hypothetical protein HPB47_008774 [Ixodes persulcatus]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||||
| AP-like_stonins_MHD | cd09255 | Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of ... |
260-579 | 1.60e-176 | ||||||
Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of proteins named stonins has been characterized as clathrin-dependent AP-2 mu2 chain related factors, which may act as cargo-specific sorting adaptors in endocytosis. Stonins include stonin 1 and stonin 2, which are only mammalian homologs of Drosophila stoned B, a presynaptic protein implicated in neurotransmission and synaptic vesicle (SV) recycling. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. This family corresponds to the mu homology domain of stonins, which is distantly related to the C-terminal domain of mu chains among AP complexes. Due to the low degree of sequence conservation of the corresponding binding site, the mu homology domain of stonins is unable to recognize tyrosine-based endocytic sorting signals. To data, little is known about the localization and function of stonin 1. Stonin 2, also known as stoned B, acts as an AP-2-dependent synaptotagmin-specific sorting adaptors for SV endocytosis. Stoned A is not a stonin. It is structurally unrelated to the adaptins and does not appear to have mammalian homologs. It is not included in this family. : Pssm-ID: 271163 [Multi-domain] Cd Length: 315 Bit Score: 503.10 E-value: 1.60e-176
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| PH-like super family | cl17171 | Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ... |
148-196 | 1.63e-03 | ||||||
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 cd13301: Pssm-ID: 473070 Cd Length: 108 Bit Score: 38.51 E-value: 1.63e-03
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| Name | Accession | Description | Interval | E-value | ||||||
| AP-like_stonins_MHD | cd09255 | Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of ... |
260-579 | 1.60e-176 | ||||||
Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of proteins named stonins has been characterized as clathrin-dependent AP-2 mu2 chain related factors, which may act as cargo-specific sorting adaptors in endocytosis. Stonins include stonin 1 and stonin 2, which are only mammalian homologs of Drosophila stoned B, a presynaptic protein implicated in neurotransmission and synaptic vesicle (SV) recycling. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. This family corresponds to the mu homology domain of stonins, which is distantly related to the C-terminal domain of mu chains among AP complexes. Due to the low degree of sequence conservation of the corresponding binding site, the mu homology domain of stonins is unable to recognize tyrosine-based endocytic sorting signals. To data, little is known about the localization and function of stonin 1. Stonin 2, also known as stoned B, acts as an AP-2-dependent synaptotagmin-specific sorting adaptors for SV endocytosis. Stoned A is not a stonin. It is structurally unrelated to the adaptins and does not appear to have mammalian homologs. It is not included in this family. Pssm-ID: 271163 [Multi-domain] Cd Length: 315 Bit Score: 503.10 E-value: 1.60e-176
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| Adap_comp_sub | pfam00928 | Adaptor complexes medium subunit family; This family also contains members which are coatomer ... |
258-577 | 7.22e-41 | ||||||
Adaptor complexes medium subunit family; This family also contains members which are coatomer subunits. Pssm-ID: 395742 Cd Length: 259 Bit Score: 149.38 E-value: 7.22e-41
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| PH1_Pleckstrin_2 | cd13301 | Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ... |
148-196 | 1.63e-03 | ||||||
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270113 Cd Length: 108 Bit Score: 38.51 E-value: 1.63e-03
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| Name | Accession | Description | Interval | E-value | ||||||
| AP-like_stonins_MHD | cd09255 | Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of ... |
260-579 | 1.60e-176 | ||||||
Mu homology domain (MHD) of adaptor-like proteins (AP-like), stonins; A small family of proteins named stonins has been characterized as clathrin-dependent AP-2 mu2 chain related factors, which may act as cargo-specific sorting adaptors in endocytosis. Stonins include stonin 1 and stonin 2, which are only mammalian homologs of Drosophila stoned B, a presynaptic protein implicated in neurotransmission and synaptic vesicle (SV) recycling. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. This family corresponds to the mu homology domain of stonins, which is distantly related to the C-terminal domain of mu chains among AP complexes. Due to the low degree of sequence conservation of the corresponding binding site, the mu homology domain of stonins is unable to recognize tyrosine-based endocytic sorting signals. To data, little is known about the localization and function of stonin 1. Stonin 2, also known as stoned B, acts as an AP-2-dependent synaptotagmin-specific sorting adaptors for SV endocytosis. Stoned A is not a stonin. It is structurally unrelated to the adaptins and does not appear to have mammalian homologs. It is not included in this family. Pssm-ID: 271163 [Multi-domain] Cd Length: 315 Bit Score: 503.10 E-value: 1.60e-176
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| AP_stonin-2_MHD | cd09263 | Mu homology domain (MHD) of adaptor-like protein (AP-like), stonin-2; A small family of ... |
264-578 | 2.52e-80 | ||||||
Mu homology domain (MHD) of adaptor-like protein (AP-like), stonin-2; A small family of proteins named stonins has been characterized as clathrin-dependent AP-2 mu2 chain related factors, which may act as cargo-specific sorting adaptors in endocytosis. Stonins include stonin 1 and stonin 2, which are the only mammalian homologs of Drosophila stoned B, a presynaptic protein implicated in neurotransmission and synaptic vesicle (SV) recycling. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. This family corresponds to the mu homology domain of stonin 2, which is distantly related to the C-terminal domain of mu chains among AP complexes. Due to the low degree of sequence conservation of the corresponding binding site, the mu homology domain of stonin-2 is unable to recognize tyrosine-based endocytic sorting signals. It acts as an AP-2-dependent synaptotagmin-specific sorting adaptor for SV endocytosis. Pssm-ID: 271169 Cd Length: 318 Bit Score: 256.48 E-value: 2.52e-80
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| AP_stonin-1_MHD | cd09262 | Mu homology domain (MHD) of adaptor-like protein (AP-like), stonin-1 (also called Stoned ... |
266-578 | 1.04e-50 | ||||||
Mu homology domain (MHD) of adaptor-like protein (AP-like), stonin-1 (also called Stoned B-like factor); A small family of proteins named stonins has been characterized as clathrin-dependent AP-2 mu2 chain related factors, which may act as cargo-specific sorting adaptors in endocytosis. Stonins include stonin 1 and stonin 2, which are the only mammalian homologs of Drosophila stoned B, a presynaptic protein implicated in neurotransmission and synaptic vesicle (SV) recycling. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. This family corresponds to the mu homology domain of stonin 1, which is distantly related to the C-terminal domain of mu chains among AP complexes. Due to the low degree of sequence conservation of the corresponding binding site, the mu homology domain of stonin-1 is unable to recognize tyrosine-based endocytic sorting signals. To data, little is known about the localization and function of stonin-1. Pssm-ID: 271168 Cd Length: 314 Bit Score: 177.83 E-value: 1.04e-50
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| Adap_comp_sub | pfam00928 | Adaptor complexes medium subunit family; This family also contains members which are coatomer ... |
258-577 | 7.22e-41 | ||||||
Adaptor complexes medium subunit family; This family also contains members which are coatomer subunits. Pssm-ID: 395742 Cd Length: 259 Bit Score: 149.38 E-value: 7.22e-41
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| AP_MHD_Cterm | cd07954 | C-terminal domain of adaptor protein (AP) complexes medium mu subunits and its homologs (MHD); ... |
270-570 | 5.29e-28 | ||||||
C-terminal domain of adaptor protein (AP) complexes medium mu subunits and its homologs (MHD); This family corresponds to the C-terminal domain of heterotetrameric AP complexes medium mu subunits and its homologs existing in monomeric stonins, delta-subunit of the heteroheptameric coat protein I (delta-COPI), a protein encoded by a pro-death gene referred as MuD (also known as MUDENG, mu-2 related death-inducing gene), an endocytic adaptor syp1, the mammalian FCH domain only proteins (FCHo1/2), SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1), and related proteins. AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. Stonins have been characterized as clathrin-dependent AP-2 mu chain related factors and may act as cargo-specific sorting adaptors in endocytosis. Coat protein complex I (COPI)-coated vesicles function in the early secretory pathway. They mediate the retrograde transport from the Golgi to the ER, and intra-Golgi transport. MuD is distantly related to the C-terminal domain of mu2 subunit of AP-2. It is able to induce cell death by itself and plays an important role in cell death in various tissues. Syp1 represents a novel type of endocytic adaptor protein that participates in endocytosis, promotes vesicle tabulation, and contributes to cell polarity and stress responses. It shares the same domain architecture with its two ubiquitously expressed mammalian counterparts, FCHo1/2, which represent key initial proteins ultimately controlling cellular nutrient uptake, receptor regulation, and synaptic vesicle retrieval. They bind specifically to the plasma membrane and recruit the scaffold proteins eps15 and intersectin, which subsequently engage the adaptor complex AP2 and clathrin, leading to coated vesicle formation. Another mammalian neuronal-specific protein SGIP1 does have a C-terminal MHD and has been classified into this family as well. It is an endophilin-interacting protein that plays an obligatory role in the regulation of energy homeostasis. It is also involved in clathrin-mediated endocytosis by interacting with phospholipids and eps15. Pssm-ID: 271157 Cd Length: 245 Bit Score: 112.88 E-value: 5.29e-28
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| AP-2_Mu2_Cterm | cd09251 | C-terminal domain of medium Mu2 subunit in ubiquitously expressed clathrin-associated adaptor ... |
302-570 | 1.05e-18 | ||||||
C-terminal domain of medium Mu2 subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-2; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, -2, -3, and -4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from the different AP complexes exhibits similarity with each other. This family corresponds to the C-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 2 (AP-2) medium mu2 subunit. Mu2 is ubiquitously expressed in mammals. In higher eukaryotes, AP-2 plays a critical role in clathrin-mediated endocytosis from the plasma membrane in different cells. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-2. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-2 mu2 subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic residue-binding. Since the Y-X-X-Phi binding site is buried in the core structure of AP-2, a phosphorylation induced conformational change is required when the cargo molecules binds to AP-2. In addition, the C-terminal domain of mu2 subunit has been shown to bind other molecules. For instance, it can bind phosphoinositides, in particular PI[4,5]P2, which might be involved in the recognition process of the tyrosine-based signals. It can also interact with synaptotagmins, a family of important modulators of calcium-dependent neurosecretion within the synaptic vesicle (SV) membrane. Since many of the other endocytic adaptors responsible for biogenesis of synaptic vesicles exist, in the absence of AP-2, clathrin-mediated endocytosis can still occur. However, the cells may not survive in the complete absence of clathrin as well as AP-2. Pssm-ID: 271159 Cd Length: 263 Bit Score: 86.11 E-value: 1.05e-18
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| AP-3_Mu3_Cterm | cd09252 | C-terminal domain of medium Mu3 subunit in adaptor protein (AP) complex AP-3; AP complexes ... |
260-570 | 2.59e-17 | ||||||
C-terminal domain of medium Mu3 subunit in adaptor protein (AP) complex AP-3; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from the different AP complexes exhibits similarity with each other. This family corresponds to the C-terminal domain of heterotetrameric adaptor protein complex 3 (AP-3) medium mu3 subunit, which includes two closely related homologs, mu3A (P47A, encoded by ap3m1) and mu1B (P47B, encoded by ap3m2). Mu3A is ubiquitously expressed, but mu3B is specifically expressed in neurons and neuroendocrine cells. AP-3 is particularly important for targeting integral membrane proteins to lysosomes and lysome-related organelles at trans-Golgi network (TGN) and/or endosomes, such as the yeast vacuole, fly pigment granules and mammalian melanosomes, platelet dense bodies and the secretory lysosomes of cytotoxic T lymphocytes. Unlike AP-1 and AP-2, which function in conjunction with clathrin which is a scaffolding protein participating in the formation of coated vesicles, the nature of the outer shell of AP-3 containing coats remains to be elucidated. Membrane-anchored cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-3 mu3 subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic residue-binding. Pssm-ID: 271160 Cd Length: 251 Bit Score: 81.86 E-value: 2.59e-17
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| AP-1_Mu1B_Cterm | cd09259 | C-terminal domain of medium Mu1B subunit in epithelial cell-specific clathrin-associated ... |
260-570 | 4.86e-15 | ||||||
C-terminal domain of medium Mu1B subunit in epithelial cell-specific clathrin-associated adaptor protein (AP) complex AP-1; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from different AP complexes exhibits similarity with each other. This subfamily corresponds to the C-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 1 (AP-1) medium mu1B subunit encoded by ap1m2 gene exclusively expressed in polarized epithelial cells. Epithelial cell-specific AP-1 is used to sort proteins to the basolateral plasma membrane, which involves the formation of clathrin-coated vesicles (CCVs) from the trans-Golgi network (TGN). Recruitment of AP-1 to the TGN membrane is regulated by a small GTPase, ADP-ribosylation factor 1 (ARF1). The phosphorylation/dephosphorylation events can also regulate the function of AP-1. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-1. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-1 mu1B subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic reside-binding. Besides, AP-1 mu1B subunit mediates the basolateral recycling of low-density lipoprotein receptor (LDLR) and transferrin receptor (TfR) from the sorting endosomes, where the basolateral sorting signal does not belong to the tyrosine-based signals. Thus, the binding site in mu1B subunit of AP-1 for the signals of LDLR and TfR might be distinct from that for YXXPhi signals. Pssm-ID: 271167 Cd Length: 268 Bit Score: 75.44 E-value: 4.86e-15
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| AP-4_Mu4_Cterm | cd09253 | C-terminal domain of medium Mu4 subunit in adaptor protein (AP) complex AP-4; AP complexes ... |
303-570 | 5.81e-14 | ||||||
C-terminal domain of medium Mu4 subunit in adaptor protein (AP) complex AP-4; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from the different AP complexes exhibits similarity with each other. This family corresponds to the C-terminal domain of heterotetrameric adaptor protein complex 4 (AP-4) medium mu4 subunit. AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells. Unlike other AP complexes, AP-4 is found only in mammals and plants. It is believed to be part of a nonclathrin coat, since it might function independently of clathrin, a scaffolding protein participating in the formation of coated vesicles. Recruitment of AP-4 to the trans-Golgi network (TGN) membrane is regulated by a small GTPase, ADP-ribosylation factor 1 (ARF1) or a related protein. Membrane-anchored cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. One of the most important sorting signals binding to mu subunits of AP complexes are tyrosine-based endocytotic signals, which are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. However, AP-4 does not bind most canonical tyrosine-based signals except for two naturally occurring ones from the lysosomal membrane proteins CD63 and LAMP-2a. It binds YX [FYL][FL]E motif, where X can be any residue, from the cytosolic tails of amyloid precursor protein (APP) family members in a distinct way. Pssm-ID: 271161 Cd Length: 271 Bit Score: 72.60 E-value: 5.81e-14
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| AP-1_Mu1A_Cterm | cd09258 | C-terminal domain of medium Mu1A subunit in ubiquitously expressed clathrin-associated adaptor ... |
260-575 | 8.81e-10 | ||||||
C-terminal domain of medium Mu1A subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-1; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from the different AP complexes exhibits similarity with each other. This subfamily corresponds to the C-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 1 (AP-1) medium mu1A subunit encoded by ap1m1 gene, which is ubiquitously expressed in all mammalian tissues and cells. AP-1 has been implicated in bidirectional transport between the trans-Golgi network (TGN) and endosomes. It is involved in the formation of clathrin-coated vesicles (CCVs) from the trans-Golgi network (TGN). The ubiquitous AP-1 is recruited to the TGN membrane, as well as to immature secretory granules. Recruitment of AP-1 to the TGN membrane is regulated by a small GTPase, ADP-ribosylation factor 1 (ARF1). Phosphorylation/dephosphorylation events can also regulate the function of AP-1. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-1. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-1 mu1A subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic residue-binding. Pssm-ID: 271166 Cd Length: 270 Bit Score: 59.90 E-value: 8.81e-10
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| AP-1_Mu1_Cterm | cd09250 | C-terminal domain of medium Mu1 subunit in clathrin-associated adaptor protein (AP) complex ... |
303-378 | 1.38e-07 | ||||||
C-terminal domain of medium Mu1 subunit in clathrin-associated adaptor protein (AP) complex AP-1; AP complexes participate in the formation of intracellular coated transport vesicles and select cargo molecules for incorporation into the coated vesicles in the late secretory and endocytic pathways. There are four AP complexes, AP-1, AP-2, AP-3, and AP-4, described in various eukaryotic organisms. Each AP complex consists of four subunits: two large chains (one each of gamma/alpha/delta/epsilon and beta1-4, respectively), a medium mu chain (mu1-4), and a small sigma chain (sigma1-4). Each of the four subunits from the different AP complexes exhibits similarity with each other. This family corresponds to the C-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 1 (AP-1) medium mu1 subunit, which includes two closely related homologs, mu1A (encoded by ap1m1) and mu1B (encoded by ap1m2). Mu1A is ubiquitously expressed, but mu1B is expressed exclusively in polarized epithelial cells. AP-1 has been implicated in bi-directional transport between the trans-Golgi network (TGN) and endosomes. It plays an essential role in the formation of clathrin-coated vesicles (CCVs) from the trans-Golgi network (TGN). Epithelial cell-specific AP-1 is also involved in sorting to the basolateral surface of polarized epithelial cells. Recruitment of AP-1 to the TGN membrane is regulated by a small GTPase, ADP-ribosylation factor 1 (ARF1). Phosphorylation/dephosphorylation events can also regulate the function of AP-1. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-1. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-1 mu1 subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic residue-binding. Pssm-ID: 271158 Cd Length: 272 Bit Score: 53.38 E-value: 1.38e-07
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| PH1_Pleckstrin_2 | cd13301 | Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ... |
148-196 | 1.63e-03 | ||||||
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes. Pssm-ID: 270113 Cd Length: 108 Bit Score: 38.51 E-value: 1.63e-03
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