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 38455422 1260 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1339
Cdd:cd14673    1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                         90       100
                 ....*....|....*....|....*
gi 38455422 1340 RLYYMVAPSAEAMRIWMDVIVTGAE 1364
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 38455422  685 ERSDEENLKEECSSTESTQQEHEDAPGAKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEAA---REAEMERALLQ 761
Cdd:COG1196  285 EAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEeelEEAEAELAEAE 364

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  762 GEREAERASLQKEQRAVDQLQEKLVALETGIQKDRDKEADALETETKLFEDLEfqQLERESRVEEERELAGQGLLRSKAE 841
Cdd:COG1196  365 EALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLE--RLEEELEELEEALAELEEEEEEEEE 442

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  842 LLRSVSKRKERLAVLDSQAGQIRAQAVQESERLAREKNAALQLLQKEKEKLNVLERRYHSlTGGRPFPKTTSTLKEMEKL 921
Cdd:COG1196  443 ALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEAD-YEGFLEGVKAALLLAGLRG 521

                        250
                 ....*....|
gi 38455422  922 LLPAVDLEQW 931
Cdd:COG1196  522 LAGAVAVLIG 531

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 38455422 1260 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1339
Cdd:cd14673    1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                         90       100
                 ....*....|....*....|....*
gi 38455422 1340 RLYYMVAPSAEAMRIWMDVIVTGAE 1364
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 38455422    1263 VCRGYLIKMG-GKIKSWKKRWFVFDRlkRTLSYYVDKHE---TKLKGVIYFQAIeEVYYDHLRSAAKSPNpalTFCVKTH 1338
Cdd:smart00233    2 IKEGWLYKKSgGGKKSWKKRYFVLFN--STLLYYKSKKDkksYKPKGSIDLSGC-TVREAPDPDSSKKPH---CFEIKTS 75

                            90       100
                    ....*....|....*....|..
gi 38455422    1339 DR-LYYMVAPSAEAMRIWMDVI 1359
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 38455422  685 ERSDEENLKEECSSTESTQQEHEDAPGAKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEAA---REAEMERALLQ 761
Cdd:COG1196  285 EAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEeelEEAEAELAEAE 364

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  762 GEREAERASLQKEQRAVDQLQEKLVALETGIQKDRDKEADALETETKLFEDLEfqQLERESRVEEERELAGQGLLRSKAE 841
Cdd:COG1196  365 EALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLE--RLEEELEELEEALAELEEEEEEEEE 442

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  842 LLRSVSKRKERLAVLDSQAGQIRAQAVQESERLAREKNAALQLLQKEKEKLNVLERRYHSlTGGRPFPKTTSTLKEMEKL 921
Cdd:COG1196  443 ALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEAD-YEGFLEGVKAALLLAGLRG 521

                        250
                 ....*....|
gi 38455422  922 LLPAVDLEQW 931
Cdd:COG1196  522 LAGAVAVLIG 531

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 38455422    702 TQQEHEDApgakhQGEVLAVEEERAQVLG-------RVEQLKIRVKELEQQLQEA--------AREAEMERALLQGEREA 766
Cdd:pfam04012   27 LEQAIRDM-----QSELVKARQALAQTIArqkqlerRLEQQTEQAKKLEEKAQAAltkgneelAREALAEKKSLEKQAEA 101

                           90       100       110
                   ....*....|....*....|....*....|..
gi 38455422    767 ERASLQKEQRAVDQLQEKLVALETGIQKDRDK 798
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 38455422    555 RQSPRAQRKLSSGDLRVPIPRERKNSITE-ISDNEDELLEYHRRQRQERLREQEMERLERQRLETILNLCAEYSRAdggp 633
Cdd:TIGR02168  719 KELEELSRQISALRKDLARLEAEVEQLEErIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQL---- 794

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422    634 eTGELPSIGEATAALALAGRRPSRGLAGAIVVSGRCGEESGGASQRLWESMERSdeENLKEECSSTEStQQEHEDAPGAK 713
Cdd:TIGR02168  795 -KEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQI--EELSEDIESLAA-EIEELEELIEE 870

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422    714 HQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEA---AREAEMERALLQGEREAERASLQKEQRAVDQLQEKL----- 785
Cdd:TIGR02168  871 LESELEALLNERASLEEALALLRSELEELSEELRELeskRSELRRELEELREKLAQLELRLEGLEVRIDNLQERLseeys 950

                          250       260
                   ....*....|....*....|....*.
gi 38455422    786 VALETGIQKDRDKEADALETETKLFE 811
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 38455422  719 LAVEEERAQVLGR-VEQLKIRVKELEQQLQEAAREAEMERALLQGEREAERASLQKEQRAVdqLQEKLVALETGIQKDRD 797
Cdd:cd16269  200 IEAERAKAEAAEQeRKLLEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERA--LESKLKEQEALLEEGFK 277

                 ....*....
gi 38455422  798 KEADALETE 806
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 38455422 1260 SSKVCRGYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 1339
Cdd:cd14673    1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                         90       100
                 ....*....|....*....|....*
gi 38455422 1340 RLYYMVAPSAEAMRIWMDVIVTGAE 1364
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 38455422   32 GLKVQTDKPHLVSLGSGRLSTAITLLPLEEGRTVIG----SAARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTID 106
Cdd:cd22732    1 GVVLDSELPHLIGIDDDLLSTGIILYHLKEGRTYVGrddaTTEQDIVLHGLDLESEHCIFENLNGTVTLIPLNGAqCSVN 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 38455422  107 GLPVRQPTRLTQGCMLCLGQSTFLRFNHPAEA 138
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 38455422 1266 GYLIKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVY-YDHLRSAAKSPNPALTFCVKTHDRLYYM 1344
Cdd:cd01235    7 GYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTpATPIIGAPKRADEGAFFDLKTNKRVYNF 86

                         90
                 ....*....|....*
gi 38455422 1345 VAPSAEAMRIWMDVI 1359
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 38455422   40 PHLVSLGSGRLSTAITLLPLEEGRTVIGSA----ARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTIDGLPVRQPT 114
Cdd:cd22705    2 PHLVNLNEDPLMSECLLYYIKPGITRVGRAdadvPQDIQLSGTHILEEHCTFENEDGVVTLEPCEGAlTYVNGKRVTEPT 81

                         90       100
                 ....*....|....*....|
gi 38455422  115 RLTQGCMLCLGQSTFLRFNH 134
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 38455422 1266 GYLIKMGGKIKSWKKRWFVFDrlKRTLSYYVDKHET--KLKGVIYFQAIEEVyydhlrsaAKSpNPALTFCVKTHDRLYY 1343
Cdd:cd13282    3 GYLTKLGGKVKTWKRRWFVLK--NGELFYYKSPNDVirKPQGQIALDGSCEI--------ARA-EGAQTFEIVTEKRTYY 71

                         90       100
                 ....*....|....*....|....
gi 38455422 1344 MVAPSAEAMRIWMDVIVTGAEGYT 1367
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 38455422 1263 VCRGYLIKMGGKIKSWKKRWFVFdRlKRTLSYYVDKHETKLKGVIYFQAIEEVYYdhLRSaAKSPNpalTFCVKTHDRLY 1342
Cdd:cd13298    7 LKSGYLLKRSRKTKNWKKRWVVL-R-PCQLSYYKDEKEYKLRRVINLSELLAVAP--LKD-KKRKN---VFGIYTPSKNL 78

                         90
                 ....*....|....*..
gi 38455422 1343 YMVAPSAEAMRIWMDVI 1359
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 38455422 1258 VLSSKvcRGYLIKMGGKIKSWKKRWFVfdrLKRT-LSYYVDKHETKLKGVIYFQAIEEVYYDHlrsaakSPNPALTFCVK 1336
Cdd:cd10573    1 SLGSK--EGYLTKLGGIVKNWKTRWFV---LRRNeLKYFKTRGDTKPIRVLDLRECSSVQRDY------SQGKVNCFCLV 69

                         90       100
                 ....*....|....*....|...
gi 38455422 1337 THDRLYYMVAPSAEAMRIWMDVI 1359
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 38455422 1266 GYLIKMGGK-IKSWKKRWFVFDRlkRTLSYYVDKHE--TKLKGVIYFQAIEEVyydhlrSAAKSPNPALTFCVKT-HDRL 1341
Cdd:cd00821    3 GYLLKRGGGgLKSWKKRWFVLFE--GVLLYYKSKKDssYKPKGSIPLSGILEV------EEVSPKERPHCFELVTpDGRT 74

                         90
                 ....*....|....*...
gi 38455422 1342 YYMVAPSAEAMRIWMDVI 1359
Cdd:cd00821   75 YYLQADSEEERQEWLKAL 92

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  685 ERSDEENLKEECSSTESTQQEHEDApGAKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQLQEAAREAEMERALLQGER 764
Cdd:COG1196  258 LEAELAELEAELEELRLELEELELE-LEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELE 336

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  765 EAERASLQKEQRAVDQLQEKLVALETGIQKDRDKEADALETETKLFEDLEFQQLERESRVEEERELAG-----QGLLRSK 839
Cdd:COG1196  337 EELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEEleeaeEALLERL 416

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 38455422  840 AELLRSVSKRKERLAVLDSQAGQIRAQAVQESERLAREKNAALQLLQKEKEKLNVLERR 898
Cdd:COG1196  417 ERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

forkhead associated (FHA) domain found in kinesin-like protein KIF1B; 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. 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 38455422   40 PHLVSLGSGRLSTAITLLPLEEGRTVIGSA----ARDISLQGPGLAPEHCY-----IENLRGTLTLYPCGNACT-IDGLP 109
Cdd:cd22727    3 PHLVNLNEDPLMSECLLYYIKDGITRVGQAdaerRQDIVLSGAHIKEEHCIfrserNNNGEVIVTLEPCERSETyVNGKR 82

                         90       100
                 ....*....|....*....|....*...
gi 38455422  110 VRQPTRLTQGCMLCLGQSTFLRFNHPAE 137
Cdd:cd22727   83 VVQPVQLRSGNRIIMGKNHVFRFNHPEQ 110

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  712 AKHQGEVLAVEEERAQVLGRVEQLKIRVKELEQQL---QEAAREAEMERALLQGEREAERASLQKEQRAVDQLQEKLVAL 788
Cdd:COG1196  249 EELEAELEELEAELAELEAELEELRLELEELELELeeaQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAEL 328

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38455422  789 ETGIQKDRDKEADALETETKLFEDLEfqqleresrveeereLAGQGLLRSKAELLRSVSKRKERLAVLDSQAGQIRAQAV 868
Cdd:COG1196  329 EEELEELEEELEELEEELEEAEEELE---------------EAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALR 393

                        170       180       190
                 ....*....|....*....|....*....|
gi 38455422  869 QESERLAREKNAALQLLQKEKEKLNVLERR 898
Cdd:COG1196  394 AAAELAAQLEELEEAEEALLERLERLEEEL 423

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 38455422   40 PHLVSLGSGRLSTAITLLPLEEGRTVIGSAAR----DISLQGPGLAPEHCYIENLRGTLTLYPCGNACTI--DGLPVRQP 113
Cdd:cd22709    1 PHLLNLNEDPQLSGVIVHFLQEGETTIGRADAepepDIVLSGLSIQKQHAVITNTDGKVTIEPVSPGAKVivNGVPVTGE 80

                         90       100
                 ....*....|....*....|..
gi 38455422  114 TRLTQGCMLCLGQSTFLRFNHP 135
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 38455422   62 GRTVIGSA----ARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTIDGLPVRQPTRLTQGCMLCLGQSTFLRFNHP 135
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 38455422 1266 GYLIKMGGKIKSWKKRWFVFdRLKRtLSYYVDKHETKLKGVIYFQAIEEVYYDHLRsaaKSPNpalTFCVKTHDRLYYMV 1345
Cdd:cd13255   10 GYLEKKGERRKTWKKRWFVL-RPTK-LAYYKNDKEYRLLRLIDLTDIHTCTEVQLK---KHDN---TFGIVTPARTFYVQ 81