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Conserved domains on  [gi|1907183925|ref|XP_036009309|]
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pleckstrin homology domain-containing family A member 4 isoform X3 [Mus musculus]

Protein Classification

PEPP family PH domain-containing protein( domain architecture ID 10192522)

PEPP (phosphoinositol 3-phosphate-binding protein) family PH (pleckstrin homology) domain-containing protein similar to PH domain region of vertebrate pleckstrin homology domain-containing family A member 4/5/6 (PLEKHA4/5/6 or PEPP1/2/3) that interact specifically with PtdIns(3,4)P3, as well as leckstrin homology domain-containing family A member 7 (PLEKHA7)

CATH:  2.30.29.30
Gene Ontology:  GO:0005543|GO:0005515
SCOP:  3000134

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
64-167 1.29e-54

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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: 270068  Cd Length: 104  Bit Score: 183.24  E-value: 1.29e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  64 RDPNLPVHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGM 143
Cdd:cd13248     1 RDPNAPVVMSGWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANM 80
                          90       100
                  ....*....|....*....|....
gi 1907183925 144 RTYVLAADTLEDLRGWLRALGRAS 167
Cdd:cd13248    81 RTYYFAADTAEEMEQWMNAMSLAA 104
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
396-484 9.93e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


:

Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 45.28  E-value: 9.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATRE---------AAASGKAWGRQRL---------LQDRLVNVRAALCH 457
Cdd:COG4372    47 LEQLREELEQAREELEQLEEELEQARSELEQLEEEleelneqlqAAQAELAQAQEELeslqeeaeeLQEELEELQKERQD 126
                          90       100
                  ....*....|....*....|....*..
gi 1907183925 458 LAQERERVWDTYSGLEQDLGTLRETLE 484
Cdd:COG4372   127 LEQQRKQLEAQIAELQSEIAEREEELK 153
 
Name Accession Description Interval E-value
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
64-167 1.29e-54

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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: 270068  Cd Length: 104  Bit Score: 183.24  E-value: 1.29e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  64 RDPNLPVHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGM 143
Cdd:cd13248     1 RDPNAPVVMSGWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANM 80
                          90       100
                  ....*....|....*....|....
gi 1907183925 144 RTYVLAADTLEDLRGWLRALGRAS 167
Cdd:cd13248    81 RTYYFAADTAEEMEQWMNAMSLAA 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
70-168 4.41e-22

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 91.46  E-value: 4.41e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925   70 VHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREE---SVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGMRTY 146
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL 80
                           90       100
                   ....*....|....*....|..
gi 1907183925  147 VLAADTLEDLRGWLRALGRASR 168
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
70-168 2.82e-19

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 83.77  E-value: 2.82e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  70 VHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDS---REESVLGSVLLPSYSVRPDGPGAPRGRRFTF---TAEHPGM 143
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFelrTGERTGK 80
                          90       100
                  ....*....|....*....|....*
gi 1907183925 144 RTYVLAADTLEDLRGWLRALGRASR 168
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
396-484 9.93e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 45.28  E-value: 9.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATRE---------AAASGKAWGRQRL---------LQDRLVNVRAALCH 457
Cdd:COG4372    47 LEQLREELEQAREELEQLEEELEQARSELEQLEEEleelneqlqAAQAELAQAQEELeslqeeaeeLQEELEELQKERQD 126
                          90       100
                  ....*....|....*....|....*..
gi 1907183925 458 LAQERERVWDTYSGLEQDLGTLRETLE 484
Cdd:COG4372   127 LEQQRKQLEAQIAELQSEIAEREEELK 153
 
Name Accession Description Interval E-value
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
64-167 1.29e-54

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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: 270068  Cd Length: 104  Bit Score: 183.24  E-value: 1.29e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  64 RDPNLPVHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGM 143
Cdd:cd13248     1 RDPNAPVVMSGWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANM 80
                          90       100
                  ....*....|....*....|....
gi 1907183925 144 RTYVLAADTLEDLRGWLRALGRAS 167
Cdd:cd13248    81 RTYYFAADTAEEMEQWMNAMSLAA 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
70-168 4.41e-22

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 91.46  E-value: 4.41e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925   70 VHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREE---SVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGMRTY 146
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTL 80
                           90       100
                   ....*....|....*....|..
gi 1907183925  147 VLAADTLEDLRGWLRALGRASR 168
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
74-163 9.91e-20

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 84.52  E-value: 9.91e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREESV--LGSVLLPS-YSVRPDGPGaprGRRFTFTAEHPGMRTYVLAA 150
Cdd:cd00821     3 GYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYkpKGSIPLSGiLEVEEVSPK---ERPHCFELVTPDGRTYYLQA 79
                          90
                  ....*....|...
gi 1907183925 151 DTLEDLRGWLRAL 163
Cdd:cd00821    80 DSEEERQEWLKAL 92
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
74-167 1.06e-19

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: 85.15  E-value: 1.06e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRL---WKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVrpDGPGAPRgRRFTFTAEHPGMRTYVLAA 150
Cdd:cd01260    17 GWLWKKKEAKSFFgqkWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKI--ERASECK-KKYAFKACHPKIKTFYFAA 93
                          90
                  ....*....|....*..
gi 1907183925 151 DTLEDLRGWLRALGRAS 167
Cdd:cd01260    94 ENLDDMNKWLSKLNMAI 110
PH pfam00169
PH domain; PH stands for pleckstrin homology.
70-168 2.82e-19

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 83.77  E-value: 2.82e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  70 VHIRGWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDS---REESVLGSVLLPSYSVRPDGPGAPRGRRFTF---TAEHPGM 143
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFelrTGERTGK 80
                          90       100
                  ....*....|....*....|....*
gi 1907183925 144 RTYVLAADTLEDLRGWLRALGRASR 168
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
67-167 5.93e-18

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 80.36  E-value: 5.93e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  67 NLPVHIRGWLHKQDSSGlRLWKRRWFVLSGHCLFYY--KDSREEsvLGSVLLPSYSVRPdgpgAPRGRRFTFTAEH--PG 142
Cdd:cd13288     5 NSPVDKEGYLWKKGERN-TSYQKRWFVLKGNLLFYFekKGDREP--LGVIVLEGCTVEL----AEDAEPYAFAIRFdgPG 77
                          90       100
                  ....*....|....*....|....*
gi 1907183925 143 MRTYVLAADTLEDLRGWLRALGRAS 167
Cdd:cd13288    78 ARSYVLAAENQEDMESWMKALSRAS 102
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
69-166 1.19e-14

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 270083  Cd Length: 114  Bit Score: 70.88  E-value: 1.19e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  69 PVHiRGWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVR-----PDGPG------APRGRRFTFT 137
Cdd:cd13263     3 PIK-SGWLKKQ-GSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKevpfnPEEPGkflfeiIPGGGGDRMT 80
                          90       100
                  ....*....|....*....|....*....
gi 1907183925 138 AEHpgmRTYVLAADTLEDLRGWLRALGRA 166
Cdd:cd13263    81 SNH---DSYLLMANSQAEMEEWVKVIRRV 106
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
74-165 7.59e-14

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241530  Cd Length: 114  Bit Score: 68.46  E-value: 7.59e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSV-----RPDGPG------APRGRRFTFTAEHpg 142
Cdd:cd13379     7 GWLRKQ-GGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVtehpcNEEEPGkflfevVPGGDRERMTANH-- 83
                          90       100
                  ....*....|....*....|...
gi 1907183925 143 mRTYVLAADTLEDLRGWLRALGR 165
Cdd:cd13379    84 -ETYLLMASTQNDMEDWVKSIRR 105
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
74-166 1.38e-13

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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: 270070  Cd Length: 98  Bit Score: 67.24  E-value: 1.38e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDS--REESVLGSVLLPSySVRPDGPGaprGRRFTFTAEHPGmRTYVLAAD 151
Cdd:cd13250     3 GYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDkkDEPTVMVEDLRLC-TVKPTEDS---DRRFCFEVISPT-KSYMLQAE 77
                          90
                  ....*....|....*
gi 1907183925 152 TLEDLRGWLRALGRA 166
Cdd:cd13250    78 SEEDRQAWIQAIQSA 92
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
74-163 1.99e-13

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 66.55  E-value: 1.99e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREES--VLGSVLLPSYSVRPDGPGAPrgrRFTFTAEHpgmRTYVLAAD 151
Cdd:cd13282     3 GYLTKL-GGKVKTWKRRWFVLKNGELFYYKSPNDVIrkPQGQIALDGSCEIARAEGAQ---TFEIVTEK---RTYYLTAD 75
                          90
                  ....*....|..
gi 1907183925 152 TLEDLRGWLRAL 163
Cdd:cd13282    76 SENDLDEWIRVI 87
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
74-167 5.95e-13

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. 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: 270126  Cd Length: 97  Bit Score: 65.47  E-value: 5.95e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGM-RTYVLAADT 152
Cdd:cd13316     4 GWMKKR-GERYGTWKTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPFRGSYGFKLVPPAVpKVHYFAVDE 82
                          90
                  ....*....|....*
gi 1907183925 153 LEDLRGWLRALGRAS 167
Cdd:cd13316    83 KEELREWMKALMKAT 97
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
74-167 6.54e-12

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 62.81  E-value: 6.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQ--DSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPdGPGAPRGRRFTFTAEH--PGMRTYVLA 149
Cdd:cd13308    13 GTLTKKggSQKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRA-AEERTSKLKFVFKIIHlsPDHRTWYFA 91
                          90
                  ....*....|....*...
gi 1907183925 150 ADTLEDLRGWLRALGRAS 167
Cdd:cd13308    92 AKSEDEMSEWMEYIRREI 109
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
74-166 7.70e-12

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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: 241282  Cd Length: 105  Bit Score: 62.22  E-value: 7.70e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKqdsSGLRL---WKRRWFVLSGHCLFYYKDSREESVLGSVLLPS----YSVRPDGP-GAPRGRRFTFTAEHPGmRT 145
Cdd:cd01251     6 GYLEK---TGPKQtdgFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIGSkeegYSVREGLPpGIKGHWGFGFTLVTPD-RT 81
                          90       100
                  ....*....|....*....|.
gi 1907183925 146 YVLAADTLEDLRGWLRALGRA 166
Cdd:cd01251    82 FLLSAETEEERREWITAIQKV 102
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
74-173 1.07e-11

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains 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: 270108  Cd Length: 103  Bit Score: 62.10  E-value: 1.07e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQ--DSSGL--RLWKRRWFVLSGHCLFYYK-DSREESVLGSVLLPSYSVRPDgpGAPRGRRFTFTAEHpgmRTYVL 148
Cdd:cd13296     3 GWLTKKggGSSTLsrRNWKSRWFVLRDTVLKYYEnDQEGEKLLGTIDIRSAKEIVD--NDPKENRLSITTEE---RTYHL 77
                          90       100
                  ....*....|....*....|....*
gi 1907183925 149 AADTLEDLRGWLRALGRASRAEGED 173
Cdd:cd13296    78 VAESPEDASQWVNVLTRVISATDLE 102
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
74-166 1.03e-10

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 59.64  E-value: 1.03e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDgpgAPRGRRFTF---TAEHPGM------- 143
Cdd:cd01252     7 GWLLKL-GGRVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREV---EDKKKPFCFelySPSNGQVikacktd 82
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907183925 144 ----------RTYVLAADTLEDLRGWLRALGRA 166
Cdd:cd01252    83 sdgkvvegnhTVYRISAASEEERDEWIKSIKAS 115
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
74-166 1.31e-10

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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: 270095  Cd Length: 106  Bit Score: 58.87  E-value: 1.31e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDS---REESVLGSVLLPS-YSVRpdgpGAPR--GRRFTFTAEHPGmRTYV 147
Cdd:cd13276     3 GWLEKQ-GEFIKTWRRRWFVLKQGKLFWFKEPdvtPYSKPRGVIDLSKcLTVK----SAEDatNKENAFELSTPE-ETFY 76
                          90
                  ....*....|....*....
gi 1907183925 148 LAADTLEDLRGWLRALGRA 166
Cdd:cd13276    77 FIADNEKEKEEWIGAIGRA 95
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
72-167 1.47e-10

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 59.75  E-value: 1.47e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSGLRlWKRRWFVLSGHCLFYYKDSREESVLGSVLLP-SYSVRPDGP-GAPRGRR-------FTFTAEHPG 142
Cdd:cd13261     7 KRGYLSKKTSDSGK-WHERWFALYQNLLFYFENESSSRPSGLYLLEgCYCERLPTPkGALKGKDhlekqhyFTISFRHEN 85
                          90       100
                  ....*....|....*....|....*
gi 1907183925 143 MRTYVLAADTLEDLRGWLRALGRAS 167
Cdd:cd13261    86 QRQYELRAETESDCDEWVEAIKQAS 110
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
73-181 2.11e-10

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. 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: 270094  Cd Length: 104  Bit Score: 58.11  E-value: 2.11e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQDSSGlRLWKRRWFVLSGHCLFYYKDS--REESVLGSVL-LPS-YSVRPdgpgAPRGRRFTF-TAEHPGMRtYV 147
Cdd:cd13275     2 KGWLMKQGSRQ-GEWSKHWFVLRGAALKYYRDPsaEEAGELDGVIdLSScTEVTE----LPVSRNYGFqVKTWDGKV-YV 75
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1907183925 148 LAADTLEDLRGWLRALGRAsraegedCGLPRSPA 181
Cdd:cd13275    76 LSAMTSGIRTNWIQALRKA-------AGLPSPPA 102
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
72-163 3.15e-10

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: 57.42  E-value: 3.15e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSGlRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGMRTYVLAAD 151
Cdd:cd13237     1 MSGYLQRRKKSK-KSWKRLWFVLKDKVLYTYKASEDVVALESVPLLGFTVVTIDESFEEDESLVFQLLHKGQLPIIFRAD 79
                          90
                  ....*....|..
gi 1907183925 152 TLEDLRGWLRAL 163
Cdd:cd13237    80 DAETAQRWIEAL 91
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
69-165 3.44e-10

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241529  Cd Length: 116  Bit Score: 58.03  E-value: 3.44e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  69 PVHIRGWLHKQDSSgLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVR--PDGPGAPRGRRFTFTAEHPGMR-- 144
Cdd:cd13378     2 GVLKAGWLKKQRSI-MKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNelPPNPEEPGKHLFEILPGGAGDRek 80
                          90       100
                  ....*....|....*....|....*..
gi 1907183925 145 ------TYVLAADTLEDLRGWLRALGR 165
Cdd:cd13378    81 vpmnheAFLLMANSQSDMEDWVKAIRR 107
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
72-163 2.07e-09

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 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 insects, spiders, mollusks, and nematodes. 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: 270135  Cd Length: 91  Bit Score: 55.04  E-value: 2.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSGLRL--WKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPdgpgAP--RGRRFTFTAEHPGMRTYv 147
Cdd:cd13326     1 YQGWLYQRRRKGKGGgkWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSP----APevKSRKYAFKVYHTGTVFY- 75
                          90
                  ....*....|....*.
gi 1907183925 148 LAADTLEDLRGWLRAL 163
Cdd:cd13326    76 FAAESQEDMKKWLDLL 91
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
74-167 2.94e-09

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: 55.22  E-value: 2.94e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQD---SSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRR-FTFTAEHPGMRTYVLA 149
Cdd:cd13266     5 GYLEKRRkdhSFFGSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNPTLRKDGKKdCCFELVCPDKRTYQFT 84
                          90
                  ....*....|....*...
gi 1907183925 150 ADTLEDLRGWLRALGRAS 167
Cdd:cd13266    85 AASPEDAEDWVDQISFIL 102
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
70-163 3.12e-08

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 52.24  E-value: 3.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  70 VHIRGWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLP---SYSVRPDgpgapRGRRFTFTAEHPGmRTY 146
Cdd:cd13298     6 VLKSGYLLKR-SRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSellAVAPLKD-----KKRKNVFGIYTPS-KNL 78
                          90
                  ....*....|....*..
gi 1907183925 147 VLAADTLEDLRGWLRAL 163
Cdd:cd13298    79 HFRATSEKDANEWVEAL 95
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
74-166 5.86e-08

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. 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: 270087  Cd Length: 126  Bit Score: 51.94  E-value: 5.86e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQ--------DSSGLRLWKRRWFVLS-----GHCLFYYKDSREESVLGSVLLPSYS--VRpdgpgAPRGRRFTFTA 138
Cdd:cd13267    10 GYLYKGpenssdsfISLAMKSFKRRFFHLKqlvdgSYILEFYKDEKKKEAKGTIFLDSCTgvVQ-----NSKRRKFCFEL 84
                          90       100
                  ....*....|....*....|....*...
gi 1907183925 139 EHPGMRTYVLAADTLEDLRGWLRALGRA 166
Cdd:cd13267    85 RMQDKKSYVLAAESEAEMDEWISKLNKI 112
PH_anillin cd01263
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
70-166 9.03e-08

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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: 269964  Cd Length: 121  Bit Score: 51.12  E-value: 9.03e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  70 VHIRGWLH-KQDSSGLRLWKRRWFVLSGHCLFYYK---DSREESVLGSVLLP---SYSVRPdgpgAPR---GRRFTF--- 136
Cdd:cd01263     2 VEYRGFLTvFEDVSGLGAWHRRWCVLRGGYLSFWKypdDEEKKKPIGSIDLTkciTEKVEP----APRelcARPNTFlle 77
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907183925 137 ----TAEHPGMRT-----YVLAADTLEDLRGWLRALGRA 166
Cdd:cd01263    78 tlrpAEDDDRDDTnekirVLLSADTKEERIEWLSALNQT 116
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
73-163 1.09e-07

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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: 270109  Cd Length: 126  Bit Score: 51.28  E-value: 1.09e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQDSSGL-RLW---KRRWFVLSGHCLFYYKDSREESV-LGSVLLPSYS--VRPDGPGAPRGRRFTFTAeHPGMRT 145
Cdd:cd13297    16 RGWLYKEGGKGGaRGNltkKKRWFVLTGNSLDYYKSSEKNSLkLGTLVLNSLCsvVPPDEKMAKETGYWTFTV-HGRKHS 94
                          90
                  ....*....|....*...
gi 1907183925 146 YVLAADTLEDLRGWLRAL 163
Cdd:cd13297    95 FRLYTKLQEEAMRWVNAI 112
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
74-163 1.18e-07

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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: 270073  Cd Length: 94  Bit Score: 50.08  E-value: 1.18e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSG-LRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPdgpgAPRGRRFTFtaeHPGMRTYVLAADT 152
Cdd:cd13253     4 GYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVR----AVGDNKFEL---VTTNRTFVFRAES 76
                          90
                  ....*....|.
gi 1907183925 153 LEDLRGWLRAL 163
Cdd:cd13253    77 DDERNLWCSTL 87
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
74-163 1.43e-07

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. 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: 269966  Cd Length: 102  Bit Score: 50.01  E-value: 1.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRL--WKRRWFVLS-GHC-LFYYKDSREESVLGSVLLP--SYSVRPD-GPGaprgrrfTFTAEHPGmRTY 146
Cdd:cd01265     4 GYLNKLETRGLGLkgWKRRWFVLDeSKCqLYYYRSPQDATPLGSIDLSgaAFSYDPEaEPG-------QFEIHTPG-RVH 75
                          90
                  ....*....|....*..
gi 1907183925 147 VLAADTLEDLRGWLRAL 163
Cdd:cd01265    76 ILKASTRQAMLYWLQAL 92
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
74-163 1.58e-07

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. 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: 270085  Cd Length: 108  Bit Score: 50.38  E-value: 1.58e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQdSSGLRLWKRRWFVLSGH-CLFYYKDSREESVLGSVLLPS--------YSVRPDGPGAPRGRRFTFTAEHPGMR 144
Cdd:cd13265     7 GWLLRQ-STILKRWKKNWFVLYGDgNLVYYEDETRREVEGRINMPRecrnirvgLECRDVQPPEGRSRDCLLQIVLRDGS 85
                          90
                  ....*....|....*....
gi 1907183925 145 TYVLAADTLEDLRGWLRAL 163
Cdd:cd13265    86 TLFLCAESADDALAWKLAL 104
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
74-163 2.00e-07

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 49.63  E-value: 2.00e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSgLRLWKRRWFVLSGHCLFYYKDSREESVLGSV-LLPSYSVRPDGpgaPRGRRFTFTAEHPGmRTYVLAADT 152
Cdd:cd10573     7 GYLTKLGGI-VKNWKTRWFVLRRNELKYFKTRGDTKPIRVLdLRECSSVQRDY---SQGKVNCFCLVFPE-RTFYMYANT 81
                          90
                  ....*....|.
gi 1907183925 153 LEDLRGWLRAL 163
Cdd:cd10573    82 EEEADEWVKLL 92
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
73-172 2.16e-07

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 49.99  E-value: 2.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQDSSgLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYS---VRPDGPGapRGRRFTFTAEHpgmRTYVLA 149
Cdd:cd13273    11 KGYLWKKGHL-LPTWTERWFVLKPNSLSYYKSEDLKEKKGEIALDSNCcveSLPDREG--KKCRFLVKTPD---KTYELS 84
                          90       100
                  ....*....|....*....|....*.
gi 1907183925 150 AdtlEDLRG---WLRALGRASRAEGE 172
Cdd:cd13273    85 A---SDHKTrqeWIAAIQTAIRLSQE 107
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
87-166 2.91e-07

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 49.72  E-value: 2.91e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  87 WKRRWFVLSGHCLFYYKDSREESVLGsvLLPSYSVRPDGPGAPRGRRFTFTAEHPGmRTYVLAADTLEDLRGWLRALGRA 166
Cdd:cd13255    22 WKKRWFVLRPTKLAYYKNDKEYRLLR--LIDLTDIHTCTEVQLKKHDNTFGIVTPA-RTFYVQADSKAEMESWISAINLA 98
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
74-170 4.48e-07

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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: 269955  Cd Length: 113  Bit Score: 48.91  E-value: 4.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLH-KQD------SSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPS---YSVR---PDGPGAPRGRRFTFTAEH 140
Cdd:cd01253     4 GWLHyKQIvtdkgkRVSDRSWKQAWAVLRGHSLYLYKDKREQTPALSIELGSeqrISIRgciVDIAYSYTKRKHVFRLTT 83
                          90       100       110
                  ....*....|....*....|....*....|
gi 1907183925 141 PGMRTYVLAADTLEDLRGWLRALGRASRAE 170
Cdd:cd01253    84 SDFSEYLFQAEDRDDMLGWIKAIQENSNAE 113
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
74-163 7.89e-07

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: 48.01  E-value: 7.89e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRLWKRRWFVLSGHCLFYYKDSREESVLgsVLLPSYS----VRPDGPgaPRGRRFTFTAEHPGMRtYVLA 149
Cdd:cd13299    10 GYLQVLKKKGVNQWKKYWLVLRNRSLSFYKDQSEYSPV--KIIPIDDiidvVELDPL--SKSKKWCLQIITPEKR-IRFC 84
                          90
                  ....*....|....
gi 1907183925 150 ADTLEDLRGWLRAL 163
Cdd:cd13299    85 ADDEESLIKWLGAL 98
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
66-163 1.82e-06

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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: 275402  Cd Length: 116  Bit Score: 47.23  E-value: 1.82e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  66 PNLPVHIR-----GWLHKQDSSGLRlWKRRWFVLSGHCLFYYKDSREESV-LGSVLLpSY--SVRPDGPGAPRGRRFTFT 137
Cdd:cd13215    12 AYLPKRSGaviksGYLSKRSKRTLR-YTRYWFVLKGDTLSWYNSSTDLYFpAGTIDL-RYatSIELSKSNGEATTSFKIV 89
                          90       100
                  ....*....|....*....|....*.
gi 1907183925 138 AEHpgmRTYVLAADTLEDLRGWLRAL 163
Cdd:cd13215    90 TNS---RTYKFKADSETSADEWVKAL 112
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
72-166 5.00e-06

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.


Pssm-ID: 405988  Cd Length: 105  Bit Score: 46.04  E-value: 5.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKqdsSGLRLWKRRWFVLSGH-CLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHP--------- 141
Cdd:pfam15413   1 IEGYLKK---KGPKTWKHRWFAVLRNgVLFYYKSEKMKVVKHVIVLSNYIVGKLGTDIISGALFKIDNIRSetsddllle 77
                          90       100
                  ....*....|....*....|....*...
gi 1907183925 142 ---GMRTYVLAADTLEDLRGWLRALGRA 166
Cdd:pfam15413  78 istETKIFFLYGDNNEETYEWVEALQEA 105
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
74-161 1.25e-05

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). 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: 270054  Cd Length: 105  Bit Score: 44.77  E-value: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRlWKRRWFVLSGHCLfYYKDSREESVLGSVL-----LPSYSV--RPDGPGaprGRRFTFTAE--HPGMR 144
Cdd:cd13234     5 GILYLEDPINHE-WYPHFFVLTSNKI-YYSEETENSPLGSLLrgildVPSCHVvkRPEGKN---SRPFVFILSpkSLSDP 79
                          90
                  ....*....|....*..
gi 1907183925 145 TYVLAADTLEDLRGWLR 161
Cdd:cd13234    80 PLDVAADSQEELQDWVQ 96
PH_dynamin cd01256
Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle ...
73-166 1.69e-05

Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle formation. It has an N-terminal GTPase domain, followed by a PH domain, a GTPase effector domain and a C-terminal proline arginine rich domain. Dynamin-like proteins, which are found in metazoa, plants and yeast have the same domain architecture as dynamin, but lack the 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: 269958  Cd Length: 112  Bit Score: 44.62  E-value: 1.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQDSSGLRLW-KRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRpDGPGAPRGRRFTFTAEHPGMR------- 144
Cdd:cd01256     6 KGWLTINNIGFMKGGsKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLR-DVEKGFMSRKHIFALFNTDQRnvykdyk 84
                          90       100
                  ....*....|....*....|..
gi 1907183925 145 TYVLAADTLEDLRGWLRALGRA 166
Cdd:cd01256    85 QLELSCETQEEVDSWKASFLRA 106
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
73-163 2.24e-05

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: 43.74  E-value: 2.24e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQDSSGLRlWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGP-GAPRGRRFTFT--AEHpgmRTYVLA 149
Cdd:cd01233     9 RGYLLFLEDATDG-WVRRWVVLRRPYLHIYSSEKDGDERGVINLSTARVEYSPDqEALLGRPNVFAvyTPT---NSYLLQ 84
                          90
                  ....*....|....
gi 1907183925 150 ADTLEDLRGWLRAL 163
Cdd:cd01233    85 ARSEKEMQDWLYAI 98
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
74-170 3.19e-05

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. 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: 270093  Cd Length: 97  Bit Score: 43.15  E-value: 3.19e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRlWKRRWFVLSGHCLFYYKDS----REESVLGSVLLPSYSVRpDGPGAprgrrftFTAEHPgMRTYVLA 149
Cdd:cd13274     4 GPLLKQTSSFQR-WKRRYFKLKGRKLYYAKDSksliFEEIDLSDASVAECSTK-NVNNS-------FTVITP-FRKLILC 73
                          90       100
                  ....*....|....*....|.
gi 1907183925 150 ADTLEDLRGWLRALGRASRAE 170
Cdd:cd13274    74 AESRKEMEEWISALKTVQQRE 94
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
63-166 4.64e-05

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. 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: 270090  Cd Length: 114  Bit Score: 43.50  E-value: 4.64e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  63 RRDPNLPVHIRGWLHKQDSSgLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPS-YSVRPDGPGAPRGRRFTFTAEHP 141
Cdd:cd13271     1 RQRAGRNVIKSGYCVKQGAV-RKNWKRRFFILDDNTISYYKSETDKEPLRTIPLREvLKVHECLVKSLLMRDNLFEIITT 79
                          90       100
                  ....*....|....*....|....*
gi 1907183925 142 GmRTYVLAADTLEDLRGWLRALGRA 166
Cdd:cd13271    80 S-RTFYIQADSPEEMHSWIKAISGA 103
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
71-163 6.42e-05

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. 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: 270098  Cd Length: 105  Bit Score: 42.63  E-value: 6.42e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  71 HIRGWL---HKQDSSGLRLWKRRWFVLSGHCLFYY-----KDSREESVLGSVLLPSYSVRPDgpgapRGRRFTFTAEHPG 142
Cdd:cd13280     1 EKSGWLymkTSVGKPNRTIWVRRWCFVKNGVFGMLslspsKTYVEETDKFGVLLCSVRYAPE-----EDRRFCFEVKIFK 75
                          90       100
                  ....*....|....*....|.
gi 1907183925 143 MRTYVLAADTLEDLRGWLRAL 163
Cdd:cd13280    76 DISIILQAETLKELKSWLTVF 96
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
396-484 9.93e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 45.28  E-value: 9.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATRE---------AAASGKAWGRQRL---------LQDRLVNVRAALCH 457
Cdd:COG4372    47 LEQLREELEQAREELEQLEEELEQARSELEQLEEEleelneqlqAAQAELAQAQEELeslqeeaeeLQEELEELQKERQD 126
                          90       100
                  ....*....|....*....|....*..
gi 1907183925 458 LAQERERVWDTYSGLEQDLGTLRETLE 484
Cdd:COG4372   127 LEQQRKQLEAQIAELQSEIAEREEELK 153
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
81-167 1.53e-04

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains 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: 270055  Cd Length: 98  Bit Score: 41.54  E-value: 1.53e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  81 SSGlrlWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHpGMRTYVLAADTLEDLRGWL 160
Cdd:cd13235    16 SNG---WQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPSEADNIDKDYVFKLQF-KSHVYFFRAESEYTFERWM 91

                  ....*..
gi 1907183925 161 RALGRAS 167
Cdd:cd13235    92 EVIRSAT 98
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
72-167 3.53e-04

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: 40.41  E-value: 3.53e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSglRLWKRRWFVLSGH---CLFYYKDSREESVLGSVLLPSYSVRPDGPGAPRGRRFTFTAEHPGmRTYVL 148
Cdd:cd13236    10 LCGFLQYSEKG--KTWQKVWCVIPRTeplVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEERLDGRHVFKLSQSK-QSHYF 86
                          90
                  ....*....|....*....
gi 1907183925 149 AADTLEDLRGWLRALGRAS 167
Cdd:cd13236    87 SAESEELQQRWLEALSRAA 105
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
72-163 3.79e-04

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: 40.56  E-value: 3.79e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSGLRlWKRRWFVLSGHCLFYYKDSREESV--LGSVLLPSYSVRPDgpgAPRGRRFTFtaeHPGMRTYVLA 149
Cdd:cd13294     1 VAGILYKWVNYGKG-WRSRWFVLQDGVLSYYKVHGPDKVkpSGEVHLKVSSIRES---RSDDKKFYI---FTGTKTLHLR 73
                          90
                  ....*....|....
gi 1907183925 150 ADTLEDLRGWLRAL 163
Cdd:cd13294    74 AESREDRAAWLEAL 87
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
392-496 4.11e-04

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


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 43.99  E-value: 4.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 392 QDRLLRQLQEDLDKRQEEKEQLEAALELTRQQLGQATREAAASGKAWGRQRL------LQDRLVNVRAALCHLAQERERv 465
Cdd:COG4717    86 KEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALeaelaeLPERLEELEERLEELRELEEE- 164
                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907183925 466 wdtYSGLEQDLGTLRETLEYLLHLGSPQDRA 496
Cdd:COG4717   165 ---LEELEAELAELQEELEELLEQLSLATEE 192
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
88-167 4.98e-04

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270078  Cd Length: 123  Bit Score: 40.77  E-value: 4.98e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  88 KRRWFVLSGHCLFYYKDSREESV---LGSVLLPSYSVRPDgPGAPRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRALG 164
Cdd:cd13258    37 KERWFKLKGNLLFYFRTNEFGDCsepIGAIVLENCRVQME-EITEKPFAFSIVFNDEPEKKYIFSCRSEEQCEQWIEALR 115

                  ...
gi 1907183925 165 RAS 167
Cdd:cd13258   116 QAS 118
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
393-512 5.34e-04

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


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 43.75  E-value: 5.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  393 DRLLRQLQEDLDKRQEEKEQLEAALELTRQQLGQATREAAASGkaWGRQRLLQDRLVNVRAALchlaQERERVWDTYSGL 472
Cdd:COG4913    294 EAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNG--GDRLEQLEREIERLEREL----EERERRRARLEAL 367
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907183925  473 -----------EQDLGTLRETLEYLLHlGSPQDRACAQQQLWMVEDTLAGL 512
Cdd:COG4913    368 laalglplpasAEEFAALRAEAAALLE-ALEEELEALEEALAEAEAALRDL 417
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
74-131 5.50e-04

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 40.01  E-value: 5.50e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907183925  74 GWLHKQdssGLRL--WKRRWFVL--SGHCLFYYKDSREESVLGSVLLPSY-SVRPDGP--GAPRG 131
Cdd:cd01235     7 GYLYKR---GALLkgWKQRWFVLdsTKHQLRYYESREDTKCKGFIDLAEVeSVTPATPiiGAPKR 68
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
396-514 6.52e-04

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


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 43.22  E-value: 6.52e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATREAAASgkAWGRQRLLQDRLVNVRAALCHLAQERERvwdtysgLEQD 475
Cdd:COG4717   158 LRELEEELEELEAELAELQEELEELLEQLSLATEEELQD--LAEELEELQQRLAELEEELEEAQEELEE-------LEEE 228
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907183925 476 LGTLRETLEyllhLGSPQDRACAQQQLWMVEDTLAGLGG 514
Cdd:COG4717   229 LEQLENELE----AAALEERLKEARLLLLIAAALLALLG 263
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
89-166 6.61e-04

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. 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: 270076  Cd Length: 110  Bit Score: 40.13  E-value: 6.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  89 RRWFVLSGHCLFYYKDSREESVLGSVL---LPSYSVRPDGPGAPRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRALGR 165
Cdd:cd13256    29 RRWCVLEDGFLSYYESERSPEPNGEIDvseIVCLAVSPPDTHPGDGFPFTFELYLESERLYLFGLETAEALHEWVKAIAK 108

                  .
gi 1907183925 166 A 166
Cdd:cd13256   109 A 109
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
396-486 7.37e-04

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 42.58  E-value: 7.37e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATREAAASgkawgRQRL--LQDRLVNVRAALCHLAQERERVWDTYSGLE 473
Cdd:COG4372    40 LDKLQEELEQLREELEQAREELEQLEEELEQARSELEQL-----EEELeeLNEQLQAAQAELAQAQEELESLQEEAEELQ 114
                          90
                  ....*....|...
gi 1907183925 474 QDLGTLRETLEYL 486
Cdd:COG4372   115 EELEELQKERQDL 127
PH_8 pfam15409
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
74-167 7.97e-04

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.


Pssm-ID: 405984  Cd Length: 89  Bit Score: 39.27  E-value: 7.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSGLRLWKRRWFVL--SGHCLFYYKDSReesvlGSVLLPSYSVRPDGPGA-PRGRRFTFTAehpGMRTYVLAA 150
Cdd:pfam15409   1 GILLKKRRKKLQGYAKRFFVLnfKSGTLSYYRDDN-----SSALRGKIPLSLAAISAnAKTREIIIDS---GMEVWHLKA 72
                          90
                  ....*....|....*..
gi 1907183925 151 DTLEDLRGWLRALGRAS 167
Cdd:pfam15409  73 LNEKDFQAWVDALEKAK 89
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
396-484 8.11e-04

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: 8.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 396 LRQLQEDLDKRQEEKEQLEAALELTRQQLGQATREAAAsgkAWGRQRLLQDRLVNVRAALCHLAQERERVWDTYSGLEQD 475
Cdd:COG1196   248 LEELEAELEELEAELAELEAELEELRLELEELELELEE---AQAEEYELLAELARLEQDIARLEERRRELEERLEELEEE 324

                  ....*....
gi 1907183925 476 LGTLRETLE 484
Cdd:COG1196   325 LAELEEELE 333
PH_CpORP2-like cd13293
Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...
72-166 1.00e-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: 1.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  72 IRGWLHKQDSSGLRlWKRRWFVLSGHCLfYYKDSREESVLGSVLLPSYSVR--PDGPgaprgRRFTFTAehpGMRTYVLA 149
Cdd:cd13293     1 MEGYLKKWTNIFNS-WKPRYFILYPGIL-CYSKQKGGPKKGTIHLKICDIRlvPDDP-----LRIIINT---GTNQLHLR 70
                          90
                  ....*....|....*..
gi 1907183925 150 ADTLEDLRGWLRALGRA 166
Cdd:cd13293    71 ASSVEEKLKWYNALKYA 87
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
74-176 1.09e-03

Grb2-associated binding protein family 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. Members here include insect, nematodes, and crustacean Gab2s. 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: 241535  Cd Length: 115  Bit Score: 39.35  E-value: 1.09e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  74 GWLHKQDSSG---LRLWKRRWFVL------SGHCLFYYKDSREESVLGSVLLP---------SYSVRPDgpgapRGRRFT 135
Cdd:cd13384     7 GWLTKSPPEKriwRAKWRRRYFVLrqseipGQYFLEYYTDRTCRKLKGSIDLDqceqvdaglTFETKNK-----LKDQHI 81
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907183925 136 FTAEHPgMRTYVLAADTLEDLRGWLRALGRAsraegedCGL 176
Cdd:cd13384    82 FDIRTP-KRTYYLVADTEDEMNKWVNCICTV-------CGL 114
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
87-166 1.10e-03

Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also called PLEKHA3/Pleckstrin homology domain-containing, family A member 3) regulates secretory transport from the trans-Golgi network to the plasma membrane. It is recruited through binding of PH domain to phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor 1 (ARF1). These two binding sites have little overlap the FAPP1 PH domain to associate with both ligands simultaneously and independently. FAPP1 has a N-terminal PH domain followed by a short proline-rich region. FAPP1 is a member of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), and Goodpasture antigen binding protein (GPBP). 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. FAPP2 (also called PLEKHA8/Pleckstrin homology domain-containing, family A member 8), a member of the Glycolipid lipid transfer protein(GLTP) family has an N-terminal PH domain that targets the TGN and C-terminal GLTP domain. FAPP2 functions to traffic glucosylceramide (GlcCer) which is made in the Golgi. It's interaction with vesicle-associated membrane protein-associated protein (VAP) could be a means of regulation. Some FAPP2s share the FFAT-like motifs found in GLTP. 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: 269951  Cd Length: 100  Bit Score: 38.93  E-value: 1.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  87 WKRRWFVLSGHCLFYYKdSREESVL---GSVLLPS--YSVRPDGPgaprgRRFTFTAehPGMRTYVLAADTLEDLRGWLR 161
Cdd:cd01247    15 WQPRWFVLDDGVLSYYK-SQEEVNQgckGSVKMSVceIIVHPTDP-----TRMDLII--PGEQHFYLKASSAAERQRWLV 86

                  ....*
gi 1907183925 162 ALGRA 166
Cdd:cd01247    87 ALGSA 91
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
87-163 1.47e-03

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 39.52  E-value: 1.47e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  87 WKRRWFVLSGHCLFYYKDSREE--SVLGSVLLPS-YSVRPDGPGAPRGRRFTFTAEHPGMRTYVLAAdTLEDLRGWLRAL 163
Cdd:cd01238    20 YKERWFVLTKSSLSYYEGDGEKrgKEKGSIDLSKvRCVEEVKDEAFFERKYPFQVVYDDYTLYVFAP-SEEDRDEWIAAL 98
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
69-168 2.01e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. 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: 241446  Cd Length: 103  Bit Score: 38.44  E-value: 2.01e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  69 PVHIRGWLHKQD--SSGlrlWKRRWFVLSGHCLFYYKDSREESVL--GSVLLPSYSVRPDgpgAPRGRRFTFTAEHPGM- 143
Cdd:cd13292     1 PPTMKGYLKKWTnyAKG---YKTRWFVLEDGVLSYYRHQDDEGSAcrGSINMKNARLVSD---PSEKLRFEVSSKTSGSp 74
                          90       100
                  ....*....|....*....|....*
gi 1907183925 144 RTYVLAADTLEDLRgWLRALGRASR 168
Cdd:cd13292    75 KWYLKANHPVEAAR-WIQALQKAIE 98
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
73-160 2.38e-03

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) 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: 270097  Cd Length: 92  Bit Score: 38.00  E-value: 2.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLH-KQDSSGLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYS--VRPDgpgaprGRRFTFTAEH-PGMRTYVL 148
Cdd:cd13279     4 SGWVSvKEDGLLSFRWSKRYLVLREQSLDFYKNESSSSASLSIPLKDISnvSRTD------LKPYCFEIVRkSSTKSIYI 77
                          90
                  ....*....|..
gi 1907183925 149 AADTLEDLRGWL 160
Cdd:cd13279    78 SVKSDDELYDWM 89
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
87-169 3.36e-03

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain 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: 270113  Cd Length: 108  Bit Score: 37.74  E-value: 3.36e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  87 WKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVrpDGPGAPRGRR-FTFTAEHPGMRTYVLAADTLEDLRGWLRALGR 165
Cdd:cd13301    19 WKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTI--TSPCLEYGKRpLVFKLTTAKGQEHFFQACSREERDAWAKDITK 96

                  ....
gi 1907183925 166 ASRA 169
Cdd:cd13301    97 AITC 100
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
87-160 3.57e-03

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: 37.91  E-value: 3.57e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907183925  87 WKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSVRPdgpgAPRGRRFT-----FTAEHPGMRTYVLAADTLEDLRGWL 160
Cdd:cd13380    21 WQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQM----APHLRKDSrrdscFELTTPGRRTYQFTAASPSEARDWV 95
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
73-163 5.11e-03

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. 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: 270101  Cd Length: 99  Bit Score: 36.97  E-value: 5.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  73 RGWLHKQdSSGLRLWKRRWFVLSGHCLFYYKDSRE--ESVLGSVLLPSYSVRPDGpgaprgrRFTFTAEHPGMRTYVLAA 150
Cdd:cd13284     2 KGWLLKW-TNYIKGYQRRWFVLSNGLLSYYRNQAEmaHTCRGTINLAGAEIHTED-------SCNFVISNGGTQTFHLKA 73
                          90
                  ....*....|...
gi 1907183925 151 DTLEDLRGWLRAL 163
Cdd:cd13284    74 SSEVERQRWVTAL 86
PH_rhotekin2 cd13249
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
78-163 5.17e-03

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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: 270069  Cd Length: 111  Bit Score: 37.36  E-value: 5.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  78 KQDSSGLRLWKRRWFVLSGHCLFYYK-----DSREESVLGSVLLPSYSVRP-DGPGAPRGRRFTFTAEHPGMR-TYVLAA 150
Cdd:cd13249    11 QQSVEGLQSWTRLYCVLKGGNLLCYYspeeiEAKVEPLLTIPINKETRIRAvEKDSKGRASSLSIINPYSGEEvTHVLSA 90
                          90
                  ....*....|...
gi 1907183925 151 DTLEDLRGWLRAL 163
Cdd:cd13249    91 DSREELQKWMEAL 103
PH_OPR5_ORP8 cd13286
Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; ...
64-141 7.41e-03

Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; Human ORP5 is proposed to function in efficient nonvesicular transfer of low-density lipoproteins-derived cholesterol (LDL-C) from late endosomes/lysosomes to the endoplasmic reticulum (ER). Human ORP8 is proposed to modulate lipid homeostasis and sterol regulatory element binding proteins (SREBP) activity. Both ORP5 and ORP8 contain a N-terminal PH domain, a C-terminal OSBP-related domain, followed by a transmembrane domain that localizes ORP5 to the ER. Unlike all the other human OSBP/ORPs they lack a FFAT motif (two phenylalanines in an acidic tract). 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: 270103  Cd Length: 130  Bit Score: 37.34  E-value: 7.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925  64 RDPNLPVhIRGWLHKQDSsgLRLWKRRWFVLSGHCLFYYKDSREESVLGSVLLPSYSV--RP---DGpgaprgrrFTFTA 138
Cdd:cd13286     3 KDPSVVV-LSDWLKIRGT--LKSWTKLWCVLKPGVLLLYKSPKHGQWVGTVLLNACEVieRPskkDG--------FCFKL 71

                  ...
gi 1907183925 139 EHP 141
Cdd:cd13286    72 YHP 74
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
393-514 9.40e-03

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


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 39.37  E-value: 9.40e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183925 393 DRLLRQLQEdLDKRQEEKEQLEAALELTRQQLgqatreaaasgkawgrQRLLQDRLVNVRAALCHLAQERERVWDTYSGL 472
Cdd:COG4717   149 EELEERLEE-LRELEEELEELEAELAELQEEL----------------EELLEQLSLATEEELQDLAEELEELQQRLAEL 211
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907183925 473 EQDLGTLRETLEYLL----HLGSPQDRACAQQQLWMVEDTLAGLGG 514
Cdd:COG4717   212 EEELEEAQEELEELEeeleQLENELEAAALEERLKEARLLLLIAAA 257
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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