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 578822079 1312 SSKVCRGYLVKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKkrffrftmvteSPN 1391
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAK-----------SPN 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 578822079 1392 PALTFCVKTHDRLYYMVAPSAEAMRIWMDVIVTGAE 1427
Cdd:cd14673    70 PALTFCVKTHDRLYYMVAPSPEAMRIWMDVIVTGAE 105

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  198 PGPPYSPVPAESESLVNGNHTPQTATRGPSACashsslvssiEKDLQEIMDSLVLEEPGAAGKKPAATSPLSPMANGGRy 277
Cdd:PHA03307   47 SAELAAVTVVAGAAACDRFEPPTGPPPGPGTE----------APANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPD- 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  278 llSPPTSPGAMSVGSSYENTSPAFSPLSSPASSGSCASHSPSGQEPGPSVPPLVPARSSSYHLALQPPQSRPSGARSESP 357
Cdd:PHA03307  116 --PPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEP 193

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  358 RLSRKGGHERPPSPGLR-------GLLTDSPAATVLAEARRATESPRLGGQLPVVAISLSEYPASGA--LSQPTSI--PG 426
Cdd:PHA03307  194 PPSTPPAAASPRPPRRSspisasaSSPAPAPGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPapITLPTRIweAS 273

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  427 SPKFQPPVPAPRNKIGTLQDRPPSPFREPPGSERVLTTSPSRQLVGRTFSDGL-ATRTLQPPESPRLGRRGLDSMRELPP 505
Cdd:PHA03307  274 GWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSsSTSSSSESSRGAAVSPGPSPSRSPSP 353

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  506 LSPSLSRRAlSPLPTRTTPDPKLNREVAESPRPRRWAAhGASPEDFSLTLGARGRRTRSPSPTLGESLAPHKGSFSGRLS 585
Cdd:PHA03307  354 SRPPPPADP-SSPRKRPRPSRAPSSPAASAGRPTRRRA-RAAVAGRARRRDATGRFPAGRPRPSPLDAGAASGAFYARYP 431

                  ....*..
gi 578822079  586 PAYSLGS 592
Cdd:PHA03307  432 LLTPSGE 438

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 578822079 1312 SSKVCRGYLVKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKkrffrftmvteSPN 1391
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAK-----------SPN 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 578822079 1392 PALTFCVKTHDRLYYMVAPSAEAMRIWMDVIVTGAE 1427
Cdd:cd14673    70 PALTFCVKTHDRLYYMVAPSPEAMRIWMDVIVTGAE 105

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  1315 VCRGYLVKMGGKIK-SWKKRWFVFDRlkRTLSYYVDK---HETKLKGVIYFQAIEEVYYDHLRSAAKKRFFRFTMVTesp 1390
Cdd:pfam00169    2 VKEGWLLKKGGGKKkSWKKRYFVLFD--GSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGE--- 76

                           90       100       110
                   ....*....|....*....|....*....|..
gi 578822079  1391 npaltfcvKTHDRLYYMVAPSAEAMRIWMDVI 1422
Cdd:pfam00169   77 --------RTGKRTYLLQAESEEERKDWIKAI 100

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 578822079   720 RLWESMER--SDEENLKEECSSTESTQQEHEDAPSTKLQgevlALEEERAQVLGHVEQLKvRVKELEQQLQESAREAEME 797
Cdd:TIGR02168  681 ELEEKIEEleEKIAELEKALAELRKELEELEEELEQLRK----ELEELSRQISALRKDLA-RLEAEVEQLEERIAQLSKE 755

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079   798 RALLQGEREAERALLQKEQKAVDQLQEKLVALETGIQK---ERDKERAELAAGRRHLEARQALYAELQTQLDNCPESVR- 873
Cdd:TIGR02168  756 LTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQlkeELKALREALDELRAELTLLNEEAANLRERLESLERRIAa 835

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079   874 -----EQLQEQLRREAEALETETKLFEDLEfqqleresRVEEERELAGQGLLRSKAELLRSIAKRKERLAILDSQAGQIR 948
Cdd:TIGR02168  836 terrlEDLEEQIEELSEDIESLAAEIEELE--------ELIEELESELEALLNERASLEEALALLRSELEELSEELRELE 907

                          250       260       270
                   ....*....|....*....|....*....|
gi 578822079   949 aQAVQESERLARDKNASLQLLQKEKEKLTV 978
Cdd:TIGR02168  908 -SKRSELRRELEELREKLAQLELRLEGLEV 936

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 578822079   741 ESTQQEHEDApSTKLQGEVLALEEERAQVLGHVEQLKVRVKE-LEQQLQESAREAEMERALLQGEREAERALLQKEQKAV 819
Cdd:pfam04012   35 QSELVKARQA-LAQTIARQKQLERRLEQQTEQAKKLEEKAQAaLTKGNEELAREALAEKKSLEKQAEALETQLAQQRSAV 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079   820 DQLQEKLVALETGIQKERDKERAELAAgrrhlEARQALYAELQTQLDNC-PESVREQLQE----QLRREAEAL---ETET 891
Cdd:pfam04012  114 EQLRKQLAALETKIQQLKAKKNLLKAR-----LKAAKAQEAVQTSLGSLsTSSATDSFERieekIEEREARADaaaELAS 188

                          170
                   ....*....|.
gi 578822079   892 KLFEDLEFQQL 902
Cdd:pfam04012  189 AVDLDAKLEQA 199

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  731 ENLKEECSSTESTQQ---EHEDAPSTKLQgEVLALEEERAQVLGHVEQLKVRVKELEqQLQESAREAEMERALLQGEREA 807
Cdd:PRK03918  179 ERLEKFIKRTENIEElikEKEKELEEVLR-EINEISSELPELREELEKLEKEVKELE-ELKEEIEELEKELESLEGSKRK 256

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  808 ERALLQKEQKAVDQLQEKLVALETGIQ----------------KERDKERAELAAGRRHLEARQALYAELQTQLDNCPES 871
Cdd:PRK03918  257 LEEKIRELEERIEELKKEIEELEEKVKelkelkekaeeyiklsEFYEEYLDELREIEKRLSRLEEEINGIEERIKELEEK 336

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  872 VRE-----QLQEQLRREAEALETETKLFEDL-----EFQQLERESRVEEERELAG--QGLLRSKAELLRSIAKRKERLAI 939
Cdd:PRK03918  337 EERleelkKKLKELEKRLEELEERHELYEEAkakkeELERLKKRLTGLTPEKLEKelEELEKAKEEIEEEISKITARIGE 416

                         250
                  ....*....|....*
gi 578822079  940 LDSQAGQIRAqAVQE 954
Cdd:PRK03918  417 LKKEIKELKK-AIEE 430

Uncharacterized family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes an uncharacterized family of proteins similar to stomatin, prohibitin, flotillin, HflK/C (SPFH) and podocin. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Many superfamily members are associated with lipid rafts. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Microdomains formed from flotillin proteins may in addition be dynamic units with their own regulatory functions. Flotillins have been implicated in signal transduction, vesicle trafficking, cytoskeleton rearrangement and are known to interact with a variety of proteins. Stomatin interacts with and regulates members of the degenerin/epithelia Na+ channel family in mechanosensory cells of Caenorhabditis elegans and vertebrate neurons and participates in trafficking of Glut1 glucose transporters. Prohibitin may act as a chaperone for the stabilization of mitochondrial proteins. Prokaryotic HflK/C plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection. Flotillins have been implicated in the progression of prion disease, in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's disease and, in cancer invasion and metastasis. Mutations in the podocin gene give rise to autosomal recessive steroid resistant nephritic syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  761 ALEEERAQVLghveqlkvrVKELEQQLQEsaREAEMER--ALLQGEREAERALLQKEQKAVDQLQEKLVAL---ETGIQK 835
Cdd:cd03406   170 AMEAEKTKLL---------IAEQHQKVVE--KEAETERkrAVIEAEKDAEVAKIQMQQKIMEKEAEKKISEiedEMHLAR 238

                          90       100       110
                  ....*....|....*....|....*....|.
gi 578822079  836 ERDKERAELAAGRRHLEARQAL----YAELQ 862
Cdd:cd03406   239 EKARADAEYYRALREAEANKLKltpeYLELK 269

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079    768 QVLGHVEQLKVRVKELEQQLQESAREAEMERALLQGERE---AERALLQKEQKAvdQLQEKLVALETGIQKERDKERAEL 844
Cdd:smart00935    8 KILQESPAGKAAQKQLEKEFKKRQAELEKLEKELQKLKEklqKDAATLSEAARE--KKEKELQKKVQEFQRKQQKLQQDL 85

                            90
                    ....*....|....*....
gi 578822079    845 AagRRHLEARQALYAELQT 863
Cdd:smart00935   86 Q--KRQQEELQKILDKINK 102

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 578822079 1312 SSKVCRGYLVKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEVYYDHLRSAAKkrffrftmvteSPN 1391
Cdd:cd14673     1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAK-----------SPN 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 578822079 1392 PALTFCVKTHDRLYYMVAPSAEAMRIWMDVIVTGAE 1427
Cdd:cd14673    70 PALTFCVKTHDRLYYMVAPSPEAMRIWMDVIVTGAE 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 578822079   78 GLKVQTDKPHLVSLGSGRLSTAITLLPLEEGRTVIG----SAARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTID 152
Cdd:cd22732     1 GVVLDSELPHLIGIDDDLLSTGIILYHLKEGRTYVGrddaTTEQDIVLHGLDLESEHCIFENLNGTVTLIPLNGAqCSVN 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 578822079  153 GLPVRQPTRLTQGCMLCLGQSTFLRFNHPAEA 184
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 578822079 1318 GYLVKMGGKIKSWKKRWFVFDRLKRTLSYYVDKHETKLKGVIYFQAIEEV-----YYDHLRSAAKKRFFRftmvtespnp 1392
Cdd:cd01235     7 GYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVtpatpIIGAPKRADEGAFFD---------- 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 578822079 1393 altfcVKTHDRLYYMVAPSAEAMRIWMDVI 1422
Cdd:cd01235    77 -----LKTNKRVYNFCAFDAESAQQWIEKI 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 578822079   86 PHLVSLGSGRLSTAITLLPLEEGRTVIGSA----ARDISLQGPGLAPEHCYIENLRGTLTLYPCGNA-CTIDGLPVRQPT 160
Cdd:cd22705     2 PHLVNLNEDPLMSECLLYYIKPGITRVGRAdadvPQDIQLSGTHILEEHCTFENEDGVVTLEPCEGAlTYVNGKRVTEPT 81

                          90       100
                  ....*....|....*....|
gi 578822079  161 RLTQGCMLCLGQSTFLRFNH 180
Cdd:cd22705    82 RLKTGSRVILGKNHVFRFNH 101

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. 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 578822079 1315 VCRGYLVKM--GGKIK--SWKKRWFVFDRLKRT-----LSYYVDKHETKLKGVIYFQAIEEVyyDHLRSAAKKRFfRFTM 1385
Cdd:cd13324     2 VYEGWLTKSppEKKIWraAWRRRWFVLRSGRLSggqdvLEYYTDDHCKKLKGIIDLDQCEQV--DAGLTFEKKKF-KNQF 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 578822079 1386 VtespnpaltFCVKTHDRLYYMVAPSAEAMRIWMDVI 1422
Cdd:cd13324    79 I---------FDIRTPKRTYYLVAETEEEMNKWVRCI 106

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  1315 VCRGYLVKMGGKIK-SWKKRWFVFDRlkRTLSYYVDK---HETKLKGVIYFQAIEEVYYDHLRSAAKKRFFRFTMVTesp 1390
Cdd:pfam00169    2 VKEGWLLKKGGGKKkSWKKRYFVLFD--GSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGE--- 76

                           90       100       110
                   ....*....|....*....|....*....|..
gi 578822079  1391 npaltfcvKTHDRLYYMVAPSAEAMRIWMDVI 1422
Cdd:pfam00169   77 --------RTGKRTYLLQAESEEERKDWIKAI 100

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 578822079 1318 GYLVKMGGKIKSWKKRWFVFDrlKRTLSYYVDKHET--KLKGVIYFQAIEEVyydhlrsaakkrffrftmvtESPNPALT 1395
Cdd:cd13282     3 GYLTKLGGKVKTWKRRWFVLK--NGELFYYKSPNDVirKPQGQIALDGSCEI--------------------ARAEGAQT 60

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 578822079 1396 FCVKTHDRLYYMVAPSAEAMRIWMDVIVTGAEGYT 1430
Cdd:cd13282    61 FEIVTEKRTYYLTADSENDLDEWIRVIQNVLRRQA 95

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  760 LALEEERAQV---LGHVEQLKVRVKELEQQLQESAREAEMERALLQgEREAERAL----LQKEQKAVDQLQEKLVALETG 832
Cdd:COG1196   218 LKEELKELEAellLLKLRELEAELEELEAELEELEAELEELEAELA-ELEAELEElrleLEELELELEEAQAEEYELLAE 296

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  833 IQKERdKERAELAAGRRHLEARQALYAELQTQLdncpESVREQLQEQLRREAEALETETKLFEDLEfQQLERESRVEEER 912
Cdd:COG1196   297 LARLE-QDIARLEERRRELEERLEELEEELAEL----EEELEELEEELEELEEELEEAEEELEEAE-AELAEAEEALLEA 370

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578822079  913 ELAGQGLLRSKAELLRSIAKRKERLAILDSQAGQIRAQAVQESERLARDKNASLQLLQKEKEKLTVLER 981
Cdd:COG1196   371 EAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEE 439

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 578822079 1310 VLSSKvcRGYLVKMGGKIKSWKKRWFVfdrLKRT-LSYYVDKHETKLKGVIYFQAIEEVYYDHlrsaakkrffrftmvte 1388
Cdd:cd10573     1 SLGSK--EGYLTKLGGIVKNWKTRWFV---LRRNeLKYFKTRGDTKPIRVLDLRECSSVQRDY----------------- 58

                          90       100       110
                  ....*....|....*....|....*....|....
gi 578822079 1389 SPNPALTFCVKTHDRLYYMVAPSAEAMRIWMDVI 1422
Cdd:cd10573    59 SQGKVNCFCLVFPERTFYMYANTEEEADEWVKLL 92

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 578822079   720 RLWESMER--SDEENLKEECSSTESTQQEHEDAPSTKLQgevlALEEERAQVLGHVEQLKvRVKELEQQLQESAREAEME 797
Cdd:TIGR02168  681 ELEEKIEEleEKIAELEKALAELRKELEELEEELEQLRK----ELEELSRQISALRKDLA-RLEAEVEQLEERIAQLSKE 755

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079   798 RALLQGEREAERALLQKEQKAVDQLQEKLVALETGIQK---ERDKERAELAAGRRHLEARQALYAELQTQLDNCPESVR- 873
Cdd:TIGR02168  756 LTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQlkeELKALREALDELRAELTLLNEEAANLRERLESLERRIAa 835

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079   874 -----EQLQEQLRREAEALETETKLFEDLEfqqleresRVEEERELAGQGLLRSKAELLRSIAKRKERLAILDSQAGQIR 948
Cdd:TIGR02168  836 terrlEDLEEQIEELSEDIESLAAEIEELE--------ELIEELESELEALLNERASLEEALALLRSELEELSEELRELE 907

                          250       260       270
                   ....*....|....*....|....*....|
gi 578822079   949 aQAVQESERLARDKNASLQLLQKEKEKLTV 978
Cdd:TIGR02168  908 -SKRSELRRELEELREKLAQLELRLEGLEV 936

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  726 ERSDEENLKEECSSTESTQQEHEDApSTKLQGEVLALEEERAQVLGHVEQLKVRVKELEQQLQESAREAEMERALLQGER 805
Cdd:COG1196   314 LEERLEELEEELAELEEELEELEEE-LEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEAL 392

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  806 EAERALLQKEQKAVDQLQEKLVALETGIQKERDKERAELAAGRRHLEARQALYAELQTQLDncpesvREQLQEQLRREAE 885
Cdd:COG1196   393 RAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAE------LEEEEEALLELLA 466

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578822079  886 ALETETKLFEDLEfQQLERESRVEEERELAGQGLLRSKAELLRSI-AKRKERLAILDSQAGQIRAQAVQESERLARD 961
Cdd:COG1196   467 ELLEEAALLEAAL-AELLEELAEAAARLLLLLEAEADYEGFLEGVkAALLLAGLRGLAGAVAVLIGVEAAYEAALEA 542

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  773 VEQLKVRVKELEQQ---------LQESAREAEMERALLQGE-REAERALLQKEQKAVDQLQEKLVALETGIQKERDKERA 842
Cdd:COG1196   195 LGELERQLEPLERQaekaeryreLKEELKELEAELLLLKLReLEAELEELEAELEELEAELEELEAELAELEAELEELRL 274

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822079  843 ELAAGRRHLEARQALYAELQTQLdncpesvrEQLQEQLRREAEALETETKlfedlEFQQLERESRV-EEERELAGQGLLR 921
Cdd:COG1196   275 ELEELELELEEAQAEEYELLAEL--------ARLEQDIARLEERRRELEE-----RLEELEEELAElEEELEELEEELEE 341

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578822079  922 SKAELLRSIAKRKERLAILDSQAGQIRAQAVQESERLARDKNASLQLLQKEKEKLTVLERR 982
Cdd:COG1196   342 LEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQL 402