ROCK1_RABIT
ID ROCK1_RABIT Reviewed; 1354 AA.
AC O77819;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Rho-associated protein kinase 1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13464};
DE AltName: Full=Corneal epithelial Rho-associated-Ser/Thr kinase 1;
DE AltName: Full=HEBM1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase I;
DE Short=ROCK-I;
DE AltName: Full=cAMP-dependent protein kinase ROCK-I;
DE Short=CePKA;
DE AltName: Full=p160 ROCK-1;
DE Short=p160ROCK;
GN Name=ROCK1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Cornea;
RX PubMed=9620089;
RA Sundar-Raj N., Kinchington P.R., Wessel H., Goldblatt B., Hassell J.,
RA Vergnes J.P., Anderson S.C.;
RT "A Rho-associated protein kinase: differentially distributed in limbal and
RT corneal epithelia.";
RL Invest. Ophthalmol. Vis. Sci. 39:1266-1272(1998).
RN [2]
RP FUNCTION, AND INTERACTION WITH MYOSIN LIGHT CHAIN.
RX PubMed=9139666; DOI=10.1074/jbc.272.19.12257;
RA Kureishi Y., Kobayashi S., Amano M., Kimura K., Kanaide H., Nakano T.,
RA Kaibuchi K., Ito M.;
RT "Rho-associated kinase directly induces smooth muscle contraction through
RT myosin light chain phosphorylation.";
RL J. Biol. Chem. 272:12257-12260(1997).
CC -!- FUNCTION: Protein kinase which is a key regulator of the actin
CC cytoskeleton and cell polarity (By similarity). Involved in regulation
CC of smooth muscle contraction, actin cytoskeleton organization, stress
CC fiber and focal adhesion formation, neurite retraction, cell adhesion
CC and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2,
CC MYL9/MLC2, TPPP, PFN1 and PPP1R12A (By similarity) (PubMed:9139666).
CC Phosphorylates FHOD1 and acts synergistically with it to promote SRC-
CC dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3
CC and regulates the recruitment of JNK to JIP3 upon UVB-induced stress
CC (By similarity). Acts as a suppressor of inflammatory cell migration by
CC regulating PTEN phosphorylation and stability (By similarity). Acts as
CC a negative regulator of VEGF-induced angiogenic endothelial cell
CC activation. Required for centrosome positioning and centrosome-
CC dependent exit from mitosis (By similarity). Plays a role in terminal
CC erythroid differentiation (By similarity). Inhibits podocyte motility
CC via regulation of actin cytoskeletal dynamics and phosphorylation of
CC CFL1 (By similarity). Promotes keratinocyte terminal differentiation
CC (By similarity). Involved in osteoblast compaction through the
CC fibronectin fibrillogenesis cell-mediated matrix assembly process,
CC essential for osteoblast mineralization (By similarity). May regulate
CC closure of the eyelids and ventral body wall by inducing the assembly
CC of actomyosin bundles (By similarity). {ECO:0000250|UniProtKB:P70335,
CC ECO:0000250|UniProtKB:Q13464, ECO:0000250|UniProtKB:Q8MIT6,
CC ECO:0000269|PubMed:9139666}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q13464};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:Q13464};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q13464};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:Q13464};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by RHOA binding. Inhibited by Y-27632
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with RHOA (activated by GTP), RHOB, RHOC,
CC GEM, MYLC2B, RHOE, PPP1R12A, LIMK1, LIMK2, TSG101, CHORDC1, DAPK3,
CC PFN1, PTEN and JIP3. Interacts with FHOD1 in a Src-dependent manner.
CC Interacts with ITGB1BP1 (via N-terminus and PTB domain). Interacts with
CC SHROOM3 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q13464}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P70335}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome,
CC centriole {ECO:0000250|UniProtKB:P70335}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q13464}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q13464}. Cell projection, bleb
CC {ECO:0000250|UniProtKB:Q13464}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P70335}. Cell membrane
CC {ECO:0000250|UniProtKB:P70335}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P70335}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:P70335}. Note=A small proportion is associated
CC with Golgi membranes (By similarity). Associated with the mother
CC centriole and an intercentriolar linker (By similarity). Colocalizes
CC with ITGB1BP1 and ITGB1 at the cell membrane predominantly in
CC lamellipodia and membrane ruffles, but also in retraction fibers (By
CC similarity). Localizes at the cell membrane in an ITGB1BP1-dependent
CC manner (By similarity). {ECO:0000250|UniProtKB:P70335,
CC ECO:0000250|UniProtKB:Q13464}.
CC -!- TISSUE SPECIFICITY: Detected in corneal epithelium.
CC {ECO:0000269|PubMed:9620089}.
CC -!- DOMAIN: The C-terminal auto-inhibitory domain interferes with kinase
CC activity. RHOA binding leads to a conformation change and activation of
CC the kinase. Truncated ROCK1 is constitutively activated.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC -!- PTM: Cleaved by caspase-3 during apoptosis. This leads to constitutive
CC activation of the kinase and membrane blebbing (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U42424; AAC36189.1; -; mRNA.
DR RefSeq; NP_001075836.1; NM_001082367.1.
DR AlphaFoldDB; O77819; -.
DR SMR; O77819; -.
DR STRING; 9986.ENSOCUP00000004197; -.
DR GeneID; 100009220; -.
DR KEGG; ocu:100009220; -.
DR CTD; 6093; -.
DR eggNOG; KOG0612; Eukaryota.
DR InParanoid; O77819; -.
DR OrthoDB; 759391at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0032059; C:bleb; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051451; P:myoblast migration; ISS:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0090521; P:podocyte cell migration; ISS:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0010604; P:positive regulation of macromolecule metabolic process; IEA:UniProt.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; IEA:InterPro.
DR CDD; cd00029; C1; 1.
DR CDD; cd11639; HR1_ROCK1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020684; ROCK1/ROCK2.
DR InterPro; IPR037310; ROCK1_HR1.
DR InterPro; IPR015008; ROCK_Rho-bd_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08912; Rho_Binding; 1.
DR PIRSF; PIRSF037568; Rho_kinase; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51860; REM_1; 1.
DR PROSITE; PS51859; RHO_BD; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; ATP-binding; Cell membrane; Cell projection;
KW Coiled coil; Cytoplasm; Cytoskeleton; Golgi apparatus; Kinase; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT CHAIN 2..1354
FT /note="Rho-associated protein kinase 1"
FT /id="PRO_0000086622"
FT DOMAIN 76..338
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 341..409
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 479..556
FT /note="REM-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 949..1015
FT /note="RhoBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01206"
FT DOMAIN 1118..1317
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 1228..1283
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 368..727
FT /note="Interaction with FHOD1"
FT /evidence="ECO:0000250"
FT REGION 707..946
FT /note="SHROOM3 binding"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT REGION 998..1010
FT /note="RHOA binding"
FT /evidence="ECO:0000250"
FT REGION 1101..1120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1115..1354
FT /note="Auto-inhibitory"
FT /evidence="ECO:0000250"
FT REGION 1333..1354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 422..692
FT /evidence="ECO:0000255"
FT COILED 1011..1102
FT /evidence="ECO:0000255"
FT ACT_SITE 198
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 82..90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 1113..1114
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT MOD_RES 1105
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT MOD_RES 1108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70335"
FT MOD_RES 1328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
SQ SEQUENCE 1354 AA; 158347 MW; 399B1899D18280D4 CRC64;
MSTGDSFETR FEKIDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK
DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF
FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA
EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY
ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP
DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS
SDIDTSNFDD LEEDKGDEET FPIPKAFVGN QLPFVGFTYY SNRRYLSPAN PNDNRTSSNV
DKSLQENLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLEST
VSQIEKEKML LQHRINEYQR KAEQENEKRR NVENEVSTLK DQLEDLKKVS QNSQLANEKL
AQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQTD
KDYYQLQAVL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKYNLERMEG ERKEAQDMLN
HSEKEKNNLE IDLNYKLKSL QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL
KEEREAREKA ENRVVQIEKQ CSMLDVDLKQ SQQKLEHLTE NKERMEDEVK NLTLQLEQES
NKRLLLQNEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR
ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLKKIQE LQNEKETLAT QLDLAETKAE
SEQLARGLLE EQYFELTQES KKAASRNRQE ITDKDHAVSR LEETNSILTK DIELLRKENE
ELTDKMRKSE EEYKLQKEEE ISNLKATYEK NINTERTLKT QAVNKLAEIM NRKDFKIDKK
KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC THRNELQMQL
ASKESDIEQL RAKLSDLSDS TSVASFPSAD ETDPNLPESR IEGWLSVPNR GNIKRYGWKK
QYVVVSSKKI LFYNDEQDKE QSNPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
ANEGECRKDV EVEPVQQAEK TNFQNHKGHE FIPTLYHFPA NCEACAKPLW HVFKPPPALE
CRRCHVKCHR DHLDKKEDLI SPCKVSYDVT SARDMLLLAC SQDEQKKWVT HLVKKIPKNP
PSGFVRASPR TLSTRSTANQ SFRKVVKNTS GKTS
