Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 284 RDMMAGFLNQQQMIGNLTSWRRLYCVLRGGKLFCYYSPEEIEAEVEPALTVSINKETRIRSVDKDSKRRTNNFSVINPVS 363
Cdd:cd13249     1 QEMMSGYLSQQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEIEAKVEPLLTIPINKETRIRAVEKDSKGRASSLSIINPYS 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2024415383 364 GEAATQLFATDSREELHKWMEAFWQHFYDLS 394
Cdd:cd13249    81 GEEVTHVLSADSREELQKWMEALWQHFYDMS 111

Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases; The HR1 domain, also called the ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. It is found in Rho effector proteins including PKC-related kinases such as vertebrate PRK1 (or PKN) and yeast PKC1 protein kinases C, as well as in rhophilins and Rho-associated kinase (ROCK). Rho family members function as molecular switches, cycling between inactive and active forms, controlling a variety of cellular processes. HR1 domains may occur in repeat arrangements (PKN contains three HR1 domains), separated by a short linker region.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024415383   19 NIQEKMDFEIRIREGIRKLLTVSTQKDQLLQAV-KNLMVCNARIHAYRTELQ 69
Cdd:smart00742   5 DLRRKIEKELKVKEGAENMRKLTSNDRKVLSEAqSMLRESNQKLDLLKEELE 56

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 284 RDMMAGFLNQQQMIGNLTSWRRLYCVLRGGKLFCYYSPEEIEAEVEPALTVSINKETRIRSVDKDSKRRTNNFSVINPVS 363
Cdd:cd13249     1 QEMMSGYLSQQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEIEAKVEPLLTIPINKETRIRAVEKDSKGRASSLSIINPYS 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2024415383 364 GEAATQLFATDSREELHKWMEAFWQHFYDLS 394
Cdd:cd13249    81 GEEVTHVLSADSREELQKWMEALWQHFYDMS 111

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383  287 MAGFLNQQQMIGNlTSWRRLYCVLRGGKLfCYYSPEEIEAEVEPALTVSINKETRIRSVDKDSKRRTNNFSVINPvsgEA 366
Cdd:smart00233   3 KEGWLYKKSGGGK-KSWKKRYFVLFNSTL-LYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTS---DR 77

                           90       100
                   ....*....|....*....|
gi 2024415383  367 ATQLFATDSREELHKWMEAF 386
Cdd:smart00233  78 KTLLLQAESEEEREKWVEAL 97

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2024415383   19 NIQEKMDFEIRIREGIRKLLTVSTQKDQLLQAV-KNLMVCNARIHAYRTELQ 69
Cdd:smart00742   5 DLRRKIEKELKVKEGAENMRKLTSNDRKVLSEAqSMLRESNQKLDLLKEELE 56

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 284 RDMMAGFLNQQQMIGNLTSWRRLYCVLRGGKLFCYYSPEEIEAEVEPALTVSINKETRIRSVDKDSKRRTNNFSVINPVS 363
Cdd:cd13249     1 QEMMSGYLSQQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEIEAKVEPLLTIPINKETRIRAVEKDSKGRASSLSIINPYS 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2024415383 364 GEAATQLFATDSREELHKWMEAFWQHFYDLS 394
Cdd:cd13249    81 GEEVTHVLSADSREELQKWMEALWQHFYDMS 111

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 287 MAGFLNQQQMIGNLTSWRRLYCVLRGGKLFCYYSPEEiEAEVEPALTVSINKET--RIRSVDKDSKRRTNNFSVINPVSG 364
Cdd:cd01263     4 YRGFLTVFEDVSGLGAWHRRWCVLRGGYLSFWKYPDD-EEKKKPIGSIDLTKCIteKVEPAPRELCARPNTFLLETLRPA 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2024415383 365 EAATQ---------LFATDSREELHKWMEAFWQHFYDL 393
Cdd:cd01263    83 EDDDRddtnekirvLLSADTKEERIEWLSALNQTLADL 120

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383  287 MAGFLNQQQMIGNlTSWRRLYCVLRGGKLfCYYSPEEIEAEVEPALTVSINKETRIRSVDKDSKRRTNNFSVINPvsgEA 366
Cdd:smart00233   3 KEGWLYKKSGGGK-KSWKKRYFVLFNSTL-LYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTS---DR 77

                           90       100
                   ....*....|....*....|
gi 2024415383  367 ATQLFATDSREELHKWMEAF 386
Cdd:smart00233  78 KTLLLQAESEEEREKWVEAL 97

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 286 MMAGFLNQQQMIGnLTSWRRLYCVLRGGKLFCYYSPEEIEAE---VEPALTVSinketriRSVDKDSKRRTNNFSVINPv 362
Cdd:cd13248     8 VMSGWLHKQGGSG-LKNWRKRWFVLKDNCLYYYKDPEEEKALgsiLLPSYTIS-------PAPPSDEISRKFAFKAEHA- 78

                          90       100
                  ....*....|....*....|...
gi 2024415383 363 sgEAATQLFATDSREELHKWMEA 385
Cdd:cd13248    79 --NMRTYYFAADTAEEMEQWMNA 99

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 301 TSWRRLYCVLRGGKLFCYYSPEEIEAE---VEPALTVSINKETrirsvdkdsKRRTNNFSVINPvsgeaATQL-FATDSR 376
Cdd:cd13326    16 GKWAKRWFVLKGSNLYGFRSQESTKADcviFLPGFTVSPAPEV---------KSRKYAFKVYHT-----GTVFyFAAESQ 81

                          90
                  ....*....|
gi 2024415383 377 EELHKWMEAF 386
Cdd:cd13326    82 EDMKKWLDLL 91

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 302 SWRRLYCVLRGGKLFCY-----YSPEEIEAEVEPaltvsINKETRIRSVDKDSKRRTNNFSVINPVSGEAatqLFATDSR 376
Cdd:cd10571    22 SWKNVYTVLRGQELSFYkdqkaAKSGITYAAEPP-----LNLYNAVCEVASDYTKKKHVFRLKLSDGAEF---LFQAKDE 93

                  ....*....
gi 2024415383 377 EELHKWMEA 385
Cdd:cd10571    94 EEMNQWVKK 102

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024415383 298 GNLTSWRRLYCVLRGGKLFcYYSPEEieaevepaltvsinkETRIRSVDKDSKRRTNNFSVINPVSGEAATQL------- 370
Cdd:cd13316    11 ERYGTWKTRYFVLKGTRLY-YLKSEN---------------DDKEKGLIDLTGHRVVPDDSNSPFRGSYGFKLvppavpk 74

                          90
                  ....*....|....*....
gi 2024415383 371 ---FATDSREELHKWMEAF 386
Cdd:cd13316    75 vhyFAVDEKEELREWMKAL 93