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Conserved domains on  [gi|2462493009|ref|XP_054186111|]
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pleckstrin homology domain-containing family M member 1 isoform X8 [Homo sapiens]

Protein Classification

PH domain-containing protein( domain architecture ID 10352569)

Pleckstrin homology (PH) domain-containing protein may be involved in targeting a protein to the appropriate cellular location or interacting with a binding partner

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 ...
325-527 2.25e-99

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: 298.76  E-value: 2.25e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 325 KLCAFSGLYYCDICHQDDASVIPARIIHNWDLTKRPICRQALKFLTQIRAQPLINLQMVNASLYEHVERMHLIGRRREQL 404
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 405 KLLGDYLGLCRSGALKELSK--RLNHRNYLLESPHRFSVADLQQIADGVYEGFLKALIEFASQHVYHCDLCTQRGFICQI 482
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2462493009 483 CQHHDIIFPFEFDTTVRCAECKTVFHQSCQAVVKKGCPRCARRRK 527
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCFRSGASPCPKCERLQK 205
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
4-108 1.83e-70

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 cd13321:

Pssm-ID: 473070  Cd Length: 132  Bit Score: 221.64  E-value: 1.83e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107
                          90       100
                  ....*....|....*....|....*
gi 2462493009  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
164-256 4.93e-04

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: 39.45  E-value: 4.93e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  164 IKESLLYLYMD---RTWMPYIFSLSLEALKCFRIRNNEKMLSDSHGVE----TIRDILPDTSLGGPSFFKIITA-KAVLK 235
Cdd:smart00233   2 IKEGWLYKKSGggkKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDlsgcTVREAPDPDSSKKPHCFEIKTSdRKTLL 81
                           90       100
                   ....*....|....*....|.
gi 2462493009  236 LQAGNAEEAALWRDLVRKVLA 256
Cdd:smart00233  82 LQAESEEEREKWVEALRKAIA 102
 
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 ...
325-527 2.25e-99

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: 298.76  E-value: 2.25e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 325 KLCAFSGLYYCDICHQDDASVIPARIIHNWDLTKRPICRQALKFLTQIRAQPLINLQMVNASLYEHVERMHLIGRRREQL 404
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 405 KLLGDYLGLCRSGALKELSK--RLNHRNYLLESPHRFSVADLQQIADGVYEGFLKALIEFASQHVYHCDLCTQRGFICQI 482
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2462493009 483 CQHHDIIFPFEFDTTVRCAECKTVFHQSCQAVVKKGCPRCARRRK 527
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCFRSGASPCPKCERLQK 205
PH_PLEKHM1 cd13321
Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; ...
4-108 1.83e-70

Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; PLEKHM1 is thought to function in vesicular transport in osteoclasts. Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C-terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. 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: 241475  Cd Length: 132  Bit Score: 221.64  E-value: 1.83e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107
                          90       100
                  ....*....|....*....|....*
gi 2462493009  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
466-519 1.27e-05

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 42.45  E-value: 1.27e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462493009  466 HVYHCDLCTQRGFiCQICQHHDIIFpfeFDTTVRCAECKTVFHQSCQAVVKKGC 519
Cdd:smart00109   1 HKHVFRTFTKPTF-CCVCRKSIWGS---FKQGLRCSECKVKCHKKCADKVPKAC 50
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
14-104 6.58e-05

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: 42.15  E-value: 6.58e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009   14 LMKLGTVERRGAMGI--WKELFCELSPLEFRLYLSNEEHTC--------VENCSLLRCESVGPAHSDGRFELVFS-GKKL 82
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSykpkgsidLSGCTVREAPDPDSSKKPHCFEIKTSdRKTL 80
                           90       100
                   ....*....|....*....|..
gi 2462493009   83 ALRASSQDEAEDWLDRVREALQ 104
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
164-256 4.93e-04

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: 39.45  E-value: 4.93e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  164 IKESLLYLYMD---RTWMPYIFSLSLEALKCFRIRNNEKMLSDSHGVE----TIRDILPDTSLGGPSFFKIITA-KAVLK 235
Cdd:smart00233   2 IKEGWLYKKSGggkKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDlsgcTVREAPDPDSSKKPHCFEIKTSdRKTLL 81
                           90       100
                   ....*....|....*....|.
gi 2462493009  236 LQAGNAEEAALWRDLVRKVLA 256
Cdd:smart00233  82 LQAESEEEREKWVEALRKAIA 102
 
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 ...
325-527 2.25e-99

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: 298.76  E-value: 2.25e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 325 KLCAFSGLYYCDICHQDDASVIPARIIHNWDLTKRPICRQALKFLTQIRAQPLINLQMVNASLYEHVERMHLIGRRREQL 404
Cdd:pfam13901   1 RLCDYTGKYYCSGCHWNDTSVIPARILHNWDFKKYPVSKFAKQLLDSIYSQPLLNLSDLNPSLYSKVKELAKVRELREQL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009 405 KLLGDYLGLCRSGALKELSK--RLNHRNYLLESPHRFSVADLQQIADGVYEGFLKALIEFASQHVYHCDLCTQRGFICQI 482
Cdd:pfam13901  81 KLLKDYLKTCRFAAEEELLKlfRLRPRHHLLEDSHLYSLQDLVDIKNGSLLPFLEELVQFAEKHVTNCELCQGKGFICEL 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2462493009 483 CQHHDIIFPFEFDTTVRCAECKTVFHQSCQAVVKKGCPRCARRRK 527
Cdd:pfam13901 161 CNSDDIIFPFDIDTTSRCEKCKAVFHKSCFRSGASPCPKCERLQK 205
PH_PLEKHM1 cd13321
Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; ...
4-108 1.83e-70

Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain; PLEKHM1 is thought to function in vesicular transport in osteoclasts. Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C-terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. 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: 241475  Cd Length: 132  Bit Score: 221.64  E-value: 1.83e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009   4 QTGLSNPFRGLMKLGTVERRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLLRCESVGPAHSDGRFELVFSGKKLA 83
Cdd:cd13321    28 QMGLSNPFRGLLKLGTLERRGAMGIWKEFYCELSPLEFRLYLSAEERVCVENCSLLRCESVGPAHSDGRFELVFPGKKLA 107
                          90       100
                  ....*....|....*....|....*
gi 2462493009  84 LRASSQDEAEDWLDRVREALQKVRP 108
Cdd:cd13321   108 LRAPSRDEAEDWLDRIREALQKVRP 132
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
466-519 1.27e-05

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 42.45  E-value: 1.27e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462493009  466 HVYHCDLCTQRGFiCQICQHHDIIFpfeFDTTVRCAECKTVFHQSCQAVVKKGC 519
Cdd:smart00109   1 HKHVFRTFTKPTF-CCVCRKSIWGS---FKQGLRCSECKVKCHKKCADKVPKAC 50
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
14-104 6.58e-05

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: 42.15  E-value: 6.58e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009   14 LMKLGTVERRGAMGI--WKELFCELSPLEFRLYLSNEEHTC--------VENCSLLRCESVGPAHSDGRFELVFS-GKKL 82
Cdd:smart00233   1 VIKEGWLYKKSGGGKksWKKRYFVLFNSTLLYYKSKKDKKSykpkgsidLSGCTVREAPDPDSSKKPHCFEIKTSdRKTL 80
                           90       100
                   ....*....|....*....|..
gi 2462493009   83 ALRASSQDEAEDWLDRVREALQ 104
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
18-99 1.87e-04

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: 40.60  E-value: 1.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  18 GTVERRGA--MGIWKELFCELSplEFRLYLSNEEH----TCVENCSLLRCESVGPAHSDGR---FELVFS-GKKLALRAS 87
Cdd:cd00821     3 GYLLKRGGggLKSWKKRWFVLF--EGVLLYYKSKKdssyKPKGSIPLSGILEVEEVSPKERphcFELVTPdGRTYYLQAD 80
                          90
                  ....*....|..
gi 2462493009  88 SQDEAEDWLDRV 99
Cdd:cd00821    81 SEEERQEWLKAL 92
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
164-256 4.93e-04

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: 39.45  E-value: 4.93e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  164 IKESLLYLYMD---RTWMPYIFSLSLEALKCFRIRNNEKMLSDSHGVE----TIRDILPDTSLGGPSFFKIITA-KAVLK 235
Cdd:smart00233   2 IKEGWLYKKSGggkKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDlsgcTVREAPDPDSSKKPHCFEIKTSdRKTLL 81
                           90       100
                   ....*....|....*....|.
gi 2462493009  236 LQAGNAEEAALWRDLVRKVLA 256
Cdd:smart00233  82 LQAESEEEREKWVEALRKAIA 102
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
14-110 2.84e-03

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 37.37  E-value: 2.84e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  14 LMKLGTverRGAMGIWKELFCELSPLEFRLYLSNEEHTCVENCSLlRCESVGPAHSDGRFELVFSGKKLALRASSQDEAE 93
Cdd:cd13253     6 LDKQGG---QGNNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPL-SAISTVRAVGDNKFELVTTNRTFVFRAESDDERN 81
                          90
                  ....*....|....*..
gi 2462493009  94 DWLdrvrEALQKVRPQQ 110
Cdd:cd13253    82 LWC----STLQAAISEY 94
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
14-110 6.55e-03

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


Pssm-ID: 270075  Cd Length: 110  Bit Score: 36.62  E-value: 6.55e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462493009  14 LMKLGtvERRGAmgiWKELFCELSPLEFRLYLSNEEHtcvencSLLR---------CESVGPAHSDGRFELVFSGKKLAL 84
Cdd:cd13255    12 LEKKG--ERRKT---WKKRWFVLRPTKLAYYKNDKEY------RLLRlidltdihtCTEVQLKKHDNTFGIVTPARTFYV 80
                          90       100
                  ....*....|....*....|....*....
gi 2462493009  85 RASSQDEAEDW---LDRVREALQKVRPQQ 110
Cdd:cd13255    81 QADSKAEMESWisaINLARQALRATITPN 109
 
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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