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Conserved domains on  [gi|1958664592|ref|XP_038943910|]
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FYVE, RhoGEF and PH domain-containing protein 4 isoform X1 [Rattus norvegicus]

Protein Classification

FYVE, RhoGEF and PH domain-containing protein 4( domain architecture ID 10069400)

FYVE, RhoGEF and PH domain-containing protein 4 (FGD4) activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP, and also plays a role in regulating the actin cytoskeleton and cell shape

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
497-590 1.54e-60

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. 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: 275434  Cd Length: 94  Bit Score: 199.84  E-value: 1.54e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd15791     1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKYTVRTRIGIDGMKVVETQNEDYPHTFQVSGKERTLELQ 80
                          90
                  ....*....|....
gi 1958664592 577 ASSEQDKEEWIKAL 590
Cdd:cd15791    81 ASSEQDKEEWIKAL 94
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
281-465 2.72e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.79  E-value: 2.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 281 LHKIATELLLTERAYVSRLNLLDQVFYCKLLEEANrgSFPAEMVNKIFSNISSINAFHSKFLLPELEKRMQEWETTPRIG 360
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL--PLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 361 DILQKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQkiCGSLTLQHHMLEPIQRIPRYEMLLKDYLKKL 440
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156
                         170       180
                  ....*....|....*....|....*
gi 1958664592 441 SPDAPDWNDAKKSLEIISTAASHSN 465
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
711-813 2.84e-49

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: 169.07  E-value: 2.84e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 711 SAEVSGNSEVCSFLQYMEKSKPWQKIWCVIPKQDPLVLYMYGAPQDVRAQATIPLLGYIVDDMPKS--ADLPHSFKLTQS 788
Cdd:cd13236     1 ASAVPENSLLCGFLQYSEKGKTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEerLDGRHVFKLSQS 80
                          90       100
                  ....*....|....*....|....*
gi 1958664592 789 KSVHSFAADSEELKQKWLKIILLAV 813
Cdd:cd13236    81 KQSHYFSAESEELQQRWLEALSRAA 105
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
628-692 7.06e-43

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


:

Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 149.56  E-value: 7.06e-43
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQIM 692
Cdd:cd15741     1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
 
Name Accession Description Interval E-value
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
497-590 1.54e-60

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. 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: 275434  Cd Length: 94  Bit Score: 199.84  E-value: 1.54e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd15791     1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKYTVRTRIGIDGMKVVETQNEDYPHTFQVSGKERTLELQ 80
                          90
                  ....*....|....
gi 1958664592 577 ASSEQDKEEWIKAL 590
Cdd:cd15791    81 ASSEQDKEEWIKAL 94
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
281-465 2.72e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.79  E-value: 2.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 281 LHKIATELLLTERAYVSRLNLLDQVFYCKLLEEANrgSFPAEMVNKIFSNISSINAFHSKFLLPELEKRMQEWETTPRIG 360
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL--PLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 361 DILQKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQkiCGSLTLQHHMLEPIQRIPRYEMLLKDYLKKL 440
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156
                         170       180
                  ....*....|....*....|....*
gi 1958664592 441 SPDAPDWNDAKKSLEIISTAASHSN 465
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
711-813 2.84e-49

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: 169.07  E-value: 2.84e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 711 SAEVSGNSEVCSFLQYMEKSKPWQKIWCVIPKQDPLVLYMYGAPQDVRAQATIPLLGYIVDDMPKS--ADLPHSFKLTQS 788
Cdd:cd13236     1 ASAVPENSLLCGFLQYSEKGKTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEerLDGRHVFKLSQS 80
                          90       100
                  ....*....|....*....|....*
gi 1958664592 789 KSVHSFAADSEELKQKWLKIILLAV 813
Cdd:cd13236    81 KQSHYFSAESEELQQRWLEALSRAA 105
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
284-465 9.11e-47

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 164.78  E-value: 9.11e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 284 IATELLLTERAYVSRLNLLDQVFyckLLEEANRGSFPAEMVNKIFSNISSINAFHSKFLLpelEKRMQEWETTPRIGDIL 363
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF---LPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLL---EELLKEWISIQRIGDIF 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 364 QKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLLKDYLKKLSPD 443
Cdd:pfam00621  75 LKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPD 154
                         170       180
                  ....*....|....*....|..
gi 1958664592 444 APDWNDAKKSLEIISTAASHSN 465
Cdd:pfam00621 155 HPDYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
284-465 1.47e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 164.01  E-value: 1.47e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  284 IATELLLTERAYVSRLNLLDQVFYCKLLEEANrgSFPAEMVNKIFSNISSINAFHSKFLLpELEKRMQEWET-TPRIGDI 362
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK--LLSPNELETLFGNIEEIYEFHRDFLD-ELEERIEEWDDsVERIGDV 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  363 LQKLAPFLKMYGEYVKGFDNAVELVKNMTERvPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLLKDYLKKLSP 442
Cdd:smart00325  78 FLKLEEFFKIYSEYCSNHPDALELLKKLKKN-PRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE 156
                          170       180
                   ....*....|....*....|...
gi 1958664592  443 DAPDWNDAKKSLEIISTAASHSN 465
Cdd:smart00325 157 DHEDREDLKKALKAIKELANQVN 179
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
628-692 7.06e-43

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 149.56  E-value: 7.06e-43
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQIM 692
Cdd:cd15741     1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
627-694 5.40e-27

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 104.44  E-value: 5.40e-27
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664592  627 APRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDG-GRLNKVCKDCYQIMSG 694
Cdd:smart00064   1 RPHWIPDEEVSNCMGCGKEFN-LTKRRHHCRNCGRIFCSKCSSKKAPLPKLGiERPVRVCDDCYENLNG 68
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
628-693 1.73e-25

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 100.15  E-value: 1.73e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQL--EYDGGRLNKVCKDCYQIMS 693
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFT-FFRRRHHCRNCGRVFCSACSSKKISLlpELGSNKPVRVCDACYDTLQ 67
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
497-595 9.98e-17

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: 76.43  E-value: 9.98e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  497 LIKEGQILKL-AARNTSAQERYLFLFNNMLLYCVPRFSlvGSKFTVRTRVGIDGMKIVETHNE---EYPHTFQV-SGKER 571
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIkTSDRK 78
                           90       100
                   ....*....|....*....|....
gi 1958664592  572 TLELQASSEQDKEEWIKALQESID 595
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKAIA 102
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
278-531 4.57e-13

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 73.39  E-value: 4.57e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  278 EQKLHKIATELLLTERAYVSRLNLLDQvFYCKLLEEANrgSFPA----EMVNKIFSNISSINAFHSKFLlPELEKRMQEW 353
Cdd:COG5422    482 EIKRQEAIYEVIYTERDFVKDLEYLRD-TWIKPLEESN--IIPEnarrNFIKHVFANINEIYAVNSKLL-KALTNRQCLS 557
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  354 ETTPRIGDILQKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLL 433
Cdd:COG5422    558 PIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLL 637
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  434 KDYLKKLSPDAPDWNDAKKSLEIISTAASHSNSAIRKMENLKKLLEIYEMLGEEEDIVN-----PSNELIKEGqILKLAA 508
Cdd:COG5422    638 EEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlglndEYRKIIFKG-VLKRKA 716
                          250       260
                   ....*....|....*....|....*..
gi 1958664592  509 RN----TSAQERYLFLFNNMLLYCVPR 531
Cdd:COG5422    717 KSktdgSLRGDIQFFLLDNMLLFCKAK 743
PH pfam00169
PH domain; PH stands for pleckstrin homology.
497-594 1.04e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.89  E-value: 1.04e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSA-QERYLFLFNNMLLYCVPRFSlvGSKFTVRTRVGIDGMKIVETHNEEY---PHTFQV----SG 568
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDKS--GKSKEPKGSISLSGCEVVEVVASDSpkrKFCFELrtgeRT 78
                          90       100
                  ....*....|....*....|....*.
gi 1958664592 569 KERTLELQASSEQDKEEWIKALQESI 594
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWIKAIQSAI 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
721-813 3.53e-09

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: 54.86  E-value: 3.53e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  721 CSFLQYME--KSKPWQKIWCVIpkqDPLVLYMY---GAPQDVRAQATIPLLGYIVDDMP--KSADLPHSFKL-TQSKSVH 792
Cdd:smart00233   4 EGWLYKKSggGKKSWKKRYFVL---FNSTLLYYkskKDKKSYKPKGSIDLSGCTVREAPdpDSSKKPHCFEIkTSDRKTL 80
                           90       100
                   ....*....|....*....|.
gi 1958664592  793 SFAADSEELKQKWLKIILLAV 813
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
729-813 3.50e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 43.71  E-value: 3.50e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 729 KSKPWQKIWCVIPKQdplVLYMY---GAPQDVRAQATIPLLGYIVDD--MPKSADLPHSFKLT----QSKSVHSFAADSE 799
Cdd:pfam00169  14 KKKSWKKRYFVLFDG---SLLYYkddKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELRtgerTGKRTYLLQAESE 90
                          90
                  ....*....|....
gi 1958664592 800 ELKQKWLKIILLAV 813
Cdd:pfam00169  91 EERKDWIKAIQSAI 104
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
607-690 4.26e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 44.31  E-value: 4.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  607 AIAKENdiplEVSTAELGK--RAPRWIRDNEVT-MCMKCKESFNALTR----RRHHCRACGHVVCWKCSDYKAQLEY--- 676
Cdd:PTZ00303   432 GVAEEN----ELNTFGLTKllHNPSWQKDDESSdSCPSCGRAFISLSRplgtRAHHCRSCGIRLCVFCITKRAHYSFakl 507
                           90       100
                   ....*....|....*....|
gi 1958664592  677 ------DGGRLNKVCKDCYQ 690
Cdd:PTZ00303   508 akpgssDEAEERLVCDTCYK 527
 
Name Accession Description Interval E-value
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
497-590 1.54e-60

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. 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: 275434  Cd Length: 94  Bit Score: 199.84  E-value: 1.54e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd15791     1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKYTVRTRIGIDGMKVVETQNEDYPHTFQVSGKERTLELQ 80
                          90
                  ....*....|....
gi 1958664592 577 ASSEQDKEEWIKAL 590
Cdd:cd15791    81 ASSEQDKEEWIKAL 94
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
281-465 2.72e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.79  E-value: 2.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 281 LHKIATELLLTERAYVSRLNLLDQVFYCKLLEEANrgSFPAEMVNKIFSNISSINAFHSKFLLPELEKRMQEWETTPRIG 360
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL--PLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 361 DILQKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQkiCGSLTLQHHMLEPIQRIPRYEMLLKDYLKKL 440
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156
                         170       180
                  ....*....|....*....|....*
gi 1958664592 441 SPDAPDWNDAKKSLEIISTAASHSN 465
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
711-813 2.84e-49

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: 169.07  E-value: 2.84e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 711 SAEVSGNSEVCSFLQYMEKSKPWQKIWCVIPKQDPLVLYMYGAPQDVRAQATIPLLGYIVDDMPKS--ADLPHSFKLTQS 788
Cdd:cd13236     1 ASAVPENSLLCGFLQYSEKGKTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEerLDGRHVFKLSQS 80
                          90       100
                  ....*....|....*....|....*
gi 1958664592 789 KSVHSFAADSEELKQKWLKIILLAV 813
Cdd:cd13236    81 KQSHYFSAESEELQQRWLEALSRAA 105
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
499-590 7.66e-48

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; 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. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). 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: 275410  Cd Length: 92  Bit Score: 164.58  E-value: 7.66e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQAS 578
Cdd:cd13328     1 KEGQILKLSAKNGTPQPRYLFLFNDMLLYCVPKLSLVGQKFSVRNRLDVAGMKVREPVNENYPHTFKISGKERSLELQAS 80
                          90
                  ....*....|..
gi 1958664592 579 SEQDKEEWIKAL 590
Cdd:cd13328    81 SAEEKDEWIQAI 92
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
284-465 9.11e-47

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 164.78  E-value: 9.11e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 284 IATELLLTERAYVSRLNLLDQVFyckLLEEANRGSFPAEMVNKIFSNISSINAFHSKFLLpelEKRMQEWETTPRIGDIL 363
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF---LPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLL---EELLKEWISIQRIGDIF 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 364 QKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLLKDYLKKLSPD 443
Cdd:pfam00621  75 LKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPD 154
                         170       180
                  ....*....|....*....|..
gi 1958664592 444 APDWNDAKKSLEIISTAASHSN 465
Cdd:pfam00621 155 HPDYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
284-465 1.47e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 164.01  E-value: 1.47e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  284 IATELLLTERAYVSRLNLLDQVFYCKLLEEANrgSFPAEMVNKIFSNISSINAFHSKFLLpELEKRMQEWET-TPRIGDI 362
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK--LLSPNELETLFGNIEEIYEFHRDFLD-ELEERIEEWDDsVERIGDV 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  363 LQKLAPFLKMYGEYVKGFDNAVELVKNMTERvPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLLKDYLKKLSP 442
Cdd:smart00325  78 FLKLEEFFKIYSEYCSNHPDALELLKKLKKN-PRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE 156
                          170       180
                   ....*....|....*....|...
gi 1958664592  443 DAPDWNDAKKSLEIISTAASHSN 465
Cdd:smart00325 157 DHEDREDLKKALKAIKELANQVN 179
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
497-590 4.38e-45

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; 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. Mutations in the FGD1 gene are responsible for 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. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. 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: 275423  Cd Length: 94  Bit Score: 156.72  E-value: 4.38e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd13388     1 LIKEGKILKISARNGDTQERYLFLFNDMLLYCSPRLRLIGQKYKVRARFDVDGMQVLEGDNLETPHTFYVRGKQRSLELQ 80
                          90
                  ....*....|....
gi 1958664592 577 ASSEQDKEEWIKAL 590
Cdd:cd13388    81 ASTQEEKAEWVDAI 94
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
497-604 5.23e-44

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; 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). 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: 275421  Cd Length: 108  Bit Score: 154.30  E-value: 5.23e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd13386     1 LLKEGPVLKISFRNNNPKERYLFLFNNMLLYCVPKVIQVGAKFQVHMRIDVDGMKVRELNDAEFPHSFLVSGKQRTLELQ 80
                          90       100
                  ....*....|....*....|....*...
gi 1958664592 577 ASSEQDKEEWIKALQESIDAFHQRHETF 604
Cdd:cd13386    81 ARSQEEMEAWIQAFQEAIDQNEKRTETF 108
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
628-692 7.06e-43

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 149.56  E-value: 7.06e-43
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQIM 692
Cdd:cd15741     1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
497-604 7.79e-39

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; 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. 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). 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: 275422  Cd Length: 108  Bit Score: 139.72  E-value: 7.79e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd13387     1 LIKEGHIQKLSAKNGTAQDRYLYLFNSMVLYCVPKLRLMGQKFSVREKIDIAGMQVQEIVKQNVPHTFTITGKKRSLELQ 80
                          90       100
                  ....*....|....*....|....*...
gi 1958664592 577 ASSEQDKEEWIKALQESIDAFHQRHETF 604
Cdd:cd13387    81 ARTEEEKKEWIQVIQATIEKHKQNSETF 108
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
497-604 1.35e-37

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; 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. Mutations in the FGD1 gene are responsible for 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). 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: 275392  Cd Length: 108  Bit Score: 135.92  E-value: 1.35e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQ 576
Cdd:cd01219     1 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPKLRLIGQKFSVRARIDVEGMELKESSSLNLPRTFLVSGKQRSLELQ 80
                          90       100
                  ....*....|....*....|....*...
gi 1958664592 577 ASSEQDKEEWIKALQESIDAFHQRHETF 604
Cdd:cd01219    81 ARTEEEKKDWIQAIQATIQRHEQTLETF 108
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
627-694 5.40e-27

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 104.44  E-value: 5.40e-27
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664592  627 APRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDG-GRLNKVCKDCYQIMSG 694
Cdd:smart00064   1 RPHWIPDEEVSNCMGCGKEFN-LTKRRHHCRNCGRIFCSKCSSKKAPLPKLGiERPVRVCDDCYENLNG 68
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
628-693 1.73e-25

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 100.15  E-value: 1.73e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQL--EYDGGRLNKVCKDCYQIMS 693
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFT-FFRRRHHCRNCGRVFCSACSSKKISLlpELGSNKPVRVCDACYDTLQ 67
FYVE_endofin cd15729
FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE ...
624-692 4.89e-21

FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE domain-containing protein 16 (ZFY16), or endosome-associated FYVE domain protein, is a FYVE domain-containing protein that is localized to EEA1-containing endosomes. It is regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Endofin is involved in Bone morphogenetic protein (BMP) signaling through interacting with Smad1 preferentially and enhancing Smad1 phosphorylation and nuclear localization upon BMP stimulation. It also functions as a scaffold protein that brings Smad4 to the proximity of the receptor complex in Transforming growth factor (TGF)-beta signaling. Moreover, endofin is a novel tyrosine phosphorylation target downstream of epidermal growth factor receptor (EGFR) in EGF-signaling. In addition, endofin plays a role in endosomal trafficking by recruiting cytosolic TOM1, an important molecule for membrane recruitment of clathrin, onto endosomal membranes.


Pssm-ID: 277268 [Multi-domain]  Cd Length: 68  Bit Score: 87.41  E-value: 4.89e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664592 624 GKRAPRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQIM 692
Cdd:cd15729     1 GKVAPVWVPDSEAPNCMQCEVKFT-FTKRRHHCRACGKVLCSACCSLKARLEYLDNKEARVCVPCYQTL 68
FYVE_FGD6 cd15743
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar ...
628-689 1.05e-20

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar proteins; FGD6, also termed zinc finger FYVE domain-containing protein 24 is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) whose biological function remains unclear. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Moreover, the FYVE domain of FGD6 is a canonical FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site.


Pssm-ID: 277282 [Multi-domain]  Cd Length: 61  Bit Score: 86.34  E-value: 1.05e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664592 628 PRWIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15743     1 PIWIPDSRVTMCMICTSEF-TVTWRRHHCRACGKVVCGSCSSNKAPLEYLKNKSARVCDECF 61
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
483-611 2.53e-20

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; 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: 275424  Cd Length: 124  Bit Score: 87.33  E-value: 2.53e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 483 MLGEEEdIVNPSNELIKEGQILKLAARNTsaQERYLFLFNNMLLYCVPrfSLVGSKFTVRTRVGIDGMKIVETHNEEYPH 562
Cdd:cd13389     1 LLGQYN-IVKPGRKLIKEGELMKVSRKEM--QPRYFFLFNDCLLYTTP--VQSSGMLKLNNELPLSGMKVKLPEDEEYSN 75
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1958664592 563 TFQVSGKERTLELQASSEQDKEEWIKALQESIDAFHQRHETFRNAIAKE 611
Cdd:cd13389    76 EFQIISTKRSFTLIASSEEERDEWVKALSRAIEEHTKKQRTFAENVSGV 124
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
490-596 6.00e-17

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; 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 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: 269928  Cd Length: 109  Bit Score: 77.36  E-value: 6.00e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 490 IVNPSNELIKEGQILKLAARntSAQERYLFLFNNMLLYcVPRFSLVGSKFTVRTRVGIDGMKIVETHNE-EYPHTFQVSG 568
Cdd:cd01220     1 LVQPGREFIREGCLQKLSKK--GLQQRMFFLFSDVLLY-TSRSPTPSLQFKVHGQLPLRGLMVEESEPEwGVAHCFTIYG 77
                          90       100
                  ....*....|....*....|....*...
gi 1958664592 569 KERTLELQASSEQDKEEWIKALQESIDA 596
Cdd:cd01220    78 GNRALTVAASSEEEKERWLEDLQRAIDA 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
497-595 9.98e-17

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: 76.43  E-value: 9.98e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  497 LIKEGQILKL-AARNTSAQERYLFLFNNMLLYCVPRFSlvGSKFTVRTRVGIDGMKIVETHNE---EYPHTFQV-SGKER 571
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIkTSDRK 78
                           90       100
                   ....*....|....*....|....
gi 1958664592  572 TLELQASSEQDKEEWIKALQESID 595
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKAIA 102
FYVE_like_SF cd00065
FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger ...
638-689 4.97e-16

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.


Pssm-ID: 277249 [Multi-domain]  Cd Length: 52  Bit Score: 72.56  E-value: 4.97e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 638 MCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDG-GRLNKVCKDCY 689
Cdd:cd00065     1 RCMLCGKKFS-LFRRRHHCRRCGRVFCSKCSSKKLPLPSFGsGKPVRVCDSCY 52
FYVE_ZFY26 cd15724
FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed ...
630-690 8.83e-16

FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed FYVE domain-containing centrosomal protein (FYVE-CENT), or spastizin, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that localizes to the centrosome and midbody. ZFY26 and its interacting partners TTC19 and KIF13A are required for cytokinesis. It also interacts with Beclin 1, a subunit of class III phosphatidylinositol 3-kinase complex, and may have potential implications for carcinogenesis. In addition, it has been considered as the causal agent of a rare form of hereditary spastic paraplegia. ZFY26 contains a FYVE domain that is important for targeting of FYVE-CENT to the midbody.


Pssm-ID: 277263 [Multi-domain]  Cd Length: 61  Bit Score: 72.16  E-value: 8.83e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 630 WIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQ 690
Cdd:cd15724     1 WVPDEAVSVCMVCQVERFSMFNRRHHCRRCGRVVCSSCSTKKMLVEGYRENPVRVCDQCYE 61
FYVE_PKHF cd15717
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), ...
630-689 9.14e-16

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), and similar proteins; This family includes protein containing both PH and FYVE domains 1 (phafin-1) and 2 (phafin-2). Phafin-1 is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway. Phafin-2 is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277257 [Multi-domain]  Cd Length: 61  Bit Score: 72.01  E-value: 9.14e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 630 WIRDNEVTMCMKCKES-FNALTRRrHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15717     2 WVPDSEAPVCMHCKKTkFTAINRR-HHCRKCGAVVCGACSSKKFLLPHQSSKPLRVCDTCY 61
FYVE_FGD3 cd15740
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar ...
632-689 1.96e-15

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar proteins; FGD3, also termed zinc finger FYVE domain-containing protein 5, is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) that undergoes the ubiquitin ligase SCFFWD1/beta-TrCP-mediated proteasomal degradation. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Due to this difference, FGD3 may play different roles from that of FGD1 to regulate cell morphology or motility. The FYVE domain of FGD3 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277279 [Multi-domain]  Cd Length: 54  Bit Score: 71.19  E-value: 1.96e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664592 632 RDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQleydGGRLNKVCKDCY 689
Cdd:cd15740     1 REKEKQTCKGCNESFNSITKRRHHCKQCGAVICGKCSEFKDL----ASRHNRVCRDCF 54
FYVE_LST2 cd15731
FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; ...
626-689 4.37e-15

FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; Lst2, also termed zinc finger FYVE domain-containing protein 28, is a monoubiquitinylated phosphoprotein that functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling. Unlike other FYVE domain-containing proteins, Lst2 displays primarily non-endosomal localization. Its endosomal localization is regulated by monoubiquitinylation. Lst2 physically binds Trim3, also known as BERP or RNF22, which is a coordinator of endosomal trafficking and interacts with Hrs and a complex that biases cargo recycling.


Pssm-ID: 277270 [Multi-domain]  Cd Length: 65  Bit Score: 70.45  E-value: 4.37e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 626 RAPRWIRDNEVTMCMKCKESFNALtRRRHHCRACGHVVCWKCSDYKAQL-EYDGGRLNKVCKDCY 689
Cdd:cd15731     1 DPPLWVPDEACPQCMACSAPFTVL-RRRHHCRNCGKIFCSRCSSNSVPLpRYGQMKPVRVCNHCF 64
PH1_FGD6 cd15793
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin ...
484-604 6.31e-15

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin Homology (PH) domain; 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: 275436  Cd Length: 123  Bit Score: 71.98  E-value: 6.31e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 484 LGEEEDIVNPSNELIKEGQILKLAARntSAQERYLFLFNNMLLYCVPRFSlvgSKFTVRTRVGIDGMKIVETHNEEYPHT 563
Cdd:cd15793     1 LNGHHEIVQPGRVFLKEGTLMKLSRK--VMQPRMFFLFNDALLYTTPVQS---GMYKLNNMLSLAGMKVSKPSQEAYQNE 75
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958664592 564 FQVSGKERTLELQASSEQDKEEWIKALQESIDAFHQRHETF 604
Cdd:cd15793    76 LNIESVERSFILSASSATERDEWLEAISRAIEEYAKKKITF 116
FYVE_RBNS5 cd15716
FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and ...
630-693 1.23e-14

FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and similar proteins; Rbsn-5, also termed zinc finger FYVE domain-containing protein 20, is a novel Rab5 effector that is complexed to the Sec1-like protein VPS45 and recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. It also binds to Rab4 and EHD1/RME-1, two regulators of the recycling route, and is involved in cargo recycling to the plasma membrane. Moreover, Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and plays a role of the apical endocytic trafficking of Fmi in the establishment of planar cell polarity (PCP).


Pssm-ID: 277256 [Multi-domain]  Cd Length: 61  Bit Score: 68.91  E-value: 1.23e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664592 630 WIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSdykaqlEYDGGRLnKVCKDCYQIMS 693
Cdd:cd15716     4 WVNDSDVPFCPDCGKKFN-LARRRHHCRLCGSIMCNKCS------QFLPLHI-RCCHHCKDLLE 59
FYVE_WDFY3 cd15719
FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar ...
630-692 1.29e-14

FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar proteins; WDFY3, also termed autophagy-linked FYVE protein (Alfy), is a ubiquitously expressed phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein required for selective macroautophagic degradation of aggregated proteins. It regulates the protein degradation through the direct interaction with the autophagy protein Atg5. Moreover, WDFY3 acts as a scaffold that bridges its cargo to the macroautophagic machinery via the creation of a greater complex with Atg12, Atg16L, and LC3. It also functionally associates with sequestosome-1/p62 (SQSTM1) in osteoclasts. WDFY3 shuttles between the nucleus and cytoplasm. It predominantly localizes to the nucleus and nuclear membrane under basal conditions, but is recruited to cytoplasmic ubiquitin-positive protein aggregates under stress conditions. WDFY3 contains a PH-BEACH domain assemblage, five WD40 repeats and a PtdIns3P-binding FYVE domain.


Pssm-ID: 277259 [Multi-domain]  Cd Length: 65  Bit Score: 68.95  E-value: 1.29e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664592 630 WIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEydggRLN-----KVCKDCYQIM 692
Cdd:cd15719     3 WVKDEGGDSCTGCSVRF-SLTERRHHCRNCGQLFCSKCSRFESEIR----RLRisrpvRVCQACYNIL 65
FYVE_PKHF2 cd15755
FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar ...
630-692 2.51e-14

FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar proteins; Phafin-2, also termed endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), or pleckstrin homology domain-containing family F member 2 (PKHF2), or PH domain-containing family F member 2, or PH and FYVE domain-containing protein 2, or zinc finger FYVE domain-containing protein 18, is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277294 [Multi-domain]  Cd Length: 64  Bit Score: 68.14  E-value: 2.51e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 630 WIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQIM 692
Cdd:cd15755     2 WVPDSEATVCMRCQKAKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQSSKPVRVCDFCYDLL 64
FYVE_FYCO1 cd15726
FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar ...
630-689 5.00e-14

FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar proteins; FYCO1, also termed zinc finger FYVE domain-containing protein 7, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport. It acts as an effector of GTP-bound Rab7, a GTPase that recruits FYCO1 to autophagosomes and has been implicated in autophagosome-lysosomal fusion. FYCO1 also interacts with two microtubule motor proteins, kinesin (KIF) 5B and KIF23, and thus functions as a platform for assembly of vesicle fusion and trafficking factors. FYCO1 contains an N-terminal alpha-helical RUN domain followed by a long central coiled-coil region, a FYVE domain and a GOLD (Golgi dynamics) domain in C-terminus.


Pssm-ID: 277265 [Multi-domain]  Cd Length: 58  Bit Score: 67.20  E-value: 5.00e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 630 WIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYkAQLEYDGGRLNKVCKDCY 689
Cdd:cd15726     1 WQDDTDVTHCLDCKSEF-SWMVRRHHCRLCGRIFCYACSNF-YVLTAHGGKKERCCKACF 58
FYVE_ZF21 cd15727
FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ...
627-689 1.41e-13

FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ZF21 is phosphoinositide-binding protein that functions as a regulator of focal adhesions and cell movement through interaction with focal adhesion kinase. It can also bind to the cytoplasmic tail of membrane type 1 matrix metalloproteinase, a potent invasion-promoting protease, and play a key role in regulating multiple aspects of cancer cell migration and invasion. ZF21 contains a FYVE domain, which corresponds to this model.


Pssm-ID: 277266 [Multi-domain]  Cd Length: 64  Bit Score: 66.25  E-value: 1.41e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664592 627 APRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEydggRLN-----KVCKDCY 689
Cdd:cd15727     1 EPPWVPDKECPVCMSCKKKFD-FFKRRHHCRRCGKCFCSDCCSNKVPLP----RMCfvdpvRVCNECA 63
FYVE_scVPS27p_like cd15760
FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 ...
629-689 1.88e-13

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and similar proteins; scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif.


Pssm-ID: 277299 [Multi-domain]  Cd Length: 59  Bit Score: 65.40  E-value: 1.88e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 629 RWIRDNevtMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLN--KVCKDCY 689
Cdd:cd15760     1 HWKPDS---RCDVCRKKFG-LFKRRHHCRNCGDSFCSEHSSRRIPLPHLGPLGVpqRVCDRCF 59
FYVE_RUFY1_like cd15721
FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; ...
630-689 2.11e-13

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277261 [Multi-domain]  Cd Length: 58  Bit Score: 65.48  E-value: 2.11e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 630 WIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEyDGGRLNKVCKDCY 689
Cdd:cd15721     1 WADDKEVTHCQQCEKEFS-LSRRKHHCRNCGGIFCNSCSDNTMPLP-SSAKPVRVCDTCY 58
FYVE_EEA1 cd15730
FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed ...
628-689 2.12e-13

FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed endosome-associated protein p162, or zinc finger FYVE domain-containing protein 2, is an essential component of the endosomal fusion machinery and required for the fusion and maturation of early endosomes in endocytosis. It forms a parallel coiled-coil homodimer in cells. EEA1 serves as the p97 ATPase substrate and the p97 ATPase may regulate the size of early endosomes by governing the oligomeric state of EEA1. It can interact with the GTP-bound form of Rab22a and be involved in endosomal membrane trafficking. EEA1 also functions as an obligate scaffold for angiotensin II-induced Akt activation in early endosomes. It can be phosphorylated by p38 mitogen-activated protein kinase (MAPK) and further regulate mu opioid receptor endocytosis. EEA1 consists of an N-terminal C2H2 Zn2+ finger, four long heptad repeats, and a C-terminal region containing a calmodulin binding (IQ) motif, a Rab5 interaction site, and a FYVE domain. This model corresponds to the FYVE domain that is responsible for binding phosphatidyl inositol-3-phosphate (PtdIns3P or PI3P) on the membrane.


Pssm-ID: 277269 [Multi-domain]  Cd Length: 63  Bit Score: 65.50  E-value: 2.12e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 628 PRWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQL-EYDggRLNKVCKDCY 689
Cdd:cd15730     1 RKWADDEEVQNCMACGKGFS-VTVRKHHCRQCGNIFCNECSSKTATTpSSK--KPVRVCDACF 60
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
278-531 4.57e-13

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 73.39  E-value: 4.57e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  278 EQKLHKIATELLLTERAYVSRLNLLDQvFYCKLLEEANrgSFPA----EMVNKIFSNISSINAFHSKFLlPELEKRMQEW 353
Cdd:COG5422    482 EIKRQEAIYEVIYTERDFVKDLEYLRD-TWIKPLEESN--IIPEnarrNFIKHVFANINEIYAVNSKLL-KALTNRQCLS 557
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  354 ETTPRIGDILQKLAPFLKMYGEYVKGFDNAVELVKNMTERVPQFKSVTEEIQKQKICGSLTLQHHMLEPIQRIPRYEMLL 433
Cdd:COG5422    558 PIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLL 637
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  434 KDYLKKLSPDAPDWNDAKKSLEIISTAASHSNSAIRKMENLKKLLEIYEMLGEEEDIVN-----PSNELIKEGqILKLAA 508
Cdd:COG5422    638 EEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlglndEYRKIIFKG-VLKRKA 716
                          250       260
                   ....*....|....*....|....*..
gi 1958664592  509 RN----TSAQERYLFLFNNMLLYCVPR 531
Cdd:COG5422    717 KSktdgSLRGDIQFFLLDNMLLFCKAK 743
FYVE_FGD5 cd15742
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar ...
628-689 4.57e-13

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar proteins; FGD5, also termed zinc finger FYVE domain-containing protein 23, is an endothelial cell (EC)-specific guanine nucleotide exchange factor (GEF) that regulates endothelial adhesion, survival, and angiogenesis by modulating phosphatidylinositol 3-kinase signaling. It functions as a novel genetic regulator of vascular pruning by activation of endothelial cell-targeted apoptosis. FGD5 is a homologue of FGD1 and contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. The FYVE domain of FGD5 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277281 [Multi-domain]  Cd Length: 67  Bit Score: 64.57  E-value: 4.57e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664592 628 PRWIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15742     1 PTLVPVSHVMMCMNCGSDF-TLTLRRHHCHACGKIVCRNCSRNKYPLKYLKDRPAKVCDGCF 61
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
471-592 4.60e-13

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 66.90  E-value: 4.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 471 MENLKKLLEIYEMLG--EEEDIVNPSNELIKEGQILKLAARNtsAQERYLFLFNNMLLYCvPRFSLVGSKFTVRTRVGID 548
Cdd:cd01224     1 MENLEKLAAWQSTVEgwEGEDLSDRSSELIHSGELTKISAGR--AQERTFFLFDHQLVYC-KKDLLRRKNYIYKGRIDTD 77
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 549 GMKIV-----ETHNEEYP--HTFQVS--GKERTLELQASSEQDKEEWIKALQE 592
Cdd:cd01224    78 NMEIEdlpdgKDDESGVTvkNAWKIYnaSKNKWYVLCAKSAEEKQRWLEAFAE 130
PH pfam00169
PH domain; PH stands for pleckstrin homology.
497-594 1.04e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.89  E-value: 1.04e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 497 LIKEGQILKLAARNTSA-QERYLFLFNNMLLYCVPRFSlvGSKFTVRTRVGIDGMKIVETHNEEY---PHTFQV----SG 568
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDKS--GKSKEPKGSISLSGCEVVEVVASDSpkrKFCFELrtgeRT 78
                          90       100
                  ....*....|....*....|....*.
gi 1958664592 569 KERTLELQASSEQDKEEWIKALQESI 594
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWIKAIQSAI 104
FYVE2_Vac1p_like cd15737
FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed ...
629-688 1.32e-12

FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The family corresponds to the second FYVE domain that is responsible for the ability of Pep7p to efficiently interact with Vac1p and Vps45p.


Pssm-ID: 277276 [Multi-domain]  Cd Length: 83  Bit Score: 64.06  E-value: 1.32e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 629 RWIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCW----KCS-----DYKAQLEYDGGRLNK--------------VC 685
Cdd:cd15737     1 PWEDDSSVTHCPICLRSFG-LLLRKHHCRLCGKVVCDdrrtKCStevplDLLSSALPDLPFVFKepqsdipddtksvrVC 79

                  ...
gi 1958664592 686 KDC 688
Cdd:cd15737    80 RDC 82
FYVE_MTMR4 cd15733
FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also ...
630-689 1.32e-12

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.


Pssm-ID: 277272 [Multi-domain]  Cd Length: 60  Bit Score: 63.22  E-value: 1.32e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 630 WIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKA-----QLeYDGGRlnkVCKDCY 689
Cdd:cd15733     1 WVPDHAASHCFGCDCEF-WLAKRKHHCRNCGNVFCADCSNYKLpipdeQL-YDPVR---VCNSCY 60
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
723-809 1.66e-12

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: 63.97  E-value: 1.66e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 723 FLQYMEKS-KPWQKIWCVIPKQdplVLYMYGAPQDVRAQATIPLLGYIVDDMPKSADLPHS--FKL-TQSKSVHSFAADS 798
Cdd:cd13237     4 YLQRRKKSkKSWKRLWFVLKDK---VLYTYKASEDVVALESVPLLGFTVVTIDESFEEDESlvFQLlHKGQLPIIFRADD 80
                          90
                  ....*....|.
gi 1958664592 799 EELKQKWLKII 809
Cdd:cd13237    81 AETAQRWIEAL 91
PH1_FGD5 cd15792
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin ...
489-604 3.83e-12

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. 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: 275435  Cd Length: 123  Bit Score: 64.09  E-value: 3.83e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 489 DIVNPSNELIKEGQILKLAARNTsaQERYLFLFNNMLLYCVPrfsLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSG 568
Cdd:cd15792     6 DLLQPGREFVKEGTLMKVSGKNR--HPRHLFLMNDVLLYTYP---QKDGKYRLKNTLAVSGMKVSRPVIEKAQNVLKIEV 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958664592 569 KERTLELQASSEQDKEEWIKALQESIDAFHQRHETF 604
Cdd:cd15792    81 SEVCLTLSASSCSERDEWYSCLSRTIPDDYKAQNAS 116
FYVE_PKHF1 cd15754
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar ...
630-690 4.59e-12

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway.


Pssm-ID: 277293 [Multi-domain]  Cd Length: 64  Bit Score: 61.90  E-value: 4.59e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 630 WIRDNEVTMCMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCYQ 690
Cdd:cd15754     2 WIPDKATDICMRCTQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPKPVRVCSLCYR 62
FYVE_PIKfyve_Fab1 cd15725
FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, ...
630-690 8.30e-12

FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, also termed FYVE finger-containing phosphoinositide kinase, or 1-phosphatidylinositol 3-phosphate 5-kinase, or phosphatidylinositol 3-phosphate 5-kinase (PIP5K3), or phosphatidylinositol 3-phosphate 5-kinase type III (PIPkin-III or type III PIP kinase), is a phosphoinositide 5-kinase that forms a complex with its regulators, the scaffolding protein Vac14 and the lipid phosphatase Fig4. The complex is responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] from phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). Then phosphatidylinositol-5-phosphate (PtdIns5P) is generated directly from PtdIns(3,5)P2. PtdIns(3,5)P2 and PtdIns5P regulate endosomal trafficking and responses to extracellular stimuli. At this point, PIKfyve is vital in early embryonic development. Moreover, PIKfyve forms a complex with ArPIKfyve (associated regulator of PIKfyve) and SAC3 at the endomembranes, which plays a role in receptor tyrosine kinase (RTK) degradation. The phosphorylation of PIKfyve by AKT can facilitate Epidermal growth factor receptor (EGFR) degradation. In addition, PIKfyve may participate in the regulation of the glutamate transporters EAAT2, EAAT3 and EAAT4, and the cystic fibrosis transmembrane conductance regulator (CFTR). It is also essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. It can be activated by protein kinase B (PKB/Akt) and further up-regulates human ether-a-go-go (hERG) channels. This family also includes the yeast and plant orthologs of human PIKfyve, Fab1. PIKfyve and its orthologs share a similar architecture. They contain an N-terminal FYVE domain, a middle region related to the CCT/TCP-1/Cpn60 chaperonins that are involved in productive folding of actin and tubulin, a second middle domain that contains a number of conserved cysteine residues (CCR) unique to this family, and a C-terminal lipid kinase domain related to PtdInsP kinases.


Pssm-ID: 277264 [Multi-domain]  Cd Length: 62  Bit Score: 60.80  E-value: 8.30e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664592 630 WIRDNEVTMCMKCKESFNALtRRRHHCRACGHVVCWKCSDYKAQ---LEYDGGRlnKVCKDCYQ 690
Cdd:cd15725     2 WMPDSSCKECYECSEKFTTF-RRRHHCRLCGQIFCSRCCNQEIPgkfIGYPGDL--RVCTYCCK 62
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
499-590 6.85e-11

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: 59.48  E-value: 6.85e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKL-AARNTSAQERYLFLFNNMLLYCVPRFSlvgSKFTVRTRVGIDG-MKIVETHNEEYPHTFQV-SGKERTLEL 575
Cdd:cd00821     1 KEGYLLKRgGGGLKSWKKRWFVLFEGVLLYYKSKKD---SSYKPKGSIPLSGiLEVEEVSPKERPHCFELvTPDGRTYYL 77
                          90
                  ....*....|....*
gi 1958664592 576 QASSEQDKEEWIKAL 590
Cdd:cd00821    78 QADSEEERQEWLKAL 92
FYVE_RUFY1 cd15758
FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; ...
630-692 1.23e-10

FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277297 [Multi-domain]  Cd Length: 71  Bit Score: 58.15  E-value: 1.23e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 630 WIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEyDGGRLNKVCKDCYQIM 692
Cdd:cd15758     6 WLKDDEATHCKQCEKEF-SISRRKHHCRNCGHIFCNTCSSNELALP-SYPKPVRVCDSCHTLL 66
FYVE_ZFYV1 cd15734
FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar ...
630-689 2.02e-10

FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar proteins; ZFYV1, also termed double FYVE-containing protein 1 (DFCP1), or SR3, or tandem FYVE fingers-1, is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYV1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by wortmannin, a PI3-kinase inhibitor. In addition to C-terminal tandem FYVE domain, ZFYV1 contains an N-terminal putative C2H2 type zinc finger and a possible nucleotide binding P-loop.


Pssm-ID: 277273 [Multi-domain]  Cd Length: 61  Bit Score: 56.96  E-value: 2.02e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 630 WIRDNEVTMCMKCKESFNaLTRRRHHCRACGHVVCWKCSDYK---AQLEYDGGrlNKVCKDCY 689
Cdd:cd15734     2 WVPDSEIKECSVCKRPFS-PRLSKHHCRACGQGVCDDCSKNRrpvPSRGWDHP--VRVCDPCA 61
FYVE_MTMR3 cd15732
FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also ...
629-689 1.80e-09

FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also termed Myotubularin-related phosphatase 3, or FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1), or zinc finger FYVE domain-containing protein 10, is a ubiquitously expressed phosphoinositide 3-phosphatase specific for phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and PIKfyve, which produces PtdIns(3,5)P2 from PtdIns3P. It regulates cell migration through modulating phosphatidylinositol 5-phosphate (PtdIns5P) levels. MTMR3 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain. Unlike conventional FYVE domains, the FYVE domain of MTMR3 neither confers endosomal localization nor binds to PtdIns3P. It is also not required for the enzyme activity of MTMR3. In contrast, the PH-G domain binds phosphoinositides.


Pssm-ID: 277271 [Multi-domain]  Cd Length: 61  Bit Score: 54.52  E-value: 1.80e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664592 629 RWIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQL-EYDGGRLNKVCKDCY 689
Cdd:cd15732     1 RWVPDHLAASCYGCEREF-WLASRKHHCRNCGNVFCGSCCNQKLPVpSQQLFEPSRVCKSCF 61
FYVE_spVPS27p_like cd15735
FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 ...
628-689 1.88e-09

FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 (spVps27p) and similar proteins; spVps27p, also termed suppressor of ste12 deletion protein 4 (Sst4p), is a conserved homolog of budding Saccharomyces cerevisiae Vps27 and of mammalian Hrs. It functions as a downstream factor for phosphatidylinositol 3-kinase (PtdIns 3-kinase) in forespore membrane formation with normal morphology. It colocalizes and interacts with Hse1p, a homolog of Saccharomyces cerevisiae Hse1p and of mammalian STAM, to form a complex whose ubiquitin-interacting motifs (UIMs) are important for sporulation. spVps27p contains a VHS (Vps27p/Hrs/Stam) domain, a FYVE domain, and two UIMs.


Pssm-ID: 277274 [Multi-domain]  Cd Length: 59  Bit Score: 54.07  E-value: 1.88e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 628 PRWIrDNEVtmCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEYDG-GRLNKVCKDCY 689
Cdd:cd15735     1 PEWV-DSDV--CMRCRTAF-TFTNRKHHCRNCGGVFCQQCSSKSLPLPHFGiNQPVRVCDGCY 59
FYVE_RABE_unchar cd15739
FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This ...
629-689 3.51e-09

FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This family includes a group of uncharacterized rab GTPase-binding effector proteins found in bilateria. Although their biological functions remain unclear, they all contain a FYVE domain that harbors a putative phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding site.


Pssm-ID: 277278 [Multi-domain]  Cd Length: 73  Bit Score: 53.88  E-value: 3.51e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 629 RWIRDNEVTMCMKCKESFNAlTRRRHHCRACGHVVCWKCSDyKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15739     3 RWQHEDDVDQCPNCKTPFSV-GKRKHHCRHCGKIFCSDCLT-KTVPSGPNRRPARVCDVCH 61
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
721-813 3.53e-09

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: 54.86  E-value: 3.53e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  721 CSFLQYME--KSKPWQKIWCVIpkqDPLVLYMY---GAPQDVRAQATIPLLGYIVDDMP--KSADLPHSFKL-TQSKSVH 792
Cdd:smart00233   4 EGWLYKKSggGKKSWKKRYFVL---FNSTLLYYkskKDKKSYKPKGSIDLSGCTVREAPdpDSSKKPHCFEIkTSDRKTL 80
                           90       100
                   ....*....|....*....|.
gi 1958664592  793 SFAADSEELKQKWLKIILLAV 813
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAI 101
FYVE_Hrs cd15720
FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) ...
639-689 2.53e-08

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.


Pssm-ID: 277260 [Multi-domain]  Cd Length: 61  Bit Score: 51.23  E-value: 2.53e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958664592 639 CMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQL-EYDGGRLNKVCKDCY 689
Cdd:cd15720     8 CHRCRVQF-GVFQRKHHCRACGQVFCGKCSSKSSTIpKFGIEKEVRVCDPCY 58
FYVE_WDFY1_like cd15718
FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and ...
628-689 2.67e-08

FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.


Pssm-ID: 277258 [Multi-domain]  Cd Length: 70  Bit Score: 51.17  E-value: 2.67e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664592 628 PRWIrdnEVTMCMKCKESF----------NALTRRRHHCRACGHVVCWKCSDYKAQL-----EYDggrlNKVCKDCY 689
Cdd:cd15718     1 PEWA---ESDNCQKCSRPFfwnfkqmwekKTLGVRQHHCRKCGKAVCDKCSSNRSTIpvmgfEFP----VRVCNECY 70
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
727-809 2.71e-08

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: 52.16  E-value: 2.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 727 MEKSKPWQKIWCVIpKQDPLVLYMYGAPQDVRAQATIPLLGYIVDDMPKSADLPHSFKL-TQSKSVHSFAADSEELKQKW 805
Cdd:cd00821    10 GGGLKSWKKRWFVL-FEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELvTPDGRTYYLQADSEEERQEW 88

                  ....
gi 1958664592 806 LKII 809
Cdd:cd00821    89 LKAL 92
FYVE_ANFY1 cd15728
FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar ...
628-692 3.31e-08

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.


Pssm-ID: 277267 [Multi-domain]  Cd Length: 63  Bit Score: 50.88  E-value: 3.31e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664592 628 PRWirdNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQ-LEYDGGRLNKVCKDCYQIM 692
Cdd:cd15728     2 PPW---ADGDYCYECGVKF-GITTRKHHCRHCGRLLCSKCSTKEVPiIKFDLNKPVRVCDVCFDVL 63
FYVE_WDFY1 cd15756
FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar ...
628-690 4.80e-08

FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar proteins; WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. In addition to FYVE domain, WDFY1 harbors multiple WD-40 repeats.


Pssm-ID: 277295 [Multi-domain]  Cd Length: 76  Bit Score: 50.84  E-value: 4.80e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664592 628 PRWIrdnEVTMCMKCKESF----------NALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLN-KVCKDCYQ 690
Cdd:cd15756     1 PQWL---ESDSCQKCEQPFfwnikqmwdtKTLGLRQHHCRKCGQAVCGKCSSKRSSYPIMGFEFQvRVCDSCFE 71
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
499-591 5.60e-08

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: 51.85  E-value: 5.60e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSlvgskftvRTRVGI---DGMkIVETHNEEYPHTFQV---SGKERT 572
Cdd:cd13288    10 KEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGD--------REPLGVivlEGC-TVELAEDAEPYAFAIrfdGPGARS 80
                          90
                  ....*....|....*....
gi 1958664592 573 LELQASSEQDKEEWIKALQ 591
Cdd:cd13288    81 YVLAAENQEDMESWMKALS 99
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
733-809 8.27e-08

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: 50.42  E-value: 8.27e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664592 733 WQKIWCVIpKQDplVLYMYGAPQDVRAQATIPLLGYIVDDMPKSADLPHSFKLTQSKSVHSFAADSEELKQKWLKII 809
Cdd:cd13326    18 WAKRWFVL-KGS--NLYGFRSQESTKADCVIFLPGFTVSPAPEVKSRKYAFKVYHTGTVFYFAAESQEDMKKWLDLL 91
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
730-806 1.15e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270058  Cd Length: 97  Bit Score: 50.34  E-value: 1.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 730 SKPWQKIWCVIpkQDPLVLYMYGAPQDVRAQATIPLLGYIVDDMPKSADL--------PHSFKLTQSKSVHSFAADSEEL 801
Cdd:cd13238    12 RKTWSRRWFAL--QPDFVLYSYKSQEDKLPLTATPVPGFLVTLLEKGSAVdplndpkrPRTFKMFHVKKSYYFQANDGDE 89

                  ....*
gi 1958664592 802 KQKWL 806
Cdd:cd13238    90 QKKWV 94
FYVE_MTMR_unchar cd15738
FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from ...
630-689 1.18e-07

FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from eumetazoa; This family includes a group of uncharacterized myotubularin-related proteins mainly found in eumetazoa. Although their biological functions remain unclear, they share similar domain architecture that consists of an N-terminal pleckstrin homology (PH) domain, a highly conserved region related to myotubularin proteins, a C-terminal FYVE domain. The model corresponds to the FYVE domain, which resembles the FYVE-related domain as it has an altered sequence in the basic ligand binding patch.


Pssm-ID: 277277 [Multi-domain]  Cd Length: 61  Bit Score: 49.25  E-value: 1.18e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 630 WIRDNEVTMCmKCKESFNALTRRrHHCRACGHVVCWKCSDYKAQLE-YDGGRLNKVCKDCY 689
Cdd:cd15738     3 WKSFRNVTEC-SCSTPFDHFSKK-HHCWRCGNVFCTRCIDKQRALPgHLSQRPVPVCRACY 61
FYVE_RUFY2 cd15759
FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; ...
630-692 2.46e-07

FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions.


Pssm-ID: 277298 [Multi-domain]  Cd Length: 71  Bit Score: 48.48  E-value: 2.46e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 630 WIRDNEVTMCMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEyDGGRLNKVCKDCYQIM 692
Cdd:cd15759     4 WLKDKEATHCKLCEKEF-SLSKRKHHCRNCGEIFCNACSDNELPLP-SSPKPVRVCDSCHAML 64
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
499-596 2.83e-07

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: 49.14  E-value: 2.83e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKlaaRNTSA----QERYLFLFNNMLLYCVPRFSLVGSKFTVRTRVgidgMKIVETHNEEYPHTFQVSGKERTLE 574
Cdd:cd13250     1 KEGYLFK---RSSNAfktwKRRWFSLQNGQLYYQKRDKKDEPTVMVEDLRL----CTVKPTEDSDRRFCFEVISPTKSYM 73
                          90       100
                  ....*....|....*....|..
gi 1958664592 575 LQASSEQDKEEWIKALQESIDA 596
Cdd:cd13250    74 LQAESEEDRQAWIQAIQSAIAS 95
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
731-812 5.67e-07

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: 48.42  E-value: 5.67e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 731 KPWQKIWCVIPKqdpLVLYMYGAPQDVRAQATIPLLGYIVDDMPKSADL--PHSFKLT-QSKSVHSFAADSEELKQKWLK 807
Cdd:cd13248    22 KNWRKRWFVLKD---NCLYYYKDPEEEKALGSILLPSYTISPAPPSDEIsrKFAFKAEhANMRTYYFAADTAEEMEQWMN 98

                  ....*
gi 1958664592 808 IILLA 812
Cdd:cd13248    99 AMSLA 103
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
472-593 7.48e-07

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 48.79  E-value: 7.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 472 ENLKKLLEIYEMLG-EEEDIVNPSNELIKEGQILKLAaRNTsAQERYLFLFNNMLLYcvprfslvGS------KFTVRTR 544
Cdd:cd01218     4 ANRRRIAAVESCFGgSGQPLVKPGRVLVGEGVLTKVC-RKK-PKPRQFFLFNDILVY--------GSivinkkKYNKQRI 73
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958664592 545 VGIDGMKIVET-HNEEYPHTFQVSGKERTLELQASSEQDKEEWIKALQES 593
Cdd:cd01218    74 IPLEDVKIEDLeDTGELKNGWQIISPKKSFVVYAATATEKSEWMDHINKC 123
FYVE_protrudin cd15723
FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc ...
639-690 7.93e-07

FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc finger FYVE domain-containing protein 27 (ZFY27 or ZFYVE27), is a FYVE domain-containing protein involved in transport of neuronal cargoes and implicated in the onset of hereditary spastic paraplegia (HSP). It is involved in neurite outgrowth through binding to spastin. Moreover, it functions as a key regulator of the Rab11-dependent membrane trafficking during neurite extension. It serves as an adaptor molecule that links its associated proteins, such as Rab11-GDP, VAP-A and -B, Surf4, and RTN3, to KIF5, a motor protein that mediates anterograde vesicular transport in neurons, and thus plays a key role in the maintenance of neuronal function. The FYVE domain of protrudin resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. In addition, unlike canonical FYVE domains that is located to early endosomes and specifically binds to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), the FYVE domain of protrudin is located to plasma membrane and preferentially binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). In addition to FYVE-related domain, protrudin also contains a Rab11-binding domain (RBD11), two hydrophobic domains, HP-1 and HP-2, an FFAT motif, and a coiled-coil domain.


Pssm-ID: 277262 [Multi-domain]  Cd Length: 62  Bit Score: 46.72  E-value: 7.93e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664592 639 CMKCKESFNALTRRRHHCRACGHVVCWKCSDYK------------AQleYDGGRlnkVCKDCYQ 690
Cdd:cd15723     2 CTGCGASFSVLLKKRRSCNNCGNAFCSRCCSKKvprsvmgatapaAQ--RETVF---VCSGCND 60
FYVE_RUFY4 cd15745
FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar ...
639-689 8.81e-07

FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.


Pssm-ID: 277284 [Multi-domain]  Cd Length: 52  Bit Score: 46.34  E-value: 8.81e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 639 CMKCKESFnALTRRRHHCRACGHVVCWKCSdYKAQLEY--DGGRLNKVCKDCY 689
Cdd:cd15745     2 CAICAKAF-SLFRRKYVCRLCGGVVCHSCS-SEDLVLSvpDTCIYLRVCKTCY 52
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
730-809 1.03e-06

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: 47.70  E-value: 1.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 730 SKPWQKIWCVIPKqdpLVLYMYGAPQDVRAQATIPLLGYIVDdMPKSADLPHS---FKLTQSKSVHSFAADSEELKQKWL 806
Cdd:cd13235    16 SNGWQKLWVVFTN---FCLFFYKSHQDEFPLASLPLLGYSVG-LPSEADNIDKdyvFKLQFKSHVYFFRAESEYTFERWM 91

                  ...
gi 1958664592 807 KII 809
Cdd:cd13235    92 EVI 94
FYVE_RUFY3 cd15744
FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar ...
639-689 1.21e-06

FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar proteins; RUFY3, also termed Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. Moreover, the FYVE domain of RUFY3 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue).


Pssm-ID: 277283 [Multi-domain]  Cd Length: 52  Bit Score: 45.87  E-value: 1.21e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 639 CMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15744     2 CSLCQEDFASLALPKHNCYNCGGTFCDACSSNELPLPSSIYEPARVCDVCY 52
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
726-813 2.66e-06

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270181  Cd Length: 106  Bit Score: 46.87  E-value: 2.66e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 726 YMEKSKP--------WQKIWCVIPKQdplVLYMYGAPQDVRAQATIPLLGYIV---DDMPKSADLPHSFK-LTQSKSVHS 793
Cdd:cd13381     6 YLEKRRKdhsffgfeWQKRWCALSNS---VFYYYGSDKDKQQKGEFAIDGYDVkmnNTLRKDAKKDCCFEiCAPDKRVYQ 82
                          90       100
                  ....*....|....*....|
gi 1958664592 794 FAADSEELKQKWLKIILLAV 813
Cdd:cd13381    83 FTAASPKEAEEWVQQIKFIL 102
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
499-591 3.95e-06

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: 45.78  E-value: 3.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKLAARNTSAQERYLFLFNNMLLYcvprFSLVGSKFTVRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQAS 578
Cdd:cd10573     5 KEGYLTKLGGIVKNWKTRWFVLRRNELKY----FKTRGDTKPIRVLDLRECSSVQRDYSQGKVNCFCLVFPERTFYMYAN 80
                          90
                  ....*....|...
gi 1958664592 579 SEQDKEEWIKALQ 591
Cdd:cd10573    81 TEEEADEWVKLLK 93
FYVE_ZFY19 cd15749
FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ...
639-689 1.13e-05

FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ZFY19, also termed mixed lineage leukemia (MLL) partner containing FYVE domain, is encoded by a novel gene, MLL partner containing FYVE domain (MPFYVE). The FYVE domain of ZFY19 resembles FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. The biological function of ZFY19 remains unclear.


Pssm-ID: 277288 [Multi-domain]  Cd Length: 51  Bit Score: 43.26  E-value: 1.13e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958664592 639 CMKCKESFnALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLNKVCKDCY 689
Cdd:cd15749     2 CFGCAAKF-SLFKKECGCKNCGRSFCKGCLTFSAVVPRKGNQKQKVCKQCH 51
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
494-590 1.67e-05

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. 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: 269963  Cd Length: 109  Bit Score: 44.66  E-value: 1.67e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 494 SNELIKEGQILKLAA--RNTsaqERYLFLFNNMLLYC-----VPRFSLVGSKFTVRTRVGIDGMKIVE-THNEEYPHTFQ 565
Cdd:cd01261     3 CNEFIMEGTLGKVGSgkRKT---ERHAFLFDGLLLLCksnrrRTSTGGPKPEYRLKEKFFIRKVEINDlEDTEELKNAFE 79
                          90       100
                  ....*....|....*....|....*.
gi 1958664592 566 -VSGKERTLELQASSEQDKEEWIKAL 590
Cdd:cd01261    80 iVPRDQPSVILFAKSAEEKNNWMAAL 105
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
490-590 2.23e-05

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating 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: 269929  Cd Length: 131  Bit Score: 44.94  E-value: 2.23e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 490 IVNPSNELIKEGQILKLAARNTSAQER--------YLFLFNNMLLYCVPRfslVGSKFTV-----RTRV-GIDGMKIVET 555
Cdd:cd01221     7 LISSSRWLVKRGELTELVEDGGSLTFRkkfsktpvYLFLFNDLLLITKKK---SEERYLVldyapRNLVqVEEVEDPLQL 83
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958664592 556 HNEEYPHTFQV------SGKERTLELQASSEQDKEEWIKAL 590
Cdd:cd01221    84 PQPLGKNLFLLtllenhEGKTVELLLSAESESDRERWLSAL 124
PH_Cool_Pix cd01225
Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There ...
498-591 2.23e-05

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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: 269932  Cd Length: 100  Bit Score: 43.84  E-value: 2.23e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 498 IKEGQILKLAARNTSAQERYLFLFNNMLLYCVPrfSLVGSKFTVRTRVGIDGMKIVETHN-EEYPHTFQVSGK--ERTLe 574
Cdd:cd01225     2 IHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSA--SPRMSGFIYEGKLPLTGISVNRLEDtEGIKNAFEISGPliERIV- 78
                          90
                  ....*....|....*..
gi 1958664592 575 LQASSEQDKEEWIKALQ 591
Cdd:cd01225    79 VICNSQQDQQEWLEHLQ 95
FYVE_SlaC2-c cd15753
FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; ...
639-670 3.25e-05

FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; SlaC2-c, also termed Rab effector MyRIP, or exophilin-8, or myosin-VIIa- and Rab-interacting protein, or synaptotagmin-like protein lacking C2 domains c, is a GTP-bound form of Rab27A-, myosin Va/VIIa-, and actin-binding protein mainly present on retinal melanosomes and secretory granules. It may play a role in insulin granule exocytosis. It is also involved in the control of isoproterenol (IPR)-induced amylase release from parotid acinar cells. SlaC2-c belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-c are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-c has a middle myosin-binding domain and a C-terminal actin-binding domain.


Pssm-ID: 277292  Cd Length: 49  Bit Score: 42.00  E-value: 3.25e-05
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1958664592 639 CMKCKESFNALTRRRHHCRACGHVVCWKCSDY 670
Cdd:cd15753     2 CMRCCSPFTFLFNRKRQCRDCKFNVCKSCASY 33
PH pfam00169
PH domain; PH stands for pleckstrin homology.
729-813 3.50e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 43.71  E-value: 3.50e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 729 KSKPWQKIWCVIPKQdplVLYMY---GAPQDVRAQATIPLLGYIVDD--MPKSADLPHSFKLT----QSKSVHSFAADSE 799
Cdd:pfam00169  14 KKKSWKKRYFVLFDG---SLLYYkddKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELRtgerTGKRTYLLQAESE 90
                          90
                  ....*....|....
gi 1958664592 800 ELKQKWLKIILLAV 813
Cdd:pfam00169  91 EERKDWIKAIQSAI 104
FYVE_scVPS27p_Vac1p_like cd15736
FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 ...
639-689 6.35e-05

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and FYVE-related domain 1 found in yeast protein VAC1 (Vac1p) and similar proteins; The family includes Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and protein VAC1 (Vac1p). scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif. Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The FYVE domain in both Vps27p and Vac1p harbors a zinc-binding site composed of seven Cysteines and one Histidine, which is different from that of other FYVE domain containing proteins.


Pssm-ID: 277275 [Multi-domain]  Cd Length: 56  Bit Score: 41.40  E-value: 6.35e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664592 639 CMKCKESFNaLTRRRHHCRACGHVVCWKCSDYKAQLEYDG-----GRLNKVCKDCY 689
Cdd:cd15736     2 CHTCSRTFN-LNIRAHHCRKCGKLFCRRHLPNMIPLNLSAydprnGKWYRCCHSCF 56
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
499-595 6.81e-05

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: 42.28  E-value: 6.81e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKLAARNTSAQERYLFLFNNMLLYCVPRfSLVGSKftVRTRVGIDGM-KIVEThneEYPHTFQVSGKERTLELQA 577
Cdd:cd13282     1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSP-NDVIRK--PQGQIALDGScEIARA---EGAQTFEIVTEKRTYYLTA 74
                          90
                  ....*....|....*...
gi 1958664592 578 SSEQDKEEWIKALQESID 595
Cdd:cd13282    75 DSENDLDEWIRVIQNVLR 92
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
726-814 6.92e-05

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: 42.89  E-value: 6.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 726 YMEKSKP--------WQKIWCVIPKQdplVLYMYGAPQDVRAQATIPLLGYIV---DDMPKSADLPHSFKLT-QSKSVHS 793
Cdd:cd13266     6 YLEKRRKdhsffgseWQKRWCAISKN---VFYYYGSDKDKQQKGEFAINGYDVrmnPTLRKDGKKDCCFELVcPDKRTYQ 82
                          90       100
                  ....*....|....*....|.
gi 1958664592 794 FAADSEELKQKWLKIILLAVT 814
Cdd:cd13266    83 FTAASPEDAEDWVDQISFILQ 103
FYVE_WDFY2 cd15757
FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also ...
628-689 7.71e-05

FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. WDFY2 contains WD40 motifs and a FYVE domain.


Pssm-ID: 277296 [Multi-domain]  Cd Length: 70  Bit Score: 41.59  E-value: 7.71e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664592 628 PRWIRDNEvtmCMKCKESF----------NALTRRRHHCRACGHVVCWKCSDYKAQLEYDGGRLN-KVCKDCY 689
Cdd:cd15757     1 PEWLDSDS---CQKCDQPFfwnfkqmwdsKKIGLRQHHCRKCGKAVCGKCSSKRSTIPLMGFEFEvRVCDSCH 70
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
498-594 9.61e-05

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: 42.69  E-value: 9.61e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 498 IKEGQILKLAARNTSAQERYLFLFNNMLLYcvprFSLVGSKfTVRTRVGIDGMKIVETHNEEYPHTFQ------------ 565
Cdd:cd01252     4 DREGWLLKLGGRVKSWKRRWFILTDNCLYY----FEYTTDK-EPRGIIPLENLSVREVEDKKKPFCFElyspsngqvika 78
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958664592 566 ---------VSGKERTLELQASSEQDKEEWIKALQESI 594
Cdd:cd01252    79 cktdsdgkvVEGNHTVYRISAASEEERDEWIKSIKASI 116
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
729-809 1.18e-04

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: 41.90  E-value: 1.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 729 KSKPWQKIWCVIpKQDPLvLYmYGAPQDV--RAQATIPLLGYIvdDMPKsADLPHSFKLTQSKSVHSFAADSEELKQKWL 806
Cdd:cd13282    11 KVKTWKRRWFVL-KNGEL-FY-YKSPNDVirKPQGQIALDGSC--EIAR-AEGAQTFEIVTEKRTYYLTADSENDLDEWI 84

                  ...
gi 1958664592 807 KII 809
Cdd:cd13282    85 RVI 87
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
731-809 2.03e-04

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: 41.60  E-value: 2.03e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 731 KPWQKIWCVIPKQDplvLYMYGAPQDVRAQATIPLLGYIVDDMPKSADLPHSFKL--------TQSKSVHS---FAADSE 799
Cdd:cd13263    17 KNWQQRWFVLRGDQ---LYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFeiipggggDRMTSNHDsylLMANSQ 93
                          90
                  ....*....|
gi 1958664592 800 ELKQKWLKII 809
Cdd:cd13263    94 AEMEEWVKVI 103
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
482-594 2.15e-04

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 41.60  E-value: 2.15e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 482 EMLGE----EEDIVNPSNELIKEGQilklaarntsaqERYLFLFNNMLLYCVP-RFSLVGSKFTVRTRVGIDGMKIVEtH 556
Cdd:cd13240    10 DSLGEvilqDSFQVWDPKQLIRKGR------------ERHVFLFELCLVFSKEvKDSNGKSKYIYKSRLMTSEIGVTE-H 76
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1958664592 557 NEEYPHTFQV-SGKERT----LELQASSEQDKEEWIKALQESI 594
Cdd:cd13240    77 IEGDPCKFALwTGRVPTsdnkIVLKASSLEVKQTWVKKLREVI 119
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
607-690 4.26e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 44.31  E-value: 4.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592  607 AIAKENdiplEVSTAELGK--RAPRWIRDNEVT-MCMKCKESFNALTR----RRHHCRACGHVVCWKCSDYKAQLEY--- 676
Cdd:PTZ00303   432 GVAEEN----ELNTFGLTKllHNPSWQKDDESSdSCPSCGRAFISLSRplgtRAHHCRSCGIRLCVFCITKRAHYSFakl 507
                           90       100
                   ....*....|....*....|
gi 1958664592  677 ------DGGRLNKVCKDCYQ 690
Cdd:PTZ00303   508 akpgssDEAEERLVCDTCYK 527
PH_PLD cd01254
Phospholipase D pleckstrin homology (PH) domain; PLD hydrolyzes phosphatidylcholine to ...
514-592 4.57e-04

Phospholipase D pleckstrin homology (PH) domain; PLD hydrolyzes phosphatidylcholine to phosphatidic acid (PtdOH), which can bind target proteins. PLD contains a PH domain, a PX domain and four conserved PLD signature domains. The PLD PH domain is specific for bisphosphorylated inositides. 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: 269956  Cd Length: 136  Bit Score: 41.09  E-value: 4.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 514 QERYLFLFNNMLLYCVPRFS-------LVGSKFTVRtrvgidgMKIVETHNEeYPHTFQVSGKERTLELQASSEQDKEEW 586
Cdd:cd01254    58 SKRWFIVKDSFLAYVKDPDSgaildvfLFDQEFKVS-------RGGKETKYG-SRHGLKITNLSRKLKLKCKSERKAKQW 129

                  ....*.
gi 1958664592 587 IKALQE 592
Cdd:cd01254   130 VESIEE 135
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
499-592 6.50e-04

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: 40.67  E-value: 6.50e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 499 KEGQILKlAARNTSA------QERYLFLFNNMLLYCVPRFslvGSKFTVRTRVGIDGMKIVE----THNEEYPHTFQVSG 568
Cdd:cd01238     1 LEGLLVK-RSQGKKRfgpvnyKERWFVLTKSSLSYYEGDG---EKRGKEKGSIDLSKVRCVEevkdEAFFERKYPFQVVY 76
                          90       100
                  ....*....|....*....|....
gi 1958664592 569 KERTLELQASSEQDKEEWIKALQE 592
Cdd:cd01238    77 DDYTLYVFAPSEEDRDEWIAALRK 100
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
451-591 8.20e-04

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 40.80  E-value: 8.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 451 KKSLEIISTAASHSNSAIRKMENLKKLLEIYEML-GEEEDIVNPSNELIKEGQILKLAARNtsaqERYLFLFNNMLLYCV 529
Cdd:cd13243     5 EEALDTMTQVAWHINDMKRKHEHAVRVQEIQSLLdGWEGPELTTYGDLVLEGTFRMAGAKN----ERLLFLFDKMLLITK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664592 530 PRfslVGSKFTVRTRVGIDGMKIVETHNEEyPHTFQV---SGKERTLELQASSEQDKEEWIKALQ 591
Cdd:cd13243    81 KR---EDGILQYKTHIMCSNLMLSESIPKE-PLSFQVlpfDNPKLQYTLQAKNQEQKRLWTQEIK 141
PH_IQSEC cd13318
IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also ...
511-594 1.10e-03

IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also called BRAG/Brefeldin A-resistant Arf-gunanine nucleotide exchange factor) family are a subset of Arf GEFs that have been shown to activate Arf6, which acts in the endocytic pathway to control the trafficking of a subset of cargo proteins including integrins and have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. The family consists of 3 members: IQSEC1 (also called BRAG2/GEP100), IQSEC2 (also called BRAG1), and IQSEC3 (also called SynArfGEF, BRAG3, or KIAA1110). IQSEC1 interacts with clathrin and modulates cell adhesion by regulating integrin surface expression and in addition to Arf6, it also activates the class II Arfs, Arf4 and Arf5. Mutations in IQSEC2 cause non-syndromic X-linked intellectual disability as well as reduced activation of Arf substrates (Arf1, Arf6). IQSEC3 regulates Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM. These members contains a IQ domain that may bind calmodulin, a PH domain that is thought to mediate membrane localization by binding of phosphoinositides, and a SEC7 domain that can promote GEF activity on ARF. 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: 270128  Cd Length: 128  Bit Score: 39.99  E-value: 1.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664592 511 TSAQERYLFLFNNMLLY---CVPRFSlvGSKFTVRTRVGIDGMKIVETHNEEYPH----TFQVSGKErTLELQASSEQDK 583
Cdd:cd13318    23 PGLHQREVFLFNDLLVVtkiFSKKKS--SVTYSFRQSFSLLGMQVLLFETSHYPFgirlTSPLDNKV-LITFNARNESDR 99
                          90
                  ....*....|.
gi 1958664592 584 EEWIKALQESI 594
Cdd:cd13318   100 KKFVEDLRESI 110
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
733-809 1.56e-03

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: 39.14  E-value: 1.56e-03
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gi 1958664592 733 WQKIWCVIpKQDplVLYMYGAPQDVR-AQATIPLlGYI--VDDMPKSADLPHSFKLTQSKSVHSFAADSEELKQKWLKII 809
Cdd:cd13215    37 YTRYWFVL-KGD--TLSWYNSSTDLYfPAGTIDL-RYAtsIELSKSNGEATTSFKIVTNSRTYKFKADSETSADEWVKAL 112
FYVE_Slp4 cd15764
FYVE-related domain found in synaptotagmin-like protein 4 (Slp4) and similar proteins; Slp4, ...
639-685 1.62e-03

FYVE-related domain found in synaptotagmin-like protein 4 (Slp4) and similar proteins; Slp4, also termed exophilin-2, or granuphilin, has been characterized as a regulator of the release of insulin granules from pancreatic beta-cells and dense core granules from PC12 neuronal cells by binding to Rab27A , and amylase granules from parotid gland acinar cells through interaction with syntaxin-2/3 in a Munc18-2-dependent manner on the apical plasma membrane. It can binds to syntaxin 2 in parotid acinar cells. It is also involved in granule transport by recruitment of the motor protein myosin Va. Moreover, it requires Rab8 to increase granule release in platelets. Slp4 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp4 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.


Pssm-ID: 277303  Cd Length: 50  Bit Score: 37.07  E-value: 1.62e-03
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gi 1958664592 639 CMKCKESFNALTRRRHHCRACGHVVCWKCSDYKAqleyDGGRLNKVC 685
Cdd:cd15764     6 CGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRP----NGSWVCSVC 48
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
733-815 1.74e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 38.93  E-value: 1.74e-03
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gi 1958664592 733 WQKIWCVIPKQDplvLYMYGAPQDVRAQATIPLLGYIVDdmpkSADLP---HSFKLT--QSKSVHsFAADSEELKQKWLK 807
Cdd:cd01260    33 WKKYWFVLKGSS---LYWYSNQQDEKAEGFINLPDFKIE----RASECkkkYAFKAChpKIKTFY-FAAENLDDMNKWLS 104

                  ....*...
gi 1958664592 808 IILLAVTG 815
Cdd:cd01260   105 KLNMAINK 112
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
561-594 1.77e-03

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: 38.84  E-value: 1.77e-03
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gi 1958664592 561 PHTFQVSGKERTLELQASSEQDKEEWIKALQESI 594
Cdd:cd13276    63 ENAFELSTPEETFYFIADNEKEKEEWIGAIGRAI 96
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
545-602 2.80e-03

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 38.19  E-value: 2.80e-03
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gi 1958664592 545 VGIDGmkivethneEYPHTFQVSGKERTLELQASSEQDKEEWIKALQESIDAFHQRHE 602
Cdd:cd13290    54 VGIDD---------EDDSTFTITVDQKTFHFQARDAEERERWIRALEDTILRHSQQYQ 102
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
495-603 2.90e-03

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: 38.05  E-value: 2.90e-03
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gi 1958664592 495 NELIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRfslvgSKFTVRTRVGIDGMKIVET--HNEEYPHTFQVSGKERT 572
Cdd:cd13273     6 LDVIKKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSE-----DLKEKKGEIALDSNCCVESlpDREGKKCRFLVKTPDKT 80
                          90       100       110
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gi 1958664592 573 LELQASSEQDKEEWIKALQESIdAFHQRHET 603
Cdd:cd13273    81 YELSASDHKTRQEWIAAIQTAI-RLSQEGKS 110
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
498-590 2.97e-03

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: 37.76  E-value: 2.97e-03
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gi 1958664592 498 IKEGQILKLAARNTSAQERYLFLFNNMLLYCVPRFSLVgskftvRTRVGIDGMKIVETHNEEYPHTFQVSGKERTLELQA 577
Cdd:cd13274     1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLI------FEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCA 74
                          90
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gi 1958664592 578 SSEQDKEEWIKAL 590
Cdd:cd13274    75 ESRKEMEEWISAL 87
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
495-592 3.68e-03

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: 37.61  E-value: 3.68e-03
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gi 1958664592 495 NELIKEGQILKLAARNTSAQERYLFLFNNMLLY------CVPRFSLVGSKFTVRTRVgidgmkivetHNEEYPHTFQVSG 568
Cdd:cd13298     4 DRVLKSGYLLKRSRKTKNWKKRWVVLRPCQLSYykdekeYKLRRVINLSELLAVAPL----------KDKKRKNVFGIYT 73
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gi 1958664592 569 KERTLELQASSEQDKEEWIKALQE 592
Cdd:cd13298    74 PSKNLHFRATSEKDANEWVEALRE 97
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
561-590 4.25e-03

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: 37.57  E-value: 4.25e-03
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gi 1958664592 561 PHTFQVSGKERTLELQASSEQDKEEWIKAL 590
Cdd:cd01233    69 PNVFAVYTPTNSYLLQARSEKEMQDWLYAI 98
PH1_AFAP cd13306
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are ...
711-809 4.50e-03

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. The amino terminal PH1 domain of AFAP1 has been known to function in intra-molecular regulation of AFAP1. In addition, the PH1 domain is a binding partner for PKCa and phospholipids. This cd is the first PH domain of AFAP. 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: 270116  Cd Length: 107  Bit Score: 37.46  E-value: 4.50e-03
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gi 1958664592 711 SAEVSGNSEVCSFLQYMEKSKPWQKIWCVIPKQDPLVlymYGAPQDVRAQATIPLLGYIVDDMPK-SADLPHSFKLT-QS 788
Cdd:cd13306     5 SMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLC---YKSSKDQQPQLELPLLGCSVIYVPKdGRRKKHELKFTpPG 81
                          90       100
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gi 1958664592 789 KSVHSFAADSEELKQKWLKII 809
Cdd:cd13306    82 AEALVLAVQSKEQAEQWLKVI 102
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
553-591 5.02e-03

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: 37.60  E-value: 5.02e-03
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gi 1958664592 553 VETHNEEYPHTFQVSGKERTLELQASSEQDKEEWIKALQ 591
Cdd:cd13215    75 LSKSNGEATTSFKIVTNSRTYKFKADSETSADEWVKALK 113
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
564-596 7.34e-03

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. 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: 241423  Cd Length: 106  Bit Score: 36.99  E-value: 7.34e-03
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1958664592 564 FQVSGKERTLELQASSEQDKEEWIKALQESIDA 596
Cdd:cd13269    70 LKITTPEESFTLVASTPQEKAEWLRAINQAIDQ 102
PH_SKIP cd13309
SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...
555-593 8.79e-03

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270119  Cd Length: 103  Bit Score: 36.59  E-value: 8.79e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958664592 555 THNEEYPHTFQVSGKERT-LELQASSEQDKEEWIKALQES 593
Cdd:cd13309    60 INNTERPHTFELILTDRSsLELAAPDEYEASEWLQSLCQS 99
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
561-600 9.78e-03

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: 36.53  E-value: 9.78e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958664592 561 PHTFQVSGKERTLELQASSEQDKEEWIKALQESIDAFHQR 600
Cdd:cd01265    63 PGQFEIHTPGRVHILKASTRQAMLYWLQALQSKRREYCNS 102
 
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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