ROCK2_PIG
ID ROCK2_PIG Reviewed; 1388 AA.
AC M3TYT0; F1SCR1;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Rho-associated protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=Rho kinase 2;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 2;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase II;
DE Short=ROCK-II;
DE AltName: Full=p164 ROCK-2;
GN Name=ROCK2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dawson H.D., Chen C.T.;
RT "Global gene expression profiling of alveolar macrophages by deep
RT sequencing.";
RL Submitted (FEB-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=23172836; DOI=10.1161/circulationaha.112.135608;
RA Saito T., Hirano M., Ide T., Ichiki T., Koibuchi N., Sunagawa K.,
RA Hirano K.;
RT "Pivotal role of Rho-associated kinase 2 in generating the intrinsic
RT circadian rhythm of vascular contractility.";
RL Circulation 127:104-114(2013).
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 ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN,
CC MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4.
CC Acts as a negative regulator of VEGF-induced angiogenic endothelial
CC cell activation. Positively regulates the activation of p42/MAPK1-
CC p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays
CC an important role in the timely initiation of centrosome duplication.
CC Inhibits keratinocyte terminal differentiation. May regulate closure of
CC the eyelids and ventral body wall through organization of actomyosin
CC bundles. Plays a critical role in the regulation of spine and synaptic
CC properties in the hippocampus. Plays an important role in generating
CC the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and
CC vascular contractility by modulating the myosin light chain
CC phosphorylation. {ECO:0000269|PubMed:23172836}.
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 -!- 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;
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 IRS1. Interacts with
CC RAF1. Interacts with RHOA (activated by GTP), RHOB and RHOC (By
CC similarity). Interacts with PPP1R12A. Interacts with EP300. Interacts
CC with CHORDC1. Interacts with BRCA2. Interacts with NPM1; this
CC interaction enhances ROCK2 activity. Interacts with SORL1 (By
CC similarity). Interacts with PJVK (By similarity).
CC {ECO:0000250|UniProtKB:O75116, ECO:0000250|UniProtKB:P70336,
CC ECO:0000250|UniProtKB:Q28021, ECO:0000250|UniProtKB:Q62868}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome {ECO:0000250}. Note=Cytoplasmic, and associated with actin
CC microfilaments and the plasma membrane.
CC -!- INDUCTION: Expression oscillates in a circadian manner in the aortic
CC smooth muscle cells (at protein level). {ECO:0000269|PubMed:23172836}.
CC -!- DOMAIN: An interaction between Thr-414 and Asp-48 is essential for
CC kinase activity and dimerization. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding
CC to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation
CC by PTPN11 stimulates its RHOA binding activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Cleaved by granzyme B 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; GACC01000348; JAA74236.1; -; mRNA.
DR EMBL; CU915597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; M3TYT0; -.
DR SMR; M3TYT0; -.
DR IntAct; M3TYT0; 1.
DR STRING; 9823.ENSSSCP00000009198; -.
DR PaxDb; M3TYT0; -.
DR PRIDE; M3TYT0; -.
DR Ensembl; ENSSSCT00050041186; ENSSSCP00050017010; ENSSSCG00050030630.
DR Ensembl; ENSSSCT00055009021; ENSSSCP00055007146; ENSSSCG00055004566.
DR Ensembl; ENSSSCT00065078518; ENSSSCP00065034131; ENSSSCG00065057361.
DR eggNOG; KOG0612; Eukaryota.
DR OMA; WTFENLR; -.
DR TreeFam; TF313551; -.
DR Reactome; R-SSC-3928662; EPHB-mediated forward signaling.
DR Reactome; R-SSC-416482; G alpha (12/13) signalling events.
DR Reactome; R-SSC-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-SSC-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-SSC-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-SSC-8980692; RHOA GTPase cycle.
DR Reactome; R-SSC-9013026; RHOB GTPase cycle.
DR Reactome; R-SSC-9013106; RHOC GTPase cycle.
DR Reactome; R-SSC-9013407; RHOH GTPase cycle.
DR Reactome; R-SSC-9013422; RHOBTB1 GTPase cycle.
DR ChiTaRS; ROCK2; pig.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
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:0003180; P:aortic valve morphogenesis; IGI:BHF-UCL.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IGI:BHF-UCL.
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:0070168; P:negative regulation of biomineral tissue development; IGI:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0010825; P:positive regulation of centrosome duplication; IEA:InterPro.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IGI:BHF-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:1901888; P:regulation of cell junction assembly; IBA:GO_Central.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006939; P:smooth muscle contraction; IEA:InterPro.
DR CDD; cd00029; C1; 1.
DR CDD; cd11638; HR1_ROCK2; 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; IPR037311; ROCK2_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 ATP-binding; Biological rhythms; Cell membrane; Coiled coil; Cytoplasm;
KW Cytoskeleton; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1388
FT /note="Rho-associated protein kinase 2"
FT /id="PRO_0000429860"
FT DOMAIN 92..354
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 357..425
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 497..573
FT /note="REM-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 979..1047
FT /note="RhoBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01206"
FT DOMAIN 1150..1349
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 1260..1315
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..784
FT /note="Interaction with PPP1R12A"
FT /evidence="ECO:0000250"
FT REGION 373..420
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000250"
FT REGION 512..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 979..1047
FT /note="RHOA binding"
FT /evidence="ECO:0000250"
FT REGION 1345..1388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1054..1126
FT /evidence="ECO:0000255"
FT COMPBIAS 1363..1388
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 214
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 98..106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 1131..1132
FT /note="Cleavage; by granzyme B"
FT /evidence="ECO:0000250"
FT MOD_RES 414
FT /note="Phosphothreonine; by ROCK2"
FT /evidence="ECO:0000250|UniProtKB:Q62868"
FT MOD_RES 722
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
SQ SEQUENCE 1388 AA; 160750 MW; CD7DEAC913D7AE04 CRC64;
MSRPPPTGKM PGAPEAVSGD GAGASRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP
ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM
KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFCAFQ DDKYLYMVME YMPGGDLVNL
MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD
ETGMVHCDTA VGTPDYISPE VLKSQGGDGY YGRECDWWSV GVFLFEMLVG DTPFYADSLV
GTYSKIMDHK NSLCFPEDAE ISKHAKNLIC AFLTDREVRL GRNGVEEIKQ HPFFKNDQWN
WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYYRENL
LLSDSPSCKE NDSIQIRKNE ESQEIQKKLY TLEEHLSTEI QAKEELEQKC KSVNTRLEKV
AKELEEEIAL RKNVESALRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL
EDLKKRNQNS QISTEKVNQL QRQLDETNAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
DLQDKNCLLE TAKLKLEKDF INLQSVLESE RRDRTHGSEI INDLQGRISG LEEDLKNGKI
LLTKVEMEKR QLQERFTDLE KEKNNMEIDM TYQLKVIQQS LEQEEAEHKA TKARLADKNK
IYESIEEAKS EAMKEMEKKL LEERTLKQKV ENLLLEAEKR CSILDCDLKQ SQQKINELLK
QKDVLNEDVR NLTLKIEQET QKRCLTQNDL KMQTQQVNTL KMSEKQLKQE NNHLMEMKMS
LEKQNAELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEECEEK TKLCKELQQK
KQELQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE
LTEKDTTIAS LEETNRTLTS DVANLANEKE ELNNKLKDAQ EQLSRLKDEE ISAAAIKAQF
EKQLLTERTL KTQAVNKLAE IMNRKEPVKR GNDTDMRRKE KENRKLHMEL KSEREKLTQQ
MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGL DSSSIGSGPG
DAEADDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EQEFPVEPVG EKSNCICHKG
HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECRRCHIKC HKDHMDKKEE IIAPCKVYYD
ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR
QLAANKPS
