Q63644 (ROCK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho-associated protein kinase 1
EC=2.7.11.1

Alternative name(s):
Liver regeneration-related protein LRRG199
Rho-associated, coiled-coil-containing protein kinase 1
Rho-associated, coiled-coil-containing protein kinase I
Short name=ROCK-I
p150 RhoA-binding kinase ROK beta
p160 ROCK-1
Short name=p160ROCK

Gene names

Name:	Rock1
ORF Names:	Ac2-154

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1369 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Ref.3 Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by RHOA binding. Inhibited by Y-27632.
Subunit structure	Homodimer By similarity. Interacts with GEM, MYLC2B, RHOE, LIMK1, LIMK2, TSG101, CHORDC1, DAPK3, PFN1, PTEN and JIP3 By similarity. Interacts with FHOD1 in a Src-dependent manner By similarity. Interacts with RHOA (activated by GTP), RHOB, RHOC and PPP1R12A. Ref.1 Ref.4
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton › centrosome › centriole. Golgi apparatus membrane; Peripheral membrane protein By similarity. Cell projection › bleb By similarity. Note: Associated with the mother centriole and an intercentriolar linker. A small proportion is associated with Golgi membranes By similarity. Ref.4
Tissue specificity	Highly expressed in brain, spleen, lung, liver, skeletal muscle, kidney and testis. Ref.1
Domain	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.
Post-translational modification	Autophosphorylated on serine and threonine residues. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing By similarity.
Involvement in disease	Note=May play a role in hypertension. Rock1-inhibitors lower the blood pressure in spontaneous hypertensive, renal hypertensive and deoxcorticosterone acetate-induced hypertensive rats, but not in normal rats.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. Contains 1 REM (Hr1) repeat.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell projection Cytoplasm Cytoskeleton Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Rho protein signal transduction Inferred from mutant phenotype. Source: MGI apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cytokinesis Inferred from electronic annotation. Source: InterPro cytoskeleton organization Inferred from mutant phenotype Ref.1. Source: RGD
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell bleb Inferred from electronic annotation. Source: UniProtKB-SubCell centriole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP-Rho binding Inferred from mutant phenotype Ref.1. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Non-traceable author statement Ref.1. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q63644-1)

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.

Isoform 2 (identifier: Q63644-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-488: Missing.
     1369-1369: S → RLMPSSPCRV...QFMHQVLVDR

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1369	1368	Rho-associated protein kinase 1		PRO_0000086623
Regions
	Domain	76 – 338	263	Protein kinase
	Domain	341 – 409	69	AGC-kinase C-terminal
	Repeat	458 – 542	85	REM
	Domain	1133 – 1332	200	PH
	Nucleotide binding	82 – 90	9	ATP By similarity
	Zinc finger	1243 – 1298	56	Phorbol-ester/DAG-type
	Region	368 – 727	360	Interaction with FHOD1 By similarity
	Region	998 – 1010	13	RHOA binding By similarity
	Region	1115 – 1369	255	Auto-inhibitory By similarity
	Coiled coil	422 – 613	192	Potential
	Coiled coil	1011 – 1102	92	Potential
	Compositional bias	636 – 980	345	Glu-rich
Sites
	Active site	198	1	Proton acceptor By similarity
	Binding site	105	1	ATP By similarity
	Site	1113 – 1114	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	455	1	Phosphothreonine By similarity
	Modified residue	456	1	Phosphoserine By similarity
	Modified residue	1105	1	Phosphoserine By similarity
	Modified residue	1195	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1 – 488	488	Missing in isoform 2.		VSP_010449
	Alternative sequence	1369	1	S → RLMPSSPCRVGVGIDKWRSH RDRKREGLLTEDVPGSRLEK KLGRIGRAARRNKDGADIQP CLDINDLLCMCRLVPLLGLP LVVTSGTAHVQFMHQVLVDR in isoform 2.		VSP_010450
Experimental info
	Sequence conflict	1118 – 1133	16	VGSAC…FYSSS → E in AAP92621. Ref.2
	Sequence conflict	1283	1	S → C in AAP92621. Ref.2
	Sequence conflict	1296	1	P → S in AAP92621. Ref.2
	Sequence conflict	1316	1	P → S in AAP92621. Ref.2
	Sequence conflict	1334 – 1335	2	KA → NP in AAP92621. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E29B9456D348C9D0	FASTA	1,369	159,626
	10 20 30 40 50 60 MSTGDSFETR FEKIDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK 70 80 90 100 110 120 DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF 130 140 150 160 170 180 FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA 190 200 210 220 230 240 EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY 250 260 270 280 290 300 ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP 310 320 330 340 350 360 DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS 370 380 390 400 410 420 SDIDTSNFDD LEEDKGDEET FPIPKAFVGN QLPFVGFTYY SNRRYLPSAN PSENRSSSNV 430 440 450 460 470 480 DKNVQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLESA 490 500 510 520 530 540 VSQIEKEKML LQHRINEYQR KVEQENEKRR NVENEVSTLK DQLEDLRKAS QSSQLANEKL 550 560 570 580 590 600 TQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSVSQLES LNRELQERNR MLENSKSQAD 610 620 630 640 650 660 KDYYQLQAVL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLERVEG ERKEAQDMLN 670 680 690 700 710 720 HSEKEKNNLE IDLNYKLKSI QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL 730 740 750 760 770 780 KEEREAREKA ENRVVETEKQ CSMLDVDLKQ SQQKLEHLTE NKERLEDAVK SLTLQLEQES 790 800 810 820 830 840 NKRILLQSEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR 850 860 870 880 890 900 ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLRKIQE LQSEKETLST QLDLAETKAE 910 920 930 940 950 960 SEQLARGILE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANNALTK DIELLRKENE 970 980 990 1000 1010 1020 ELNERMRTAE EEYKLKKEEE ISNLKAAFEK NISTERTLKT QAVNKLAEIM NRKDFKIDRK 1030 1040 1050 1060 1070 1080 KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC THRNELQMQL 1090 1100 1110 1120 1130 1140 ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPVGS ACIPYLFIFY SSSSRIEGWL 1150 1160 1170 1180 1190 1200 SVPNRGNIKR YGWKKQYVVV SSKKMLFYND EQDKEQSSPS MVLDIDKLFH VRPVTQGDVY 1210 1220 1230 1240 1250 1260 RAETEEIPKI FQILYANEGE CRKDIEVEPV QQGEKTNFQN HKGHEFIPTL YHFPANCEAC 1270 1280 1290 1300 1310 1320 AKPLWHVFKP PPALECRRCH VKSHRDHLDK KEDLIPPCKV SYDVTSARDM LLLACPQDEQ 1330 1340 1350 1360 KKWVTHLVKK IPKKAPSGFV RASPRTLSTR STANQSFRKV VKNTSGKTS
	Isoform 2 [UniParc]. Checksum: 1465C2DFEC01255D	FASTA	980	114,243
	10 20 30 40 50 60 MLLQHRINEY QRKVEQENEK RRNVENEVST LKDQLEDLRK ASQSSQLANE KLTQLQKQLE 70 80 90 100 110 120 EANDLLRTES DTAVRLRKSH TEMSKSVSQL ESLNRELQER NRMLENSKSQ ADKDYYQLQA 130 140 150 160 170 180 VLEAERRDRG HDSEMIGDLQ ARITSLQEEV KHLKHNLERV EGERKEAQDM LNHSEKEKNN 190 200 210 220 230 240 LEIDLNYKLK SIQQRLEQEV NEHKVTKARL TDKHQSIEEA KSVAMCEMEK KLKEEREARE 250 260 270 280 290 300 KAENRVVETE KQCSMLDVDL KQSQQKLEHL TENKERLEDA VKSLTLQLEQ ESNKRILLQS 310 320 330 340 350 360 ELKTQAFEAD NLKGLEKQMK QEINTLLEAK RLLEFELAQL TKQYRGNEGQ MRELQDQLEA 370 380 390 400 410 420 EQYFSTLYKT QVKELKEEIE EKNRENLRKI QELQSEKETL STQLDLAETK AESEQLARGI 430 440 450 460 470 480 LEEQYFELTQ ESKKAASRNR QEITDKDHTV SRLEEANNAL TKDIELLRKE NEELNERMRT 490 500 510 520 530 540 AEEEYKLKKE EEISNLKAAF EKNISTERTL KTQAVNKLAE IMNRKDFKID RKKANTQDLR 550 560 570 580 590 600 KKEKENRKLQ LELNQEREKF NQMVVKHQKE LNDMQAQLVE ECTHRNELQM QLASKESDIE 610 620 630 640 650 660 QLRAKLLDLS DSTSVASFPS ADETDGNLPV GSACIPYLFI FYSSSSRIEG WLSVPNRGNI 670 680 690 700 710 720 KRYGWKKQYV VVSSKKMLFY NDEQDKEQSS PSMVLDIDKL FHVRPVTQGD VYRAETEEIP 730 740 750 760 770 780 KIFQILYANE GECRKDIEVE PVQQGEKTNF QNHKGHEFIP TLYHFPANCE ACAKPLWHVF 790 800 810 820 830 840 KPPPALECRR CHVKSHRDHL DKKEDLIPPC KVSYDVTSAR DMLLLACPQD EQKKWVTHLV 850 860 870 880 890 900 KKIPKKAPSG FVRASPRTLS TRSTANQSFR KVVKNTSGKT RLMPSSPCRV GVGIDKWRSH 910 920 930 940 950 960 RDRKREGLLT EDVPGSRLEK KLGRIGRAAR RNKDGADIQP CLDINDLLCM CRLVPLLGLP 970 980 LVVTSGTAHV QFMHQVLVDR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton." Leung T., Chen X.-Q., Manser E., Lim L. Mol. Cell. Biol. 16:5313-5327(1996) [PubMed: 8816443] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RHOA; RHOB AND RHOC, TISSUE SPECIFICITY. Tissue: Brain and Liver.
[2]	"Liver regeneration after PH." Xu C.S., Li W.Q., Li Y.C., Yang K.J., Yan H.M., Chang C.F., Zhao L.F., Ma H., Wang L., Wang S.F., Han H.P., Wang G.P., Chai L.Q., Yuan J.Y., Shi J.B., Rahman S., Wang Q.N., Zhang J.B. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Liver.
[3]	"Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension." Uehata M., Ishizaki T., Satoh H., Ono T., Kawahara T., Morishita T., Tamakawa H., Yamagami K., Inui J., Maekawa M., Narumiya S. Nature 389:990-994(1997) [PubMed: 9353125] [Abstract] Cited for: FUNCTION, ROLE IN SMOOTH MUSCLE CONTRACTION AND HYPERTENSION, INHIBITION BY Y-27632.
[4]	"ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells." Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X., Surks H.K. Circ. Res. 104:531-540(2009) [PubMed: 19131646] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPP1R12A, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U61266 mRNA. Translation: AAB37571.1. AY325220 mRNA. Translation: AAP92621.1.
IPI	IPI00211045. IPI00951118.
RefSeq	NP_112360.1. NM_031098.1.
UniGene	Rn.89756.
3D structure databases
ProteinModelPortal	Q63644.
SMR	Q63644. Positions 6-405, 946-1013, 1134-1303.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4599076.
STRING	Q63644.
PTM databases
PhosphoSite	Q63644.
Proteomic databases
PRIDE	Q63644.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	81762.
KEGG	rno:81762.
Organism-specific databases
CTD	6093.
RGD	620424. Rock1.
Phylogenomic databases
eggNOG	roNOG04526.
GeneTree	ENSGT00560000076870.
HOVERGEN	HBG053111.
InParanoid	Q63644.
PhylomeDB	Q63644.
Gene expression databases
ArrayExpress	Q63644.
Genevestigator	Q63644.
GermOnline	ENSRNOG00000031092. Rattus norvegicus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011072. HR1_rho-bd. IPR011009. Kinase-like_dom. IPR011993. PH_type. IPR017892. Pkinase_C. IPR001849. Pleckstrin_homology. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR020684. Rho-assoc_coiled-coil_kin-like. IPR015751. Rho-assoc_coiled-coil_kinase. IPR015008. Rho-bd. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 2 hits. G3DSA:1.20.5.730. Rho_bd. 1 hit.
KO	K04514.
PANTHER	PTHR22988:SF3. Rho_kinase. 1 hit.
Pfam	PF02185. HR1. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. PF08912. Rho_Binding. 1 hit. [Graphical view]
PIRSF	PIRSF037568. Rho_kinase. 1 hit.
SMART	SM00109. C1. 1 hit. SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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. PS00479. ZF_DAG_PE_1. False negative. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	615550.

Entry information

Entry name

ROCK1_RAT

Accession

Primary (citable) accession number: Q63644
Secondary accession number(s): Q7TP31

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program