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Conserved domains on  [gi|2462610039|ref|XP_054212141|]
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stromal membrane-associated protein 1 isoform X3 [Homo sapiens]

Protein Classification

ADP-ribosylation factor GTPase-activating family protein( domain architecture ID 1001504)

ADP-ribosylation factor GTPase-activating family protein may play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
ArfGap super family cl28907
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
1-35 1.78e-15

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


The actual alignment was detected with superfamily member cd08839:

Pssm-ID: 355783 [Multi-domain]  Cd Length: 103  Bit Score: 71.53  E-value: 1.78e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRPQTDQAVEFFIR 35
Cdd:cd08839    66 MQEMGNARANAYYEANLPDGFRRPQTDSALENFIR 100
Med15 super family cl26621
ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of ...
225-373 7.92e-03

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.


The actual alignment was detected with superfamily member pfam09606:

Pssm-ID: 312941 [Multi-domain]  Cd Length: 732  Bit Score: 38.45  E-value: 7.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610039 225 GTGTIQQQSTPGVFMGPTNIPFTSQAPAAFQGFPSMgvpvpaaPGLIGNVMGQSPSMMVGMPMPNGFMGNAQTGVMPLPQ 304
Cdd:pfam09606 154 QAGGMMQPSSGQPGSGTPNQMGPNGGPGQGQAGGMN-------GGQQGPMGGQMPPQMGVPGMPGPADAGAQMGQQAQAN 226
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462610039 305 NVVGPQGGMVGQMGAPQskfglpQAQQPQwslSQMNQQMAGMSISSATPTAGfGQPSSTTAGWSGSSSG 373
Cdd:pfam09606 227 GGMNPQQMGGAPNQVAM------QQQQPQ---QQGQQSQLGMGINQMQQMPQ-GVGGGAGQGGPGQPMG 285
 
Name Accession Description Interval E-value
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
1-35 1.78e-15

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 71.53  E-value: 1.78e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRPQTDQAVEFFIR 35
Cdd:cd08839    66 MQEMGNARANAYYEANLPDGFRRPQTDSALENFIR 100
Med15 pfam09606
ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of ...
225-373 7.92e-03

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.


Pssm-ID: 312941 [Multi-domain]  Cd Length: 732  Bit Score: 38.45  E-value: 7.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610039 225 GTGTIQQQSTPGVFMGPTNIPFTSQAPAAFQGFPSMgvpvpaaPGLIGNVMGQSPSMMVGMPMPNGFMGNAQTGVMPLPQ 304
Cdd:pfam09606 154 QAGGMMQPSSGQPGSGTPNQMGPNGGPGQGQAGGMN-------GGQQGPMGGQMPPQMGVPGMPGPADAGAQMGQQAQAN 226
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462610039 305 NVVGPQGGMVGQMGAPQskfglpQAQQPQwslSQMNQQMAGMSISSATPTAGfGQPSSTTAGWSGSSSG 373
Cdd:pfam09606 227 GGMNPQQMGGAPNQVAM------QQQQPQ---QQGQQSQLGMGINQMQQMPQ-GVGGGAGQGGPGQPMG 285
PABP-1234 TIGR01628
polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins ...
239-353 9.79e-03

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.


Pssm-ID: 130689 [Multi-domain]  Cd Length: 562  Bit Score: 37.86  E-value: 9.79e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610039 239 MGPTNIPFTSQAPAAFQGFPSMGVPVPAapGLIGNVMGQSPSMMVGMPMPNGFMGNAQTGVMPLPQNVVGPQGGMVGQMG 318
Cdd:TIGR01628 387 MGSPMGGAMGQPPYYGQGPQQQFNGQPL--GWPRMSMMPTPMGPGGPLRPNGLAPMNAVRAPSRNAQNAAQKPPMQPVMY 464
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462610039 319 AP--QSKFGLPQAQQPQWSLSQMNQ-QMAGMSISSATP 353
Cdd:TIGR01628 465 PPnyQSLPLSQDLPQPQSTASQGGQnKKLAQVLASATP 502
 
Name Accession Description Interval E-value
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
1-35 1.78e-15

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 71.53  E-value: 1.78e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRPQTDQAVEFFIR 35
Cdd:cd08839    66 MQEMGNARANAYYEANLPDGFRRPQTDSALENFIR 100
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
1-35 3.95e-14

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 68.09  E-value: 3.95e-14
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRPQTDQAVEFFIR 35
Cdd:cd08859    66 MQEMGNGKANRLYEAFLPENFRRPQTDQAVEGFIR 100
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
1-35 1.17e-07

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 49.42  E-value: 1.17e-07
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRP---QTDQAVEFFIR 35
Cdd:cd08204    66 MKAIGNARANAYYEANLPPGFKKPtpdSSDEEREQFIR 103
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
1-35 2.52e-03

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 37.24  E-value: 2.52e-03
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2462610039   1 MQDMGNTKARLLYEANLPENFRRPQ-TDQAV--EFFIR 35
Cdd:cd08832    73 MEENGNEKAKAKYEAHVPAFYRRPTpTDPQVlrEQWIR 110
Med15 pfam09606
ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of ...
225-373 7.92e-03

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.


Pssm-ID: 312941 [Multi-domain]  Cd Length: 732  Bit Score: 38.45  E-value: 7.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610039 225 GTGTIQQQSTPGVFMGPTNIPFTSQAPAAFQGFPSMgvpvpaaPGLIGNVMGQSPSMMVGMPMPNGFMGNAQTGVMPLPQ 304
Cdd:pfam09606 154 QAGGMMQPSSGQPGSGTPNQMGPNGGPGQGQAGGMN-------GGQQGPMGGQMPPQMGVPGMPGPADAGAQMGQQAQAN 226
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462610039 305 NVVGPQGGMVGQMGAPQskfglpQAQQPQwslSQMNQQMAGMSISSATPTAGfGQPSSTTAGWSGSSSG 373
Cdd:pfam09606 227 GGMNPQQMGGAPNQVAM------QQQQPQ---QQGQQSQLGMGINQMQQMPQ-GVGGGAGQGGPGQPMG 285
PABP-1234 TIGR01628
polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins ...
239-353 9.79e-03

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.


Pssm-ID: 130689 [Multi-domain]  Cd Length: 562  Bit Score: 37.86  E-value: 9.79e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610039 239 MGPTNIPFTSQAPAAFQGFPSMGVPVPAapGLIGNVMGQSPSMMVGMPMPNGFMGNAQTGVMPLPQNVVGPQGGMVGQMG 318
Cdd:TIGR01628 387 MGSPMGGAMGQPPYYGQGPQQQFNGQPL--GWPRMSMMPTPMGPGGPLRPNGLAPMNAVRAPSRNAQNAAQKPPMQPVMY 464
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462610039 319 AP--QSKFGLPQAQQPQWSLSQMNQ-QMAGMSISSATP 353
Cdd:TIGR01628 465 PPnyQSLPLSQDLPQPQSTASQGGQnKKLAQVLASATP 502
 
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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