Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 47086917   1 MRFNEKELVFLSRQPTQRA---AELGMRGPKKGDVVKKRFVKLIVNFLFYFRTDE----DEPIGALLLEQCRVERED--- 70
Cdd:cd13258   1 MRFNEKELAALSSQPAEKEgkiAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEfgdcSEPIGAIVLENCRVQMEEite 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 47086917  71 -LQVFSIVFLDEAERKYLFECDSQEQCAEWIDAIIKASYEFMR 112
Cdd:cd13258  81 kPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASYEYLR 123

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 47086917   1 MRFNEKELVFLSRQPTQRA---AELGMRGPKKGDVVKKRFVKLIVNFLFYFRTDE----DEPIGALLLEQCRVERED--- 70
Cdd:cd13258   1 MRFNEKELAALSSQPAEKEgkiAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEfgdcSEPIGAIVLENCRVQMEEite 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 47086917  71 -LQVFSIVFLDEAERKYLFECDSQEQCAEWIDAIIKASYEFMR 112
Cdd:cd13258  81 kPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASYEYLR 123

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086917    34 KKRFVKLIVNFLFYFRTD----EDEPIGALLLEQCRVEREDLQ-------VFSIVFLDEAE-RKYLFECDSQEQCAEWID 101
Cdd:pfam00169  19 KKRYFVLFDGSLLYYKDDksgkSKEPKGSISLSGCEVVEVVASdspkrkfCFELRTGERTGkRTYLLQAESEEERKDWIK 98

                  ....*..
gi 47086917   102 AIIKASY 108
Cdd:pfam00169  99 AIQSAIR 105

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 47086917   1 MRFNEKELVFLSRQPTQRA---AELGMRGPKKGDVVKKRFVKLIVNFLFYFRTDE----DEPIGALLLEQCRVERED--- 70
Cdd:cd13258   1 MRFNEKELAALSSQPAEKEgkiAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEfgdcSEPIGAIVLENCRVQMEEite 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 47086917  71 -LQVFSIVFLDEAERKYLFECDSQEQCAEWIDAIIKASYEFMR 112
Cdd:cd13258  81 kPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASYEYLR 123

Type I inositol 3,4-bisphosphate 4-phosphatase and Type II inositol 3,4-bisphosphate 4-phosphatase Pleckstrin homology (PH) domain; INPP4A (also called Inositol polyphosphate 4-phosphatase type I) and INPP4B (also called Inositol polyphosphate 4-phosphatase type II) both catalyze the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate and inositol 1,3,4-trisphosphate. They differ in that INPP4A additionally catalyzes the hydrolysis of the 4-position phosphate of inositol 3,4-bisphosphate, while INPP4B catalyzes the hydrolysis of the 4-position phosphate of inositol 1,4-bisphosphate. They both have a single PH domain followed by a C2 domain. 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 47086917   1 MRFNEKELVFLSRQPTQRAAELGMRGPK--------KGDVVKKRFVKLIVNFLFYFRTDE--DEPIGALLLEQC----RV 66
Cdd:cd13272   1 MRFNKQELATLASQPSTKFDKEGLLIITerqegffrRSEGSLERWCRLRGNLLFYLKSKDpwSEPAGVIVLEQCrpriQN 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 47086917  67 EREDLQ--VFSIVFldEAERKYLFECDSQEQCAEWIDAIIKASYEFMRKNLVYYRTEIHRLTGKDP 130
Cdd:cd13272  81 DERDSGgyPFDLVF--EDGLCQRLATRTEAERLSWVQAIELASYEVIRAQLKALREQIERARGHTH 144

Pleckstrin homology (PH) domain; 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 47086917  24 MRGPKKGDVVKKRFVKLIVNFLFYFRTDED---EPIGALLLEQCRVEREDLQ-----VFSIVFLDEaeRKYLFECDSQEQ 95
Cdd:cd00821   7 KRGGGGLKSWKKRWFVLFEGVLLYYKSKKDssyKPKGSIPLSGILEVEEVSPkerphCFELVTPDG--RTYYLQADSEEE 84

                ....*...
gi 47086917  96 CAEWIDAI 103
Cdd:cd00821  85 RQEWLKAL 92

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47086917    34 KKRFVKLIVNFLFYFRTD----EDEPIGALLLEQCRVEREDLQ-------VFSIVFLDEAE-RKYLFECDSQEQCAEWID 101
Cdd:pfam00169  19 KKRYFVLFDGSLLYYKDDksgkSKEPKGSISLSGCEVVEVVASdspkrkfCFELRTGERTGkRTYLLQAESEEERKDWIK 98

                  ....*..
gi 47086917   102 AIIKASY 108
Cdd:pfam00169  99 AIQSAIR 105

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 47086917  34 KKRFVKLIVNFLFYFRTDED-EPIGALLLEQC-RVEREDLQ----VFSIVFldeAERKYLFECDSQEQCAEWIDAI 103
Cdd:cd10573  20 KTRWFVLRRNELKYFKTRGDtKPIRVLDLRECsSVQRDYSQgkvnCFCLVF---PERTFYMYANTEEEADEWVKLL 92

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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 47086917  27 PKKGDVVKKRFVKLIVNFLFYFRTDED-EPIGALLLE--QCRVERE---DLQ-VFSIVFLDEAERKYLFECDSQEQCAEW 99
Cdd:cd13308  22 QKTLQNWQLRYVIIHQGCVYYYKNDQSaKPKGVFSLNgyNRRAAEErtsKLKfVFKIIHLSPDHRTWYFAAKSEDEMSEW 101

                ....*...
gi 47086917 100 IDAIIKAS 107
Cdd:cd13308 102 MEYIRREI 109

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 47086917  24 MRgpKKGD---VVKKRFVKLIVNFLFYFRTDEDEPI-GALLLEQCRVEREDLQV-------FSIVfLDEAERKYLFECDS 92
Cdd:cd13316   6 MK--KRGErygTWKTRYFVLKGTRLYYLKSENDDKEkGLIDLTGHRVVPDDSNSpfrgsygFKLV-PPAVPKVHYFAVDE 82

                        90
                ....*....|....*
gi 47086917  93 QEQCAEWIDAIIKAS 107
Cdd:cd13316  83 KEELREWMKALMKAT 97

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain; APPL (also called DCC-interacting protein (DIP)-13alpha) interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. 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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 47086917  53 DEPIGALLLE--QCRVEREDLQ----VFSIVFLDEaERKYLFECDSQEQCAEWIDAI 103
Cdd:cd13247  64 DEVAGSLVLDldNCSVQAADCEdrrnVFQITSPDG-KKAIVLQAESKKDYEEWIATI 119