ROCK1_PANTR
ID ROCK1_PANTR Reviewed; 1003 AA.
AC P61584;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Rho-associated protein kinase 1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13464};
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=p160 ROCK-1;
DE Short=p160ROCK;
DE Flags: Fragment;
GN Name=ROCK1;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=14962675; DOI=10.1016/j.ygeno.2003.08.017;
RA Dennehey B.K., Gutches D.G., McConkey E.H., Krauter K.S.;
RT "Inversion, duplication, and changes in gene context are associated with
RT human chromosome 18 evolution.";
RL Genomics 83:493-501(2004).
CC -!- FUNCTION: Protein kinase which is a key regulator of actin cytoskeleton
CC and cell polarity. Involved in regulation of smooth muscle contraction,
CC actin cytoskeleton organization, stress fiber and focal adhesion
CC formation, neurite retraction, cell adhesion and motility via
CC phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and
CC PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to
CC promote SRC-dependent non-apoptotic plasma membrane blebbing.
CC Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon
CC UVB-induced stress (By similarity). Acts as a suppressor of
CC inflammatory cell migration by regulating PTEN phosphorylation and
CC stability (By similarity). Acts as a negative regulator of VEGF-induced
CC angiogenic endothelial cell activation. Required for centrosome
CC positioning and centrosome-dependent exit from mitosis (By similarity).
CC Plays a role in terminal erythroid differentiation (By similarity). May
CC regulate closure of the eyelids and ventral body wall by inducing the
CC assembly of actomyosin bundles (By similarity). Promotes keratinocyte
CC terminal differentiation (By similarity). Involved in osteoblast
CC compaction through the fibronectin fibrillogenesis cell-mediated matrix
CC assembly process, essential for osteoblast mineralization (By
CC similarity). {ECO:0000250|UniProtKB:P70335,
CC ECO:0000250|UniProtKB:Q13464, ECO:0000250|UniProtKB:Q8MIT6}.
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 (By similarity). Interacts with RHOA (activated by
CC GTP), RHOB, RHOC, GEM, MYLC2B, RHOE, PPP1R12A, LIMK1, LIMK2, TSG101,
CC CHORDC1, DAPK3, PFN1, PTEN and JIP3. Interacts with ITGB1BP1 (via N-
CC terminus and PTB domain) (By similarity). Interacts with FHOD1 in a
CC Src-dependent manner (By similarity). Interacts with SHROOM3 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q13464}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole. Golgi apparatus membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell
CC projection, bleb {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cell membrane {ECO:0000250}. Cell projection, lamellipodium
CC {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Note=Associated
CC with the mother centriole and an intercentriolar linker. A small
CC proportion is associated with Golgi membranes. Colocalizes with
CC ITGB1BP1 and ITGB1 at the cell membrane predominantly in lamellipodia
CC and membrane ruffles, but also in retraction fibers. Localizes at the
CC cell membrane in an ITGB1BP1-dependent manner (By similarity).
CC {ECO:0000250}.
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; AY191612; AAP23262.1; -; Genomic_DNA.
DR AlphaFoldDB; P61584; -.
DR SMR; P61584; -.
DR STRING; 9598.ENSPTRP00000016847; -.
DR PaxDb; P61584; -.
DR eggNOG; KOG0612; Eukaryota.
DR InParanoid; P61584; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0032059; C:bleb; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0010494; C:cytoplasmic stress granule; IBA:GO_Central.
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:0072518; F:Rho-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central.
DR GO; GO:0000281; P:mitotic cytokinesis; IBA:GO_Central.
DR GO; GO:0051451; P:myoblast migration; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
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:1901888; P:regulation of cell junction assembly; IBA:GO_Central.
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; IBA:GO_Central.
DR CDD; cd00029; C1; 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; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR015008; ROCK_Rho-bd_dom.
DR Pfam; PF08912; Rho_Binding; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS51860; REM_1; 1.
DR PROSITE; PS51859; RHO_BD; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 3: Inferred from homology;
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 CHAIN <1..1003
FT /note="Rho-associated protein kinase 1"
FT /id="PRO_0000086621"
FT DOMAIN <1..58
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 128..205
FT /note="REM-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 598..664
FT /note="RhoBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01206"
FT DOMAIN 767..966
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 877..930
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 17..376
FT /note="Interaction with FHOD1"
FT /evidence="ECO:0000250"
FT REGION 356..595
FT /note="SHROOM3 binding"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT REGION 647..659
FT /note="RHOA binding"
FT /evidence="ECO:0000250"
FT REGION 764..1003
FT /note="Auto-inhibitory"
FT /evidence="ECO:0000250"
FT REGION 968..1003
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 71..341
FT /evidence="ECO:0000255"
FT COILED 660..751
FT /evidence="ECO:0000255"
FT COMPBIAS 975..1003
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 762..763
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 296
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT MOD_RES 754
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT MOD_RES 757
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70335"
FT MOD_RES 977
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13464"
FT NON_TER 1
SQ SEQUENCE 1003 AA; 117524 MW; 18C6F52FBF012A83 CRC64;
VAPVVPDLSS DIDTSNFDDL EEDKGEEETF PIPKAFVGNQ LPFVGFTYYS NRRYLSSANP
NDNRTSSNAD KSLQESLQKT IYKLEEQLHN EMQLKDEMEQ KCRTSNIKLD KIMKELDEEG
NQRRNLESTV SQIEKEKMLL QHRINEYQRK AEQENEKRRN VENEVSTLKD QLEDLKKVSQ
NSQLANEKLS QLQKQLEEAN DLLRTESDTA VRLRKSHTEM SKSISQLESL NRELQERNRI
LENSKSQTDK DYYQLQAILE AERRDRGHDS EMIGDLQARI TSLQEEVKHL KHNLEKVEGE
RKEAQDMLNH SEKEKNNLEI DLNYKLKSLQ QRLEQEVNEH KVTKARLTDK HQSIEEAKSV
AMCEMEKKLK EEREAREKAE NRVVQIEKQC SMLDVDLKQS QQKLEHLTGN KERMEDEVKN
LTLQLEQESN KRLLLQNELK TQAFEADNLK GLEKQMKQEI NTLLEAKRLL EFELAQLTKQ
YRGNEGQMRE LQDQLEAEQY FSTLYKTQVK ELKEEIEEKN RENLKKIQEL QNEKETLATQ
LDLAETKAES EQLARGLLEE QYFELTQESK KAASRNRQEI TDKDHTVSRL EEANSMLTKD
IEILRRENEE LTEKMKKAEE EYKLEKEEEI SNLKAAFEKN INTERTLKTQ AVNKLAEIMN
RKDFKIDRKK ANTQDLRKKE KENRKLQLEL NQEREKFNQM VVKHQKELND MQAQLVEECA
HRNELQMQLA SKESDIEQLR AKLLDLSDST SVASFPSADE TDGNLPESRI EGWLSVPNRG
NIKRYGWKKQ YVVVSSKKIL FYNDEQDKEQ SNPSMVLDID KLFHVRPVTQ GDVYRAETEE
IPKIFQILYA NEGECRKDVE MEPVQQAEKT NFQNHKGHEF IPTLYHFPAN CDACAKPLWH
VFKPPPALEC RRCHVKCHRD HLDKKEDLIC PCKVSYDVTS ARDMLLLACS QDEQKKWVTH
LVKKIPKNPP SGFVRASPRT LSTRSTANQS FRKVVKNTSG KTR
