Hr1

Rho effector or protein kinase C-related kinase homology region 1 homologues

• SMART accession number: SM00742
• Description: Alpha-helical domain found in vertebrate PRK1 and yeast PKC1 protein kinases C. The HR1 in rhophilin bind RhoGTP; those in PRK1 bind RhoA and RhoB. Also called RBD - Rho-binding domain
• Interpro abstract (IPR011072):

  HR1 was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN) [ (PUBMED:7851406) ]. The first two of these repeats were later shown to bind the small G protein rho [ (PUBMED:8647255) (PUBMED:9446575) ] known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. This domain contains two long alpha helices forming a left-handed antiparallel coiled-coil fold termed the antiparallel coiled- coil (ACC) finger domain. The two long helices encompass the basic region and the leucine repeat region, which are identified as the Rho-binding region [ (PUBMED:10619026) (PUBMED:14514689) (PUBMED:27129201) ].

  This entry also includes Transducer of Cdc42-dependent actin assembly protein (TOCA) family proteins which contains a central HR1 (also known as Rho effector motif class 1, REM-1) which is closely related to Cdc42-interacting protein 4 (CIP4), effectors of the Rho family small G protein Cdc2 [ (PUBMED:27129201) ].

• GO process: signal transduction (GO:0007165)

There are 6745 Hr1 domains in 3157 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling
Binding / catalysis: RhoGTP-binding

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
6.12	map04530	Tight junction
6.12	map04370	VEGF signaling pathway
6.12	map04010	MAPK signaling pathway
6.12	map04070	Phosphatidylinositol signaling system
6.12	map04510	Focal adhesion
6.12	map04670	Leukocyte transendothelial migration
6.12	map04012	ErbB signaling pathway
6.12	map05214	Glioma
6.12	map04310	Wnt signaling pathway
6.12	map04540	Gap junction
6.12	map04020	Calcium signaling pathway
6.12	map04720	Long-term potentiation
6.12	map04916	Melanogenesis
6.12	map04730	Long-term depression
6.12	map05223	Non-small cell lung cancer
6.12	map04650	Natural killer cell mediated cytotoxicity
1.02	map00562	Inositol phosphate metabolism
1.02	map00632	Benzoate degradation via CoA ligation

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Hr1 domain which could be assigned to a KEGG orthologous group, and not all proteins containing Hr1 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of Hr1 domains in PDB

PDB code	Title
1cxz	CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK1
1urf	HR1b domain from PRK1
2rmk	Rac1/PRK1 Complex
4nkg	Crystal structure of SspH1 LRR domain in complex PKN1 HR1b domain

Links (links to other resources describing this domain)

• INTERPRO: IPR011072
• PFAM: HR1