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Conserved domains on  [gi|24667845|ref|NP_649283|]
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islet cell autoantigen 69 kDa, isoform A [Drosophila melanogaster]

Protein Classification

islet cell autoantigen 1 family protein( domain architecture ID 10166605)

islet cell autoantigen 1 family protein, similar to human islet cell autoantigen 1 which functions as an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
BAR_ICA69 cd07661
The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of ...
 33-235 3.13e-124

The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Islet cell autoantigen 69-kDa (ICA69) is a diabetes-associated autoantigen that is highly expressed in brain and beta cells. It is involved in membrane trafficking at the Golgi complex in neurosecretory cells. It is coexpressed with Protein Interacting with C Kinase 1 (PICK1), also a the BAR domain containing protein, in many tissues at different developmental stages. In neurons, ICA69 colocalizes with PICK1 in cell bodies and dendrites but is absent in synapses where PICK1 is enriched. ICA69 contains an N-terminal BAR domain and a conserved C-terminal domain of unknown function. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. ICA69 associates with PICK1 through their BAR domains to form a heterodimer which is involved in regulating the synaptic targeting and surface expression of AMPA receptors. Autoantibodies against ICA69 have been identified in patients with insulin-dependent diabetes mellitus, rheumatoid arthritis, and primary Sjogren's syndrome. ICA69 has also been shown to be released by pancreatic cancer cells.


:

Pssm-ID: 153345  Cd Length: 204  Bit Score: 357.56  E-value: 3.13e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845  33 DAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRTTGGSI-AHTAKAVSFAGQQRMCVRV 111
Cdd:cd07661   1 DAELDAKLELFRSVQDTCLELLKIIDNYQERLCILSQEENVLGKFLKEQGKIDKTTAGKMmAATGKALSFSSQQRLALRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845 112 PLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAKHNFDGYSMDS 191
Cdd:cd07661  81 PLLRLYQEVETFRERAIADTLQTIQRMEKCRTEYRAALLWMKSVSQELDPDTYKQLEKFRKAQAQVRSAKERFDKLKMDV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 24667845 192 IQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTFQTISKAL 235
Cdd:cd07661 161 CQKVDLLGASRCNLLSHALVTYQNTLLQFWEKTSRTMATIHEAF 204
ICA69 super family cl04636
Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which ...
 345-396 4.89e-05

Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which has been identified as an islet cell autoantigen in type I diabetes mellitus. Its precise function is unknown.


The actual alignment was detected with superfamily member pfam04629:

Pssm-ID: 461374  Cd Length: 241  Bit Score: 44.39  E-value: 4.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 24667845   345 SQQNQQPIPSQVATDSKASAGGATPvpsksqttnnpWLDLFADLDPLANPQA 396
Cdd:pfam04629 188 QSPNQNVSKPKKKEKAPNSNKDMSA-----------WFNLFADLDPLSNPDA 228
 
Name Accession Description Interval E-value
BAR_ICA69 cd07661
The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of ...
 33-235 3.13e-124

The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Islet cell autoantigen 69-kDa (ICA69) is a diabetes-associated autoantigen that is highly expressed in brain and beta cells. It is involved in membrane trafficking at the Golgi complex in neurosecretory cells. It is coexpressed with Protein Interacting with C Kinase 1 (PICK1), also a the BAR domain containing protein, in many tissues at different developmental stages. In neurons, ICA69 colocalizes with PICK1 in cell bodies and dendrites but is absent in synapses where PICK1 is enriched. ICA69 contains an N-terminal BAR domain and a conserved C-terminal domain of unknown function. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. ICA69 associates with PICK1 through their BAR domains to form a heterodimer which is involved in regulating the synaptic targeting and surface expression of AMPA receptors. Autoantibodies against ICA69 have been identified in patients with insulin-dependent diabetes mellitus, rheumatoid arthritis, and primary Sjogren's syndrome. ICA69 has also been shown to be released by pancreatic cancer cells.


Pssm-ID: 153345  Cd Length: 204  Bit Score: 357.56  E-value: 3.13e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845  33 DAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRTTGGSI-AHTAKAVSFAGQQRMCVRV 111
Cdd:cd07661   1 DAELDAKLELFRSVQDTCLELLKIIDNYQERLCILSQEENVLGKFLKEQGKIDKTTAGKMmAATGKALSFSSQQRLALRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845 112 PLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAKHNFDGYSMDS 191
Cdd:cd07661  81 PLLRLYQEVETFRERAIADTLQTIQRMEKCRTEYRAALLWMKSVSQELDPDTYKQLEKFRKAQAQVRSAKERFDKLKMDV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 24667845 192 IQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTFQTISKAL 235
Cdd:cd07661 161 CQKVDLLGASRCNLLSHALVTYQNTLLQFWEKTSRTMATIHEAF 204
Arfaptin pfam06456
Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding ...
 24-228 7.23e-91

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.


Pssm-ID: 399453  Cd Length: 207  Bit Score: 273.08  E-value: 7.23e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845    24 KEDKHIISSDAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKR--SRTTGGSIAHTAKAVSF 101
Cdd:pfam06456   1 KEDSHAITSDDELDAKLEVLRSIQRTYLGLVKLARNYSKRLYDLSQTQKELGDFFKDLGKHekQQAAGEAFTAFGETHRF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845   102 AGQQRMCVRVPLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAK 181
Cdd:pfam06456  81 LAKQGLALLVPLNRFISSVNTFVNKAIPDTLLTIKRYEDARTEYRAYLLWMKEASDELDPDVAKQMPKFRVAQGNYQEAK 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 24667845   182 HNFDGYSMDSIQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTF 228
Cdd:pfam06456 161 AKFDKLRTDVLQKMDLLEANRINVLSHQLTLYQNTLAAYYSKNAKAL 207
Arfaptin smart01015
Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding ...
 8-228 1.16e-85

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.


Pssm-ID: 214974  Cd Length: 217  Bit Score: 259.90  E-value: 1.16e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845      8 HQFWITKKVVQRKLGTKEDKHIISSDAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRT 87
Cdd:smart01015   1 KTYKKTKQVLIEKLGKKEDEHVVASDAELDAKLELLRSTQRTYEDLLKLIEKYQQRLCNLSQTENELGDFFRDLSEKDPT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845     88 --TGGSIAHTAKAVSFAGQQRmcvRVPLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAalsWMKSASQELDPDTGK 165
Cdd:smart01015  81 lkAFGMMAETQKALCKSGEQL---LAPLNPFISDVNTFVNKAIEDTLLTIKRYEDARTEYRA---WMKDVSEELDPEEYK 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24667845    166 GLDKFRTAQAHVRVAKHNFDGYSMDSIQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTF 228
Cdd:smart01015 155 QLEKFRKAQRQVQEAKAKFEKLRNDVCQKVDLLEASRVNVLSHQLLLFQNALAAYWEKTAHAL 217
ICA69 pfam04629
Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which ...
 345-396 4.89e-05

Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which has been identified as an islet cell autoantigen in type I diabetes mellitus. Its precise function is unknown.


Pssm-ID: 461374  Cd Length: 241  Bit Score: 44.39  E-value: 4.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 24667845   345 SQQNQQPIPSQVATDSKASAGGATPvpsksqttnnpWLDLFADLDPLANPQA 396
Cdd:pfam04629 188 QSPNQNVSKPKKKEKAPNSNKDMSA-----------WFNLFADLDPLSNPDA 228
 
Name Accession Description Interval E-value
BAR_ICA69 cd07661
The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of ...
 33-235 3.13e-124

The Bin/Amphiphysin/Rvs (BAR) domain of Islet Cell Autoantigen 69-kDa; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization and lipid binding module that can detect and drive membrane curvature. Islet cell autoantigen 69-kDa (ICA69) is a diabetes-associated autoantigen that is highly expressed in brain and beta cells. It is involved in membrane trafficking at the Golgi complex in neurosecretory cells. It is coexpressed with Protein Interacting with C Kinase 1 (PICK1), also a the BAR domain containing protein, in many tissues at different developmental stages. In neurons, ICA69 colocalizes with PICK1 in cell bodies and dendrites but is absent in synapses where PICK1 is enriched. ICA69 contains an N-terminal BAR domain and a conserved C-terminal domain of unknown function. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. ICA69 associates with PICK1 through their BAR domains to form a heterodimer which is involved in regulating the synaptic targeting and surface expression of AMPA receptors. Autoantibodies against ICA69 have been identified in patients with insulin-dependent diabetes mellitus, rheumatoid arthritis, and primary Sjogren's syndrome. ICA69 has also been shown to be released by pancreatic cancer cells.


Pssm-ID: 153345  Cd Length: 204  Bit Score: 357.56  E-value: 3.13e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845  33 DAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRTTGGSI-AHTAKAVSFAGQQRMCVRV 111
Cdd:cd07661   1 DAELDAKLELFRSVQDTCLELLKIIDNYQERLCILSQEENVLGKFLKEQGKIDKTTAGKMmAATGKALSFSSQQRLALRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845 112 PLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAKHNFDGYSMDS 191
Cdd:cd07661  81 PLLRLYQEVETFRERAIADTLQTIQRMEKCRTEYRAALLWMKSVSQELDPDTYKQLEKFRKAQAQVRSAKERFDKLKMDV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 24667845 192 IQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTFQTISKAL 235
Cdd:cd07661 161 CQKVDLLGASRCNLLSHALVTYQNTLLQFWEKTSRTMATIHEAF 204
Arfaptin pfam06456
Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding ...
 24-228 7.23e-91

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.


Pssm-ID: 399453  Cd Length: 207  Bit Score: 273.08  E-value: 7.23e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845    24 KEDKHIISSDAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKR--SRTTGGSIAHTAKAVSF 101
Cdd:pfam06456   1 KEDSHAITSDDELDAKLEVLRSIQRTYLGLVKLARNYSKRLYDLSQTQKELGDFFKDLGKHekQQAAGEAFTAFGETHRF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845   102 AGQQRMCVRVPLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAK 181
Cdd:pfam06456  81 LAKQGLALLVPLNRFISSVNTFVNKAIPDTLLTIKRYEDARTEYRAYLLWMKEASDELDPDVAKQMPKFRVAQGNYQEAK 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 24667845   182 HNFDGYSMDSIQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTF 228
Cdd:pfam06456 161 AKFDKLRTDVLQKMDLLEANRINVLSHQLTLYQNTLAAYYSKNAKAL 207
Arfaptin smart01015
Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding ...
 8-228 1.16e-85

Arfaptin-like domain; Arfaptin interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The structure of arfaptin shows that upon binding to a small GTPase, arfaptin forms an elongated, crescent-shaped dimer of three-helix coiled-coils. The N-terminal region of ICA69 is similar to arfaptin.


Pssm-ID: 214974  Cd Length: 217  Bit Score: 259.90  E-value: 1.16e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845      8 HQFWITKKVVQRKLGTKEDKHIISSDAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRT 87
Cdd:smart01015   1 KTYKKTKQVLIEKLGKKEDEHVVASDAELDAKLELLRSTQRTYEDLLKLIEKYQQRLCNLSQTENELGDFFRDLSEKDPT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845     88 --TGGSIAHTAKAVSFAGQQRmcvRVPLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAalsWMKSASQELDPDTGK 165
Cdd:smart01015  81 lkAFGMMAETQKALCKSGEQL---LAPLNPFISDVNTFVNKAIEDTLLTIKRYEDARTEYRA---WMKDVSEELDPEEYK 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24667845    166 GLDKFRTAQAHVRVAKHNFDGYSMDSIQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTF 228
Cdd:smart01015 155 QLEKFRKAQRQVQEAKAKFEKLRNDVCQKVDLLEASRVNVLSHQLLLFQNALAAYWEKTAHAL 217
BAR_Arfaptin_like cd00011
The Bin/Amphiphysin/Rvs (BAR) domain of Arfaptin-like proteins, a dimerization module that ...
 33-234 1.54e-35

The Bin/Amphiphysin/Rvs (BAR) domain of Arfaptin-like proteins, a dimerization module that binds and bends membranes; The BAR domain of Arfaptin-like proteins, also called the Arfaptin domain, is a dimerization, lipid binding and curvature sensing module present in Arfaptins, PICK1, ICA69, and similar proteins. Arfaptins are ubiquitously expressed proteins implicated in mediating cross-talk between Rac, a member of the Rho family GTPases, and Arf (ADP-ribosylation factor) small GTPases. Arfaptins bind to GTP-bound Arf1, Arf5, and Arf6, with strongest binding to GTP-Arf1. Arfaptins also binds to Rac-GTP and Rac-GDP with similar affinities. The Arfs are thought to bind to the same surface as Rac, and their binding is mutually exclusive. Protein Interacting with C Kinase 1 (PICK1) plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory. Islet cell autoantigen 69-kDa (ICA69) is a diabetes-associated autoantigen that is involved in membrane trafficking at the Golgi complex in neurosecretory cells. ICA69 associates with PICK1 through their BAR domains to form a heterodimer which is involved in regulating the synaptic targeting and surface expression of AMPA receptors. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153270  Cd Length: 203  Bit Score: 129.66  E-value: 1.54e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845  33 DAELDSKIEVFKSISDTSLNLCKIIDQYQERLCILSQEECVFGRFLKEAGKRSRTTGGS-IAHTAKAVSFAGQQRMCVRV 111
Cdd:cd00011   1 DLELELQLELLRETKRKYESVLQLGRALTAHLYSLSQTQHALGDAFADLSQKDPELAGEeFGYNAEAQKLLCKNGETLLG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24667845 112 PLLRLQHEVDVFRCRAIKDTEQTLQTMEKERTEYRAALSWMKSASQELDPDTGKGLDKFRTAQAHVRVAKHNFDGYSMDS 191
Cdd:cd00011  81 AVNFFVSSINTLVTKAIEDTLLTVKQYEAARLEYDAYRLDLKELSLEPRDDTAGTRGRLRSAQATFQEHRDKFEKLRGDV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 24667845 192 IQKIDLLAAARCNMYSHALVAYVTELKNFAQKAASTFQTISKA 234
Cdd:cd00011 161 AIKLKFLEENKIKVMHKQLLLFHNTVSAYFAGNQKVLEQTLQQ 203
ICA69 pfam04629
Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which ...
 345-396 4.89e-05

Islet cell autoantigen ICA69, C-terminal domain; This family includes a 69 kD protein which has been identified as an islet cell autoantigen in type I diabetes mellitus. Its precise function is unknown.


Pssm-ID: 461374  Cd Length: 241  Bit Score: 44.39  E-value: 4.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 24667845   345 SQQNQQPIPSQVATDSKASAGGATPvpsksqttnnpWLDLFADLDPLANPQA 396
Cdd:pfam04629 188 QSPNQNVSKPKKKEKAPNSNKDMSA-----------WFNLFADLDPLSNPDA 228
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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