NCBI Conserved Domain Search

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

19-171

6.27e-07

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 54.17 E-value: 6.27e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   19 LTLETQLFRFRLQASKIRELLAD------KMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLK---NVDSEGSLHRKY 89
Cdd:COG1196   218 LKEELKELEAELLLLKLRELEAEleeleaELEELEAELEELEAELAELEAELEELRLELEELELEleeAQAEEYELLAEL 297

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   90 QELLKAIKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEW---VTLKLAKLEMENQHLKSHNQRLVEQVGSLQDA 166
Cdd:COG1196   298 ARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELeeeLEEAEEELEEAEAELAEAEEALLEAEAELAEA 377


                  ....*
gi 767981142  167 LEAIQ 171
Cdd:COG1196   378 EEELE 382

PH_GPBP

cd13283

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...

581-669

7.38e-07

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 270100 [Multi-domain] Cd Length: 100 Bit Score: 48.82 E-value: 7.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVDLnsRCQIV--------RgegsqtFQLISEKKTYYL 652
Cdd:cd13283     1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISL--SKAVIkphefdecR------FDVSVNDSVWYL 72

                          90
                  ....*....|....*..
gi 767981142  653 TADSPSLLEEWIRVLQS 669
Cdd:cd13283    73 RAESPEERQRWIDALES 89

PH_ORP3_ORP6_ORP7

cd13287

Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; ...

577-668

7.89e-07

Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; Human ORP3 is proposed to function in regulating the cell-matrix and cell-cell adhesion. A proposed specific function for Human ORP6 was not found at present. Human ORP7is proposed to function in negatively regulating the Golgi soluble NSF attachment protein receptor (SNARE) of 28kDa (GS28) protein stability via sequestration of Golgi-associated ATPase enhancer of 16 kDa (GATE-16). ORP3 has 2 isoforms: the longer ORP3(1) and the shorter ORP3(2). ORP3(1), ORP6, and ORP7 all contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. The shorter ORP3(2) is missing the C-terminal portion of its OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 270104 Cd Length: 123 Bit Score: 49.25 E-value: 7.89e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  577 ESLEKSGYLLKMGSQ-VKTWKRRWFVLRQGQIMYYKSPSDVIR-KPQGQVDLNSRCQIVRGEgSQTFQLISEKKTYYLTA 654
Cdd:cd13287    20 EPGKQEGYLLKKRKWpLKGWHKRFFVLEKGILKYAKSPLDIAKgKLHGSIDVGLSVMSIKKK-ARRIDLDTEEFIYHLKV 98

                          90
                  ....*....|....
gi 767981142  655 DSPSLLEEWIRVLQ 668
Cdd:cd13287    99 KSQDLFDSWVAKLR 112

COG4372

Uncharacterized protein, contains DUF3084 domain [Function unknown];

21-171

8.22e-07

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 52.98 E-value: 8.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   21 LETQLFRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLHRKYQELLKAIKGKD 100
Cdd:COG4372     4 LGEKVGKARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELE 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767981142  101 ELISQLEAQLEKQKQMRaEEAKTVQEKAAKIKEwvtlKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4372    84 ELNEQLQAAQAELAQAQ-EELESLQEEAEELQE----ELEELQKERQDLEQQRKQLEAQIAELQSEIAERE 149

COG4372

Uncharacterized protein, contains DUF3084 domain [Function unknown];

15-179

1.36e-06

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 52.21 E-value: 1.36e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   15 QKRCLTLETQLFRFRLQASKIRELLA---DKMQELEQRLLEAEQRAENAETQVGVMEEKvklsnLKNVDSEgslhrkyqe 91
Cdd:COG4372    44 QEELEQLREELEQAREELEQLEEELEqarSELEQLEEELEELNEQLQAAQAELAQAQEE-----LESLQEE--------- 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   92 llkaikgKDELISQLEaQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKlaklEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4372   110 -------AEELQEELE-ELQKERQDLEQQRKQLEAQIAELQSEIAER----EEELKELEEQLESLQEELAALEQELQALS 177


                  ....*...
gi 767981142  172 IAPSRKLL 179
Cdd:COG4372   178 EAEAEQAL 185

Mplasa_alph_rch

TIGR04523

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...

22-171

1.67e-06

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 52.72 E-value: 1.67e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    22 ETQLFRFRLQASKIRELLADKMQELEQrlleAEQRAENAETQVGvmEEKVKLSNLKNVDSEGsLHRKYQELLKAIKGK-- 99
Cdd:TIGR04523  252 QTQLNQLKDEQNKIKKQLSEKQKELEQ----NNKKIKELEKQLN--QLKSEISDLNNQKEQD-WNKELKSELKNQEKKle 324

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   100 ---------DELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWVTlKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAI 170
Cdd:TIGR04523  325 eiqnqisqnNKIISQLNEQISQLKKELTNSESENSEKQRELEEKQN-EIEKLKKENQSYKQEIKNLESQINDLESKIQNQ 403


                   .
gi 767981142   171 Q 171
Cdd:TIGR04523  404 E 404

FERM1_F1_Myosin-VII

cd17092

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, ...

1024-1127

1.86e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

Pssm-ID: 340612 Cd Length: 99 Bit Score: 47.63 E-value: 1.86e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142 1024 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRkpSHSGFALF---TDDPS--GRDLEHclqgsvkICDAISKWE 1098
Cdd:cd17092     1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLK--DTFGFSLYialFDKVSslGSGTDH-------VMDAISQCE 71

                          90       100
                  ....*....|....*....|....*....
gi 767981142 1099 QAMKElhPGKSEGGTrvvklmyKNRLYFR 1127
Cdd:cd17092    72 QYAKE--KGAQEREA-------PWRLYFR 91

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

32-194

2.21e-06

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 52.61 E-value: 2.21e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   32 ASKIrELLADKMQELEQRLLEAEQRAENAETQVGVMEE-KVKLSNLKNVDSE----GSLHRKYQEL---LKAI-KGKDEL 102
Cdd:COG4913   609 RAKL-AALEAELAELEEELAEAEERLEALEAELDALQErREALQRLAEYSWDeidvASAEREIAELeaeLERLdASSDDL 687

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  103 iSQLEAQLEKQkqmRAEEAKTVQEKAAKIKEwvtlkLAKLEMENQHLkshnQRLVEQVGSLQDALEAIQIAPSRKLLVPP 182
Cdd:COG4913   688 -AALEEQLEEL---EAELEELEEELDELKGE-----IGRLEKELEQA----EEELDELQDRLEAAEDLARLELRALLEER 754

                         170
                  ....*....|..
gi 767981142  183 YGAAEQDSVPSE 194
Cdd:COG4913   755 FAAALGDAVERE 766

FERM_F0_F1

cd01765

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found ...

1025-1106

2.39e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found in FERM (Four.1/Ezrin/Radixin/Moesin) family proteins; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling functions. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N), which is structurally similar to ubiquitin.

Pssm-ID: 340464 Cd Length: 80 Bit Score: 46.81 E-value: 2.39e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142 1025 FSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRkpSHSGFALFTDDPSgrDLEHCLQGSvkicDAISKWeqaMKEL 1104
Cdd:cd01765     1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLL--EKDYFGLFYEDND--GQKHWLDLD----KKISKQ---LKRS 69


                  ..
gi 767981142 1105 HP 1106
Cdd:cd01765    70 GP 71

PH_IRS

cd01257

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...

581-677

2.57e-06

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.

Pssm-ID: 269959 Cd Length: 106 Bit Score: 47.28 E-value: 2.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLKmgsqVKTWKRRWFVLR------QGQIMYYKSPSDVIRK--PQGQVDLNSRCQIVR---GEGSQTFQLISEKKT 649
Cdd:cd01257     5 KSGYLKK----LKTMRKRYFVLRaeshggPARLEYYENEKKFRRNaePKRVIPLSSCFNINKradAKHKHLIALYTKDEC 80

                          90       100
                  ....*....|....*....|....*...
gi 767981142  650 YYLTADSPSLLEEWirvLQSLLKVQATG 677
Cdd:cd01257    81 FGLVAESEEEQDEW---YQALLELQRPA 105

PH_Skap_family

cd13266

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...

581-673

2.68e-06

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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.

Pssm-ID: 270086 Cd Length: 106 Bit Score: 47.52 E-value: 2.68e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLK-------MGSQvktWKRRWFVLRQGQIMYYKSPSDviRKPQGQVDLNS----RCQIVRGEGSQ--TFQLIS-E 646
Cdd:cd13266     3 KAGYLEKrrkdhsfFGSE---WQKRWCAISKNVFYYYGSDKD--KQQKGEFAINGydvrMNPTLRKDGKKdcCFELVCpD 77

                          90       100
                  ....*....|....*....|....*..
gi 767981142  647 KKTYYLTADSPSLLEEWIRVLQSLLKV 673
Cdd:cd13266    78 KRTYQFTAASPEDAEDWVDQISFILQD 104

YhaN

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

27-171

2.72e-06

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 52.08 E-value: 2.72e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   27 RFRLQASKIRELLA--DKMQELEQRLLEAEQRAENAETQVGVMEEKVKLsnLKNVDSEGSLHRKYQELLKAIKGKDELIS 104
Cdd:COG4717    72 ELKELEEELKEAEEkeEEYAELQEELEELEEELEELEAELEELREELEK--LEKLLQLLPLYQELEALEAELAELPERLE 149

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  105 QLEAQLEKQKQMRAEEA---KTVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4717   150 ELEERLEELRELEEELEeleAELAELQEELEELLEQLSLATEEELQDLAEELEELQQRLAELEEELEEAQ 219

PH_KIFIA_KIFIB

cd01233

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...

581-671

2.73e-06

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). 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.

Pssm-ID: 269939 Cd Length: 103 Bit Score: 47.20 E-value: 2.73e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRkpQGQVDLnSRCQIVRGEGSQ-------TFQLISEKKTYYLT 653
Cdd:cd01233     8 KRGYLLFLEDATDGWVRRWVVLRRPYLHIYSSEKDGDE--RGVINL-STARVEYSPDQEallgrpnVFAVYTPTNSYLLQ 84

                          90
                  ....*....|....*...
gi 767981142  654 ADSPSLLEEWIRVLQSLL 671
Cdd:cd01233    85 ARSEKEMQDWLYAIDPLL 102

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

13-172

2.79e-06

chromosome segregation protein SMC, primarily archaeal 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. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 51.99 E-value: 2.79e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    13 DWQKRCLTLETQLFRFRLQASKIRELLADKM---QELEQRLLEAEQRAENAETQVGVMEEKvklsnlknvdsegsLHrKY 89
Cdd:TIGR02169  713 DASRKIGEIEKEIEQLEQEEEKLKERLEELEedlSSLEQEIENVKSELKELEARIEELEED--------------LH-KL 777

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    90 QELLKAIKGK--DELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEwVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDAL 167
Cdd:TIGR02169  778 EEALNDLEARlsHSRIPEIQAELSKLEEEVSRIEARLREIEQKLNR-LTLEKEYLEKEIQELQEQRIDLKEQIKSIEKEI 856


                   ....*
gi 767981142   168 EAIQI 172
Cdd:TIGR02169  857 ENLNG 861

PH_PHLDB1_2

cd14673

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...

583-667

3.03e-06

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.

Pssm-ID: 270192 Cd Length: 105 Bit Score: 47.18 E-value: 3.03e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  583 GYLLKMGSQVKTWKRRWFV--LRQGQIMYYKSPSDviRKPQGQVDLNS---------RCQIVRGEGSQTFQLISEKKTYY 651
Cdd:cd14673     7 GFLTKMGGKIKTWKKRWFVfdRNKRTLSYYVDKHE--KKLKGVIYFQAieevyydhlRSAAKSPNPALTFCVKTHDRLYY 84

                          90
                  ....*....|....*.
gi 767981142  652 LTADSPSLLEEWIRVL 667
Cdd:cd14673    85 MVAPSPEAMRIWMDVI 100

SMC_prok_B

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

2-173

3.22e-06

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]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 51.98 E-value: 3.22e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142     2 AELKVEAPASVDWQKRCLTLETQLFRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSN--LKNV 79
Cdd:TIGR02168  305 QILRERLANLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEeqLETL 384

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    80 DSEGSLHRKYQELLKA-IKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAakiKEWVTLKLAKLEMENQHLKSHNQRLVE 158
Cdd:TIGR02168  385 RSKVAQLELQIASLNNeIERLEARLERLEDRRERLQQEIEELLKKLEEAE---LKELQAELEELEEELEELQEELERLEE 461

                          170
                   ....*....|....*
gi 767981142   159 QVGSLQDALEAIQIA 173
Cdd:TIGR02168  462 ALEELREELEEAEQA 476

PH2_FGD4_insect-like

cd13238

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...

582-667

3.64e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. 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.

Pssm-ID: 270058 Cd Length: 97 Bit Score: 46.87 E-value: 3.64e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  582 SGYLLKMGSQVKTWKRRWFVLRQGQIMY-YKSPSDVIRK-----PQGQVDLNSRCQIVRG----EGSQTFQLISEKKTYY 651
Cdd:cd13238     2 SGYLKLKTNGRKTWSRRWFALQPDFVLYsYKSQEDKLPLtatpvPGFLVTLLEKGSAVDPlndpKRPRTFKMFHVKKSYY 81

                          90
                  ....*....|....*.
gi 767981142  652 LTADSPSLLEEWIRVL 667
Cdd:cd13238    82 FQANDGDEQKKWVLTL 97

CwlO1

COG3883

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function ...

20-266

5.32e-06

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

Pssm-ID: 443091 [Multi-domain] Cd Length: 379 Bit Score: 50.60 E-value: 5.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   20 TLETQLFRFRLQASKIREL---LADKMQELEQRLLEAEQRAENAETQVGVMEEKVK------------------------ 72
Cdd:COG3883    34 AAQAELDALQAELEELNEEyneLQAELEALQAEIDKLQAEIAEAEAEIEERREELGeraralyrsggsvsyldvllgses 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   73 ----LSNLKNVDSegsLHRKYQELLKAIKGKDELISQLEAQLEKQKQmraeEAKTVQEKAAKIKEWVTLKLAKLEMENQH 148
Cdd:COG3883   114 fsdfLDRLSALSK---IADADADLLEELKADKAELEAKKAELEAKLA----ELEALKAELEAAKAELEAQQAEQEALLAQ 186

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  149 LKSHNQRLVEQVGSLQDALEAIQIAPSrkllvppygAAEQDSVPSEPGIQPMGQDSGSQAQGLKAAVLAPSPGALQSKDS 228
Cdd:COG3883   187 LSAEEAAAEAQLAELEAELAAAEAAAA---------AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAASAAGAGAAGAAGA 257

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 767981142  229 VSEAASPLEDSSSSTVHSGETVEAKPLQPHLGRESPPH 266
Cdd:COG3883   258 AAGSAGAAGAAAGAAGAGAAAASAAGGGAGGAGGGGGG 295

PH_ORP9

cd13290

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...

583-668

5.43e-06

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241444 Cd Length: 102 Bit Score: 46.28 E-value: 5.43e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  583 GYLLKMGSQVKTWKRRWFVLRQ--GQIMYYKSPSDVIRKPQ-GQVDLNSRCQIVRGEGSQTFQLISEKKTYYLTADSPSL 659
Cdd:cd13290     3 GPLSKWTNVMKGWQYRWFVLDDnaGLLSYYTSKEKMMRGSRrGCVRLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEE 82


                  ....*....
gi 767981142  660 LEEWIRVLQ 668
Cdd:cd13290    83 RERWIRALE 91

PRK03918

DNA double-strand break repair ATPase Rad50;

33-173

5.76e-06

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 50.83 E-value: 5.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   33 SKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKV-KLSNLKNVDSEgsLHRKYQELLKAIKgKDELISQLEAQLE 111
Cdd:PRK03918  299 SEFYEEYLDELREIEKRLSRLEEEINGIEERIKELEEKEeRLEELKKKLKE--LEKRLEELEERHE-LYEEAKAKKEELE 375

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767981142  112 KQKQMRA----EEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKShnqrlveQVGSLQDALEAIQIA 173
Cdd:PRK03918  376 RLKKRLTgltpEKLEKELEELEKAKEEIEEEISKITARIGELKK-------EIKELKKAIEELKKA 434

PH2_FGD5_FGD6

cd13237

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...

582-667

5.88e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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.

Pssm-ID: 270057 Cd Length: 91 Bit Score: 45.87 E-value: 5.88e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  582 SGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVirkpqgqVDLNSR-------CQIVRGEGSQT---FQLISEKKTYY 651
Cdd:cd13237     2 SGYLQRRKKSKKSWKRLWFVLKDKVLYTYKASEDV-------VALESVpllgftvVTIDESFEEDEslvFQLLHKGQLPI 74

                          90
                  ....*....|....*..
gi 767981142  652 -LTADSPSLLEEWIRVL 667
Cdd:cd13237    75 iFRADDAETAQRWIEAL 91

SMC_prok_B

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

21-171

6.23e-06

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 50.83 E-value: 6.23e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    21 LETQLFRFRLQASK----------IREL-----------LADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNv 79
Cdd:TIGR02168  198 LERQLKSLERQAEKaerykelkaeLRELelallvlrleeLREELEELQEELKEAEEELEELTAELQELEEKLEELRLEV- 276

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    80 dseGSLHRKYQELLKAIKGKDELISQLE---------------------AQLEKQKQMR---AEEAKTVQEKAAKIKEWV 135
Cdd:TIGR02168  277 ---SELEEEIEELQKELYALANEISRLEqqkqilrerlanlerqleeleAQLEELESKLdelAEELAELEEKLEELKEEL 353

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 767981142   136 TL---KLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:TIGR02168  354 ESleaELEELEAELEELESRLEELEEQLETLRSKVAQLE 392

Myosin_tail_1

pfam01576

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...

37-133

6.29e-06

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 50.94 E-value: 6.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    37 ELLADKMQELEQRL------LEAE----QRAENAETQvgvMEEKVKLSNLKNVDSEGSLHRKYQELLKAIKGKdelISQL 106
Cdd:pfam01576  906 ELLNDRLRKSTLQVeqltteLAAErstsQKSESARQQ---LERQNKELKAKLQEMEGTVKSKFKSSIAALEAK---IAQL 979

                           90       100
                   ....*....|....*....|....*..
gi 767981142   107 EAQLEKQKQMRAEEAKTVQEKAAKIKE 133
Cdd:pfam01576  980 EEQLEQESRERQAANKLVRRTEKKLKE 1006

PH_PKB

cd01241

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the ...

581-669

6.88e-06

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. 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.

Pssm-ID: 269947 Cd Length: 107 Bit Score: 46.09 E-value: 6.88e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLKMGSQVKTWKRRWFVLRQ-GQIMYYKspsdviRKPQGQVD---LNS----RCQIVRGE--GSQTF-----QLIS 645
Cdd:cd01241     5 KEGWLLKRGEYIKNWRPRYFVLKSdGSFIGYK------EKPKPNQDpppLNNfsvaECQLMKTEkpKPNTFiirclQWTT 78

                          90       100
                  ....*....|....*....|....*
gi 767981142  646 E-KKTYYltADSPSLLEEWIRVLQS 669
Cdd:cd01241    79 ViERTFH--VESEEEREEWMKAIQG 101

PRK12704

phosphodiesterase; Provisional

41-143

1.53e-05

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 49.39 E-value: 1.53e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   41 DKMQELEQRLLEAEQRAENAETQVGVMEEKVKlsnlknvDSEGSLHRKYQELLKAIKGKDELISQLEAQLEKQKQMRAEE 120
Cdd:PRK12704   82 NELQKLEKRLLQKEENLDRKLELLEKREEELE-------KKEKELEQKQQELEKKEEELEELIEEQLQELERISGLTAEE 154

                          90       100       110
                  ....*....|....*....|....*....|...
gi 767981142  121 AK----------TVQEKAAKIKEWVtlKLAKLE 143
Cdd:PRK12704  155 AKeillekveeeARHEAAVLIKEIE--EEAKEE 185

PH_ORP_plant

cd13294

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...

583-669

1.67e-05

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241448 Cd Length: 100 Bit Score: 44.79 E-value: 1.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  583 GYLLKMGSQVKTWKRRWFVLRQGQIMYYK--SPSDVirKPQGQVDLnsRCQIVRGEGS--QTFQLISEKKTYYLTADSPS 658
Cdd:cd13294     3 GILYKWVNYGKGWRSRWFVLQDGVLSYYKvhGPDKV--KPSGEVHL--KVSSIRESRSddKKFYIFTGTKTLHLRAESRE 78

                          90
                  ....*....|.
gi 767981142  659 LLEEWIRVLQS 669
Cdd:cd13294    79 DRAAWLEALQA 89

PH2_PH_fungal

cd13299

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...

577-671

1.91e-05

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second 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.

Pssm-ID: 270111 Cd Length: 102 Bit Score: 44.93 E-value: 1.91e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  577 ESLEKSGYLLKM-GSQVKTWKRRWFVLRQGQIMYYKSPSDVirKPQGQVDLNSRCQIVRGEG-SQT----FQLISEKKTY 650
Cdd:cd13299     4 ERVIEQGYLQVLkKKGVNQWKKYWLVLRNRSLSFYKDQSEY--SPVKIIPIDDIIDVVELDPlSKSkkwcLQIITPEKRI 81

                          90       100
                  ....*....|....*....|.
gi 767981142  651 YLTADSPSLLEEWIRVLQSLL 671
Cdd:cd13299    82 RFCADDEESLIKWLGALKSLL 102

PH_Skap-hom_Skap2

cd13381

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...

581-672

2.00e-05

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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.

Pssm-ID: 270181 Cd Length: 106 Bit Score: 44.95 E-value: 2.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLK-------MGSQvktWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVD-----LNSrcqIVRGEGSQ--TFQLIS- 645
Cdd:cd13381     3 KAGYLEKrrkdhsfFGFE---WQKRWCALSNSVFYYYGSDKDKQQKGEFAIDgydvkMNN---TLRKDAKKdcCFEICAp 76

                          90       100
                  ....*....|....*....|....*..
gi 767981142  646 EKKTYYLTADSPSLLEEWIRVLQSLLK 672
Cdd:cd13381    77 DKRVYQFTAASPKEAEEWVQQIKFILQ 103

Smc

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

36-223

2.39e-05

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 49.16 E-value: 2.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   36 RELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLHRKYQELLKAIKGKDELISQLE-------- 107
Cdd:COG1196   332 LEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEeleeaeea 411

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  108 -----AQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQIApsrkllvpp 182
Cdd:COG1196   412 llerlERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAEL--------- 482

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 767981142  183 yGAAEQDSVPSEPGIQPMGQDSGSQAQGLKAAVLAPSPGAL 223
Cdd:COG1196   483 -LEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAGLRGL 522

Smc

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

21-173

2.47e-05

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 48.78 E-value: 2.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   21 LETQLFRFRLQASKI---RELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLHRKYQElLKAIK 97
Cdd:COG1196   251 LEAELEELEAELAELeaeLEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEE-LAELE 329

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767981142   98 GKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQIA 173
Cdd:COG1196   330 EELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEEL 405

FERM_F1_Myo10_like

cd17110

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional ...

1024-1126

2.48e-05

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional myosin-X and similar proteins; Myosin-X, also termed myosin-10 (Myo10), is an untraditional member of myosin superfamily. It is an actin-based motor protein that plays a critical role in diverse cellular motile events, such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance, as well as a number of disease states including cancer metastasis and pathogen infection. Myosin-X functions as an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. It regulates neuronal radial migration through interacting with N-cadherin. Like other unconventional myosins, Myosin-X is composed of a conserved motor head, a neck region and a variable tail. The neck region consists of three IQ motifs (light chain-binding sites), and a predicted stalk of coiled coil. The tail contains three PEST regions, three PH domains, a MyTH4 domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Amoebozoan Dictyostelium discoideum myosin VII (DdMyo7) and uncharacterized pleckstrin homology domain-containing family H member 3 (PLEKHH3) are also included in this family. Like metazoan Myo10, DdMyo7 is essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin.

Pssm-ID: 340630 Cd Length: 97 Bit Score: 44.30 E-value: 2.48e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142 1024 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRKpSHSGFALFtdDPSGrDLEHCLQGSVKICDAISKWE-QAMK 1102
Cdd:cd17110     3 ELTVTVTCQGGRTCKVAIDSWTTCGEVSKDLARRLGLER-SRNGFALF--ETSG-DIERALEAKTRVVDVLSKWEkLAAT 78

                          90       100
                  ....*....|....*....|....
gi 767981142 1103 ELHPGKSEggtrvVKLMYKNRLYF 1126
Cdd:cd17110    79 GSSPGDDG-----WKLLFKLYLFL 97

SMC_prok_B

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

15-171

2.53e-05

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 48.90 E-value: 2.53e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    15 QKRCLTLETQLFRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVK-----LSNLKNVDSE-----GS 84
Cdd:TIGR02168  742 VEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKalreaLDELRAELTLlneeaAN 821

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    85 LHRKYQELLKAIKGKDELISQLEAQLEKQKQMRAEEAKTV---QEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVG 161
Cdd:TIGR02168  822 LRERLESLERRIAATERRLEDLEEQIEELSEDIESLAAEIeelEELIEELESELEALLNERASLEEALALLRSELEELSE 901

                          170
                   ....*....|
gi 767981142   162 SLQDALEAIQ 171
Cdd:TIGR02168  902 ELRELESKRS 911

FERM_C-lobe

cd00836

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...

1254-1335

3.86e-05

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

Pssm-ID: 275389 Cd Length: 93 Bit Score: 43.52 E-value: 3.86e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142 1254 GAKLFaaqPAQLSSKENALVWIAVNEDGVSILDHNTMQVHITYPYSSVTTFG-GCRDDFMLVIRsipdkssGKSHIEKLI 1332
Cdd:cd00836     1 GVEFF---PVKDKSKKGSPIILGVNPEGISVYDELTGQPLVLFPWPNIKKISfSGAKKFTIVVA-------DEDKQSKLL 70


                  ...
gi 767981142 1333 FRM 1335
Cdd:cd00836    71 FQT 73

PH_SKIP

cd13309

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...

581-677

4.53e-05

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. 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.

Pssm-ID: 270119 Cd Length: 103 Bit Score: 43.91 E-value: 4.53e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLL-KMGSQ---VKTWKRRWFVLRQGQIMYYKSPSDVIrkPQGQVDL-NSRCQ----IVRGEGSQTFQLI-SEKKTY 650
Cdd:cd13309     2 KEGMLMyKTGTSylgGETWKPGYFLLKNGVLYQYPDRSDRL--PLLSISLgGEQCGgcrrINNTERPHTFELIlTDRSSL 79

                          90       100
                  ....*....|....*....|....*..
gi 767981142  651 YLTADSPSLLEEWirvLQSLLKVQATG 677
Cdd:cd13309    80 ELAAPDEYEASEW---LQSLCQSASGG 103

PH_Skap1

cd13380

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...

581-672

5.15e-05

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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.

Pssm-ID: 270180 Cd Length: 106 Bit Score: 43.69 E-value: 5.15e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLK-------MGSQvktWKRRWFVLRQGQIMYYKSPSDviRKPQGQVDL-NSRCQIV-----RGEGSQTFQLISE- 646
Cdd:cd13380     3 KQGYLEKrskdhsfFGSE---WQKRWCVLTNRAFYYYASEKS--KQPKGGFLIkGYSAQMAphlrkDSRRDSCFELTTPg 77

                          90       100
                  ....*....|....*....|....*.
gi 767981142  647 KKTYYLTADSPSLLEEWIRVLQSLLK 672
Cdd:cd13380    78 RRTYQFTAASPSEARDWVDQIQFLLK 103

PH_ORP10_ORP11

cd13291

Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...

583-641

5.88e-05

Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin homology (PH) domain; Human ORP10 is involvedt in intracellular transport or organelle positioning and is proposed to function as a regulator of cellular lipid metabolism. Human ORP11 localizes at the Golgi-late endosome interface and is thought to form a dimer with ORP9 functioning as an intracellular lipid sensor or transporter. Both ORP10 and ORP11 contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 270106 Cd Length: 107 Bit Score: 43.44 E-value: 5.88e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767981142  583 GYLLKMGSQVKTWKRRWFVL--RQGQIMYYKSPSDVIRKPQGQVDLNSRCQIVRGEGSQTF 641
Cdd:cd13291     3 GQLLKYTNVVKGWQNRWFVLdpDTGILEYFLSEESKNQKPRGSLSLAGAVISPSDEDSHTF 63

YhaN

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

21-173

7.82e-05

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 47.07 E-value: 7.82e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   21 LETQLFRFRlQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEG-----SLHRK---YQEL 92
Cdd:COG4717    83 AEEKEEEYA-ELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELAELperleELEERleeLREL 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   93 LKAIKGKDELISQLEAQL-EKQKQMRAEEAKTVQEKAAKIKEWvTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4717   162 EEELEELEAELAELQEELeELLEQLSLATEEELQDLAEELEEL-QQRLAELEEELEEAQEELEELEEELEQLENELEAAA 240


                  ..
gi 767981142  172 IA 173
Cdd:COG4717   241 LE 242

DR0291

COG1579

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...

37-126

9.23e-05

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 45.69 E-value: 9.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   37 ELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKlsnlknvdsegslhrKYQELLKAIKGK-DELISQLEAQLEKQKQ 115
Cdd:COG1579    99 ESLKRRISDLEDEILELMERIEELEEELAELEAELA---------------ELEAELEEKKAElDEELAELEAELEELEA 163

                          90
                  ....*....|.
gi 767981142  116 MRAEEAKTVQE 126
Cdd:COG1579   164 EREELAAKIPP 174

GumC

COG3206

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

21-171

1.03e-04

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 46.93 E-value: 1.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   21 LETQLFRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVM----EEKVKLSNLKNVDSE--------GSLHRK 88
Cdd:COG3206   162 LEQNLELRREEARKALEFLEEQLPELRKELEEAEAALEEFRQKNGLVdlseEAKLLLQQLSELESQlaearaelAEAEAR 241

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   89 YQELLKAIKGK---------DELISQLEAQLEKQKQMRAEEAKT-------VQEKAAKIKEWVTLKLAKLEMENQHLKSH 152
Cdd:COG3206   242 LAALRAQLGSGpdalpellqSPVIQQLRAQLAELEAELAELSARytpnhpdVIALRAQIAALRAQLQQEAQRILASLEAE 321

                         170
                  ....*....|....*....
gi 767981142  153 NQRLVEQVGSLQDALEAIQ 171
Cdd:COG3206   322 LEALQAREASLQAQLAQLE 340

PH_Bem3

cd13277

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...

581-671

1.06e-04

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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.

Pssm-ID: 270096 Cd Length: 111 Bit Score: 43.04 E-value: 1.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  581 KSGYLLKMG----SQVKTWKRRWFVLRQGQIMYYKSPSDVIrkpQGQVDLNSrCQIvrgeGSQT------------FQLI 644
Cdd:cd13277     5 KEGYLLKRRkktlGSTGGWKLRYGVLDGNILELYESRGGQL---LESIKLRN-AQI----ERQPnlpddkygtrhgFLIN 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 767981142  645 SEKKT-------YYLTADSPSLLEEWIRVLQSLL 671
Cdd:cd13277    77 EHKKSglssttkYYLCAETDKERDEWVSALSEYI 110

Mplasa_alph_rch

TIGR04523

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...

21-171

1.12e-04

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 46.55 E-value: 1.12e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    21 LETQLFRFRLQASKIRELLADKMQEL---EQRLLEAEQRAENAETQVGVMEEKV--------KLSNLKN-VDSE-GSLHR 87
Cdd:TIGR04523  466 LETQLKVLSRSINKIKQNLEQKQKELkskEKELKKLNEEKKELEEKVKDLTKKIsslkekieKLESEKKeKESKiSDLED 545

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    88 ---------KYQELLKAIKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWV------TLKLAKLEMENQHLKSH 152
Cdd:TIGR04523  546 elnkddfelKKENLEKEIDEKNKEIEELKQTQKSLKKKQEEKQELIDQKEKEKKDLIkeieekEKKISSLEKELEKAKKE 625

                          170
                   ....*....|....*....
gi 767981142   153 NQRLVEQVGSLQDALEAIQ 171
Cdd:TIGR04523  626 NEKLSSIIKNIKSKKNKLK 644

COG1340

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

1-133

1.24e-04

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 45.67 E-value: 1.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    1 MAELKVEAPASVDWQKRCLTLETQLFRFRLQASKIREL---LADKMQELEQRLLEA-----EQRAENAETQvgvmEEKVK 72
Cdd:COG1340   145 LEKELEKAKKALEKNEKLKELRAELKELRKEAEEIHKKikeLAEEAQELHEEMIELykeadELRKEADELH----KEIVE 220

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767981142   73 LSnlKNVDsegSLHRKYQELLKAIKGKDELISQLEAQLEKQKqmRAEEAKTVQEKAAKIKE 133
Cdd:COG1340   221 AQ--EKAD---ELHEEIIELQKELRELRKELKKLRKKQRALK--REKEKEELEEKAEEIFE 274

PH_Bud4

cd13278

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...

577-679

1.88e-04

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. 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.

Pssm-ID: 241432 Cd Length: 139 Bit Score: 42.96 E-value: 1.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  577 ESLEKSGYLLKMGSQVKTWKRRWFVLRQGQIMYYkspSDVIRKPQGQVDLNSRCQIV-----RGEGSQT----------- 640
Cdd:cd13278    17 QKITKEGYLLQEGGDCEYWRRRFFKLQGTKLVAY---HEVTRKPRATINLLKVVDVVddddaRERTSSFkrnftdlvlfe 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 767981142  641 --FQLISEKKTY-YLTADSPSLLEEWIRVLQSLLKVQATGPP 679
Cdd:cd13278    94 ecFRLVFANGEViDFYADSKEEKADWYSKLKEVVELNRFHQP 135

PH_Gab3

cd13385

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...

595-665

2.13e-04

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They 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. The members in this cd include the Gab1, Gab2, and Gab3 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.

Pssm-ID: 270184 Cd Length: 125 Bit Score: 42.65 E-value: 2.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  595 WKRRWFVLRQGQIM-------YYKS-----PSDVIRKPQGQVDLNSRCQIVRGEGSQTFQLI--SEKKTYYLTADSPSLL 660
Cdd:cd13385    26 WRKRWFVLRRGRMSgnpdvleYYRNnhskkPIRVIDLSECEVLKHSGPNFIRKEFQNNFVFIvkTTYRTFYLVAKTEEEM 105


                  ....*
gi 767981142  661 EEWIR 665
Cdd:cd13385   106 QVWVH 110

Smc

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

39-171

2.22e-04

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 45.70 E-value: 2.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   39 LADKMQELEQRL--LEAEqrAENAE------TQVGVMEEKVKLSNLKNVDSE-GSLHRKYQELLKAIKGKDELISQLEAQ 109
Cdd:COG1196   191 LEDILGELERQLepLERQ--AEKAEryrelkEELKELEAELLLLKLRELEAElEELEAELEELEAELEELEAELAELEAE 268

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767981142  110 LEKQKQMRAEEAKTVQEKAAKIKEwVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG1196   269 LEELRLELEELELELEEAQAEEYE-LLAELARLEQDIARLEERRRELEERLEELEEELAELE 329

SMC_N

pfam02463

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...

21-177

2.53e-04

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 45.73 E-value: 2.53e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    21 LETQLFRFRLQASK--------IRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLHRKYQEL 92
Cdd:pfam02463  163 AGSRLKRKKKEALKklieetenLAELIIDLEELKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLL 242

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    93 LKAIKGKDELISQLEAQLEKQKQMRAEEAKtVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQI 172
Cdd:pfam02463  243 QELLRDEQEEIESSKQEIEKEEEKLAQVLK-ENKEEEKEKKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEK 321


                   ....*
gi 767981142   173 APSRK 177
Cdd:pfam02463  322 EKKKA 326

PH_rhotekin2

cd13249

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...

582-667

2.86e-04

Pssm-ID: 270069 Cd Length: 111 Bit Score: 41.60 E-value: 2.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  582 SGYL--LKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRK--PQGQVDLNSRCQIVRGEG-----SQTFQLIS----EKK 648
Cdd:cd13249     5 SGYLsqQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEIEAKvePLLTIPINKETRIRAVEKdskgrASSLSIINpysgEEV 84

                          90
                  ....*....|....*....
gi 767981142  649 TYYLTADSPSLLEEWIRVL 667
Cdd:cd13249    85 THVLSADSREELQKWMEAL 103

Smc

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

19-173

3.53e-04

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 45.31 E-value: 3.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   19 LTLETQLFRFRLQASKIRELLADKmQELEQRLLEAEQRAENAETQVGVMEEKvklsnlknvdsEGSLHRKYQELLKAIKG 98
Cdd:COG1196   281 LELEEAQAEEYELLAELARLEQDI-ARLEERRRELEERLEELEEELAELEEE-----------LEELEEELEELEEELEE 348

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767981142   99 KDELISQLEAQLEKQKQMRAEEAktvQEKAAKIKEWVTLKLAKLEMENQH--LKSHNQRLVEQVGSLQDALEAIQIA 173
Cdd:COG1196   349 AEEELEEAEAELAEAEEALLEAE---AELAEAEEELEELAEELLEALRAAaeLAAQLEELEEAEEALLERLERLEEE 422

PRK03918

DNA double-strand break repair ATPase Rad50;

29-170

3.64e-04

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 45.05 E-value: 3.64e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   29 RLQASKIRELLADK-MQELEQRLLEAEQRAENAETQVGVMEEKVKlsNLKNVDSEGSLHRKYQELLKAIKGKDELISQLE 107
Cdd:PRK03918  239 EIEELEKELESLEGsKRKLEEKIRELEERIEELKKEIEELEEKVK--ELKELKEKAEEYIKLSEFYEEYLDELREIEKRL 316

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767981142  108 AQLEKQKQMRAEEAKTVQEKAAKIkEWVTLKLAKLEMENQHLKShNQRLVEQVGSLQDALEAI 170
Cdd:PRK03918  317 SRLEEEINGIEERIKELEEKEERL-EELKKKLKELEKRLEELEE-RHELYEEAKAKKEELERL 377

Tropomyosin

pfam00261

Tropomyosin; Tropomyosin is an alpha-helical protein that forms a coiled-coil structure of 2 ...

41-145

3.99e-04

Tropomyosin; Tropomyosin is an alpha-helical protein that forms a coiled-coil structure of 2 parallel helices containing 2 sets of 7 alternating actin binding sites. The protein is best known for its role in regulating the interaction between actin and myosin in muscle contraction, but is also involved in the organization and dynamics of the cytoskeleton in non-muscle cells. There are multiple cell-specific isoforms, expressed by alternative promoters and alternative RNA processing of at least four genes. Muscle isoforms of tropomyosin are characterized by having 284 amino acid residues and a highly conserved N-terminal region, whereas non-muscle forms are generally smaller and are heterogeneous in their N-terminal region.

Pssm-ID: 459736 [Multi-domain] Cd Length: 235 Bit Score: 43.48 E-value: 3.99e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    41 DKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLHRKYQELLKAIKGKDEL-----------------I 103
Cdd:pfam00261   15 ERLKEAMKKLEEAEKRAEKAEAEVAALNRRIQLLEEELERTEERLAEALEKLEEAEKAADESergrkvlenralkdeekM 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 767981142   104 SQLEAQLekqkqmraEEAKTVQEKAAKIKEWVTLKLAKLEME 145
Cdd:pfam00261   95 EILEAQL--------KEAKEIAEEADRKYEEVARKLVVVEGD 128

YhaN

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

26-166

4.29e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 44.76 E-value: 4.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   26 FRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEgsLHRKYQELLKAIKGKDELISQ 105
Cdd:COG4717   387 LRAALEQAEEYQELKEELEELEEQLEELLGELEELLEALDEEELEEELEELEEELEE--LEEELEELREELAELEAELEQ 464

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767981142  106 LEAQLEKQkQMRAEEAKTVQEKAAKIKEWVTLKLAkLEMENQHLKSHNQRLVEQVgsLQDA 166
Cdd:COG4717   465 LEEDGELA-ELLQELEELKAELRELAEEWAALKLA-LELLEEAREEYREERLPPV--LERA 521

EnvC

COG4942

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...

21-171

5.39e-04

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 43.98 E-value: 5.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   21 LETQLFRFRLQASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSnLKNVDSEGSLHRKYQELLKAIKGKD 100
Cdd:COG4942    81 LEAELAELEKEIAELRAELEAQKEELAELLRALYRLGRQPPLALLLSPEDFLDA-VRRLQYLKYLAPARREQAEELRADL 159

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767981142  101 ELISQLEAQLEKQkqmRAEEAKTVQEKAAKIKEWVTLK------LAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4942   160 AELAALRAELEAE---RAELEALLAELEEERAALEALKaerqklLARLEKELAELAAELAELQQEAEELEALIARLE 233

DUF4200

pfam13863

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil ...

39-164

6.44e-04

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil domain of unknwon function.

Pssm-ID: 464003 [Multi-domain] Cd Length: 119 Bit Score: 41.01 E-value: 6.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    39 LADKMQELE--QRLLEaEQRAEnaetqvgvMEEKVKLSNLKnvdsEGSLHRKYQELLKAIKGKDELISQLEAQLEKQKQM 116
Cdd:pfam13863    1 LLEKKREMFlvQLALD-AKREE--------IERLEELLKQR----EEELEKKEQELKEDLIKFDKFLKENDAKRRRALKK 67

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 767981142   117 RAEEAKTVQEKAAKIKewvtlklaKLEMENQHLKSHNQRLVEQVGSLQ 164
Cdd:pfam13863   68 AEEETKLKKEKEKEIK--------KLTAQIEELKSEISKLEEKLEEYK 107

Tropomyosin

pfam00261

Tropomyosin; Tropomyosin is an alpha-helical protein that forms a coiled-coil structure of 2 ...

41-149

7.26e-04

Pssm-ID: 459736 [Multi-domain] Cd Length: 235 Bit Score: 42.71 E-value: 7.26e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    41 DKMQELEQRLLEAEQRAENAETQVGVMEEKVKLsnlknvdSEGSLHR----------KYQELLKAIKGKDELISQLEAQL 110
Cdd:pfam00261   92 EKMEILEAQLKEAKEIAEEADRKYEEVARKLVV-------VEGDLERaeeraelaesKIVELEEELKVVGNNLKSLEASE 164

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 767981142   111 EK--QKQMRAEEA-KTVQEkaaKIKEWVTL------KLAKLEMENQHL 149
Cdd:pfam00261  165 EKasEREDKYEEQiRFLTE---KLKEAETRaefaerSVQKLEKEVDRL 209

COG1340

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

29-167

7.62e-04

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 43.36 E-value: 7.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   29 RLQASKIREL---LADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVdSEGSLHRKYQELLKAIKGKD----- 100
Cdd:COG1340    56 REEAQELREKrdeLNEKVKELKEERDELNEKLNELREELDELRKELAELNKAGG-SIDKLRKEIERLEWRQQTEVlspee 134

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767981142  101 -----ELISQLEAQLEKQKQMRaEEAKTVQEKAAKIKEWvtlklaKLEMENQHLKSHNqrLVEQVGSLQDAL 167
Cdd:COG1340   135 ekelvEKIKELEKELEKAKKAL-EKNEKLKELRAELKEL------RKEAEEIHKKIKE--LAEEAQELHEEM 197

Atg16_CCD

cd22887

Coiled-coiled domain of autophagy-related 16 (Atg16) family proteins; The Atg16 family ...

91-166

9.68e-04

Pssm-ID: 439196 [Multi-domain] Cd Length: 91 Bit Score: 39.47 E-value: 9.68e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   91 ELLKAIKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIK----EWVTL---------KLAKLEMENQHLKshnQRLV 157
Cdd:cd22887     1 ELESELQELEKRLAELEAELASLEEEIKDLEEELKEKNKANEilndELIALqiennlleeKLRKLQEENDELV---ERWM 77


                  ....*....
gi 767981142  158 EQVGslQDA 166
Cdd:cd22887    78 AKKQ--QEA 84

ClyA_Cry6Aa-like

cd22656

Bacillus thuringiensis crystal 6Aa (Cry6Aa) toxin, and similar proteins; This model includes ...

48-171

9.96e-04

Bacillus thuringiensis crystal 6Aa (Cry6Aa) toxin, and similar proteins; This model includes pesticidal Cry6Aa toxin from Bacillus thuringiensis, one of the many parasporal crystal (Cry) toxins produced during the sporulation phase of growth. Many of these proteins are toxic to numerous insect species and have been effectively used as proteinaceous insecticides to directly kill insect pests; some have been used to control insect growth on transgenic agricultural plants. Cry6Aa exists as a protoxin, which is activated by cleavage using trypsin. Structure studies for Cry6Aa support a mechanism of action by pore formation, similar to cytolysin A (ClyA)-type alpha pore-forming toxins (alpha-PFTs) such as HblB, and bioassay and mutation studies show that Cry6Aa is an active pore-forming toxin. Cry6Aa shows atypical features compared to other members of alpha-PFTs, including internal repeat sequences and small loop regions within major alpha helices.

Pssm-ID: 439154 [Multi-domain] Cd Length: 309 Bit Score: 42.74 E-value: 9.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   48 QRLLEAEQR-AENAETQVGVMEEKVK--LSNLKNVDSE-GSLHRKYQELLKAIKGKDEL--ISQLEAQLEKQKQMRAEEA 121
Cdd:cd22656   120 KALLDDLLKeAKKYQDKAAKVVDKLTdfENQTEKDQTAlETLEKALKDLLTDEGGAIARkeIKDLQKELEKLNEEYAAKL 199

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767981142  122 K-TVQEKAAKIKEWvTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:cd22656   200 KaKIDELKALIADD-EAKLAAALRLIADLTAADTDLDNLLALIGPAIPALE 249

MukB

COG3096

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell ...

37-171

1.07e-03

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 442330 [Multi-domain] Cd Length: 1470 Bit Score: 43.79 E-value: 1.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   37 ELLADKMQELEQRLLEAEQRAE---NAETQvgvMEEKVKLSNlKNVDSEGSLHRKYQELlkaikgkDELISQLEAQLEKQ 113
Cdd:COG3096   508 QALAQRLQQLRAQLAELEQRLRqqqNAERL---LEEFCQRIG-QQLDAAEELEELLAEL-------EAQLEELEEQAAEA 576

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767981142  114 KQMRAEEAKTVQEKAAKIKEwvtlkLAKLEMENQHLKSHNQRLVEQVG----SLQDALEAIQ 171
Cdd:COG3096   577 VEQRSELRQQLEQLRARIKE-----LAARAPAWLAAQDALERLREQSGealaDSQEVTAAMQ 633

TPH

pfam13868

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...

1-156

1.15e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 42.98 E-value: 1.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142     1 MAELKVEAPASVDWQKRCLTLETQLFRFRLQAsKIRELLADKMQELEQRLLEAEQRAENAEtQVGVMEEKVKLSNLKNVD 80
Cdd:pfam13868   49 MEEERERALEEEEEKEEERKEERKRYRQELEE-QIEEREQKRQEEYEEKLQEREQMDEIVE-RIQEEDQAEAEEKLEKQR 126

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    81 SEGSLHRKYQELLKAIKGKDELISQLE----AQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRL 156
Cdd:pfam13868  127 QLREEIDEFNEEQAEWKELEKEEEREEderiLEYLKEKAEREEEREAEREEIEEEKEREIARLRAQQEKAQDEKAERDEL 206

tolA

PRK09510

cell envelope integrity inner membrane protein TolA; Provisional

29-132

1.27e-03

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 42.87 E-value: 1.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   29 RLQASKirellADKMQELEQRLLEAEQRAENAETQVGVMEEKVKlsnlknvdsegslhRKYQELLKAIKGKDELISQleA 108
Cdd:PRK09510   66 RQQQQQ-----KSAKRAEEQRKKKEQQQAEELQQKQAAEQERLK--------------QLEKERLAAQEQKKQAEEA--A 124

                          90       100
                  ....*....|....*....|....
gi 767981142  109 QLEKQKQMRAEEAKTVQEKAAKIK 132
Cdd:PRK09510  125 KQAALKQKQAEEAAAKAAAAAKAK 148

SMC_prok_B

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

21-156

1.42e-03

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 43.12 E-value: 1.42e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    21 LETQLFRFRLQASKIR---ELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKlsnlknvdsegSLHRKYQELLKAIK 97
Cdd:TIGR02168  857 LAAEIEELEELIEELEselEALLNERASLEEALALLRSELEELSEELRELESKRS-----------ELRRELEELREKLA 925

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 767981142    98 GKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEmenQHLKSHNQRL 156
Cdd:TIGR02168  926 QLELRLEGLEVRIDNLQERLSEEYSLTLEEAEALENKIEDDEEEAR---RRLKRLENKI 981

Smc

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

29-148

1.54e-03

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

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 43.00 E-value: 1.54e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   29 RLQASKIRELLADKMQELEQRLLEAEQRAENAETQvgvmEEKVKLSNLKNVDSEGSLHRKYQELLKAIKGKDELISQLEA 108
Cdd:COG1196   388 LLEALRAAAELAAQLEELEEAEEALLERLERLEEE----LEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLE 463

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 767981142  109 QLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEMENQH 148
Cdd:COG1196   464 LLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADY 503

PH_CpORP2-like

cd13293

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...

583-668

1.57e-03

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.

Pssm-ID: 241447 Cd Length: 88 Bit Score: 38.85 E-value: 1.57e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  583 GYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSdviRKPQGQVDLNSrCQI-VRGEGSQTFQLISEKKTYYLTADSPSLLE 661
Cdd:cd13293     3 GYLKKWTNIFNSWKPRYFILYPGILCYSKQKG---GPKKGTIHLKI-CDIrLVPDDPLRIIINTGTNQLHLRASSVEEKL 78


                  ....*..
gi 767981142  662 EWIRVLQ 668
Cdd:cd13293    79 KWYNALK 85

TACC_C

pfam05010

Transforming acidic coiled-coil-containing protein (TACC), C-terminal; This entry represents a ...

42-133

1.72e-03

Transforming acidic coiled-coil-containing protein (TACC), C-terminal; This entry represents a C-terminal domain found in the the proteins TACC 1, 2 and 3 (TACC1-3). TACC1 is found concentrated in the centrosomes of eukaryotes which may play a conserved role in organizing centrosomal microtubules. The human TACC proteins have been linked to cancer and TACC2 has been identified as a possible tumour suppressor (AZU-1). TACC 3 from Xenopus laevis, also known as maskin, associates XMAP215 and promotes efficient microtubule elongation during mitosis. Maskin is also found to bind CPEB and elF-4E. Interestingly, the functional homolog (Alp7) in Schizosaccharomyces pombe (not included in this entry) has been shown to be required for organization of bipolar spindles.

Pssm-ID: 461517 [Multi-domain] Cd Length: 201 Bit Score: 41.20 E-value: 1.72e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142    42 KMQELEQRlleaeQRAENAETQVGVMEEKVKLSNLknvdsegslHRKYQELLKAIKGKDELISQLEAQLEKQKQM-RAEE 120
Cdd:pfam05010    5 DMDAALEK-----ARNEIEEKELEINELKAKYEEL---------RRENLEMRKIVAEFEKTIAQMIEEKQKQKELeHAEI 70

                           90
                   ....*....|...
gi 767981142   121 AKTVQEKAAKIKE 133
Cdd:pfam05010   71 QKVLEEKDQALAD 83

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

15-171

1.78e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 42.98 E-value: 1.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   15 QKRCLTLETQLFRFRL-QASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVklsnlknvdsegslhRKYQELL 93
Cdd:COG4913   268 RERLAELEYLRAALRLwFAQRRLELLEAELEELRAELARLEAELERLEARLDALREEL---------------DELEAQI 332

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   94 KAIKGKDelISQLEAQ---LEKQKQMRAEEAKTVQEKAAKI--------KEWVTLKL---AKLEMENQHLKSHNQRLVEQ 159
Cdd:COG4913   333 RGNGGDR--LEQLEREierLERELEERERRRARLEALLAALglplpasaEEFAALRAeaaALLEALEEELEALEEALAEA 410

                         170
                  ....*....|..
gi 767981142  160 VGSLQDALEAIQ 171
Cdd:COG4913   411 EAALRDLRRELR 422

PRK12704

phosphodiesterase; Provisional

37-131

1.82e-03

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 42.46 E-value: 1.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   37 ELLADKMQELEQR---LLEAEQRAENAETQVGVMEEKVKlsnlknvdsegSLHRKYQELLKAIKG------KDELISQLE 107
Cdd:PRK12704   96 ENLDRKLELLEKReeeLEKKEKELEQKQQELEKKEEELE-----------ELIEEQLQELERISGltaeeaKEILLEKVE 164

                          90       100
                  ....*....|....*....|....*....
gi 767981142  108 AQLEKQKQMRA----EEAK-TVQEKAAKI 131
Cdd:PRK12704  165 EEARHEAAVLIkeieEEAKeEADKKAKEI 193

PH2_FGD1-4

cd13236

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...

582-667

2.07e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. 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.

Pssm-ID: 270056 Cd Length: 105 Bit Score: 39.26 E-value: 2.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  582 SGYLLKMGSQvKTWKRRWFVL--RQGQIMY-YKSPSDVirKPQGQV-----DLNSRCQIVRGEGSQTFQLISEKKTYYLT 653
Cdd:cd13236    11 CGFLQYSEKG-KTWQKVWCVIprTEPLVLYlYGAPQDV--RAQRTIplpgcEVTVPPPEERLDGRHVFKLSQSKQSHYFS 87

                          90
                  ....*....|....
gi 767981142  654 ADSPSLLEEWIRVL 667
Cdd:cd13236    88 AESEELQQRWLEAL 101

COG5022

Myosin heavy chain [General function prediction only];

19-164

2.19e-03

Myosin heavy chain [General function prediction only];

Pssm-ID: 227355 [Multi-domain] Cd Length: 1463 Bit Score: 42.76 E-value: 2.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   19 LTLETQLFRFRlqaSKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDS-EGSLHRKYQELLKAIK 97
Cdd:COG5022   902 LELESEIIELK---KSLSSDLIENLEFKTELIARLKKLLNNIDLEEGPSIEYVKLPELNKLHEvESKLKETSEEYEDLLK 978

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767981142   98 GKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWVTLKlaKLEMENQHLKSHNQRLVEQVGSLQ 164
Cdd:COG5022   979 KSTILVREGNKANSELKNFKKELAELSKQYGALQESTKQLK--ELPVEVAELQSASKIISSESTELS 1043

PRK03918

DNA double-strand break repair ATPase Rad50;

32-171

2.51e-03

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 42.36 E-value: 2.51e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   32 ASKIRELLADKMQELEQRLleaeQRAENAETQVGVMEEKV--KLSNLKNVDSE--------GSLHRKYQELlKAIKgkdE 101
Cdd:PRK03918  167 LGEVIKEIKRRIERLEKFI----KRTENIEELIKEKEKELeeVLREINEISSElpelreelEKLEKEVKEL-EELK---E 238

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  102 LISQLEAQLEK-QKQMRAEEAKTVQ------EKAAKIKE------------WVTLKLAKLEMENQHLKSHNQRLVEQVGS 162
Cdd:PRK03918  239 EIEELEKELESlEGSKRKLEEKIREleerieELKKEIEEleekvkelkelkEKAEEYIKLSEFYEEYLDELREIEKRLSR 318


                  ....*....
gi 767981142  163 LQDALEAIQ 171
Cdd:PRK03918  319 LEEEINGIE 327

EnvC

COG4942

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...

31-171

2.52e-03

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 42.06 E-value: 2.52e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   31 QASKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKNVDSEGSLhrkyQELLKAIKGKDELISQLEAQL 110
Cdd:COG4942    24 EAEAELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQEL----AALEAELAELEKEIAELRAEL 99

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767981142  111 EKQKQMRAEEAKTVQekaaKIKEWVTLKL-------AKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG4942   100 EAQKEELAELLRALY----RLGRQPPLALllspedfLDAVRRLQYLKYLAPARREQAEELRADLAELA 163

PH_CNK_mammalian-like

cd01260

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...

595-675

2.72e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. 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.

Pssm-ID: 269962 Cd Length: 114 Bit Score: 38.93 E-value: 2.72e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  595 WKRRWFVLRQGQIMYYKSPSDviRKPQGQVDLnSRCQIVRGEGSQ---TFQLISEK-KTYYLTADSPSLLEEWIRVLQSL 670
Cdd:cd01260    33 WKKYWFVLKGSSLYWYSNQQD--EKAEGFINL-PDFKIERASECKkkyAFKACHPKiKTFYFAAENLDDMNKWLSKLNMA 109


                  ....*
gi 767981142  671 LKVQA 675
Cdd:cd01260   110 INKYA 114

PRK00409

recombination and DNA strand exchange inhibitor protein; Reviewed

58-173

3.47e-03

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 41.74 E-value: 3.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   58 ENAETQVGvmEEKVKLSNL--KNVDSEGSLHRKYQELLKAIKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIkewv 135
Cdd:PRK00409  505 EEAKKLIG--EDKEKLNELiaSLEELERELEQKAEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQA---- 578

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 767981142  136 tLKLAKLEMEnQHLKSHNQRLVEQVGS-----LQDALEAIQIA 173
Cdd:PRK00409  579 -IKEAKKEAD-EIIKELRQLQKGGYASvkaheLIEARKRLNKA 619

PRK03918

DNA double-strand break repair ATPase Rad50;

16-170

3.56e-03

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 41.97 E-value: 3.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   16 KRCLTLETQLFRFRLQASKIRELlADKMQELEQRLLEAEQRAENAETQVgvmeEKVKLSNLKNVDSE----GSLHRKYQE 91
Cdd:PRK03918  532 EKLIKLKGEIKSLKKELEKLEEL-KKKLAELEKKLDELEEELAELLKEL----EELGFESVEELEERlkelEPFYNEYLE 606

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142   92 LLKA---IKGKDELISQLEAQLEKQKQMRAEEAKTVQEKAAKIKEWVTL----KLAKLEMENQHLKSHNQRLVEQVGSLQ 164
Cdd:PRK03918  607 LKDAekeLEREEKELKKLEEELDKAFEELAETEKRLEELRKELEELEKKyseeEYEELREEYLELSRELAGLRAELEELE 686


                  ....*.
gi 767981142  165 DALEAI 170
Cdd:PRK03918  687 KRREEI 692

PH_RIP

cd01236

Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen ...

591-668

4.58e-03

Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen for proteins that bind to wild-type RhoA. RIP2, RIP3, and RIP4 were isolated from cDNA libraries with constitutively active V14RhoA (containing the C190R mutation). RIP2 represents a novel GDP/GTP exchange factor (RhoGEF), while RIP3 (p116Rip) and RIP4 are thought to be structural proteins. RhoGEF contains a Dbl(DH)/PH region, a a zinc finger motif, a leucine-rich domain, and a coiled-coil region. The last 2 domains are thought to be involved in mediating protein-protein interactions. RIP3 is a negative regulator of RhoA signaling that inhibits, either directly or indirectly, RhoA-stimulated actomyosin contractility. In plants RIP3 is localized at microtubules and interacts with the kinesin-13 family member AtKinesin-13A, suggesting a role for RIP3 in microtubule reorganization and a possible function in Rho proteins of plants (ROP)-regulated polar growth. It has a PH domain, two proline-rich regions which are putative binding sites for SH3 domains, and a COOH-terminal coiled-coil region which overlaps with the RhoA-binding region. 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.

Pssm-ID: 269942 Cd Length: 136 Bit Score: 38.96 E-value: 4.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767981142  591 QVKTWKRRWFVL-RQGQIMYY--KSPSDVirkPQGQVDLNSRCQIVRGEG--SQTFQL--ISEKKTYYLTADSPSLLEEW 663
Cdd:cd01236    50 RSKRWQRRWFVLyDDGELTYAldEMPDTL---PQGSIDMSQCTEVTDAEArtGHPHSLaiTTPERIHFVKADSKEEIRWW 126


                  ....*
gi 767981142  664 IRVLQ 668
Cdd:cd01236   127 LELLA 131

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