NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|768024567|ref|XP_011528425|]
View 

ADP-ribosylation factor-binding protein GGA1 isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
VHS_ENTH_ANTH super family cl02544
VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a ...
 7-156 1.95e-90

VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a VHS, CID, ENTH, or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It is located at the N-termini of proteins involved in intracellular membrane trafficking. The CTD-Interacting Domain (CID) is present in several RNA-processing factors and binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II or Pol II). The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. A set of proteins previously designated as harboring an ENTH domain in fact contains a highly similar, yet unique module referred to as an AP180 N-Terminal Homology (ANTH) domain. VHS, ENTH, and ANTH domains are structurally similar and are composed of a superhelix of eight alpha helices. ENTH and ANTH (E/ANTH) domains bind both inositol phospholipids and proteins and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. E/ANTH domain-bearing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.


The actual alignment was detected with superfamily member cd17009:

Pssm-ID: 470608 [Multi-domain]  Cd Length: 139  Bit Score: 276.87  E-value: 1.95e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd17009    7 NRATNPLNKELDWASINGFCEQLNEEFEGPPLATRLLAHKIQSPQEWEAIQALTV-----------------LETCMKSC 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 156
Cdd:cd17009   70 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTPEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 139
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
 219-307 1.43e-55

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of which belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have a multidomain structure consisting of an N-terminal VHS (Vps27/Hrs/Stam) domain, a GAT (GGA and TOM) domain, a largely unstructured hinge region that contains clathrin-binding motifs, and a C-terminal GAE (gamma-adaptin ear homology) domain. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).


:

Pssm-ID: 410586  Cd Length: 88  Bit Score: 183.33  E-value: 1.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 219 KISKRVNAIEEVNNNVKLLTEMVMSHSQGGAAaGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQ 298
Cdd:cd14239    1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79


                 ....*....
gi 768024567 299 VINLYKQLV 307
Cdd:cd14239   80 VINLYKQLV 88
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
 526-640 2.45e-28

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


:

Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 109.25  E-value: 2.45e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   526 VYDQHGFRILFHFARdplpgRSDVLVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNPivhpsaITQVL 605
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQ------ITQVL 69

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768024567   606 LLANPQKEKVRLRYKLTFTMGDQTYNEMGDVDQFP 640
Cdd:smart00809  70 KVENPGKFPLRLRLRLSYLLGGSAVTEQGDVLKFP 104
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
 178-216 6.92e-18

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


:

Pssm-ID: 465702  Cd Length: 39  Bit Score: 77.34  E-value: 6.92e-18
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 768024567  178 FEDEEKSKMLARLLKSSHPEDLRAANKLIKEMVQEDQKR 216
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
 
Name Accession Description Interval E-value
VHS_GGA1 cd17009
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation ...
 7-156 1.95e-90

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation factor-binding protein GGA1 (Golgi-localized, Gamma-ear-containing, Arf-binding 1) is also called Gamma-adaptin-related protein 1. It is expressed in human brain and affects the generation of amyloid beta-peptide, and may be involved in the pathogenesis of Alzheimer disease. It is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340806 [Multi-domain]  Cd Length: 139  Bit Score: 276.87  E-value: 1.95e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd17009    7 NRATNPLNKELDWASINGFCEQLNEEFEGPPLATRLLAHKIQSPQEWEAIQALTV-----------------LETCMKSC 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 156
Cdd:cd17009   70 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTPEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 139
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
 219-307 1.43e-55

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of which belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have a multidomain structure consisting of an N-terminal VHS (Vps27/Hrs/Stam) domain, a GAT (GGA and TOM) domain, a largely unstructured hinge region that contains clathrin-binding motifs, and a C-terminal GAE (gamma-adaptin ear homology) domain. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).


Pssm-ID: 410586  Cd Length: 88  Bit Score: 183.33  E-value: 1.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 219 KISKRVNAIEEVNNNVKLLTEMVMSHSQGGAAaGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQ 298
Cdd:cd14239    1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79


                 ....*....
gi 768024567 299 VINLYKQLV 307
Cdd:cd14239   80 VINLYKQLV 88
VHS pfam00790
VHS domain; Domain present in VPS-27, Hrs and STAM.
 7-152 1.05e-40

VHS domain; Domain present in VPS-27, Hrs and STAM.


Pssm-ID: 395638  Cd Length: 136  Bit Score: 144.75  E-value: 1.05e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567    7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTvrrgeatirpppcddtkVLETCMKSC 86
Cdd:pfam00790   7 DKATDPSLREEDWSLILDICDLINETETGPKEAVRLIKKRINSPNPHVALLALT-----------------LLDACVKNC 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567   87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTseKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:pfam00790  70 GSKFHLEIASKEFLNELVKLIPNKPYGKPA--KVKKKILELIQEWADAFkndPDLKYIRDMYKLLKRKG 136
VHS smart00288
Domain present in VPS-27, Hrs and STAM; Unpublished observations. Domain of unknown function.
 7-152 9.43e-38

Domain present in VPS-27, Hrs and STAM; Unpublished observations. Domain of unknown function.


Pssm-ID: 197630 [Multi-domain]  Cd Length: 133  Bit Score: 136.66  E-value: 9.43e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567     7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTvrrgeatirpppcddtkVLETCMKSC 86
Cdd:smart00288   6 DKATSPSLLEEDWELILEICDLINSTPDGPKDAVRLLKKRLNNKNPHVALLALT-----------------LLDACVKNC 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567    87 GKRFHDEVGKFRFLNELIKVVSPKYlgsrTSEKVKNKILELLYSWTVGLPEEVK---IAEAYQMLKKQG 152
Cdd:smart00288  69 GSKFHLEVASKEFLNELVKLIKPKY----PLPLVKKRILELIQEWADAFKNDPDlsqIVDVYDLLKKKG 133
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
 526-640 2.45e-28

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 109.25  E-value: 2.45e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   526 VYDQHGFRILFHFARdplpgRSDVLVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNPivhpsaITQVL 605
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQ------ITQVL 69

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768024567   606 LLANPQKEKVRLRYKLTFTMGDQTYNEMGDVDQFP 640
Cdd:smart00809  70 KVENPGKFPLRLRLRLSYLLGGSAVTEQGDVLKFP 104
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
 231-309 9.50e-26

GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of the ARF family including ARF1 and ARF3. The GAT domain stabilizes membrane bound ARF1 in its GTP bound state, by interfering with GAP proteins.


Pssm-ID: 460818  Cd Length: 76  Bit Score: 100.69  E-value: 9.50e-26
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  231 NNNVKLLTEMVMSHSQGGaaaGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQLVRG 309
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDE---ELDNELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
Alpha_adaptinC2 pfam02883
Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud ...
 523-640 4.50e-25

Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in alpha, beta and gamma adaptins.


Pssm-ID: 460735  Cd Length: 111  Bit Score: 100.09  E-value: 4.50e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  523 PVTVYDQHGFRILFHFARDplpGRSDVLVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNpivhPSAIT 602
Cdd:pfam02883   2 PVVLYESDGLQIGFSFERS---RRPGQIRITLTFTNKSSSPISNFSFQAAVPKSLKLQLQPPSSNVLPPNP----GGQIT 74

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 768024567  603 QVLLLANPQKEKVRLRYKLTFTMGdQTYNEMGDVDQFP 640
Cdd:pfam02883  75 QVLLIENPGKKPLRMRLKISYLNG-GAVQEQGDVLKFP 111
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
 178-216 6.92e-18

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


Pssm-ID: 465702  Cd Length: 39  Bit Score: 77.34  E-value: 6.92e-18
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 768024567  178 FEDEEKSKMLARLLKSSHPEDLRAANKLIKEMVQEDQKR 216
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
 
Name Accession Description Interval E-value
VHS_GGA1 cd17009
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation ...
 7-156 1.95e-90

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA1; ADP-ribosylation factor-binding protein GGA1 (Golgi-localized, Gamma-ear-containing, Arf-binding 1) is also called Gamma-adaptin-related protein 1. It is expressed in human brain and affects the generation of amyloid beta-peptide, and may be involved in the pathogenesis of Alzheimer disease. It is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340806 [Multi-domain]  Cd Length: 139  Bit Score: 276.87  E-value: 1.95e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd17009    7 NRATNPLNKELDWASINGFCEQLNEEFEGPPLATRLLAHKIQSPQEWEAIQALTV-----------------LETCMKSC 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 156
Cdd:cd17009   70 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTPEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 139
VHS_GGA_metazoan cd03567
VHS (Vps27/Hrs/STAM) domain of metazoan GGA (Golgi-localized, Gamma-ear-containing, ...
 7-155 1.82e-82

VHS (Vps27/Hrs/STAM) domain of metazoan GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) proteins; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprises a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. Jawed vertebrates contain as many as three GGA proteins: GGA1, GGA2, and GGA3. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340769  Cd Length: 139  Bit Score: 255.98  E-value: 1.82e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd03567    7 NKATNPFNTEEDWEAIDAFCDRVNKEPEGPQIAVRLLAHKIQSPNEKEALRALTV-----------------LEACVKNC 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVK 155
Cdd:cd03567   70 GPRFHSEVGKFRFLNELIKLVSPKYLGNRTPEEVKQKIIELLYSWTRSLPHEPKIKEAYDMLKKQGIIK 138
VHS_GGA3 cd17008
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA3; ADP-ribosylation ...
 7-156 4.00e-76

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA3; ADP-ribosylation factor-binding protein GGA3 (Golgi-localized, Gamma-ear-containing, Arf-binding 3) regulates the trafficking and is required for the lysosomal degradation of BACE (beta-site APP-cleaving enzyme), the protease that initiates the production of beta-amyloid, which causes Alzheimer's disease. It also plays a key role in GABA (+) transmission, which is important in the regulation of anxiety-like behaviors. GGA3 is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340805 [Multi-domain]  Cd Length: 141  Bit Score: 239.55  E-value: 4.00e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd17008    9 NKATNPSNRQEDWEYIIGFCDQINKELEGPQIAVRLLAHKIQSPQEWEALQALTV-----------------LEACMKNC 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVKS 156
Cdd:cd17008   72 GRRFHNEVGKFRFLNELIKVVSPKYLGDRVSEKVKTKVIELLYSWTVALPEEAKIKDAYHMLKRQGIVQS 141
VHS_GGA cd16977
VHS (Vps27/Hrs/STAM) domain of GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) ...
 7-151 7.63e-74

VHS (Vps27/Hrs/STAM) domain of GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) subfamily; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprises a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340774  Cd Length: 133  Bit Score: 233.23  E-value: 7.63e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd16977    6 NRATNPSNAEPDWALILGFCDQINEDGEGPRDAARLLAHKIQSPQEWEAIQALTV-----------------LEVCMKNC 68

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQ 151
Cdd:cd16977   69 GYRFHLEVGKFRFLNELIKVVSPKYLGSRRSEKVKRKILELLYSWTVTLPEEGKIRDAYQMLKKQ 133
VHS_GGA2 cd17010
VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA2; ADP-ribosylation ...
 7-155 1.80e-69

VHS (Vps27/Hrs/STAM) domain of ADP-ribosylation factor-binding protein GGA2; ADP-ribosylation factor-binding protein GGA2 (Golgi-localized, Gamma-ear-containing, Arf-binding 2) is also called Gamma-adaptin-related protein 2 and VHS domain and ear domain of gamma-adaptin (Vear). It is a member of the GGA subfamily, which is comprised of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340807  Cd Length: 139  Bit Score: 222.07  E-value: 1.80e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd17010    7 NKATDPSNSEEDWECIQGFCEQVNKEPEGPQIATRLLAHKIQSPQEREALHALTV-----------------LEMCMNNC 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWTVGLPEEVKIAEAYQMLKKQGIVK 155
Cdd:cd17010   70 GERFHSEVAKFRFLNELIKVLSPKYLGTWSSEKVKSRVIEVLFSWTVWLPEEVKIRDAYQMLKKQGIIK 138
GAT_GGA1_GGA2 cd14239
canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; ...
 219-307 1.43e-55

canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2; This subfamily includes GGA1 and GGA2, both of which belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGA1, also called gamma-adaptin-related protein 1, or Golgi-localized gamma ear-containing Arf-binding protein 1, regulates the low-density lipoprotein and sorting receptor LR11/SorLA endocytic traffic and further alters amyloid-beta precursor protein (APP) intracellular distribution and amyloid-beta production. It is also critical for the effects of beta-site APP-cleaving enzyme-1 (BACE1) on amyloid-beta generation. It interacts with BACE1 and promotes its traffic from early endosomes to late endocytic compartments or the TGN. Moreover, GGA1 acts as a clathrin assembly protein with the ability to polymerize clathrin into tubules. GGA2, also called gamma-adaptin-related protein 2, Golgi-localized gamma ear-containing Arf-binding protein 2, or VHS domain and ear domain of gamma-adaptin (Vear), interacts with the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR) and further plays a major role in the sorting of lysosomal enzymes. It also mediates a vital function that cannot be compensated for by GGA1 and/or GGA3. Both GGA1 and GGA2 have a multidomain structure consisting of an N-terminal VHS (Vps27/Hrs/Stam) domain, a GAT (GGA and TOM) domain, a largely unstructured hinge region that contains clathrin-binding motifs, and a C-terminal GAE (gamma-adaptin ear homology) domain. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).


Pssm-ID: 410586  Cd Length: 88  Bit Score: 183.33  E-value: 1.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 219 KISKRVNAIEEVNNNVKLLTEMVMSHSQGGAAaGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQ 298
Cdd:cd14239    1 KVSKRVNAIEEVNNNVKLLTEMLMSYSRGELS-ESSEELMKELYQRCEKMRPTLFRLASDTEDNDEALAEILQANDNLTQ 79


                 ....*....
gi 768024567 299 VINLYKQLV 307
Cdd:cd14239   80 VINLYKQLV 88
VHS pfam00790
VHS domain; Domain present in VPS-27, Hrs and STAM.
 7-152 1.05e-40

VHS domain; Domain present in VPS-27, Hrs and STAM.


Pssm-ID: 395638  Cd Length: 136  Bit Score: 144.75  E-value: 1.05e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567    7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTvrrgeatirpppcddtkVLETCMKSC 86
Cdd:pfam00790   7 DKATDPSLREEDWSLILDICDLINETETGPKEAVRLIKKRINSPNPHVALLALT-----------------LLDACVKNC 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567   87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTseKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:pfam00790  70 GSKFHLEIASKEFLNELVKLIPNKPYGKPA--KVKKKILELIQEWADAFkndPDLKYIRDMYKLLKRKG 136
VHS smart00288
Domain present in VPS-27, Hrs and STAM; Unpublished observations. Domain of unknown function.
 7-152 9.43e-38

Domain present in VPS-27, Hrs and STAM; Unpublished observations. Domain of unknown function.


Pssm-ID: 197630 [Multi-domain]  Cd Length: 133  Bit Score: 136.66  E-value: 9.43e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567     7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTvrrgeatirpppcddtkVLETCMKSC 86
Cdd:smart00288   6 DKATSPSLLEEDWELILEICDLINSTPDGPKDAVRLLKKRLNNKNPHVALLALT-----------------LLDACVKNC 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567    87 GKRFHDEVGKFRFLNELIKVVSPKYlgsrTSEKVKNKILELLYSWTVGLPEEVK---IAEAYQMLKKQG 152
Cdd:smart00288  69 GSKFHLEVASKEFLNELVKLIKPKY----PLPLVKKRILELIQEWADAFKNDPDlsqIVDVYDLLKKKG 133
GAT_GGA_meta cd14234
canonical GAT domain found in metazoan ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
 222-306 1.26e-37

canonical GAT domain found in metazoan ADP-ribosylation factor (Arf)-binding proteins (GGAs); GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. Moreover, GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Three GGAs (GGA1, GGA2, and GGA3) have been identified in mammals. They may appear to behave similarly, since all of them have a multidomain structure consisting of: an N-terminal VHS (Vps27/Hrs/Stam) domain that binds the acidic-cluster dileucine (DxxLL)-type sorting signals (where x is any amino acid) found in the cytoplasmic tail of TGN sorting receptors; a GAT (GGA and TOM) domain that interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and the tumor susceptibility gene 101 product (TSG101); a largely unstructured hinge region that contains clathrin-binding motifs; and a C-terminal GAE (gamma-adaptin ear homology) domain that binds accessory proteins. However, the three GGAs have some differences, which suggest they may possess their own distinct roles. For instance, both GGA1 and GGA3, but not GGA2, contains an internal DxxLL motif that binds to it own VHS domain. Only a portion of the VHS domain of GGA2 possesses distant structural homology to that of GGA1 or GGA3. Moreover, the binding affinity of GGA2 to ubiquitin is quite lower than that of GGA1 or GGA3. In addition, GGA3 has a short splicing variant that is predominantly expressed in human cell lines and tissues except the brain. It does have a VHS domain, but it is unable to bind to the DxxLL motif. GGA2 and GGA3 undergo epidermal growth factor (EGF)-induced phosphorylation.


Pssm-ID: 410582  Cd Length: 84  Bit Score: 134.27  E-value: 1.26e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 222 KRVNAIEEVNNNVKLLTEMVMSHSQGGAAAGSSEdLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVIN 301
Cdd:cd14234    1 KRLLELEEVNNNVKLLNEMLDHYSPGESSQDELE-LMKELYESCEKMRPTLFRLASETDDDDEGLADILQANDELTRVMQ 79


                 ....*
gi 768024567 302 LYKQL 306
Cdd:cd14234   80 RYKNL 84
GAT_GGA3 cd14240
canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called ...
 222-309 1.39e-32

canonical GAT domain found in ADP-ribosylation factor-binding protein GGA3; GGA3, also called Golgi-localized gamma ear-containing Arf-binding protein 3, belongs to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGA3 interacts selectively with the Met/Hepatocyte Growth Factor receptor tyrosine kinase (RTK) when stimulated. It functions as a specific cargo adaptor to target the Met RTK into recycling tubules, and further coordinates the recycling, signaling and degradative fates of the Met RTK. Moreover, GGA3, together with PACS-1 and the protein kinase CK2, forms a complex that regulates cation-independent mannose-6-phosphate receptor (CI-MPR) trafficking. Furthermore, GGA3 has been identified as an interacting protein of the beta-site APP-cleaving enzyme-1 (BACE1), a stress-related protease that is involved in Alzheimer's disease (AD) pathology. GGA3 has a multidomain structure consisting of an N-terminal VHS (Vps27/Hrs/Stam) domain, a GAT (GGA and TOM) domain, a largely unstructured hinge region that contains clathrin-binding motifs, and a C-terminal GAE (gamma-adaptin ear homology) domain. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).


Pssm-ID: 410587  Cd Length: 87  Bit Score: 120.34  E-value: 1.39e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 222 KRVNAIEEVNNNVKLLTEMVMSHSQGGAAAGSSEdLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVIN 301
Cdd:cd14240    1 KRLHTLEEVNNNVRLLNEMLAHYSKEDSSDGDKE-LMKELYDRCEKKRRTLFKLASETEDNDNSLGDILQASDDLSRVIN 79


                 ....*...
gi 768024567 302 LYKQLVRG 309
Cdd:cd14240   80 SYKKIVEG 87
VHS_ENTH_ANTH cd00197
VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a ...
 7-132 4.00e-30

VHS, ENTH and ANTH domain superfamily; This superfamily is composed of proteins containing a VHS, CID, ENTH, or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It is located at the N-termini of proteins involved in intracellular membrane trafficking. The CTD-Interacting Domain (CID) is present in several RNA-processing factors and binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II or Pol II). The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. A set of proteins previously designated as harboring an ENTH domain in fact contains a highly similar, yet unique module referred to as an AP180 N-Terminal Homology (ANTH) domain. VHS, ENTH, and ANTH domains are structurally similar and are composed of a superhelix of eight alpha helices. ENTH and ANTH (E/ANTH) domains bind both inositol phospholipids and proteins and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. E/ANTH domain-bearing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.


Pssm-ID: 340764  Cd Length: 115  Bit Score: 114.44  E-value: 4.00e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd00197    6 EKATSNENMGPDWPLIMEICDLINETNVGPKEAVDAIKKRINNKNPHVVLKALTL-----------------LEYCVKNC 68

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 768024567  87 GKRFHDEVGKFRFLNELIKVVSPKYLGSRTSEKVKNKILELLYSWT 132
Cdd:cd00197   69 GERFHQEVASNDFAVELLKFDKSGLLGDDVSTNVREKAIELVQLWA 114
Alpha_adaptinC2 smart00809
Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link ...
 526-640 2.45e-28

Adaptin C-terminal domain; Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Gamma-adaptin is a subunit of the golgi adaptor. Alpha adaptin is a heterotetramer that regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This Ig-fold domain is found in alpha, beta and gamma adaptins and consists of a beta-sandwich containing 7 strands in 2 beta-sheets in a greek-key topology.. The adaptor appendage contains an additional N-terminal strand.


Pssm-ID: 197886 [Multi-domain]  Cd Length: 104  Bit Score: 109.25  E-value: 2.45e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   526 VYDQHGFRILFHFARdplpgRSDVLVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNPivhpsaITQVL 605
Cdd:smart00809   1 AYEKNGLQIGFKFER-----RPGLIRITLTFTNKSPSPITNFSFQAAVPKSLKLQLQPPSSPTLPPGGQ------ITQVL 69

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 768024567   606 LLANPQKEKVRLRYKLTFTMGDQTYNEMGDVDQFP 640
Cdd:smart00809  70 KVENPGKFPLRLRLRLSYLLGGSAVTEQGDVLKFP 104
VHS cd03561
VHS (Vps27/Hrs/STAM) domain family; The VHS domain is present in Vps27 (Vacuolar Protein ...
 8-150 9.08e-26

VHS (Vps27/Hrs/STAM) domain family; The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It has a superhelical structure similar to that of the ARM (Armadillo) repeats and is present at the N-termini of proteins involved in intracellular membrane trafficking. There are four general groups of VHS domain containing proteins based on their association with other domains. The first group consists of proteins of the STAM/EAST/Hbp family, which has the domain composition of VHS-SH3-ITAM. The second consists of proteins with a FYVE domain C-terminal to VHS. The third consists of GGA proteins with a domain composition of VHS-GAT (GGA and TOM)-GAE (Gamma-Adaptin Ear) domain. The fourth consists of proteins with a VHS domain alone or with domains other than those mentioned above. In GGA proteins, VHS domains are involved in cargo recognition in trans-Golgi, thereby having a general membrane targeting/cargo recognition role in vesicular trafficking.


Pssm-ID: 340765  Cd Length: 131  Bit Score: 102.73  E-value: 9.08e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSCG 87
Cdd:cd03561    7 KATSESLTEPDWALNLEICDLVNSDPAQAKDAVRALRKRLQSKNPKVQLLALTL-----------------LETLVKNCG 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768024567  88 KRFHDEVGKFRFLNELIKVVSPKylgsRTSEKVKNKILELLYSWTVGLPEEVK---IAEAYQMLKK 150
Cdd:cd03561   70 APFHSEVASRDFLQELVKLVKKK----KTSPEVREKALALIQEWAEAFQGDGRlplFYDTYQQLRR 131
GAT pfam03127
GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of ...
 231-309 9.50e-26

GAT domain; The GAT domain is responsible for binding of GGA proteins to several members of the ARF family including ARF1 and ARF3. The GAT domain stabilizes membrane bound ARF1 in its GTP bound state, by interfering with GAP proteins.


Pssm-ID: 460818  Cd Length: 76  Bit Score: 100.69  E-value: 9.50e-26
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  231 NNNVKLLTEMVMSHSQGGaaaGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQLVRG 309
Cdd:pfam03127   1 RNNAKLLNEMLSSTDPDE---ELDNELIKELYERCKSAQPKIQKLIEETSDEDDLLAELLQLNDDLNNVLERYERLKKG 76
Alpha_adaptinC2 pfam02883
Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud ...
 523-640 4.50e-25

Adaptin C-terminal domain; Alpha adaptin is a heterotetramer which regulates clathrin-bud formation. The carboxyl-terminal appendage of the alpha subunit regulates translocation of endocytic accessory proteins to the bud site. This ig-fold domain is found in alpha, beta and gamma adaptins.


Pssm-ID: 460735  Cd Length: 111  Bit Score: 100.09  E-value: 4.50e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  523 PVTVYDQHGFRILFHFARDplpGRSDVLVVVVSMLSTAPQPIRNIVFQSAVPKVMKVKLQPPSGTELPAFNpivhPSAIT 602
Cdd:pfam02883   2 PVVLYESDGLQIGFSFERS---RRPGQIRITLTFTNKSSSPISNFSFQAAVPKSLKLQLQPPSSNVLPPNP----GGQIT 74

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 768024567  603 QVLLLANPQKEKVRLRYKLTFTMGdQTYNEMGDVDQFP 640
Cdd:pfam02883  75 QVLLIENPGKKPLRMRLKISYLNG-GAVQEQGDVLKFP 111
GAT_GGA cd14230
canonical GAT domain found in metazoan and fungal ADP-ribosylation factor (Arf)-binding ...
 227-306 6.91e-22

canonical GAT domain found in metazoan and fungal ADP-ribosylation factor (Arf)-binding proteins (GGAs); GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGAs also play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. The family includes three GGAs (GGA1, GGA2, and GGA3) identified in mammals and two GGAs (Gga1p and Gga2p) identified in the budding yeast Saccharomyces cerevisiae. All these GGAs have a multidomain structure consisting of: an N-terminal VHS (Vps27/Hrs/Stam) domain that binds acidic-cluster dileucine (DxxLL)-type sorting signals (where x is any amino acid) found in the cytoplasmic tail of TGN sorting receptors; a GAT (GGA and TOM) domain that interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and the tumor susceptibility gene 101 product (TSG101); a largely unstructured hinge region that contains clathrin-binding motifs; and a C-terminal GAE (gamma-adaptin ear homology) domain that binds accessory proteins. In contrast to other GGAs-like proteins, members of this family contain a GAT N-terminal region, a helix-loop-helix in the complex with Arf1-GTP.


Pssm-ID: 410578  Cd Length: 80  Bit Score: 89.91  E-value: 6.91e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 227 IEEVNNNVKLLTEMVMSHSQGGAAAGSSEdLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQVINLYKQL 306
Cdd:cd14230    2 LEEAKNNVDLLDEMLLSYSQEDSSDGDNE-LMKELYDQLENMRPTLFKLASETEENDNSLGDVLQASDNVNRVINKYKDI 80
VHS_Tom1_like cd03565
VHS (Vps27/Hrs/STAM) domain of Tom1 subfamily; This subfamily is composed of Tom1 (Target of ...
 8-152 5.55e-18

VHS (Vps27/Hrs/STAM) domain of Tom1 subfamily; This subfamily is composed of Tom1 (Target of myb1 - retroviral oncogene) protein, Tom1L1 (Tom1-like1), Tom1L2 (Tom1-like2), and similar proteins. Proteins belonging to this subfamily are characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Yeast do not contain homologous proteins of the Tom1 subfamily, suggesting these proteins have evolved to accommodate more complex cellular processes. Tom1 is essential for the negative regulation of Interleukin-1 and Tumor Necrosis Factor-induced signaling pathways. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.


Pssm-ID: 340768  Cd Length: 138  Bit Score: 80.77  E-value: 5.55e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQ---EWEAIQALTVrrgeatirpppcddtkvLETCMK 84
Cdd:cd03565    8 RATDSGLSSEDWALNMEICDMINETDDGPKDAIKAIKKRLSTNAgknHTVVMYTLTL-----------------LETCVK 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768024567  85 SCGKRFHDEVGKFRFLNELIKVVSPKYlgsRTSEKVKNKILELLYSWT---VGLPEEVKIAEAYQMLKKQG 152
Cdd:cd03565   71 NCGHRFHVLVANKDFLQELVKLIGPKN---DPPTIVQEKVLSLIQSWAdafRGQPDLQEVVKVYQELKAKG 138
GGA_N-GAT pfam18308
N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA ...
 178-216 6.92e-18

N-terminal extension of GAT domain; This region is found in the N-terminal region of the GGA and Tom1 (GAT) domain in Golgi-localizing gamma-adaptin ARF-binding protein 1 (GGA1) present in Homo sapiens. The GAT domain is the key region in GGA that interacts with ARF. ARF plays a crucial role in docking adaptor proteins to membranes. This region is referred to as N-GAT and it interacts extensively with ARF.


Pssm-ID: 465702  Cd Length: 39  Bit Score: 77.34  E-value: 6.92e-18
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 768024567  178 FEDEEKSKMLARLLKSSHPEDLRAANKLIKEMVQEDQKR 216
Cdd:pfam18308   1 FDDEEKSKLLARLLKSKNPEDLQAANRLIKSMVKEDDER 39
VHS_Hrs cd03569
VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, ...
 8-152 9.10e-16

VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs; Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) plays a role in at least three vesicle trafficking events: exocytosis, endocytosis, and endosome to lysosome trafficking. Hrs is involved in promoting rapid recycling of endocytosed signaling receptors to the plasma membrane. Together with STAM or STAM2, it comprises the ESCRT (Endosomal Sorting Complex Required for Transport)-0 machinery, which functions to bind and sequester cargoes for downstream sorting into intralumenal vesicles. Hrs contains an N-terminal VHS domain, which has a superhelical structure similar to the structure of ARM (Armadillo) repeats, a FYVE (Fab1p, YOTB, Vac1p, and EEA1) zinc finger domain, a Double Ubiquitin-Interacting Motif (DUIM), a P(S/T)XP motif that recruit ESCRT-I, a GAT (GGA and TOM) domain, and a short peptide motif near the C-terminus that recruits clathrin.


Pssm-ID: 340771  Cd Length: 138  Bit Score: 74.60  E-value: 9.10e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSCG 87
Cdd:cd03569    9 KATSQLLLEPDWESILQICDLIRQGDVTPKYAVSAIKKKLNDQNPHVALYALQV-----------------LESVVKNCG 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768024567  88 KRFHDEVGKFRFLNELIKVVSpkylgSRTSEKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:cd03569   72 TPVHDEVATKEFMEELRDLVK-----TTTSENVRNKILELIQAWAHAFrnePKYKIVQDTYNIMKMEG 134
GAT_SF cd12930
GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, ...
 228-306 9.03e-15

GAT domain found in eukaryotic GGAs, metazoan Tom1-like proteins, metazoan STAMs, fungal Vps27, and similar proteins; The GAT (GGA and Tom1) domain superfamily includes the canonical GAT domain found in ADP-ribosylation factor (Arf)-binding proteins (GGAs) from eukaryotes, myb protein 1 (Tom1)-like proteins from metazoa, and LAS seventeen-binding protein 5 (Lsb5p)-like proteins from fungi. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin. GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS-domain followed by a GAT domain. Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain. They do not associate with either Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. The GAT domain superfamily also includes the non-canonical GAT domain found in several components of the ESCRT-0 complex, including signal transducing adapter molecules (STAMs) and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) from metazoa, as well as vacuolar protein sorting-associated protein 27 (Vps27) and class E vacuolar protein-sorting machinery protein Hse1 from fungi. Hrs, together with STAM, forms a Hrs/STAM core complex. Vps27, together with Hse1, forms a Vps27/Hse1 core complex. Those complexes consist of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The intertwined GAT heterodimer acts as a scaffold for binding of ubiquitinated cargo proteins and coordinating ubiquitination and deubiquitination reactions that regulate sorting.


Pssm-ID: 410577  Cd Length: 77  Bit Score: 69.57  E-value: 9.03e-15
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567 228 EEVNNNVKLLTEMVMSHSQGGAAAGSSEdLMKELYQRCERMRPTLFRLASDTEDnDEALAEILQANDNLTQVINLYKQL 306
Cdd:cd12930    1 EEVKDNVR*FSELLEK*KSRPLEILDDE-LLQELAQRCFASKARLNYLLNDKAD-DQKYNTLLE*NDNLSEV*NIYDRL 77
VHS_Tom1L2 cd16996
VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 2; TOM1-like protein 2 (Tom1L2) is a member ...
 8-152 6.20e-13

VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 2; TOM1-like protein 2 (Tom1L2) is a member of the Tom1 (Target of myb1) subfamily, characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Studies in Tom1L2 hypomorphic mice suggest that Tom1L2 may play roles in immune responses and tumor suppression. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.


Pssm-ID: 340793 [Multi-domain]  Cd Length: 137  Bit Score: 66.21  E-value: 6.20e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEW-EAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd16996    8 KATDGSLQSEDWTLNMEICDIINETEEGPKDAIRALKKRLNGNKNYrEVMLALTV-----------------LETCVKNC 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFLNE-LIKVVSPKylgSRTSEKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:cd16996   71 GHRFHVLVASRDFIDGvLVKIISPK---NNPPTIVQDKVLALIQAWADAFrssPDLTGVVHIYEELKRKG 137
GAT_GGA_Tom1-like cd21383
canonical GAT domain found in eukaryotic ADP-ribosylation factor (Arf)-binding proteins (GGAs), ...
 227-306 3.46e-12

canonical GAT domain found in eukaryotic ADP-ribosylation factor (Arf)-binding proteins (GGAs), metazoan myb protein 1 (Tom1)-like proteins, and similar proteins; This model represents the canonical GAT (GGA and Tom1) domain found in GGAs from eukaryotes, Tom1-like proteins from metazoa, and LAS seventeen-binding protein 5 (Lsb5p)-like proteins from fungi. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin. GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. GGAs play important roles in ubiquitin-dependent sorting of cargo proteins both in biosynthetic and endocytic pathways. Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS-domain followed by a GAT domain. Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain. They do not associate with either Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. In addition, Tom1 family proteins recruit clathrin onto endosomes through their C-terminal region. The C-terminal clathrin-binding region of Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1.


Pssm-ID: 410588  Cd Length: 80  Bit Score: 62.28  E-value: 3.46e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 227 IEEVNNNVKLLTEMVmshSQGGAAAGSSEDLMKELYQRCERMRPTLFRLASDTED--NDEALAEILQANDNLTQVINLYK 304
Cdd:cd21383    2 LEEVKENASLLNEML---SAASPEELLDNELLQELVEFCRACQPRIVELIEATTDglDEDTLEELLELNDELNEALQRYD 78


                 ..
gi 768024567 305 QL 306
Cdd:cd21383   79 DL 80
VHS_STAM cd03568
VHS (Vps27/Hrs/STAM) domain of the STAM (Signal Transducing Adaptor Molecule) subfamily; STAM ...
 8-152 1.94e-10

VHS (Vps27/Hrs/STAM) domain of the STAM (Signal Transducing Adaptor Molecule) subfamily; STAM (Signal Transducing Adaptor Molecule) subfamily members have at their N-termini a VHS domain, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM (Armadillo) repeats, followed by a Ubiquitin-Interacting Motif (UIM) and a SH3 (Src Homology 3) domain, which is a well-established protein-protein interaction domain, and a GAT (GGA and TOM) domain. At the C-termini of most vertebrate STAMs, an Immunoreceptor Tyrosine-based Activation Motif (ITAM) is present, which mediates the binding of HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in endocytic and exocytic machineries. STAM is a component of the ESCRT (Endosomal Sorting Complex Required for Transport)-0 machinery and together with Hrs, functions to bind and sequester cargoes for downstream sorting into intralumenal vesicles. Jawed vertebrates have two STAM subfamily members, STAM1 and STAM2.


Pssm-ID: 340770  Cd Length: 132  Bit Score: 58.84  E-value: 1.94e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSCG 87
Cdd:cd03568    7 KATSEKNTSENWSLILDICDKVGRSPNGAKDCLKSIMKRLNHKDPHVALQALTL-----------------LDACVKNCG 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  88 KRFHDEVGKFRFLNELIKVVspkylgSRTSEKVKNKILELLYSWTVGL----PEEVKIAEAYQMLKKQG 152
Cdd:cd03568   70 KIFHLEVCSRDFESELRKLL------TKSHPKVAEKLKELLKKWAEEEfkddPQLSLIPSLYKKLKAEG 132
VHS_Tom1 cd16995
VHS (Vps27/Hrs/STAM) domain of Target of Myb protein 1; Tom1 (Target of myb1 - retroviral ...
 8-152 9.51e-10

VHS (Vps27/Hrs/STAM) domain of Target of Myb protein 1; Tom1 (Target of myb1 - retroviral oncogene) is a novel negative regulator of interleukin-1 and tumor necrosis factor-induced signaling pathways. It also plays important roles in protein-degradation systems in Alzheimer's disease pathogenesis. Tom1 contains VHS and GAT domains in the N-terminal and central region, respectively. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting. The VHS domain of Tom1 is essential for its function as a negative regulator.


Pssm-ID: 340792  Cd Length: 137  Bit Score: 57.23  E-value: 9.51e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEW-EAIQALTVrrgeatirpppcddtkvLETCMKSC 86
Cdd:cd16995    8 KATDGSLQSEDWGLNMEICDIINETEEGPKDAIRAIKKRIVGNKNFrEVMLALTV-----------------LETCVKNC 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  87 GKRFHDEVGKFRFL-NELIKVVSPKylgSRTSEKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:cd16995   71 GHRFHVLVASQDFVeGVLVKTILPK---NNPPAIVHDKVLNLIQAWADAFrssPDLTGVVTVYEDLRRKG 137
VHS_Tom1L1 cd16997
VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 1; TOM1-like protein 1 (Tom1L1) is also ...
 18-152 7.47e-09

VHS (Vps27/Hrs/STAM) domain of TOM1-like protein 1; TOM1-like protein 1 (Tom1L1) is also called Src-activating and signaling molecule protein (Srcasm). It is a member of the Tom1 (Target of myb1) subfamily, characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Tom1L1 has been implicated in multivesicular body (MVB) formation, viral egress from the cell, and cytokinesis. Its amplification enhances the metastatic progression of ERBB2-positive breast cancers. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.


Pssm-ID: 340794  Cd Length: 137  Bit Score: 54.45  E-value: 7.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  18 DWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQaLTVrrgeatirpppcddtKVLETCMKSCGKRFHDEVGKF 97
Cdd:cd16997   18 DWGQFMHICDIINTTEDGPKDAVKALKKRISKNYNHKEIR-LTL---------------SLLDMCMQNCGPSFQSLVVKK 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  98 RFLNE-LIKVVSPKYlgsRTSEKVKNKILELLYSWTVGLPEEV---KIAEAYQMLKKQG 152
Cdd:cd16997   82 EFVKDvLVKLLNPRY---NLPVDLQNKILNFIMTWAQGFQGGVdvsEVKEVYLDLVKKG 137
VHS_HSE1 cd16978
VHS (Vps27/Hrs/STAM) domain of Class E vacuolar protein-sorting machinery protein HSE1; Class ...
 7-152 2.30e-08

VHS (Vps27/Hrs/STAM) domain of Class E vacuolar protein-sorting machinery protein HSE1; Class E vacuolar protein-sorting machinery protein HSE1, together with Vps27, comprise the ESCRT-0 complex, the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB). The complex directly binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. It is also required the efficient recycling of late Golgi proteins including the carboxypeptidase Y (CPY) sorting receptor, Vps10. Similar to metazoan STAMs, HSE1 contain: an N-terminal VHS domain, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM (Armadillo) repeats; a Ubiquitin-Interacting Motif (UIM); a SH3 (Src Homology 3) domain, a well-established protein-protein interaction domain; and a GAT (GGA and TOM) domain, which is essential for the normal sorting function of HSE1.


Pssm-ID: 340775  Cd Length: 134  Bit Score: 52.96  E-value: 2.30e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDfegPPLATRllahkiqspqewEAIQALTVRRGeatirpppCDDTKV-------L 79
Cdd:cd16978    6 IKATDETLTSENWQYILDVCDKVNSD---PEDGAR------------EAIAAIQKRLQ--------HRNANVqlrslslA 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  80 ETCMKSCGKRFHDEVGKFRFLNELIKVVspkyLGSRTSEKVKNKILELLYSWTvglpEEVK-------IAEAYQMLKKQG 152
Cdd:cd16978   63 DALAKNCGSRLHQEISSRSFTQTLLRLI----NDRTTHATVKKRILELIKQLS----DSFKsdpslglMSDTYDQLKSKY 134
VHS_Vps27 cd16979
VHS (Vps27/Hrs/STAM) domain of Vacuolar protein sorting-associated protein 27; Vacuolar ...
 77-153 1.87e-07

VHS (Vps27/Hrs/STAM) domain of Vacuolar protein sorting-associated protein 27; Vacuolar protein sorting-associated protein 27 (Vps27 or Vps27p) is also called Golgi retention defective protein 11, and is the yeast homolog of Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate). Together with class E vacuolar protein-sorting machinery protein HSE1, it comprises the ESCRT-0 complex, the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB). The complex directly binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. It is also required the efficient recycling of late Golgi proteins including the carboxypeptidase Y (CPY) sorting receptor, Vps10. Vps27 contain similar domains and motifs to Hrs; it contains an N-terminal VHS domain, which has a superhelical structure similar to the structure of ARM (Armadillo) repeats, a FYVE (Fab1p, YOTB, Vac1p, and EEA1) zinc finger domain, two Ubiquitin-Interacting Motifs (UIMs), a GAT (GGA and TOM) domain, two a P(S/T)XP motifs that recruit ESCRT-I, and a short peptide motif near the C-terminus that recruits clathrin.


Pssm-ID: 340776  Cd Length: 141  Bit Score: 50.66  E-value: 1.87e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  77 KVLETCMKSCGKRFHDEVGKFRFLNELIKVVspkyLGSRTSEKVKNKILELLYSWTV---GLPEEVKIAEAYQMLKKQGI 153
Cdd:cd16979   63 KLTDVCVKNGGDHFLVEIASREFMDNLVSLI----RSTGVNPEVKEKILRLIQEWALafkSKSQLSYVVEVYKKLKSEGI 138
VHS_STAM2 cd16999
VHS (Vps27/Hrs/STAM) domain of Signal Transducing Adapter Molecule 2; Signal Transducing ...
 8-154 2.89e-07

VHS (Vps27/Hrs/STAM) domain of Signal Transducing Adapter Molecule 2; Signal Transducing Adapter Molecule 2 (STAM2) is also called EAST (EGFR-Associated protein with SH3 and TAM domain) and Hbp (Hrs-binding protein). It is highly expressed in neurons, where it is localized in the nucleus. STAM (Signal Transducing Adaptor Molecule) subfamily members have at their N-termini a VHS domain, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM (Armadillo) repeats, followed by a Ubiquitin-Interacting Motif (UIM) and a SH3 (Src Homology 3) domain, which is a well-established protein-protein interaction domain, and a GAT (GGA and TOM) domain. At the C-termini of most vertebrate STAMS, an Immunoreceptor Tyrosine-based Activation Motif (ITAM) is present, which mediates the binding of HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in endocytic and exocytic machineries. STAM is a component of the ESCRT (Endosomal Sorting Complex Required for Transport)-0 machinery and together with Hrs, functions to bind and sequester cargoes for downstream sorting into intralumenal vesicles.


Pssm-ID: 340796 [Multi-domain]  Cd Length: 139  Bit Score: 49.97  E-value: 2.89e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTVrrgeatirpppcddtkvLETCMKSCG 87
Cdd:cd16999    7 KATNEYNTSEDWSLIMDICDKVGSTPNGAKDCLKAIMKRVNHKVPHVALQALTL-----------------LGACVSNCG 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567  88 KRFHDEVGKFRFLNELIKVVSPKylgsrTSEKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQGIV 154
Cdd:cd16999   70 KIFHLEVCSRDFATEVRAVIKNK-----AHPKVCEKLKALMVEWSEEFqkdPQFSLISATIKSLKEEGIT 134
GAT_TM1L2 cd14238
canonical GAT domain found in target of Myb-like protein 2 (Tom1L2); Tom1L2, together with Myb ...
 218-308 7.57e-07

canonical GAT domain found in target of Myb-like protein 2 (Tom1L2); Tom1L2, together with Myb protein 1 (Tom1) and target of Myb-like protein 1 (Tom1L1), constitute the Tom1 family. Tom1L2 can interact with Toll-interacting protein (Tollip), clathrin, and ubiquitin. It may play a potential role in endosomal sorting, as well as in the regulation of membrane trafficking that is linked to immunity and cell proliferation. Tom1L2 contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain, a GAT (GGA and TOM1) domain, and a C-terminal clathrin-binding region, both of which are conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). It interacts with Tollip through their GAT domain and recuits clathrin onto endosomes through their C-terminal region. However, in the C-terminal clathrin-binding region, Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.


Pssm-ID: 410585  Cd Length: 92  Bit Score: 47.73  E-value: 7.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 218 EKISKRVNAIEEVNNNVKLLTEMVMSHSQGGAAAgSSEDLMKELYQRCERMRPTLFRLASDTEdNDEALAEILQANDNLT 297
Cdd:cd14238    2 EQIARLRSELDIVRGNTKVMSEMLTEMVPGQEDP-SDLELLQELNRTCRAMQQRIVELISRVS-NEEVTEELLHVNDDLN 79

                         90
                 ....*....|.
gi 768024567 298 QVINLYKQLVR 308
Cdd:cd14238   80 NVFLRYERFER 90
GAT_GGA_fungi cd14235
canonical GAT domain found in fungal ADP-ribosylation factor (Arf)-binding proteins (GGAs); ...
 221-309 1.27e-06

canonical GAT domain found in fungal ADP-ribosylation factor (Arf)-binding proteins (GGAs); GGAs, also called Golgi-localized gamma-ear-containing Arf-binding proteins, belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. Two GGAs (Gga1p and Gga2p) have been identified in the budding yeast Saccharomyces cerevisiae. Yeast GGAs play important roles in the carboxypeptidase Y (CPY) pathway, vacuole biogenesis, alpha-factor maturation, and interactions with clathrin. They have a multidomain structure consisting of VHS (Vps27/Hrs/ STAM), GAT (GGA and TOM), hinge, and GAE (gamma-adaptin ear) domains. Both Gga1p and Gga2p function as effectors of Arf in yeast. They interact with Arf1p and Arf2p in a GTP-dependent manner. Moreover, Gga2p mediates sequential ubiquitin-independent and ubiquitin-dependent steps in the trafficking of ARN1, a ferrichrome transporter in S. cerevisiae, from the TGN to the vacuole. It also acts as a phosphatidylinositol 4-phosphate effector at the Golgi exit, which binds directly to the TGN PtdIns(4)-kinase Pik1p and contributes to Pik1p recruitment. In addition, Gga2p is required for sorting of the yeast siderophore iron transporter1 (Sit1) to the vacuolar pathway. The GAT domain of GGAs interacts with class I GTP-bound form of Arf proteins, Rabaptin-5, ubiquitin, and/or the tumor susceptibility gene 101 product (TSG101).


Pssm-ID: 410583  Cd Length: 92  Bit Score: 46.84  E-value: 1.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 221 SKRVNA-IEEVNNNVKLLTEMVMSHSQGgaAAGSSEDLMKELYQRCERMRPTLFRLASDTEDNDEALAEILQANDNLTQV 299
Cdd:cd14235    3 KAQVAEeLEKLKRKAILLNEMLNNATPG--EIDVEGDTYDELASSLKSAQPKIQKIIEEESEDEESVQKLLELNDLINSL 80

                         90
                 ....*....|
gi 768024567 300 INLYKQLVRG 309
Cdd:cd14235   81 LERYDLLKKG 90
VHS_STAM1 cd17000
VHS (Vps27/Hrs/STAM) domain of Signal Transducing Adapter Molecule 1; Signal Transducing ...
 8-152 3.37e-06

VHS (Vps27/Hrs/STAM) domain of Signal Transducing Adapter Molecule 1; Signal Transducing Adapter Molecule 1 (STAM1) is part of a crucial regulatory axis for the ventral axonal trajectory of developing spinal motor neurons. It forms a complex with beta-arrestin, which regulates lysosomal trafficking of the chemokine receptor CXCR4 and also mediates CXCR4-dependent chemotaxis. STAM (Signal Transducing Adaptor Molecule) subfamily members have at their N-termini a VHS domain, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM (Armadillo) repeats, followed by a Ubiquitin-Interacting Motif (UIM) and a SH3 (Src Homology 3) domain, which is a well-established protein-protein interaction domain, and a GAT (GGA and TOM) domain. At the C-termini of most vertebrate STAMS, an Immunoreceptor Tyrosine-based Activation Motif (ITAM) is present, which mediates the binding of HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in endocytic and exocytic machineries. STAM is a component of the ESCRT (Endosomal Sorting Complex Required for Transport)-0 machinery and together with Hrs, functions to bind and sequester cargoes for downstream sorting into intralumenal vesicles.


Pssm-ID: 340797  Cd Length: 131  Bit Score: 46.98  E-value: 3.37e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   8 RATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQSPQEWEAIQALTvrrgeatirpppcddtkVLETCMKSCG 87
Cdd:cd17000    7 KATSEMNTAEDWGLILDICDKVGQSRTGPKDCLRSIMRRVNHKDPHVAMQALT-----------------LLGACVSNCG 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768024567  88 KRFHDEVGKFRFLNELIKVVspkylgSRTSEKVKNKILELLYSWTVGL---PEEVKIAEAYQMLKKQG 152
Cdd:cd17000   70 KIFHLEVCSRDFASEVSNVL------NKGHPKVCEKLKALMVEWTEEFkndPQLSLISAMIKNLKEQG 131
VHS_Lsb5 cd16980
VHS (Vps27/Hrs/STAM) domain of LAS seventeen-binding protein 5; LAS seventeen-binding protein ...
 7-150 5.79e-06

VHS (Vps27/Hrs/STAM) domain of LAS seventeen-binding protein 5; LAS seventeen-binding protein 5 (LAS17-binding protein 5, Lsb5, or Lsb5p) localizes to the plasma membrane and plays a role in endocytosis in yeast. It interacts with actin regulators Sla1p and Las17p, ubiquitin, and Arf3p, coupling actin dynamics to membrane trafficking processes. Lsb5p contains an N-terminal VHS domain and a GAT (GGA and TOM) domain. The VHS domain has a superhelical structure similar to the structure of ARM (Armadillo) repeats. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.


Pssm-ID: 340777  Cd Length: 132  Bit Score: 46.06  E-value: 5.79e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567   7 NRATNPLNKELDWASINGFCEQLNEDFEGPPLATRLLAHKIQ--SPQEweAIQALTVrrgeatirpppcddtkvLETCMK 84
Cdd:cd16980    6 ERLTSSEYEEEDWSLVLELCELINLIESGAKEAARALRKKLKygNPHQ--QLRALTL-----------------LDLLVE 66

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567  85 SCGKRFHDEVGKFRFLNELIKVVSPKylgSRTSEKVKNKILELLYSWT---VGLPEEVKIAEAYQMLKK 150
Cdd:cd16980   67 NGGKKFQAQFASDKKLEDLLRLIASD---PSTDPKVRKKLLELLGGWAyefKGDPGLSGIASLYKKVKP 132
GAT_GGA-like_plant cd14231
canonical GAT domain found in uncharacterized Golgi-localized gamma ear-containing Arf-binding ...
 227-306 5.91e-06

canonical GAT domain found in uncharacterized Golgi-localized gamma ear-containing Arf-binding protein (GGA)-like proteins mainly found in plants; The family includes a group of uncharacterized plant proteins containing an N-terminal VHS (Vps27p/Hrs/STAM)-domain and a GAT (GGA and TOM1) domain. Both domains are also present in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs), which belong to a family of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins that regulate clathrin-mediated trafficking of cargo proteins from the trans-Golgi network (TGN) to endosomes. In contrast to GGA proteins, members in this family do not have either a GAE (gamma-adaptin ear homology) domain or a clathrin-binding motif. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.


Pssm-ID: 410579  Cd Length: 79  Bit Score: 44.56  E-value: 5.91e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 227 IEEVNNNVKLLTEMVMSHSQGGAAAgSSEDLMKELYQRCERMRPTLFRLASDTEDnDEALAEILQANDNLTQVINLYKQL 306
Cdd:cd14231    2 LQVARNSLELLSDMLNAVDPRDPEA-LKDELTVDLVEQCRQSQPRVMQLVESTGD-EGLLFQALELNDELQRVLSKHDAI 79
GAT_TOM1_like cd14233
canonical GAT domain found in target of myb protein 1 (Tom1) protein family; Tom1 and its ...
 230-308 1.11e-05

canonical GAT domain found in target of myb protein 1 (Tom1) protein family; Tom1 and its related proteins, Tom1L1 and Tom1L2, form a protein family sharing an N-terminal VHS (Vps27p/Hrs/STAM)-domain followed by a GAT (GGA and TOM1) domain, both of which are also conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). In contrast to GGAs, the Tom1 family proteins bind to ubiquitin, ubiquitinated proteins, and Toll-interacting protein (Tollip) through its GAT domain, but do not associate with Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. In addition, the Tom1 family proteins recruit clathrin onto endosomes through their C-terminal region. In their C-terminal clathrin-binding regions, Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1. The yeast S. cerevisiae does not contain homologous proteins of the Tom1 family. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.


Pssm-ID: 410581  Cd Length: 87  Bit Score: 44.11  E-value: 1.11e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768024567 230 VNNNVKLLTEMVMSHSQGGAAAGSSEdLMKELYQRCERMRPTLFRLASdTEDNDEALAEILQANDNLTQVINLYKQLVR 308
Cdd:cd14233   11 VEGNLKVMSEMLTELVPGQENPDDLE-LLQELNSTCRAMQQRVVELIS-QVSNEEVTEELLRVNDDLNNVFLRYERFER 87
GAT_TM1L1 cd14237
canonical GAT domain found in target of Myb-like protein 1 (Tom1L1); Tom1L1, also called ...
 218-308 2.89e-05

canonical GAT domain found in target of Myb-like protein 1 (Tom1L1); Tom1L1, also called Src-activating and signaling molecule protein (Srcasm), was identified as a substrate of the Src family of protein kinases. It is tyrosine-phosphorylated by Src family kinases and modulates growth factor and Src-mediated signaling pathways. It also plays a potential role in endosomal sorting and ligand-stimulated endocytosis of EGF receptors (EGFR). Tom1L1 is predominantly present in the cytosol and can interact with Toll-interacting protein (Tollip), Hrs or TSG101, clathrin, and ubiquitinated proteins. It contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain, a GAT (GGA and TOM1) domain, and a C-terminal clathrin-binding region, both of which are conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). It interacts with Tollip through their GAT domain and recuits clathrin onto endosomes through their C-terminal region. However, in the C-terminal clathrin-binding region, Tom1 and Tom1L2 are similar to each other, but distinguishable from Tom1L1. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.


Pssm-ID: 410584  Cd Length: 92  Bit Score: 42.93  E-value: 2.89e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 218 EKISKRVNAIEEVNNNVKLLTEMVMSHSQGgAAAGSSEDLMKELYQRCERMRPTLFRLASDTEdNDEALAEILQANDNLT 297
Cdd:cd14237    2 EQIGKLYSELDIVKMNVRVMSAILLENTPG-AENPEDMELLEKLYKTCREMQERIMKLLETVE-NEDVIIELIQVNDDLN 79

                         90
                 ....*....|.
gi 768024567 298 QVINLYKQLVR 308
Cdd:cd14237   80 NVFLRHERFSR 90
VHS_GGA_fungi cd16998
VHS (Vps27/Hrs/STAM) domain of fungal GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) ...
 78-135 1.72e-04

VHS (Vps27/Hrs/STAM) domain of fungal GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) proteins; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprises a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins involved in membrane trafficking between the Trans-Golgi Network (TGN) and endosomes. Yeast GGAs facilitate the specific and direct delivery of vacuolar sorting receptor Vps10p and the processing protease Kex2p from the TGN to the late endosome/prevacuolar compartment (PVC). The VHS domain has a superhelical structure similar to the structure of the ARM (Armadillo) repeats and is present at the N-termini of proteins. GGA proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain. The VHS domain of GGA proteins binds to the acidic-cluster dileucine (DxxLL) motif found on the cytoplasmic tails of cargo proteins trafficked between the Trans-Golgi Network and the endosomal system.


Pssm-ID: 340795 [Multi-domain]  Cd Length: 139  Bit Score: 41.93  E-value: 1.72e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768024567  78 VLETCMKSCGKRFHDEVGKFRFLNELIKVV---SPKYLGsrtseKVKNKILELLYSWTVGL 135
Cdd:cd16998   61 LLDVCVKNCGYPFHLQIASKEFLNELVRRFperPPSRLN-----PVQHKILELIEEWKQTL 116
GAT_TOM1 cd14236
canonical GAT domain found in target of Myb protein 1 (Tom1); Tom1 was originally identified ...
 218-308 4.04e-04

canonical GAT domain found in target of Myb protein 1 (Tom1); Tom1 was originally identified by its induced expression by the v-Myb oncogene. It is predominantly present in the cytosol and can interact with clathrin, endofin, Toll-interacting protein (Tollip), and ubiquitinated proteins. It acts as a linker protein to regulate the ability of endofin to recruit clathrin onto the sorting endosome. Moreover, Tom1 functions as a negative regulator of IL-1beta and tumor necrosis factor (TNF)-alpha-induced signaling pathways. It also plays a role in the TLR2/4 signaling pathways. Tom1 contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain, a GAT (GGA and TOM1) domain and a C-terminal clathrin-binding region, both of which are conserved in Golgi-localized gamma ear-containing Arf-binding proteins (GGAs). In contrast to GGAs, Tom1 binds to ubiquitin, ubiquitinated proteins, and Tollip through its GAT domain, but does not associate with Arf GTPases through its GAT domain nor with acidic cluster-dileucine sequences through its VHS domain. The canonical GAT domain is a monomeric three-helix bundle that binds ubiquitin.


Pssm-ID: 260094  Cd Length: 95  Bit Score: 40.02  E-value: 4.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768024567 218 EKISKRVNAIEEVNNNVKLLTEMvMSHSQGGAAAGSSEDLMKELYQRCERMRPTLFRLASDTEdNDEALAEILQANDNLT 297
Cdd:cd14236    2 EQIGKLRSELEMVSGNVRVMSEM-LTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIA-NEQLTEELLIVNDNLN 79

                         90
                 ....*....|.
gi 768024567 298 QVINLYKQLVR 308
Cdd:cd14236   80 NVFLRHERFER 90
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH