
PaxDbiQ13464.
PeptideAtlasiQ13464.
PRIDEiQ13464.

PTM databases

iPTMnetiQ13464.
PhosphoSitePlusiQ13464.
SwissPalmiQ13464.

Miscellaneous databases

PMAP-CutDBiB0YJ91.

Expressioni

Tissue specificityi

Detected in blood platelets.1 Publication

Gene expression databases

BgeeiENSG00000067900.
CleanExiHS_ROCK1.
ExpressionAtlasiQ13464. baseline and differential.
GenevisibleiQ13464. HS.

Organism-specific databases

HPAiCAB004562.
HPA007567.
HPA045639.

Interactioni

Subunit structurei

Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN. Interacts with ITGB1BP1 (via N-terminus and PTB domain) (By similarity). Interacts with RHOA (activated by GTP), CHORDC1, DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101. Interacts with FHOD1 in a Src-dependent manner.By similarity16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112020. 45 interactors.
DIPiDIP-35645N.
ELMiQ13464.
IntActiQ13464. 22 interactors.
MINTiMINT-1195170.
STRINGi9606.ENSP00000382697.

Chemistry databases

BindingDBiQ13464.

Structurei

Secondary structure

11354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 19Combined sources11
Helixi27 – 41Combined sources15
Helixi44 – 47Combined sources4
Helixi50 – 69Combined sources20
Helixi73 – 75Combined sources3
Beta strandi76 – 84Combined sources9
Beta strandi86 – 95Combined sources10
Turni96 – 98Combined sources3
Beta strandi101 – 108Combined sources8
Helixi109 – 114Combined sources6
Helixi121 – 130Combined sources10
Beta strandi139 – 144Combined sources6
Beta strandi146 – 153Combined sources8
Beta strandi157 – 160Combined sources4
Helixi161 – 167Combined sources7
Helixi172 – 191Combined sources20
Helixi201 – 203Combined sources3
Beta strandi204 – 206Combined sources3
Beta strandi212 – 214Combined sources3
Helixi217 – 219Combined sources3
Beta strandi227 – 230Combined sources4
Helixi238 – 240Combined sources3
Helixi243 – 247Combined sources5
Turni248 – 252Combined sources5
Beta strandi254 – 256Combined sources3
Helixi258 – 273Combined sources16
Helixi283 – 291Combined sources9
Helixi293 – 296Combined sources4
Helixi307 – 316Combined sources10
Helixi320 – 322Combined sources3
Turni324 – 327Combined sources4
Helixi329 – 333Combined sources5
Helixi336 – 338Combined sources3
Turni345 – 347Combined sources3
Helixi348 – 350Combined sources3
Helixi365 – 367Combined sources3
Helixi392 – 394Combined sources3
Beta strandi399 – 402Combined sources4
Helixi535 – 540Combined sources6
Helixi544 – 691Combined sources148
Helixi840 – 902Combined sources63
Helixi947 – 982Combined sources36
Helixi984 – 1011Combined sources28

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S1CX-ray2.60X/Y947-1015[»]
2ESMX-ray3.20A/B6-415[»]
2ETKX-ray2.96A/B6-415[»]
2ETRX-ray2.60A/B6-415[»]
2V55X-ray3.70A/C1-406[»]
3D9VX-ray3.30A/B6-415[»]
3NCZX-ray3.00A/B/C/D6-415[»]
3NDMX-ray3.30A/B/C/D6-415[»]
3O0ZX-ray2.33A/B/C/D535-700[»]
3TV7X-ray2.75A/B/C/D6-415[»]
3TWJX-ray2.90A/B/C/D6-415[»]
3V8SX-ray2.29A/B/C/D6-415[»]
4L2WX-ray2.49A/B/C/D834-914[»]
4W7PX-ray2.80A/B/C/D2-410[»]
4YVCX-ray3.20A/B6-415[»]
4YVEX-ray3.40A/B6-415[»]
5BMLX-ray2.95A/B6-415[»]
5F5PX-ray3.57C/D/E/F834-913[»]
5HVUX-ray2.80A/B6-415[»]
ProteinModelPortaliQ13464.
SMRiQ13464.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13464.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 338Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini341 – 409AGC-kinase C-terminalAdd BLAST69
Repeati458 – 542REMAdd BLAST85
Domaini1118 – 1317PHPROSITE-ProRule annotationAdd BLAST200

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni368 – 727Interaction with FHOD11 PublicationAdd BLAST360
Regioni998 – 1010RHOA bindingAdd BLAST13
Regioni1115 – 1354Auto-inhibitoryAdd BLAST240

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili422 – 612Sequence analysisAdd BLAST191
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 – 1281Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST54

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG0612. Eukaryota.
ENOG410XR1Q. LUCA.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000017259.
HOVERGENiHBG053111.
InParanoidiQ13464.
KOiK04514.
OMAiSMLDVDL.
OrthoDBiEOG091G0BOR.
PhylomeDBiQ13464.
TreeFamiTF313551.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiView protein in InterPro
IPR000961. 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.
IPR029876. ROCK1.
IPR020684. ROCK1/ROCK2.
IPR008271. Ser/Thr_kinase_AS.
PANTHERiPTHR22988:SF51. PTHR22988:SF51. 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.
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF56112. 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.
PS50081. ZF_DAG_PE_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q13464-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTGDSFETR FEKMDNLLRD 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 LEEDKGEEET FPIPKAFVGN QLPFVGFTYY
410 420 430 440 450
SNRRYLSSAN PNDNRTSSNA DKSLQESLQK TIYKLEEQLH NEMQLKDEME
460 470 480 490 500
QKCRTSNIKL DKIMKELDEE GNQRRNLEST VSQIEKEKML LQHRINEYQR
510 520 530 540 550
KAEQENEKRR NVENEVSTLK DQLEDLKKVS QNSQLANEKL SQLQKQLEEA
560 570 580 590 600
NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQTD
610 620 630 640 650
KDYYQLQAIL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLEKVEG
660 670 680 690 700
ERKEAQDMLN HSEKEKNNLE IDLNYKLKSL QQRLEQEVNE HKVTKARLTD
710 720 730 740 750
KHQSIEEAKS VAMCEMEKKL KEEREAREKA ENRVVQIEKQ CSMLDVDLKQ
760 770 780 790 800
SQQKLEHLTG NKERMEDEVK NLTLQLEQES NKRLLLQNEL KTQAFEADNL
810 820 830 840 850
KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR ELQDQLEAEQ
860 870 880 890 900
YFSTLYKTQV KELKEEIEEK NRENLKKIQE LQNEKETLAT QLDLAETKAE
910 920 930 940 950
SEQLARGLLE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANSMLTK
960 970 980 990 1000
DIEILRRENE ELTEKMKKAE EEYKLEKEEE ISNLKAAFEK NINTERTLKT
1010 1020 1030 1040 1050
QAVNKLAEIM NRKDFKIDRK KANTQDLRKK EKENRKLQLE LNQEREKFNQ
1060 1070 1080 1090 1100
MVVKHQKELN DMQAQLVEEC AHRNELQMQL ASKESDIEQL RAKLLDLSDS
1110 1120 1130 1140 1150
TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK QYVVVSSKKI
1160 1170 1180 1190 1200
LFYNDEQDKE QSNPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
1210 1220 1230 1240 1250
ANEGECRKDV EMEPVQQAEK TNFQNHKGHE FIPTLYHFPA NCDACAKPLW
1260 1270 1280 1290 1300
HVFKPPPALE CRRCHVKCHR DHLDKKEDLI CPCKVSYDVT SARDMLLLAC
1310 1320 1330 1340 1350
SQDEQKKWVT HLVKKIPKNP PSGFVRASPR TLSTRSTANQ SFRKVVKNTS

GKTS
Length:1,354
Mass (Da):158,175
Last modified:November 1, 1996 - v1
Checksum:i93078CBB009A6F27
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti170V → A in AAI13115 (PubMed:15489334).Curated1
Sequence conflicti197R → G in AAI13115 (PubMed:15489334).Curated1
Sequence conflicti220C → R in AAI13115 (PubMed:15489334).Curated1
Sequence conflicti323 – 325RLG → GTR in BAD92202 (Ref. 5) Curated3
Sequence conflicti521D → N in AAI13115 (PubMed:15489334).Curated1
Sequence conflicti965K → R in AAI13115 (PubMed:15489334).Curated1
Sequence conflicti1354S → R in ACA06069 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041055108S → N1 PublicationCorresponds to variant dbSNP:rs55811609Ensembl.1
Natural variantiVAR_041056773T → S1 PublicationCorresponds to variant dbSNP:rs45562542Ensembl.1
Natural variantiVAR_0410571112T → P1 PublicationCorresponds to variant dbSNP:rs35881519Ensembl.1
Natural variantiVAR_0410581193P → S in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0410591217Q → E1 PublicationCorresponds to variant dbSNP:rs2847092Ensembl.1
Natural variantiVAR_0410601262R → Q1 PublicationCorresponds to variant dbSNP:rs1045142Ensembl.1
Natural variantiVAR_0410611264C → R1 PublicationCorresponds to variant dbSNP:rs2663698Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43195 mRNA. Translation: AAB02814.1.
EF445027 Genomic DNA. Translation: ACA06069.1.
BC113114 mRNA. Translation: AAI13115.1.
AB208965 mRNA. Translation: BAD92202.1.
CCDSiCCDS11870.2.
PIRiS69211.
RefSeqiNP_005397.1. NM_005406.2.
UniGeneiHs.306307.

Genome annotation databases

EnsembliENST00000399799; ENSP00000382697; ENSG00000067900.
GeneIDi6093.
KEGGihsa:6093.
UCSCiuc002kte.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiROCK1_HUMAN
AccessioniPrimary (citable) accession number: Q13464
Secondary accession number(s): B0YJ91, Q2KHM4, Q59GZ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: November 1, 1996
Last modified: August 30, 2017
This is version 183 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families