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Conserved domains on  [gi|17137644|ref|NP_477416|]
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TNF-receptor-associated factor 4, isoform A [Drosophila melanogaster]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
 331-479 1.54e-98

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF4 is highly expressed during embryogenesis, especially in the central and peripheral nervous system. Studies using TRAF4-deficient mice show that TRAF4 is required for neurogenesis, as well as the development of the trachea and the axial skeleton. In addition, TRAF4 augments nuclear factor-kappaB activation triggered by GITR (glucocorticoid-induced TNFR), a receptor expressed in T-cells, B-cells and macrophages. It also participates in counteracting the signaling mediated by Toll-like receptors through its association with TRAF6 and TRIF. DTRAF1 plays a pivotal role in the development of eye imaginal discs and photosensory neuron arrays in Drosophila. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


:

Pssm-ID: 239750  Cd Length: 154  Bit Score: 293.25  E-value: 1.54e-98
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17137644 411 FTLFEQGAQ--SGQGGVAESFVPDPTWENFQRPSN---EPDQLGFGFPRFISHELLHSRPFIKGDTVFLRVKVD 479
Cdd:cd03781  81 FTLLDQSDPslSKPQHITETFTPDPTWKNFQKPSAsrlDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
zf-TRAF super family cl44369
TRAF-type zinc finger;
233-292 1.18e-09

TRAF-type zinc finger;


The actual alignment was detected with superfamily member pfam02176:

Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 54.00  E-value: 1.18e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644   233 HAAQCPRAPLACPQRCDAGPIPRGELEAHLRDECQSLAVSCSFKEAGCRFKGPRQMLEAH 292
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
PLN03086 super family cl29366
PRLI-interacting factor K; Provisional
 109-206 4.07e-05

PRLI-interacting factor K; Provisional


The actual alignment was detected with superfamily member PLN03086:

Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 46.02  E-value: 4.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644  109 HKQGCKWSDELRKLKGHLNACkHDATQCPnkCGAQIPRIMMTDHLQYTCTMRRTRCEFC----QSEFSGA-------GLE 177
Cdd:PLN03086 455 HCEKCGQAFQQGEMEKHMKVF-HEPLQCP--CGVVLEKEQMVQHQASTCPLRLITCRFCgdmvQAGGSAMdvrdrlrGMS 531

                         90       100
                 ....*....|....*....|....*....
gi 17137644  178 EHNGSCGQEPVYCEAkCGQRILRGRMTLH 206
Cdd:PLN03086 532 EHESICGSRTAPCDS-CGRSVMLKEMDIH 559
 
Name Accession Description Interval E-value
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
 331-479 1.54e-98

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF4 is highly expressed during embryogenesis, especially in the central and peripheral nervous system. Studies using TRAF4-deficient mice show that TRAF4 is required for neurogenesis, as well as the development of the trachea and the axial skeleton. In addition, TRAF4 augments nuclear factor-kappaB activation triggered by GITR (glucocorticoid-induced TNFR), a receptor expressed in T-cells, B-cells and macrophages. It also participates in counteracting the signaling mediated by Toll-like receptors through its association with TRAF6 and TRIF. DTRAF1 plays a pivotal role in the development of eye imaginal discs and photosensory neuron arrays in Drosophila. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239750  Cd Length: 154  Bit Score: 293.25  E-value: 1.54e-98
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17137644 411 FTLFEQGAQ--SGQGGVAESFVPDPTWENFQRPSN---EPDQLGFGFPRFISHELLHSRPFIKGDTVFLRVKVD 479
Cdd:cd03781  81 FTLLDQSDPslSKPQHITETFTPDPTWKNFQKPSAsrlDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
zf-TRAF pfam02176
TRAF-type zinc finger;
233-292 1.18e-09

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 54.00  E-value: 1.18e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644   233 HAAQCPRAPLACPQRCDAGPIPRGELEAHLRDECQSLAVSCSFKEAGCRFKGPRQMLEAH 292
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
MATH smart00061
meprin and TRAF homology;
333-456 5.30e-07

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 47.68  E-value: 5.30e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644    333 LLWKITDWSakmaeaRGKDGLELVSPPFYTSQYGYKLQASmflngngpGENTHVSVYIKVLPGEYDAlLKWPFSHSITFT 412
Cdd:smart00061   2 LSHTFKNVS------RLEEGESYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDS-RKWSIEAEFTLK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 17137644    413 LFeqgAQSGQggvaesFVPDPTWENFQRPSnepdqlGFGFPRFI 456
Cdd:smart00061  67 LV---SQNGK------SLSKKDKHVFEKPS------GWGFSKFI 95
PLN03086 PLN03086
PRLI-interacting factor K; Provisional
 109-206 4.07e-05

PRLI-interacting factor K; Provisional


Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 46.02  E-value: 4.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644  109 HKQGCKWSDELRKLKGHLNACkHDATQCPnkCGAQIPRIMMTDHLQYTCTMRRTRCEFC----QSEFSGA-------GLE 177
Cdd:PLN03086 455 HCEKCGQAFQQGEMEKHMKVF-HEPLQCP--CGVVLEKEQMVQHQASTCPLRLITCRFCgdmvQAGGSAMdvrdrlrGMS 531

                         90       100
                 ....*....|....*....|....*....
gi 17137644  178 EHNGSCGQEPVYCEAkCGQRILRGRMTLH 206
Cdd:PLN03086 532 EHESICGSRTAPCDS-CGRSVMLKEMDIH 559
zf-TRAF pfam02176
TRAF-type zinc finger;
125-179 1.84e-04

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 39.36  E-value: 1.84e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644   125 HLNACKHDATQCPNKCGAQ-IPRIMMTDHLQYTCTMRRTRCEF----CQSEFSGAGLEEH 179
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKkILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60
 
Name Accession Description Interval E-value
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
 331-479 1.54e-98

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF4 is highly expressed during embryogenesis, especially in the central and peripheral nervous system. Studies using TRAF4-deficient mice show that TRAF4 is required for neurogenesis, as well as the development of the trachea and the axial skeleton. In addition, TRAF4 augments nuclear factor-kappaB activation triggered by GITR (glucocorticoid-induced TNFR), a receptor expressed in T-cells, B-cells and macrophages. It also participates in counteracting the signaling mediated by Toll-like receptors through its association with TRAF6 and TRIF. DTRAF1 plays a pivotal role in the development of eye imaginal discs and photosensory neuron arrays in Drosophila. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239750  Cd Length: 154  Bit Score: 293.25  E-value: 1.54e-98
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17137644 411 FTLFEQGAQ--SGQGGVAESFVPDPTWENFQRPSN---EPDQLGFGFPRFISHELLHSRPFIKGDTVFLRVKVD 479
Cdd:cd03781  81 FTLLDQSDPslSKPQHITETFTPDPTWKNFQKPSAsrlDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
MATH_TRAF_C cd00270
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal ...
 331-479 3.47e-74

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link cell surface TNFRs and receptors of the interleukin-1/Toll-like family to downstream kinase signaling cascades which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. There are at least six mammalian and three Drosophila proteins containing TRAF domains. The mammalian TRAFs display varying expression profiles, indicating independent and cell type-specific regulation. They display distinct, as well as overlapping functions and interactions with receptors. Most TRAFs, except TRAF1, share N-terminal homology and contain a RING domain, multiple zinc finger domains, and a TRAF domain. TRAFs form homo- and heterotrimers through its TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 238168  Cd Length: 149  Bit Score: 230.57  E-value: 3.47e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd00270   1 GVLIWKIKDYSRKLQEAVAGSNTVLYSPPFYTSRYGYKLCLRLYLNGDGTGKGTHLSLFVHVMKGEYDALLEWPFRGKIT 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17137644 411 FTLFEQGAQSGQGGVAESFVPDPTWENFQRPSNEPDQLGFGFPRFISHELLHSRPFIKGDTVFLRVKVD 479
Cdd:cd00270  81 LTLLDQSDDSKRKHITETFMPDPNSSAFQRPPTGENNIGFGYPEFVPLEKLESRGYVKDDTLFIKVEVD 149
MATH_TRAF3 cd03777
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF ...
 291-481 3.33e-44

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. However, it is not required for CD40 signaling. More recently, TRAF3 has been identified as a key regulator of type I interferon (IFN) production and the mammalian innate antiviral immunity. It mediates IFN responses in Toll-like receptor (TLR)-dependent as well as TLR-independent viral recognition pathways. It is also a key element in immunological homeostasis through its regulation of the anti-inflammatory cytokine interleukin-10. TRAF3 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239746  Cd Length: 186  Bit Score: 153.57  E-value: 3.33e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 291 AHLESNAAAHLSLMVALSSRQGQ---QIQMLKSAvsklsiNYTGTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGY 367
Cdd:cd03777   2 GLLESQLSRHDQMLSVHDIRLADmdlRFQVLETA------SYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGY 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 368 KLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSITFTLFEQGaqSGQGGVAESFVPDPTWENFQRPSNEPDq 447
Cdd:cd03777  76 KMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQG--SSRRHLGDAFKPDPNSSSFKKPTGEMN- 152

                       170       180       190
                ....*....|....*....|....*....|....
gi 17137644 448 LGFGFPRFISHELLHSRPFIKGDTVFLRVKVDPS 481
Cdd:cd03777 153 IASGCPVFVAQTVLENGTYIKDDTIFIKVIVDTS 186
MATH_TRAF5 cd03780
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 subfamily, TRAF ...
 331-479 1.95e-40

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 subfamily, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF5 was identified as an activator of nuclear factor-kappaB and a regulator of lymphotoxin-beta receptor and CD40 signaling. Its interaction with CD40 is indirect, involving hetero-oligomerization with TRAF3. In addition, TRAF5 has been shown to associate with other TNFRs including CD27, CD30, OX40 and GITR (glucocorticoid-induced TNFR). It plays a role in modulating Th2 immune responses (driven by OX40 costimulation) and T-cell activation (triggered by GITR). It is also involved in osteoclastogenesis. TRAF5 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239749 [Multi-domain]  Cd Length: 148  Bit Score: 142.47  E-value: 1.95e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03780   1 GKLIWKVTDYKMKKKEAVDGHTVSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHLSLYFVVMRGEFDSLLQWPFRQRVT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17137644 411 FTLFEQgaQSGQGGVAESFVPDPTWENFQRPSNEPDqLGFGFPRFISHELLHS--RPFIKGDTVFLRVKVD 479
Cdd:cd03780  81 LMLLDQ--SGKKNHIMETFKADPNSSSFKRPDGEMN-IASGCPRFVAHSVLENakNTYIKDDTLFLKVAVD 148
MATH_TRAF1 cd03779
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF ...
 331-479 9.75e-34

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF1 expression is the most restricted among the TRAFs. It is found exclusively in activated lymphocytes, dendritic cells and certain epithelia. TRAF1 associates, directly or indirectly through heterodimerization with TRAF2, with the TNFR family receptors TNFR-2, CD30, RANK, CD40 and LMP1, among others. It also binds the intracellular proteins TRADD, TANK, TRIP, RIP1, RIP2 and FLIP. TRAF1 is unique among the TRAFs in that it lacks a RING domain, which is critical for the activation of nuclear factor-kappaB and Jun NH2-terminal kinase. Studies on TRAF1-deficient mice suggest that TRAF1 has a negative regulatory role in TNFR-mediated signaling events. TRAF1 contains one zinc finger and one TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239748  Cd Length: 147  Bit Score: 124.23  E-value: 9.75e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03779   1 GTFLWKITDVSQKQRESSHGRDVSLCSPAFYTAKYGYKVCLRLYLNGDGAGKGTHISLFFVIMKGEYDALLPWPFRHKVT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17137644 411 FTLFEQGAQSgqgGVAESFVPDPTWENFQRPSNEPDqLGFGFPRFISHELLHS--RPFIKGDTVFLRVKVD 479
Cdd:cd03779  81 FMLLDQNNRE---HVIDAFRPDLSSASFQRPVSDMN-VASGCPLFFPLKKLQSpkHAYCKDDTIYIKCVVD 147
MATH_TRAF2 cd03778
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF ...
 329-479 2.17e-32

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239747  Cd Length: 164  Bit Score: 121.26  E-value: 2.17e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 329 YTGTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHS 408
Cdd:cd03778  17 YDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQK 96

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17137644 409 ITFTLFEqgaQSGQGGVAESFVPDPTWENFQRPSNEPDqLGFGFPRFISHELLHSR-PFIKGDTVFLRVKVD 479
Cdd:cd03778  97 VTLMLLD---QNNREHVIDAFRPDVTSSSFQRPVNDMN-IASGCPLFCPVSK*EAKnSYVRDDAIFIKAIVD 164
MATH_TRAF6 cd03776
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF ...
 331-478 8.95e-29

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF6 is the most divergent in its TRAF domain among the mammalian TRAFs. In addition to mediating TNFR family signaling, it is also an essential signaling molecule of the interleukin-1/Toll-like receptor superfamily. Whereas other TRAF molecules display similar and overlapping TNFR-binding specificities, TRAF6 binds completely different sites on receptors such as CD40 and RANK. TRAF6 serves as a molecular bridge between innate and adaptive immunity and plays a central role in osteoimmunology. DTRAF2, as an activator of nuclear factor-kappaB, plays a pivotal role in Drosophila development and innate immunity. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239745  Cd Length: 147  Bit Score: 110.87  E-value: 8.95e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEARGKDGLELVSPPFYTSQYGYKLQASMFLNGNGPGENTHVSVYIKVLPGEYDALLKWPFSHSIT 410
Cdd:cd03776   1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEARCPNYISLFVHLMQGENDSHLDWPFQGTIT 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17137644 411 FTLFEQgAQSGQgGVAESFVPDPTWENFQRPSNEPDQLGFGFPRFISHELLHSRPFIKGDTVFLRVKV 478
Cdd:cd03776  81 LTLLDQ-SEPRQ-NIHETMMSKPELLAFQRPTTDRNPKGFGYVEFAHIEDLLQRGFVKNDTLLIKIEV 146
MATH cd00121
MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded ...
 331-479 5.48e-16

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.


Pssm-ID: 238068  Cd Length: 126  Bit Score: 74.34  E-value: 5.48e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 331 GTLLWKITDWSAKMAEArgkdgleLVSPPFYTsqYGYKLQASMFLNGNGPGENtHVSVYIKVLPGEYDaLLKWPFSHSIT 410
Cdd:cd00121   1 GKHTWKIVNFSELEGES-------IYSPPFEV--GGYKWRIRIYPNGDGESGD-YLSLYLELDKGESD-LEKWSVRAEFT 69

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17137644 411 FTLFeqgAQSGQGGVAESFVPDPTWENFQrpsnepdqlGFGFPRFISHELLHSRPFIKGDTVFLRVKVD 479
Cdd:cd00121  70 LKLV---NQNGGKSLSKSFTHVFFSEKGS---------GWGFPKFISWDDLEDSYYLVDDSLTIEVEVK 126
MATH_Meprin cd03771
Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular ...
 335-479 1.31e-13

Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular metalloproteases, which are either anchored to the membrane or secreted into extracellular spaces. They are expressed in renal and intestinal brush border membranes, leukocytes, and cancer cells, and are capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. Meprin proteases are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. Despite their similarity, the two subunits differ in their ability to self-associate, in proteolytic processing during biosynthesis and in substrate specificity. Both subunits are synthesized as membrane spanning proteins, however, the alpha subunit is cleaved during biosynthesis and loses its transmembrane domain. Meprin beta forms homodimers or heterotetramers while meprin alpha oligomerizes into large complexes containing 10-100 subunits. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239740  Cd Length: 167  Bit Score: 68.58  E-value: 1.31e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 335 WKITDWSAKMAEArgKDGLELVSPPFYTSQyGYKLQASMFLNGNgPGENTHVSVYIKVLPGEYDALLKWP-FSHSITFTL 413
Cdd:cd03771   6 WRVRNFSQLLETT--PKGTKIYSPRFYSPE-GYAFQVGLYPNGT-ESYPGYTGLYFHLCSGENDDVLEWPcPNRQATMTL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 414 FEQGAQSGQG-GVAESFVPDPT----------WEN---------FQRPSNEPDQLGFGFPRFISHELLHSRPFIKGDTVF 473
Cdd:cd03771  82 LDQDPDIQQRmSNQRSFTTDPSmtssdngeyfWDRpskvgsydtDTNGCTCYRGPGYGWSTFISHSRLRRRDFLKGDDLI 161


                ....*.
gi 17137644 474 LRVKVD 479
Cdd:cd03771 162 ILLDFE 167
MATH_Meprin_Beta cd03782
Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular ...
 334-474 1.51e-10

Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The beta subunit is a type I membrane protein, which forms homodimers or heterotetramers (alpha2beta2 or alpha3beta). Meprin beta shows preference for acidic residues at the P1 and P1' sites of its substrate. Among its best substrates are growth factors and chemokines such as gastrin and osteopontin. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239751  Cd Length: 167  Bit Score: 59.88  E-value: 1.51e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 334 LWKITDWSAKMAEArgKDGLELVSPPFYTSQyGYKLQASMFLNG--NGPGentHVSVYIKVLPGEYDALLKWPFS-HSIT 410
Cdd:cd03782   5 IWHIRNFTQLLATT--PPNGKIYSPPFLSST-GYSFQVGLYLNGtdDYPG---NLAIYLHLTSGPNDDQLQWPCPwQQAT 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 411 FTLFEQGAQSGQG-GVAESFVPDP---TWENFQRPSNEPDQL----------------GFGFPRFISHELLHSRPFIKGD 470
Cdd:cd03782  79 MMLLDQHPDIRQRmSNQRSVTTDPnmtSTDSDEYFWDDPRKVgsevtdtdgstfyrgpGYGTSAFITHLRLRSRDFIKGD 158


                ....
gi 17137644 471 TVFL 474
Cdd:cd03782 159 DVIF 162
zf-TRAF pfam02176
TRAF-type zinc finger;
233-292 1.18e-09

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 54.00  E-value: 1.18e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644   233 HAAQCPRAPLACPQRCDAGPIPRGELEAHLRDECQSLAVSCSFKEAGCRFKGPRQMLEAH 292
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
MATH_Meprin_Alpha cd03783
Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular ...
 332-479 3.35e-07

Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The alpha subunit is synthesized as a membrane spanning protein, however, it is cleaved during biosynthesis and loses its transmembrane domain. It oligomerizes into large complexes, containing 10-100 subunits (dimers that associate noncovalently), which are secreted as latent proteases and can move through extracellular spaces in a nondestructive manner. This allows delivery of the concentrated protease to sites containing activating enzymes, such as sites of inflammation, infection or cancerous growth. Meprin alpha shows preference for small or hydrophobic residues at the P1 and P1' sites of its substrate. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239752  Cd Length: 167  Bit Score: 50.25  E-value: 3.35e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 332 TLLWKITDWSAKMAEARGKDGLElvSPPFYTSQyGYKLQASMFLNGN-GPGENTHVSVYIKVLPGEYDALLKWP-FSHSI 409
Cdd:cd03783   3 NAVWRVRNFSQILENTTKGDVLQ--SPRFYSPE-GYGYGVSLYPLSNeSDYSGNYTGLYFHLCSGENDAVLEWPaLNRQA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 410 TFTLFEQ---------GAQS---GQGGVAESFVPDPTWEnfqRPSN----EPD-----QLGFGFPRFISHELLHSRPFIK 468
Cdd:cd03783  80 IITVLDQdpdvrlrmsSSRSfttDKSQTSSAINGTLRWD---RPSRvgtyDTScdcfrGIDFGWSTFISHSQLRRRSFLK 156

                       170
                ....*....|.
gi 17137644 469 GDTVFLRVKVD 479
Cdd:cd03783 157 NDDLIIFVDFE 167
MATH smart00061
meprin and TRAF homology;
333-456 5.30e-07

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 47.68  E-value: 5.30e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644    333 LLWKITDWSakmaeaRGKDGLELVSPPFYTSQYGYKLQASmflngngpGENTHVSVYIKVLPGEYDAlLKWPFSHSITFT 412
Cdd:smart00061   2 LSHTFKNVS------RLEEGESYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDS-RKWSIEAEFTLK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 17137644    413 LFeqgAQSGQggvaesFVPDPTWENFQRPSnepdqlGFGFPRFI 456
Cdd:smart00061  67 LV---SQNGK------SLSKKDKHVFEKPS------GWGFSKFI 95
PLN03086 PLN03086
PRLI-interacting factor K; Provisional
 109-206 4.07e-05

PRLI-interacting factor K; Provisional


Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 46.02  E-value: 4.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644  109 HKQGCKWSDELRKLKGHLNACkHDATQCPnkCGAQIPRIMMTDHLQYTCTMRRTRCEFC----QSEFSGA-------GLE 177
Cdd:PLN03086 455 HCEKCGQAFQQGEMEKHMKVF-HEPLQCP--CGVVLEKEQMVQHQASTCPLRLITCRFCgdmvQAGGSAMdvrdrlrGMS 531

                         90       100
                 ....*....|....*....|....*....
gi 17137644  178 EHNGSCGQEPVYCEAkCGQRILRGRMTLH 206
Cdd:PLN03086 532 EHESICGSRTAPCDS-CGRSVMLKEMDIH 559
zf-TRAF pfam02176
TRAF-type zinc finger;
125-179 1.84e-04

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 39.36  E-value: 1.84e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644   125 HLNACKHDATQCPNKCGAQ-IPRIMMTDHLQYTCTMRRTRCEF----CQSEFSGAGLEEH 179
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKkILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60
MATH_TRIM37 cd03773
Tripartite motif containing protein 37 (TRIM37) family, MATH domain; TRIM37 is a peroxisomal ...
 355-480 3.00e-03

Tripartite motif containing protein 37 (TRIM37) family, MATH domain; TRIM37 is a peroxisomal protein and is a member of the tripartite motif (TRIM) protein subfamily, also known as the RING-B-box-coiled-coil (RBCC) subfamily of zinc-finger proteins. Mutations in the human TRIM37 gene (also known as MUL) cause Mulibrey (muscle-liver-brain-eye) nanism, a rare growth disorder of prenatal onset characterized by dysmorphic features, pericardial constriction and hepatomegaly. TRIM37, similar to other TRIMs, contains a cysteine-rich, zinc-binding RING-finger domain followed by another cysteine-rich zinc-binding domain, the B-box, and a coiled-coil domain. TRIM37 is autoubiquitinated in a RING domain-dependent manner, indicating that it functions as an ubiquitin E3 ligase. In addition to the tripartite motif, TRIM37 also contains a MATH domain C-terminal to the coiled-coil domain. The MATH domain of TRIM37 has been shown to interact with the TRAF domain of six known TRAFs in vitro, however, it is unclear whether this is physiologically relevant. Eleven TRIM37 mutations have been associated with Mulibrey nanism so far. One mutation, Gly322Val, is located in the MATH domain and is the only mutation that does not affect the length of the protein. It results in the incorrect subcellular localization of TRIM37.


Pssm-ID: 239742  Cd Length: 132  Bit Score: 37.78  E-value: 3.00e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137644 355 LVSPPFYTSQYGYKLQasMFLNGNGPGENTHVSVYIkvlpgEYDALLKWPFSHSITFTLFEQGaqsgqggvaesfvpDPT 434
Cdd:cd03773  24 VYSDPLNVDGLCWRLK--VYPDGNGEVRGNFLSVFL-----ELCSGLGEASKYEYRVEMVHQA--------------NPT 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17137644 435 wENFQRPSNEPDQLG--FGFPRFISHELLHSRPFIK--GDTVFLRVKVDP 480
Cdd:cd03773  83 -KNIKREFASDFEVGecWGYNRFFRLDLLINEGYLLpeNDTLILRFSVRP 131
 
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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