Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 1907194282 1425 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1504
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 1907194282 1505 RLYYMVAPSAEAMRIWMDVIVTGAE 1529
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  783 ERSDEENLKEECSSTESTQQEHEDApGAKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEAAREAEMERALLQGER 862
Cdd:COG1196    258 LEAELAELEAELEELRLELEELELE-LEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELE 336

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  863 EAERASLQKEQRAVDQLQEKLVALETGIQKDRDKEADALETETKLFEDLEFQQLERESRVEEERELAG-----QGLLRSK 937
Cdd:COG1196    337 EELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEEleeaeEALLERL 416

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907194282  938 AELLRSVSKRKERLAVLDSQAGQIRAQAVQESERLAREKNAALQLLQKEKEKLNVLERR 996
Cdd:COG1196    417 ERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 1907194282 1425 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1504
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 1907194282 1505 RLYYMVAPSAEAMRIWMDVIVTGAE 1529
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

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 1907194282  1428 VCRGYLIKMG-GKIKSWKKRWFVFDRlkRTLSYYVDKHE---TKLKGVIYFQAIeEVYYDHLRSAAKSPNpalTFCVKTH 1503
Cdd:smart00233    2 IKEGWLYKKSgGGKKSWKKRYFVLFN--STLLYYKSKKDkksYKPKGSIDLSGC-TVREAPDPDSSKKPH---CFEIKTS 75

                            90       100
                    ....*....|....*....|..
gi 1907194282  1504 DR-LYYMVAPSAEAMRIWMDVI 1524
Cdd:smart00233   76 DRkTLLLQAESEEEREKWVEAL 97

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  783 ERSDEENLKEECSSTESTQQEHEDApGAKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEAAREAEMERALLQGER 862
Cdd:COG1196    258 LEAELAELEAELEELRLELEELELE-LEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELE 336

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  863 EAERASLQKEQRAVDQLQEKLVALETGIQKDRDKEADALETETKLFEDLEFQQLERESRVEEERELAG-----QGLLRSK 937
Cdd:COG1196    337 EELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEEleeaeEALLERL 416

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907194282  938 AELLRSVSKRKERLAVLDSQAGQIRAQAVQESERLAREKNAALQLLQKEKEKLNVLERR 996
Cdd:COG1196    417 ERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

PspA/IM30 family; This family includes PspA a protein that suppresses sigma54-dependent transcription. The PspA protein, a negative regulator of the Escherichia coli phage shock psp operon, is produced when virulence factors are exported through secretins in many Gram-negative pathogenic bacteria and its homolog in plants, VIPP1, plays a critical role in thylakoid biogenesis, essential for photosynthesis. Activation of transcription by the enhancer-dependent bacterial sigma(54) containing RNA polymerase occurs through ATP hydrolysis-driven protein conformational changes enabled by activator proteins that belong to the large AAA(+) mechanochemical protein family. It has been shown that PspA directly and specifically acts upon and binds to the AAA(+) domain of the PspF transcription activator.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  800 TQQEHEDApgakhQGEVLAVEEERAQVLG-------RVEQLKIRVKELEQQLQEA--------AREAEMERALLQGEREA 864
Cdd:pfam04012   27 LEQAIRDM-----QSELVKARQALAQTIArqkqlerRLEQQTEQAKKLEEKAQAAltkgneelAREALAEKKSLEKQAEA 101

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907194282  865 ERASLQKEQRAVDQLQEKLVALETGIQKDRDK 896
Cdd:pfam04012  102 LETQLAQQRSAVEQLRKQLAALETKIQQLKAK 133

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  653 RQSPRAQRKLSSGDLRVPIPRERKNSITE-ISDNEDELLEYHRRQRQERLREQEMERLERQRLETILNLCAEYSRAdggp 731
Cdd:TIGR02168  719 KELEELSRQISALRKDLARLEAEVEQLEErIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQL---- 794

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  732 eTGELPSIGEATAALALAGRRPSRGLAGAIVVSGRCGEESGGASQRLWESMERSdeENLKEECSSTEStQQEHEDAPGAK 811
Cdd:TIGR02168  795 -KEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQI--EELSEDIESLAA-EIEELEELIEE 870

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  812 HQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEA---AREAEMERALLQGEREAERASLQKEQRAVDQLQEKL----- 883
Cdd:TIGR02168  871 LESELEALLNERASLEEALALLRSELEELSEELRELeskRSELRRELEELREKLAQLELRLEGLEVRIDNLQERLseeys 950

                          250       260
                   ....*....|....*....|....*.
gi 1907194282  884 VALETGIQKDRDKEADALETETKLFE 909
Cdd:TIGR02168  951 LTLEEAEALENKIEDDEEEARRRLKR 976

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  817 LAVEEERAQVLGR-VEQLKIRVKELEQQLQEAAREAEMERALLQGEREAERASLQKEQRAVdqLQEKLVALETGIQKDRD 895
Cdd:cd16269    200 IEAERAKAEAAEQeRKLLEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERA--LESKLKEQEALLEEGFK 277

                   ....*....
gi 1907194282  896 KEADALETE 904
Cdd:cd16269    278 EQAELLQEE 286

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 1907194282 1425 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1504
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 1907194282 1505 RLYYMVAPSAEAMRIWMDVIVTGAE 1529
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

forkhead associated (FHA) domain found in kinesin-like protein KIF16B; KIF16B, also called sorting nexin-23, is a plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. It regulates the plus end motility of early endosomes and the balance between recycling and degradation of receptors such as EGF receptor (EGFR) and FGF receptor (FGFR). It regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  130 GLKVQTDKPHLVSLGSGRLSTAITLLPLEEGRTVIG----SAARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTID 204
Cdd:cd22732      1 GVVLDSELPHLIGIDDDLLSTGIILYHLKEGRTYVGrddaTTEQDIVLHGLDLESEHCIFENLNGTVTLIPLNGAqCSVN 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907194282  205 GLPVRQPTRLTQGCMLCLGQSTFLRFNHPAEA 236
Cdd:cd22732     81 GVQITEATQLNQGAVILLGRTNMFRFNHPKEA 112

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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 1907194282 1431 GYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVY-YDHLRSAAKSPNPALTFCVKTHDRLYYM 1509
Cdd:cd01235      7 GYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTpATPIIGAPKRADEGAFFDLKTNKRVYNF 86

                           90
                   ....*....|....*
gi 1907194282 1510 VAPSAEAMRIWMDVI 1524
Cdd:cd01235     87 CAFDAESAQQWIEKI 101

forkhead associated (FHA) domain found in the kinesin-like protein KIF1 family; The KIF1 family includes KIF1A, KIF1B, and KIF1C. KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. KIF1B, also called Klp, is a motor for anterograde transport of mitochondria. It has a microtubule plus end-directed motility. Isoform 1 mediates the transport of synaptic vesicles in neuronal cells, while isoform 2 is required for induction of neuronal apoptosis. KIF1C is a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum. It has a microtubule plus end-directed motility. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  138 PHLVSLGSGRLSTAITLLPLEEGRTVIGSA----ARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTIDGLPVRQPT 212
Cdd:cd22705      2 PHLVNLNEDPLMSECLLYYIKPGITRVGRAdadvPQDIQLSGTHILEEHCTFENEDGVVTLEPCEGAlTYVNGKRVTEPT 81

                           90       100
                   ....*....|....*....|
gi 1907194282  213 RLTQGCMLCLGQSTFLRFNH 232
Cdd:cd22705     82 RLKTGSRVILGKNHVFRFNH 101

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. 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 1907194282 1431 GYLIKMGGKIKSWKKRWFVFDrlKRTLSYYVDKHET--KLKGVIYFQAIEEVyydhlrsaAKSpNPALTFCVKTHDRLYY 1508
Cdd:cd13282      3 GYLTKLGGKVKTWKRRWFVLK--NGELFYYKSPNDVirKPQGQIALDGSCEI--------ARA-EGAQTFEIVTEKRTYY 71

                           90       100
                   ....*....|....*....|....
gi 1907194282 1509 MVAPSAEAMRIWMDVIVTGAEGYT 1532
Cdd:cd13282     72 LTADSENDLDEWIRVIQNVLRRQA 95

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. 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 1907194282 1428 VCRGYLIKMGGKIKSWKKRWFVFdRlKRTLSYYVDKHETKLKGVIYFQAIEEVYYdhLRSaAKSPNpalTFCVKTHDRLY 1507
Cdd:cd13298      7 LKSGYLLKRSRKTKNWKKRWVVL-R-PCQLSYYKDEKEYKLRRVINLSELLAVAP--LKD-KKRKN---VFGIYTPSKNL 78

                           90
                   ....*....|....*..
gi 1907194282 1508 YMVAPSAEAMRIWMDVI 1524
Cdd:cd13298     79 HFRATSEKDANEWVEAL 95

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 1907194282 1423 VLSSKvcRGYLIKMGGKIKSWKKRWFVfdrLKRT-LSYYVDKHETKLKGVIYFQAIEEVYYDHlrsaakSPNPALTFCVK 1501
Cdd:cd10573      1 SLGSK--EGYLTKLGGIVKNWKTRWFV---LRRNeLKYFKTRGDTKPIRVLDLRECSSVQRDY------SQGKVNCFCLV 69

                           90       100
                   ....*....|....*....|...
gi 1907194282 1502 THDRLYYMVAPSAEAMRIWMDVI 1524
Cdd:cd10573     70 FPERTFYMYANTEEEADEWVKLL 92

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 1907194282 1431 GYLIKMGGK-IKSWKKRWFVFDRlkRTLSYYVDKHE--TKLKGVIYFQAIEEVyydhlrSAAKSPNPALTFCVKT-HDRL 1506
Cdd:cd00821      3 GYLLKRGGGgLKSWKKRWFVLFE--GVLLYYKSKKDssYKPKGSIPLSGILEV------EEVSPKERPHCFELVTpDGRT 74

                           90
                   ....*....|....*...
gi 1907194282 1507 YYMVAPSAEAMRIWMDVI 1524
Cdd:cd00821     75 YYLQADSEEERQEWLKAL 92

forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  139 HLVSLGSGRLSTAItllPLEEGRTVIGSAAR-DISLQGPGLAPEHCYIENLRGTLTLYPCG--NACTIDGLPVRQPTRLT 215
Cdd:cd00060      1 RLIVLDGDGGGREF---PLTKGVVTIGRSPDcDIVLDDPSVSRRHARIEVDGGGVYLEDLGstNGTFVNGKRITPPVPLQ 77

                           90
                   ....*....|..
gi 1907194282  216 QGCMLCLGQSTF 227
Cdd:cd00060     78 DGDVIRLGDTTF 89

forkhead associated (FHA) domain found in afadin and similar proteins; Afadin, also called ALL1-fused gene from chromosome 6 protein, protein AF-6, Afadin adherens junction formation factor, or MLLT4, is a nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. It is essential for the organization of adherens junctions. It may play a key role in the organization of epithelial structures of the embryonic ectoderm. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  138 PHLVSLG-SGRLSTAITLLPLEEGRTVIGS------AARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA--CTIDGLPV 208
Cdd:cd22711      2 PYLLELSpDGSDRDKPRRHRLQPNVTEVGSerspanSGQFIQLFGPDILPRHCVITHMEGVVTVTPASQDaeTYVNGQRI 81

                           90       100
                   ....*....|....*....|....*
gi 1907194282  209 RQPTRLTQGCMLCLGQSTFLRFNHP 233
Cdd:cd22711     82 YETTMLQHGMVVQFGRSHTFRFCDP 106

forkhead associated (FHA) domain found in kinesin-like protein KIF28P and similar proteins; KIF28P, also called kinesin-like protein 6 (KLP6), is a microtubule-dependent motor protein required for mitochondrion morphology and transport of mitochondria in neuronal cells. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194282  138 PHLVSLGSGRLSTAITLLPLEEGRTVIGSAAR----DISLQGPGLAPEHCYIENLRGTLTLYPCGNACTI--DGLPVRQP 211
Cdd:cd22709      1 PHLLNLNEDPQLSGVIVHFLQEGETTIGRADAepepDIVLSGLSIQKQHAVITNTDGKVTIEPVSPGAKVivNGVPVTGE 80

                           90       100
                   ....*....|....*....|..
gi 1907194282  212 TRLTQGCMLCLGQSTFLRFNHP 233
Cdd:cd22709     81 TELHHLDRVILGSNHLYVFVGP 102

forkhead associated (FHA) domain found in the kinesin-like protein KIF13 family; The KIF13 family includes KIF13A and KIF13B. KIF13A, also called kinesin-like protein RBKIN, is a plus end-directed microtubule-dependent motor protein involved in intracellular transport and in regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis, and cytokinesis. It mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, KIF13A is required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. It is also required for the abscission step in cytokinesis: it mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. KIF13B, also called kinesin-like protein GAKIN, is a novel kinesin-like protein that associates with the human homolog of the Drosophila discs large tumor suppressor in T lymphocytes. It is involved in reorganization of the cortical cytoskeleton. It regulates axon formation by promoting the formation of extra axons. KIF13B may be functionally important for the intracellular trafficking of membrane-associated guanylate kinase homologs (MAGUKs) and associated protein complexes. The FHA domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907194282  160 GRTVIGSA----ARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTIDGLPVRQPTRLTQGCMLCLGQSTFLRFNHP 233
Cdd:cd22706     23 EHTLIGRSdaptQQDIQLSGLGIQPEHCIITIENEDVYLTPLEGArTCVNGSIVTEKTQLRHGDRILWGNNHFFRLNCP 101

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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 1907194282 1431 GYLIKMGGKIKSWKKRWFVFdRLKRtLSYYVDKHETKLKGVIYFQAIEEVYYDHLRsaaKSPNpalTFCVKTHDRLYYMV 1510
Cdd:cd13255     10 GYLEKKGERRKTWKKRWFVL-RPTK-LAYYKNDKEYRLLRLIDLTDIHTCTEVQLK---KHDN---TFGIVTPARTFYVQ 81

                           90
                   ....*....|....
gi 1907194282 1511 APSAEAMRIWMDVI 1524
Cdd:cd13255     82 ADSKAEMESWISAI 95

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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 1907194282 1431 GYLIKMGGKIKSWKKRWFVFDrlKRTLSYYVDKHETKLKGVIYFQAIeEVYYDHLRSAA------KSPNPALTFCVKT-- 1502
Cdd:cd01252      7 GWLLKLGGRVKSWKRRWFILT--DNCLYYFEYTTDKEPRGIIPLENL-SVREVEDKKKPfcfelySPSNGQVIKACKTds 83

                           90       100       110
                   ....*....|....*....|....*....|
gi 1907194282 1503 --------HDrLYYMVAPSAEAMRIWMDVI 1524
Cdd:cd01252     84 dgkvvegnHT-VYRISAASEEERDEWIKSI 112