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 350535667   1 MRFNNKEMIHVSHSNPVLEGRMSYAKMSNGYASKGFKERWFRLKYNLLFYFKINGFGqvDLHQPAGVFVLENSIVRLENN 80
Cdd:cd13258    1 MRFNEKELAALSSQPAEKEGKIAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEFG--DCSEPIGAIVLENCRVQMEEI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 350535667  81 TPgTLFSFSLSFKDEPDKKYIISSQSEDHVHQWIKCIQSSTYEYMR 126
Cdd:cd13258   79 TE-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 350535667   1 MRFNNKEMIHVSHSNPVLEGRMSYAKMSNGYASKGFKERWFRLKYNLLFYFKINGFGqvDLHQPAGVFVLENSIVRLENN 80
Cdd:cd13258    1 MRFNEKELAALSSQPAEKEGKIAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEFG--DCSEPIGAIVLENCRVQMEEI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 350535667  81 TPgTLFSFSLSFKDEPDKKYIISSQSEDHVHQWIKCIQSSTYEYMR 126
Cdd:cd13258   79 TE-KPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASYEYLR 123

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 350535667    33 SKGFKERWFRLKYNLLFYFKINgfGQVDLHQPAGVFVLENSIVRL--ENNTPGTLFSFSLSFKDEpdKKYIISSQSEDHV 110
Cdd:smart00233  15 KKSWKKRYFVLFNSTLLYYKSK--KDKKSYKPKGSIDLSGCTVREapDPDSSKKPHCFEIKTSDR--KTLLLQAESEEER 90

                           90
                   ....*....|..
gi 350535667   111 HQWIKCIQSSTY 122
Cdd:smart00233  91 EKWVEALRKAIA 102

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 350535667   1 MRFNNKEMIHVSHSNPVLEGRMSYAKMSNGYASKGFKERWFRLKYNLLFYFKINGFGqvDLHQPAGVFVLENSIVRLENN 80
Cdd:cd13258    1 MRFNEKELAALSSQPAEKEGKIAERQMGGPKKSEVFKERWFKLKGNLLFYFRTNEFG--DCSEPIGAIVLENCRVQMEEI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 350535667  81 TPgTLFSFSLSFKDEPDKKYIISSQSEDHVHQWIKCIQSSTYEYMR 126
Cdd:cd13258   79 TE-KPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALRQASYEYLR 123

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single 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 350535667  34 KGFKERWFRLKYNLLFYFKingfGQVDlHQPAGVFVLENSIVRLENNtpGTLFSFSLSFKDEPDKKYIISSQSEDHVHQW 113
Cdd:cd13288   22 TSYQKRWFVLKGNLLFYFE----KKGD-REPLGVIVLEGCTVELAED--AEPYAFAIRFDGPGARSYVLAAENQEDMESW 94

                         90       100
                 ....*....|....*....|....*.
gi 350535667 114 IKCIQSSTYEYMRTRMTSIQKKIVEL 139
Cdd:cd13288   95 MKALSRASYDYLRLTVEELEKQLEEL 120

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350535667   21 RMSYAKMSNGYASKGFKERWFRLKYNLLFYFKINGFGQvdLHQPAGVFVLENSIV--RLENNTPGTLFSFSLSFKDE-PD 97
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGK--SKEPKGSISLSGCEVveVVASDSPKRKFCFELRTGERtGK 80

                          90       100
                  ....*....|....*....|....*
gi 350535667   98 KKYIISSQSEDHVHQWIKCIQSSTY 122
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105

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 350535667  30 GYASKGFKERWFRLKYNLLFYFKINgfgQVDLHQPAGVFVLENSIVRLENNTPGTLFSFSLSFKDEpdKKYIISSQSEDH 109
Cdd:cd00821   10 GGGLKSWKKRWFVLFEGVLLYYKSK---KDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDG--RTYYLQADSEEE 84

                 ....*...
gi 350535667 110 VHQWIKCI 117
Cdd:cd00821   85 RQEWLKAL 92

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350535667  30 GYASKGFKERWFRLKYNLLFYFKingfGQVDLhQPAGVFVLENSIVRLENNTPGTLFSFSLSFkdePDKKYIISSQSEDH 109
Cdd:cd10573   13 GGIVKNWKTRWFVLRRNELKYFK----TRGDT-KPIRVLDLRECSSVQRDYSQGKVNCFCLVF---PERTFYMYANTEEE 84

                         90
                 ....*....|
gi 350535667 110 VHQWIKCIQS 119
Cdd:cd10573   85 ADEWVKLLKW 94

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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 350535667  27 MSNGYASKGFKERWFRLKYNLLFYFKINgfgqvDLHQPAGVFVL-ENSIVRLENNTPGTLFSFSLSfkdEPDKKYIISSQ 105
Cdd:cd13273   15 WKKGHLLPTWTERWFVLKPNSLSYYKSE-----DLKEKKGEIALdSNCCVESLPDREGKKCRFLVK---TPDKTYELSAS 86

                         90
                 ....*....|....
gi 350535667 106 SEDHVHQWIKCIQS 119
Cdd:cd13273   87 DHKTRQEWIAAIQT 100