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Conserved domains on  [gi|2756223972|ref|NP_001418184|]
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pleckstrin homology domain containing M3 [Rattus norvegicus]

Protein Classification

PH domain-containing protein; PH domain-containing RhoGEF family protein( domain architecture ID 10199815)

Pleckstrin homology (PH) domain-containing protein may be involved in targeting a protein to the appropriate cellular location or interacting with a binding partner; similar to the PH region of pleckstrin homology domain-containing family A member 2 (PLEKHA2/TAAP2) that binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2)| PH domain-containing RhoGEF family protein may function as a guanine nucleotide exchange factor; similar to Homo sapiens pleckstrin homology domain-containing family G member 4B and Danio rerio quattro

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
zf-RING_9 pfam13901
Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members ...
529-729 4.06e-97

Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members also carry a pleckstrin-homology domain, pfam00169


:

Pssm-ID: 464030  Cd Length: 205  Bit Score: 299.53  E-value: 4.06e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 529 KVCNYSGWYYCSSCHVDDSFLIPARIVHNWDTSKYKVSKQAKEFLEYVYEEPLIDIQQENPMLYLHAEPLATVARLRQRL 608
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 609 KSLRAYLFSCRAAVAEDLRR--RIFPREYLLQQIHLYSLADLQQVIEGKLAPFLGKVIKFATAHVYSCSLCSQKGFICEI 686
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 2756223972 687 CNNGEILYPFEDISTSRCESCGSVFHSEC-KEKSVPCPRCVRRE 729
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCfRSGASPCPKCERLQ 204
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
364-451 1.01e-60

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13327:

Pssm-ID: 473070  Cd Length: 88  Bit Score: 199.11  E-value: 1.01e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 364 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 443
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 2756223972 444 AQEWMEAL 451
Cdd:cd13327    81 AQEWMEAL 88
PH_PLEKHM3_1 cd14674
Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 ...
215-304 1.71e-55

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 (also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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: 270193  Cd Length: 90  Bit Score: 184.75  E-value: 1.71e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 215 KKGYLEIRKNHDSYWQSCYAELSPYNLNFYSLDSSGNQNLYATYQLSHFQSISVLGNLEARMVDTVLYDNSQLQLKAESP 294
Cdd:cd14674     1 KKGYLEIRIDPDSYWQGCYAELSPYELYIYGLDSSGNQNLTDTYHLSHFQSITVTGSHEAKLVNVVLTDNRQLQLKAESA 80
                          90
                  ....*....|
gi 2756223972 295 WEALDWGQKL 304
Cdd:cd14674    81 WEALDWGQKL 90
 
Name Accession Description Interval E-value
zf-RING_9 pfam13901
Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members ...
529-729 4.06e-97

Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members also carry a pleckstrin-homology domain, pfam00169


Pssm-ID: 464030  Cd Length: 205  Bit Score: 299.53  E-value: 4.06e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 529 KVCNYSGWYYCSSCHVDDSFLIPARIVHNWDTSKYKVSKQAKEFLEYVYEEPLIDIQQENPMLYLHAEPLATVARLRQRL 608
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 609 KSLRAYLFSCRAAVAEDLRR--RIFPREYLLQQIHLYSLADLQQVIEGKLAPFLGKVIKFATAHVYSCSLCSQKGFICEI 686
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 2756223972 687 CNNGEILYPFEDISTSRCESCGSVFHSEC-KEKSVPCPRCVRRE 729
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCfRSGASPCPKCERLQ 204
PH_PLEKHM3_2 cd13327
Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 ...
364-451 1.01e-60

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 (also called differentiation associated protein/DAPR)(also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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: 270136  Cd Length: 88  Bit Score: 199.11  E-value: 1.01e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 364 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 443
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 2756223972 444 AQEWMEAL 451
Cdd:cd13327    81 AQEWMEAL 88
PH_PLEKHM3_1 cd14674
Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 ...
215-304 1.71e-55

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 (also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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: 270193  Cd Length: 90  Bit Score: 184.75  E-value: 1.71e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 215 KKGYLEIRKNHDSYWQSCYAELSPYNLNFYSLDSSGNQNLYATYQLSHFQSISVLGNLEARMVDTVLYDNSQLQLKAESP 294
Cdd:cd14674     1 KKGYLEIRIDPDSYWQGCYAELSPYELYIYGLDSSGNQNLTDTYHLSHFQSITVTGSHEAKLVNVVLTDNRQLQLKAESA 80
                          90
                  ....*....|
gi 2756223972 295 WEALDWGQKL 304
Cdd:cd14674    81 WEALDWGQKL 90
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
362-456 8.61e-08

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: 50.62  E-value: 8.61e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972  362 ILKSGTLYRLTVQNN--WKAFTFVLSKAYLMAF--HPGKLDEDPLLSYNVDVCLAVQTDNLDGCDS--CFQVIFPQ-DVL 434
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYksKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKphCFEIKTSDrKTL 80
                           90       100
                   ....*....|....*....|..
gi 2756223972  435 RLRAETRQRAQEWMEALKTAAN 456
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
362-454 4.77e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.02  E-value: 4.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 362 ILKSGTLYRLTVQN--NWKAFTFVLSKAYLMAFHPGKL--DEDPLLSYNVDVCLAVQTDNLDGC--DSCFQVIFPQ---- 431
Cdd:pfam00169   1 VVKEGWLLKKGGGKkkSWKKRYFVLFDGSLLYYKDDKSgkSKEPKGSISLSGCEVVEVVASDSPkrKFCFELRTGErtgk 80
                          90       100
                  ....*....|....*....|...
gi 2756223972 432 DVLRLRAETRQRAQEWMEALKTA 454
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSA 103
 
Name Accession Description Interval E-value
zf-RING_9 pfam13901
Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members ...
529-729 4.06e-97

Putative zinc-RING and/or ribbon; This is a family of cysteine-rich proteins. Many members also carry a pleckstrin-homology domain, pfam00169


Pssm-ID: 464030  Cd Length: 205  Bit Score: 299.53  E-value: 4.06e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 529 KVCNYSGWYYCSSCHVDDSFLIPARIVHNWDTSKYKVSKQAKEFLEYVYEEPLIDIQQENPMLYLHAEPLATVARLRQRL 608
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 609 KSLRAYLFSCRAAVAEDLRR--RIFPREYLLQQIHLYSLADLQQVIEGKLAPFLGKVIKFATAHVYSCSLCSQKGFICEI 686
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 2756223972 687 CNNGEILYPFEDISTSRCESCGSVFHSEC-KEKSVPCPRCVRRE 729
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCfRSGASPCPKCERLQ 204
PH_PLEKHM3_2 cd13327
Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 ...
364-451 1.01e-60

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 2; PLEKHM3 (also called differentiation associated protein/DAPR)(also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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: 270136  Cd Length: 88  Bit Score: 199.11  E-value: 1.01e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 364 KSGTLYRLTVQNNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQR 443
Cdd:cd13327     1 KSGTLYRLTVQNNWKAFTFVLSRSYLMAFQPGCLDEDPLLSYNVDVCLAVQMDMLDGCDSCFQVIFPQDVLRLRAETRQR 80

                  ....*...
gi 2756223972 444 AQEWMEAL 451
Cdd:cd13327    81 AQEWMEAL 88
PH_PLEKHM3_1 cd14674
Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 ...
215-304 1.71e-55

Pleckstrin homology domain-containing family M member 3 Pleckstrin homology domain 1; PLEKHM3 (also called differentiation associated protein/DAPR) exists as three alternatively spliced isoforms that participate in metal ion binding. It contains 2 PH domains and 1 phorbol-ester/DAG-type zinc finger domain. PLEKHM3 is found in Humans, canines, bovine, mouse, rat, chicken and zebrafish. 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: 270193  Cd Length: 90  Bit Score: 184.75  E-value: 1.71e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 215 KKGYLEIRKNHDSYWQSCYAELSPYNLNFYSLDSSGNQNLYATYQLSHFQSISVLGNLEARMVDTVLYDNSQLQLKAESP 294
Cdd:cd14674     1 KKGYLEIRIDPDSYWQGCYAELSPYELYIYGLDSSGNQNLTDTYHLSHFQSITVTGSHEAKLVNVVLTDNRQLQLKAESA 80
                          90
                  ....*....|
gi 2756223972 295 WEALDWGQKL 304
Cdd:cd14674    81 WEALDWGQKL 90
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
376-452 3.34e-09

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: 54.64  E-value: 3.34e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2756223972 376 NWKAFTFVLSKaYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQDVLRLRAETRQRAQEWMEALK 452
Cdd:cd10573    18 NWKTRWFVLRR-NELKYFKTRGDTKPIRVLDLRECSSVQRDYSQGKVNCFCLVFPERTFYMYANTEEEADEWVKLLK 93
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
362-456 8.61e-08

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: 50.62  E-value: 8.61e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972  362 ILKSGTLYRLTVQNN--WKAFTFVLSKAYLMAF--HPGKLDEDPLLSYNVDVCLAVQTDNLDGCDS--CFQVIFPQ-DVL 434
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYksKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKphCFEIKTSDrKTL 80
                           90       100
                   ....*....|....*....|..
gi 2756223972  435 RLRAETRQRAQEWMEALKTAAN 456
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
364-451 1.22e-06

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: 47.15  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 364 KSGTLYRLT--VQNNWKAFTFVLSKAYLMAF-HPGKLDEDPLLSYNVDVCLAVQTDNLDGCDSCFQVIFPQD-VLRLRAE 439
Cdd:cd00821     1 KEGYLLKRGggGLKSWKKRWFVLFEGVLLYYkSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGrTYYLQAD 80
                          90
                  ....*....|..
gi 2756223972 440 TRQRAQEWMEAL 451
Cdd:cd00821    81 SEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
362-454 4.77e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 46.02  E-value: 4.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 362 ILKSGTLYRLTVQN--NWKAFTFVLSKAYLMAFHPGKL--DEDPLLSYNVDVCLAVQTDNLDGC--DSCFQVIFPQ---- 431
Cdd:pfam00169   1 VVKEGWLLKKGGGKkkSWKKRYFVLFDGSLLYYKDDKSgkSKEPKGSISLSGCEVVEVVASDSPkrKFCFELRTGErtgk 80
                          90       100
                  ....*....|....*....|...
gi 2756223972 432 DVLRLRAETRQRAQEWMEALKTA 454
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSA 103
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
375-458 2.70e-03

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: 37.97  E-value: 2.70e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 375 NNWKAFTFVLSKAYLMAFHPGKLDEDPLLSYNVDVCLAVQTDNLDgCDSCFQVIFPQDVLRLRAETRQRAQEWMEALKTA 454
Cdd:cd13250    14 KTWKRRWFSLQNGQLYYQKRDKKDEPTVMVEDLRLCTVKPTEDSD-RRFCFEVISPTKSYMLQAESEEDRQAWIQAIQSA 92

                  ....
gi 2756223972 455 ANAA 458
Cdd:cd13250    93 IASA 96
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
360-452 3.41e-03

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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: 270080  Cd Length: 103  Bit Score: 37.71  E-value: 3.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2756223972 360 QNILKSGTLYRLTVQNN-WKAFTFVL--SKAYLMAF-HPGKLDEDPLLSYNVDVCLAVQtDNLDGCDSCFQVifpqdVLR 435
Cdd:cd13260     1 KGIDKKGYLLKKGGKNKkWKNLYFVLegKEQHLYFFdNEKRTKPKGLIDLSYCSLYPVH-DSLFGRPNCFQI-----VVR 74
                          90       100
                  ....*....|....*....|....*.
gi 2756223972 436 ---------LRAETRQRAQEWMEALK 452
Cdd:cd13260    75 alnestityLCADTAELAQEWMRALR 100
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
401-455 3.80e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 37.71  E-value: 3.80e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2756223972 401 PLLSYNVDVclAVQTDNLDGcDSCFQVIFPQDVLRLRAETRQRAQEWMEALKTAA 455
Cdd:cd13236    54 PLPGCEVTV--PPPEERLDG-RHVFKLSQSKQSHYFSAESEELQQRWLEALSRAA 105
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
407-456 5.25e-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: 36.99  E-value: 5.25e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2756223972 407 VDVCLAvQTDNLDGCDScFQVIFPQDVLRLRAETRQRAQEWMEALKTAAN 456
Cdd:cd13274    45 SDASVA-ECSTKNVNNS-FTVITPFRKLILCAESRKEMEEWISALKTVQQ 92
 
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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