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Conserved domains on  [gi|22027622|ref|NP_004286|]
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TNF receptor-associated factor 4 [Homo sapiens]

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 ...
308-463 1.81e-113

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: 330.62  E-value: 1.81e-113
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
mRING-HC-C3HC3D_TRAF4 cd16641
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
15-59 8.46e-23

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) and similar proteins; TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of the TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in nervous system, as well as in carcinogenesis. TRAF4 promotes the growth and invasion of colon cancer through the Wnt/beta-catenin pathway. It contributes to the TNFalpha-induced activation of the 70 kDa ribosomal protein S6 kinase (p70s6k) signaling pathway, and activation of transforming growth factor beta (TGF-beta)-induced SMAD-dependent signaling and non-SMAD signaling in breast cancer. It also enhances osteosarcoma cell proliferation and invasion by the Akt signaling pathway. Moreover, TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. TRAF4 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


:

Pssm-ID: 438303 [Multi-domain]  Cd Length: 45  Bit Score: 90.59  E-value: 8.46e-23
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPEDQL 59
Cdd:cd16641   1 RLLCPLCRLPMREPVQISTCGHRFCDTCLQEFLSEGVFKCPEDQL 45
zf-TRAF pfam02176
TRAF-type zinc finger;
210-269 2.52e-20

TRAF-type zinc finger;


:

Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 84.43  E-value: 2.52e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
zf-TRAF pfam02176
TRAF-type zinc finger;
102-156 1.89e-15

TRAF-type zinc finger;


:

Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 70.56  E-value: 1.89e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   102 HLNTCSFNVIPCPNRCPMK-LSRRDLPAHLQHDCPKRRLKCEF----CGCDFSGEAYESH 156
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKkILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60
PLN03086 super family cl29366
PRLI-interacting factor K; Provisional
113-211 2.46e-03

PRLI-interacting factor K; Provisional


The actual alignment was detected with superfamily member PLN03086:

Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 40.24  E-value: 2.46e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622  113 CPnrCPMKLSRRDLPAHLQHDCPKRRLKCEFCG--CDFSGEAYESHE---GMCPQESVycenkcgarmmrrllaqhatse 187
Cdd:PLN03086 481 CP--CGVVLEKEQMVQHQASTCPLRLITCRFCGdmVQAGGSAMDVRDrlrGMSEHESI---------------------- 536
                         90       100
                 ....*....|....*....|....
gi 22027622  188 CPKRTQPCTYCTKEFVFDTIQSHQ 211
Cdd:PLN03086 537 CGSRTAPCDSCGRSVMLKEMDIHQ 560
 
Name Accession Description Interval E-value
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
308-463 1.81e-113

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: 330.62  E-value: 1.81e-113
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
mRING-HC-C3HC3D_TRAF4 cd16641
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
15-59 8.46e-23

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) and similar proteins; TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of the TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in nervous system, as well as in carcinogenesis. TRAF4 promotes the growth and invasion of colon cancer through the Wnt/beta-catenin pathway. It contributes to the TNFalpha-induced activation of the 70 kDa ribosomal protein S6 kinase (p70s6k) signaling pathway, and activation of transforming growth factor beta (TGF-beta)-induced SMAD-dependent signaling and non-SMAD signaling in breast cancer. It also enhances osteosarcoma cell proliferation and invasion by the Akt signaling pathway. Moreover, TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. TRAF4 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 438303 [Multi-domain]  Cd Length: 45  Bit Score: 90.59  E-value: 8.46e-23
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPEDQL 59
Cdd:cd16641   1 RLLCPLCRLPMREPVQISTCGHRFCDTCLQEFLSEGVFKCPEDQL 45
zf-TRAF pfam02176
TRAF-type zinc finger;
210-269 2.52e-20

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 84.43  E-value: 2.52e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
zf-TRAF pfam02176
TRAF-type zinc finger;
102-156 1.89e-15

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 70.56  E-value: 1.89e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   102 HLNTCSFNVIPCPNRCPMK-LSRRDLPAHLQHDCPKRRLKCEF----CGCDFSGEAYESH 156
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKkILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60
MATH smart00061
meprin and TRAF homology;
327-440 7.27e-09

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 53.07  E-value: 7.27e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622    327 KPNLECFSPAFYTHKYGYKLQVSaflngngsGEGTHLSLYIRVLPGAFDNLlEWPFARRVTFSLLDQSDPglakpqhvte 406
Cdd:smart00061  13 EEGESYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDSR-KWSIEAEFTLKLVSQNGK---------- 73
                           90       100       110
                   ....*....|....*....|....*....|....
gi 22027622    407 tFHPDPNWKNFQKPGTWrgsldesslgfGYPKFI 440
Cdd:smart00061  74 -SLSKKDKHVFEKPSGW-----------GFSKFI 95
COG5222 COG5222
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
12-75 7.01e-08

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];


Pssm-ID: 227547 [Multi-domain]  Cd Length: 427  Bit Score: 54.37  E-value: 7.01e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22027622  12 PKRRLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE--------DQLPLDYakiypDPELEVQ 75
Cdd:COG5222 271 PNISLKCPLCHCLLRNPMKTPCCGHTFCDECIGTALLDSDFKCPNcsrkdvllDGLTPDI-----DKKLEVE 337
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
18-55 1.93e-05

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 41.73  E-value: 1.93e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 22027622     18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCP 38
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
18-56 6.99e-05

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.


Pssm-ID: 395049 [Multi-domain]  Cd Length: 40  Bit Score: 40.03  E-value: 6.99e-05
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 22027622    18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE 56
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPL 39
PLN03086 PLN03086
PRLI-interacting factor K; Provisional
113-211 2.46e-03

PRLI-interacting factor K; Provisional


Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 40.24  E-value: 2.46e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622  113 CPnrCPMKLSRRDLPAHLQHDCPKRRLKCEFCG--CDFSGEAYESHE---GMCPQESVycenkcgarmmrrllaqhatse 187
Cdd:PLN03086 481 CP--CGVVLEKEQMVQHQASTCPLRLITCRFCGdmVQAGGSAMDVRDrlrGMSEHESI---------------------- 536
                         90       100
                 ....*....|....*....|....
gi 22027622  188 CPKRTQPCTYCTKEFVFDTIQSHQ 211
Cdd:PLN03086 537 CGSRTAPCDSCGRSVMLKEMDIHQ 560
cdk7 TIGR00570
CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions ...
18-76 2.46e-03

CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions are known are cyclin dependent protein kinases that are components of TFIIH, a complex that is involved in nucleotide excision repair and transcription initiation. Also known as MAT1 (menage a trois 1). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129661 [Multi-domain]  Cd Length: 309  Bit Score: 39.79  E-value: 2.46e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22027622    18 CPLC-GKPMREP---VQVSTCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAK----IYPDPELEVQV 76
Cdd:TIGR00570   6 CPRCkTTKYRNPslkLMVNVCGHTLCESCVDLLFVRGSGSCPECDTPLRKNNfrvqLFEDPTVEKEV 72
 
Name Accession Description Interval E-value
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
308-463 1.81e-113

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: 330.62  E-value: 1.81e-113
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154
MATH_TRAF_C cd00270
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal ...
308-463 1.76e-78

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: 240.97  E-value: 1.76e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd00270   1 GVLIWKIKDYSRKLQEAVAGSNTVLYSPPFYTSRYGYKLCLRLYLNGDGTGKGTHLSLFVHVMKGEYDALLEWPFRGKIT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPglAKPQHVTETFHPDPNWKNFQKPGTwrgslDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd00270  81 LTLLDQSDD--SKRKHITETFMPDPNSSAFQRPPT-----GENNIGFGYPEFVPLEKLESRGYVKDDTLFIKVEVD 149
MATH_TRAF5 cd03780
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 subfamily, TRAF ...
308-463 1.12e-43

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: 150.56  E-value: 1.12e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03780   1 GKLIWKVTDYKMKKKEAVDGHTVSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHLSLYFVVMRGEFDSLLQWPFRQRVT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22027622 388 FSLLDQSdpglAKPQHVTETFHPDPNWKNFQKPGtwrgslDESSLGFGYPKFISHQDIR--KRNYVRDDAVFIRAAVE 463
Cdd:cd03780  81 LMLLDQS----GKKNHIMETFKADPNSSSFKRPD------GEMNIASGCPRFVAHSVLEnaKNTYIKDDTLFLKVAVD 148
MATH_TRAF2 cd03778
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF ...
288-463 1.19e-42

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: 148.61  E-value: 1.19e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 288 QRQELQELRRELEELSVgsDGVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYI 367
Cdd:cd03778   1 A*ADLEQKVLE*EASTY--DGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 368 RVLPGAFDNLLEWPFARRVTFSLLDQSDpglakPQHVTETFHPDPNWKNFQKPgtwrgsLDESSLGFGYPKFIS-HQDIR 446
Cdd:cd03778  79 VVMKGPNDALLRWPFNQKVTLMLLDQNN-----REHVIDAFRPDVTSSSFQRP------VNDMNIASGCPLFCPvSK*EA 147
                       170
                ....*....|....*..
gi 22027622 447 KRNYVRDDAVFIRAAVE 463
Cdd:cd03778 148 KNSYVRDDAIFIKAIVD 164
MATH_TRAF3 cd03777
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF ...
294-463 1.97e-41

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: 145.86  E-value: 1.97e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 294 ELRRELEElSVGSDGVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGA 373
Cdd:cd03777  26 DLRFQVLE-TASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGE 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 374 FDNLLEWPFARRVTFSLLDQsDPGlakPQHVTETFHPDPNWKNFQKPGTwrgsldESSLGFGYPKFISHQDIRKRNYVRD 453
Cdd:cd03777 105 YDALLPWPFKQKVTLMLMDQ-GSS---RRHLGDAFKPDPNSSSFKKPTG------EMNIASGCPVFVAQTVLENGTYIKD 174
                       170
                ....*....|
gi 22027622 454 DAVFIRAAVE 463
Cdd:cd03777 175 DTIFIKVIVD 184
MATH_TRAF1 cd03779
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF ...
308-463 9.65e-35

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: 126.93  E-value: 9.65e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03779   1 GTFLWKITDVSQKQRESSHGRDVSLCSPAFYTAKYGYKVCLRLYLNGDGAGKGTHISLFFVIMKGEYDALLPWPFRHKVT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22027622 388 FSLLDQSDpglakPQHVTETFHPDPNWKNFQKPgtwrgsLDESSLGFGYPKFISHQDIR--KRNYVRDDAVFIRAAVE 463
Cdd:cd03779  81 FMLLDQNN-----REHVIDAFRPDLSSASFQRP------VSDMNVASGCPLFFPLKKLQspKHAYCKDDTIYIKCVVD 147
MATH_TRAF6 cd03776
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF ...
308-462 1.95e-34

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: 125.90  E-value: 1.95e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03776   1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEARCPNYISLFVHLMQGENDSHLDWPFQGTIT 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22027622 388 FSLLDQSDPGlakpQHVTETFHPDPNWKNFQKPGTWRgsldeSSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAV 462
Cdd:cd03776  81 LTLLDQSEPR----QNIHETMMSKPELLAFQRPTTDR-----NPKGFGYVEFAHIEDLLQRGFVKNDTLLIKIEV 146
mRING-HC-C3HC3D_TRAF4 cd16641
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
15-59 8.46e-23

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) and similar proteins; TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of the TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in nervous system, as well as in carcinogenesis. TRAF4 promotes the growth and invasion of colon cancer through the Wnt/beta-catenin pathway. It contributes to the TNFalpha-induced activation of the 70 kDa ribosomal protein S6 kinase (p70s6k) signaling pathway, and activation of transforming growth factor beta (TGF-beta)-induced SMAD-dependent signaling and non-SMAD signaling in breast cancer. It also enhances osteosarcoma cell proliferation and invasion by the Akt signaling pathway. Moreover, TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. TRAF4 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 438303 [Multi-domain]  Cd Length: 45  Bit Score: 90.59  E-value: 8.46e-23
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPEDQL 59
Cdd:cd16641   1 RLLCPLCRLPMREPVQISTCGHRFCDTCLQEFLSEGVFKCPEDQL 45
zf-TRAF pfam02176
TRAF-type zinc finger;
210-269 2.52e-20

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 84.43  E-value: 2.52e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60
MATH cd00121
MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded ...
308-463 1.04e-19

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: 84.74  E-value: 1.04e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 308 GVLIWKIGSYGRRLQEAkakpnleCFSPAFYThkYGYKLQVSAFLNGNGSGeGTHLSLYIRVLPGAFDnLLEWPFARRVT 387
Cdd:cd00121   1 GKHTWKIVNFSELEGES-------IYSPPFEV--GGYKWRIRIYPNGDGES-GDYLSLYLELDKGESD-LEKWSVRAEFT 69
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPglakpQHVTETFHPdpnWKNFQKPGTWrgsldesslgfGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd00121  70 LKLVNQNGG-----KSLSKSFTH---VFFSEKGSGW-----------GFPKFISWDDLEDSYYLVDDSLTIEVEVK 126
MATH_Meprin cd03771
Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular ...
311-463 2.52e-18

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: 82.06  E-value: 2.52e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 311 IWKIGSYGRRLQeaKAKPNLECFSPAFYTHKyGYKLQVSAFLNGNGSgEGTHLSLYIRVLPGAFDNLLEWPFARR-VTFS 389
Cdd:cd03771   5 VWRVRNFSQLLE--TTPKGTKIYSPRFYSPE-GYAFQVGLYPNGTES-YPGYTGLYFHLCSGENDDVLEWPCPNRqATMT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 390 LLDQsDPGLAKPQHVTETFHPDPN----------WKNFQKPGTWRGSLDES----SLGFGYPKFISHQDIRKRNYVRDDA 455
Cdd:cd03771  81 LLDQ-DPDIQQRMSNQRSFTTDPSmtssdngeyfWDRPSKVGSYDTDTNGCtcyrGPGYGWSTFISHSRLRRRDFLKGDD 159

                ....*...
gi 22027622 456 VFIRAAVE 463
Cdd:cd03771 160 LIILLDFE 167
zf-TRAF pfam02176
TRAF-type zinc finger;
102-156 1.89e-15

TRAF-type zinc finger;


Pssm-ID: 280357 [Multi-domain]  Cd Length: 60  Bit Score: 70.56  E-value: 1.89e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   102 HLNTCSFNVIPCPNRCPMK-LSRRDLPAHLQHDCPKRRLKCEF----CGCDFSGEAYESH 156
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKkILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60
MATH_Meprin_Beta cd03782
Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular ...
311-463 2.77e-14

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: 70.66  E-value: 2.77e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 311 IWKIGSYGRRLqeAKAKPNLECFSPAFYTHKyGYKLQVSAFLNGNGSGEGtHLSLYIRVLPGAFDNLLEWPFA-RRVTFS 389
Cdd:cd03782   5 IWHIRNFTQLL--ATTPPNGKIYSPPFLSST-GYSFQVGLYLNGTDDYPG-NLAIYLHLTSGPNDDQLQWPCPwQQATMM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 390 LLDQsDPGLAKPQHVTETFHPDPN----------WKNFQKPGT----------WRGSldesslGFGYPKFISHQDIRKRN 449
Cdd:cd03782  81 LLDQ-HPDIRQRMSNQRSVTTDPNmtstdsdeyfWDDPRKVGSevtdtdgstfYRGP------GYGTSAFITHLRLRSRD 153
                       170
                ....*....|....
gi 22027622 450 YVRDDAVFIRAAVE 463
Cdd:cd03782 154 FIKGDDVIFLLTME 167
MATH_Meprin_Alpha cd03783
Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular ...
311-458 3.91e-13

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: 67.20  E-value: 3.91e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 311 IWKIGSYGRRLQEAKAKPNLEcfSPAFYTHK-YGYKLQVSAfLNGNGSGEGTHLSLYIRVLPGAFDNLLEWP-FARRVTF 388
Cdd:cd03783   5 VWRVRNFSQILENTTKGDVLQ--SPRFYSPEgYGYGVSLYP-LSNESDYSGNYTGLYFHLCSGENDAVLEWPaLNRQAII 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 389 SLLDQsDPGLAK-----------PQHVTETFHPDPNWKNFQKPGTWRGSLD-ESSLGFGYPKFISHQDIRKRNYVRDDAV 456
Cdd:cd03783  82 TVLDQ-DPDVRLrmsssrsfttdKSQTSSAINGTLRWDRPSRVGTYDTSCDcFRGIDFGWSTFISHSQLRRRSFLKNDDL 160

                ..
gi 22027622 457 FI 458
Cdd:cd03783 161 II 162
mRING-HC-C3HC3D_TRAF6 cd16643
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
15-69 2.11e-10

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 438305 [Multi-domain]  Cd Length: 58  Bit Score: 56.23  E-value: 2.11e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAKIYPD 69
Cdd:cd16643   1 KYECPICLMALREPVQ-TPCGHRFCKACILKSIREAGHKCPVDNEPLLENQLFPD 54
MATH smart00061
meprin and TRAF homology;
327-440 7.27e-09

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 53.07  E-value: 7.27e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622    327 KPNLECFSPAFYTHKYGYKLQVSaflngngsGEGTHLSLYIRVLPGAFDNLlEWPFARRVTFSLLDQSDPglakpqhvte 406
Cdd:smart00061  13 EEGESYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDSR-KWSIEAEFTLKLVSQNGK---------- 73
                           90       100       110
                   ....*....|....*....|....*....|....
gi 22027622    407 tFHPDPNWKNFQKPGTWrgsldesslgfGYPKFI 440
Cdd:smart00061  74 -SLSKKDKHVFEKPSGW-----------GFSKFI 95
COG5222 COG5222
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
12-75 7.01e-08

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];


Pssm-ID: 227547 [Multi-domain]  Cd Length: 427  Bit Score: 54.37  E-value: 7.01e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22027622  12 PKRRLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE--------DQLPLDYakiypDPELEVQ 75
Cdd:COG5222 271 PNISLKCPLCHCLLRNPMKTPCCGHTFCDECIGTALLDSDFKCPNcsrkdvllDGLTPDI-----DKKLEVE 337
mRING-HC-C3HC3D_TRAF4-like cd23126
Modified RING finger, HC subclass (C3HC3D-type), found in uncharacterized proteins similar to ...
13-62 7.95e-08

Modified RING finger, HC subclass (C3HC3D-type), found in uncharacterized proteins similar to tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4); This subfamily corresponds to a group of uncharacterized proteins that shows high sequence similarity with tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, or metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in the nervous system, as well as in carcinogenesis. Like TRAF4, members of this subfamily contain a modified C3HC3D-type RING-HC finger.


Pssm-ID: 438488 [Multi-domain]  Cd Length: 52  Bit Score: 48.49  E-value: 7.95e-08
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 22027622  13 KRRLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLsEGVFKCPEDQLPLD 62
Cdd:cd23126   2 DKKYECPVCCQVLRYPVQFEECGHRVCSSCLPELL-RVEPRCPIDQGPID 50
vRING-HC-C4C4_RBBP6 cd16620
Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) ...
16-55 2.38e-07

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.


Pssm-ID: 438282 [Multi-domain]  Cd Length: 55  Bit Score: 47.40  E-value: 2.38e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16620   4 LKCPICKDLMKDAVLTPCCGNSFCDECIRTALLEEDFTCP 43
mRING-HC-C3HC3D_TRAF7 cd16644
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
11-61 2.21e-06

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.


Pssm-ID: 438306 [Multi-domain]  Cd Length: 47  Bit Score: 44.27  E-value: 2.21e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 22027622  11 KPKRRLLCPLCGKPMREPVqVSTCGHRFCDTCLqefLSEGVFKCPEDQLPL 61
Cdd:cd16644   1 PPSVKLYCPLCQRVFKDPV-ITSCGHTFCRRCA---LTAPGEKCPVDNMKL 47
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type ...
16-57 6.36e-06

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 438113 [Multi-domain]  Cd Length: 41  Bit Score: 42.86  E-value: 6.36e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 22027622  16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEFLSEGVFKCPED 57
Cdd:cd16449   1 LECPICLERLKDPV-LLPCGHVFCRECIRRLLESGSIKCPIC 41
RING-HC_TRIM21_C-IV cd16596
RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar ...
9-76 8.08e-06

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438258 [Multi-domain]  Cd Length: 77  Bit Score: 43.73  E-value: 8.08e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22027622   9 LEKPKRRLLCPLCGKPMREPVQVStCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAKIYPDPELEVQV 76
Cdd:cd16596   3 LTMMWEEVTCPICLDPFVEPVSIE-CGHSFCQECISQVGKGGGSVCPVCRQRFLLKNLRPNRQLANMV 69
RING-HC_RNF138 cd16544
RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; ...
16-55 1.67e-05

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).


Pssm-ID: 438206 [Multi-domain]  Cd Length: 53  Bit Score: 42.01  E-value: 1.67e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16544   3 LTCPVCQEVLKDPVELPPCRHIFCKACILLALRSSGARCP 42
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
18-55 1.93e-05

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 41.73  E-value: 1.93e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 22027622     18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCP 38
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
18-56 6.99e-05

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.


Pssm-ID: 395049 [Multi-domain]  Cd Length: 40  Bit Score: 40.03  E-value: 6.99e-05
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 22027622    18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE 56
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPL 39
SPL-RING_NSE2 cd16651
SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as ...
16-76 8.12e-05

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.


Pssm-ID: 438313 [Multi-domain]  Cd Length: 67  Bit Score: 40.71  E-value: 8.12e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFL--SEGVFKCPEDQL--PLDYAKIYPDPELEVQV 76
Cdd:cd16651   1 LKCPITQQLMVDPVRNKKCGHTYEKAAILQYLqsRKKKAKCPVAGCrnTVSKSDLVPDPELKRRI 65
mRING-HC-C3HC3D_Nrdp1 cd16634
Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation ...
16-58 1.43e-04

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promotes the degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates the activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.


Pssm-ID: 438296 [Multi-domain]  Cd Length: 43  Bit Score: 39.33  E-value: 1.43e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVfKCPEDQ 58
Cdd:cd16634   2 LICPICSGVLEEPLQAPHCEHAFCNACITEWLSRQQ-TCPVDR 43
COG5152 COG5152
Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function ...
9-42 1.89e-04

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];


Pssm-ID: 227481 [Multi-domain]  Cd Length: 259  Bit Score: 43.14  E-value: 1.89e-04
                        10        20        30
                ....*....|....*....|....*....|....
gi 22027622   9 LEKPKRRLLCPLCGKPMREPVqVSTCGHRFCDTC 42
Cdd:COG5152 190 GPGEKIPFLCGICKKDYESPV-VTECGHSFCSLC 222
RING-HC_TRIM40-C-V cd16583
RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar ...
17-55 2.93e-04

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.


Pssm-ID: 438245 [Multi-domain]  Cd Length: 63  Bit Score: 39.04  E-value: 2.93e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  17 LCPLCGKPMREPVQvSTCGHRFCDTCL----QEFLSEGVFKCP 55
Cdd:cd16583   7 VCPICQEPLKEAVS-TDCGHLFCRMCLtqhaKKASASGVFSCP 48
mRING_PEX12 cd16451
Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as ...
17-55 2.94e-04

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.


Pssm-ID: 438115 [Multi-domain]  Cd Length: 54  Bit Score: 38.76  E-value: 2.94e-04
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 22027622  17 LCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEgVFKCP 55
Cdd:cd16451   2 ICPLCRKKRTNPTALATSGYVFCYPCIYRYVKE-HGRCP 39
RING-HC_TRIM39_C-IV cd16601
RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar ...
16-56 4.27e-04

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438263 [Multi-domain]  Cd Length: 44  Bit Score: 37.85  E-value: 4.27e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQVsTCGHRFCDTCLQEFLSE--GVFKCPE 56
Cdd:cd16601   2 ASCSLCKEYLKDPVII-ECGHNFCRACITRFWEEldGDFPCPQ 43
mRING-HC-C3HC3D_LNX1-like cd16637
Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, ...
15-57 6.55e-04

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.


Pssm-ID: 438299 [Multi-domain]  Cd Length: 42  Bit Score: 37.38  E-value: 6.55e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  15 RLLCPLCGKPMREPVQVStCGHRFCDTCLQEFLSEGVFkCPED 57
Cdd:cd16637   1 DLTCHICLQPLVEPLDTP-CGHTFCYKCLTNYLKIQQC-CPLD 41
RING-HC_BRCA1 cd16498
RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and ...
16-48 1.18e-03

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.


Pssm-ID: 438161 [Multi-domain]  Cd Length: 94  Bit Score: 38.05  E-value: 1.18e-03
                        10        20        30
                ....*....|....*....|....*....|....
gi 22027622  16 LLCPLCGKPMREPVqvST-CGHRFCDTCLQEFLS 48
Cdd:cd16498  17 LECPICLELLKEPV--STkCDHQFCRFCILKLLQ 48
RING-Ubox_PUB cd16664
U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and ...
16-61 1.23e-03

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.


Pssm-ID: 438326 [Multi-domain]  Cd Length: 53  Bit Score: 36.77  E-value: 1.23e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 22027622  16 LLCPLCGKPMREPVQVSTcGHRFCDTCLQEFLSEGVFKCPEDQLPL 61
Cdd:cd16664   4 FICPISLELMKDPVILAT-GQTYERAAIEKWLDSGNNTCPITGQPL 48
RING-HC_RING1-like cd16531
RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and ...
16-55 1.36e-03

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.


Pssm-ID: 438193 [Multi-domain]  Cd Length: 66  Bit Score: 37.25  E-value: 1.36e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16531   2 LMCPICLGIIKNTMTVKECLHRFCAECIEKALRLGNKECP 41
RING-HC_RNF222 cd16564
RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; ...
18-56 1.41e-03

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.


Pssm-ID: 438226 [Multi-domain]  Cd Length: 50  Bit Score: 36.61  E-value: 1.41e-03
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 22027622  18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE 56
Cdd:cd16564   3 CPVCYEDFDDAPRILSCGHSFCEDCLVKQLVSMTISCPI 41
RING-HC_TRIM4_C-IV cd16590
RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar ...
10-69 1.45e-03

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.


Pssm-ID: 438252 [Multi-domain]  Cd Length: 61  Bit Score: 36.93  E-value: 1.45e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22027622  10 EKPKRRLLCPLCGKPMREPVQVStCGHRFCDTCLQEFLSE--GVFKCPEDQLPLDYAKIYPD 69
Cdd:cd16590   1 EDIQEELTCPICLDYFQDPVSIE-CGHNFCRGCLHRNWAPggGPFPCPECRHPSAPAALRPN 61
RING-HC_TRIM69_C-IV cd16611
RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar ...
16-56 1.61e-03

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438273 [Multi-domain]  Cd Length: 59  Bit Score: 36.66  E-value: 1.61e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEF--LSEGVFKCPE 56
Cdd:cd16611   5 LHCPLCLDFFRDPV-MLSCGHNFCQSCITGFweLQAEDTTCPE 46
Ubox smart00504
Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2 ...
16-72 1.68e-03

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.


Pssm-ID: 128780 [Multi-domain]  Cd Length: 63  Bit Score: 36.83  E-value: 1.68e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 22027622     16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEFLSEgVFKCPEDQLPLDYAKIYPDPEL 72
Cdd:smart00504   2 FLCPISLEVMKDPV-ILPSGQTYERSAIEKWLLS-HGTDPVTGQPLTHEDLIPNLAL 56
mRING-HC-C3HC3D_arc-1-like cd23124
Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative ...
15-61 1.70e-03

Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative GTP-binding protein trim-23 homolog (arc-1) and similar proteins; arc-1, also called RING-type E3 ubiquitin transferase arc-1, is an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. arc-1 contains a modified C3HC3D-type RING-HC finger.


Pssm-ID: 438486 [Multi-domain]  Cd Length: 55  Bit Score: 36.71  E-value: 1.70e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGK------PMREPVQVSTCGHRFCDTCLQEFL--SEGVFKCPEDQLPL 61
Cdd:cd23124   1 ELECGICQQeysaddPLLIPRILTECGHTICTNCAGTILgqSSGSIFCPFDRIVT 55
RING-H2_Pirh2-like cd16464
RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; ...
18-55 1.80e-03

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.


Pssm-ID: 438127 [Multi-domain]  Cd Length: 45  Bit Score: 36.10  E-value: 1.80e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22027622  18 CPLCGKPM---REPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16464   2 CPVCLEDLftsREPVHVLPCGHLMHSTCFEEYLKSGNYRCP 42
zf-RING_UBOX pfam13445
RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.
18-55 1.82e-03

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.


Pssm-ID: 463881 [Multi-domain]  Cd Length: 38  Bit Score: 35.84  E-value: 1.82e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 22027622    18 CPLCGKPMREPVqvSTCGHRFCDTCLQEFL--SEGVFKCP 55
Cdd:pfam13445   1 CPICLELFTDPV--LPCGHTFCRECLEEMSqkKGGKFKCP 38
mRING-HC-C3HC3D_LNX2 cd16780
Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); ...
16-58 2.05e-03

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); LNX2, also known as numb-binding protein 2, or PDZ domain-containing RING finger protein 1 (PDZRN1), is a PDZ domain-containing RING-type E3 ubiquitin ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. It interacts with contactin-associated protein 4 (Caspr4, also known as CNTNAP4) in a PDZ domain-dependent manner, which modulates the proliferation and neuronal differentiation of neural progenitor cells (NPCs). LNX2 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAF motif for Numb/ Numblike-LNX interaction, and four PDZ domains necessary for the binding of substrates, including ErbB2, RhoC, the presynaptic protein CAST, the melanoma/cancer-testis antigen MAGEB18 and several proteins associated with cell junctions, such as JAM4 and the Coxsackievirus and adenovirus receptor (CAR).


Pssm-ID: 319694 [Multi-domain]  Cd Length: 45  Bit Score: 36.01  E-value: 2.05e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSEGVFkCPEDQ 58
Cdd:cd16780   4 LVCHICLQPLLQPLD-TPCGHTFCFKCLRNFLQEKDF-CPLDR 44
PLN03086 PLN03086
PRLI-interacting factor K; Provisional
113-211 2.46e-03

PRLI-interacting factor K; Provisional


Pssm-ID: 178635 [Multi-domain]  Cd Length: 567  Bit Score: 40.24  E-value: 2.46e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622  113 CPnrCPMKLSRRDLPAHLQHDCPKRRLKCEFCG--CDFSGEAYESHE---GMCPQESVycenkcgarmmrrllaqhatse 187
Cdd:PLN03086 481 CP--CGVVLEKEQMVQHQASTCPLRLITCRFCGdmVQAGGSAMDVRDrlrGMSEHESI---------------------- 536
                         90       100
                 ....*....|....*....|....
gi 22027622  188 CPKRTQPCTYCTKEFVFDTIQSHQ 211
Cdd:PLN03086 537 CGSRTAPCDSCGRSVMLKEMDIHQ 560
cdk7 TIGR00570
CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions ...
18-76 2.46e-03

CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions are known are cyclin dependent protein kinases that are components of TFIIH, a complex that is involved in nucleotide excision repair and transcription initiation. Also known as MAT1 (menage a trois 1). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129661 [Multi-domain]  Cd Length: 309  Bit Score: 39.79  E-value: 2.46e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22027622    18 CPLC-GKPMREP---VQVSTCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAK----IYPDPELEVQV 76
Cdd:TIGR00570   6 CPRCkTTKYRNPslkLMVNVCGHTLCESCVDLLFVRGSGSCPECDTPLRKNNfrvqLFEDPTVEKEV 72
RING-HC_RNF166 cd16549
RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; ...
16-60 2.48e-03

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).


Pssm-ID: 438211 [Multi-domain]  Cd Length: 47  Bit Score: 35.94  E-value: 2.48e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPEDQLP 60
Cdd:cd16549   2 FSCPICLEVYHKPVVITSCGHTFCGECLQPCLQVASPLCPLCRMP 46
RING-HC_TRIM58_C-IV cd16606
RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar ...
18-60 2.58e-03

RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar proteins; TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization. TRIM58 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438268 [Multi-domain]  Cd Length: 53  Bit Score: 35.99  E-value: 2.58e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22027622  18 CPLCGKPMREPVQVStCGHRFCDTCLQEFLSE------GVFKCPEDQLP 60
Cdd:cd16606   5 CPVCLDFLQEPVSVD-CGHSFCLRCISEFCEKsdsaqgGVYACPQCRGP 52
RING-HC_TRIM8_C-V cd16580
RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar ...
16-56 3.09e-03

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.


Pssm-ID: 438242 [Multi-domain]  Cd Length: 67  Bit Score: 36.02  E-value: 3.09e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQVStCGHRFCDTCLQEFLSE--GVFKCPE 56
Cdd:cd16580  12 LICPICLHVFVEPVQLP-CKHNFCRGCIGEAWAKdaGLVRCPE 53
RING-HC_TRIM38_C-IV cd16600
RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar ...
18-60 5.08e-03

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438262 [Multi-domain]  Cd Length: 58  Bit Score: 35.13  E-value: 5.08e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 22027622  18 CPLCGKPMREPVQVStCGHRFCDTCLQEFL--------SEGVFKCPEDQLP 60
Cdd:cd16600   8 CSICLQLMTEPVSIN-CGHSYCKRCIVSFLenqsqlepGLETFSCPQCRAP 57
RING-HC_TRIM65_C-IV cd16609
RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar ...
16-56 6.40e-03

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438271 [Multi-domain]  Cd Length: 58  Bit Score: 35.04  E-value: 6.40e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22027622  16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEFL---SEGVFKCPE 56
Cdd:cd16609   4 LTCSICLGLYQDPV-TLPCQHSFCRACIEDHWrqkDEGSFSCPE 46
RING-HC_TRIM35_C-IV cd16599
RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar ...
13-43 7.30e-03

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 438261 [Multi-domain]  Cd Length: 66  Bit Score: 35.13  E-value: 7.30e-03
                        10        20        30
                ....*....|....*....|....*....|.
gi 22027622  13 KRRLLCPLCGKPMREPVQVStCGHRFCDTCL 43
Cdd:cd16599   2 KEELLCPICYEPFREAVTLR-CGHNFCKGCV 31
RING-HC_TRAF2 cd16639
RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 ...
17-56 7.55e-03

RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins; TRAF2, also known as tumor necrosis factor type 2 receptor-associated protein 3, is an E3 ubiquitin-protein ligase that was identified as a 75 kDa tumor necrosis factor receptor (TNF-R2)-associated signaling protein. It interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It also mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Moreover, TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15. It also acts as an important biological suppressor of necroptosis. It inhibits TNF-related apoptosis inducing ligand (TRAIL)- and CD95L-induced apoptosis and necroptosis. TRAF2 contains an N-terminal domain with a typical C3HC4-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 438301 [Multi-domain]  Cd Length: 43  Bit Score: 34.35  E-value: 7.55e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  17 LCPLCGKPMREPVQVStCGHRFCDTCLQEFLSEGVFKCPE 56
Cdd:cd16639   3 LCSDCRNILRRPFQAQ-CGHRYCSYCLKKILSSGPQKCAA 41
mRING-HC-C3HC3D_TRAF5 cd16642
Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) ...
15-57 7.68e-03

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) and similar proteins; TRAF5, also known as RING finger protein 84 (RNF84), is an important signal transducer for a wide range of TNF receptor superfamily members, including tumor necrosis factor receptor 1 (TNFR1), TNFR2, CD40, and other lymphocyte costimulatory receptors, RANK/TRANCE-R, ectodysplasin-A Receptor (EDAR), lymphotoxin-beta receptor (LT-betaR), latent membrane protein 1 (LMP1), and IRE1. It functions as an activator of NF-kappaB, MAPK, and JNK, and is involved in both RANKL- and TNFalpha-induced osteoclastogenesis. It mediates CD40 signaling by associating with the cytoplasmic tail of CD40. It also negatively regulates Toll-like receptor (TLR) signaling and functions as a negative regulator of the interleukin 6 (IL-6) receptor signaling pathway that limits the differentiation of inflammatory CD4(+) T cells. TRAF5 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.


Pssm-ID: 438304 [Multi-domain]  Cd Length: 56  Bit Score: 34.72  E-value: 7.68e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22027622  15 RLLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSE-GVFKCPED 57
Cdd:cd16642   4 RYKCATCHFVLHNPHQ-TGCGHRFCQHCILSLLELnTTPICPID 46
RING-HC_BARD1 cd16496
RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar ...
9-55 8.13e-03

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.


Pssm-ID: 438159 [Multi-domain]  Cd Length: 86  Bit Score: 35.39  E-value: 8.13e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 22027622   9 LEKPKRRLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGvfkCP 55
Cdd:cd16496   9 LDELENLLRCSRCASILKEPVTLGGCEHVFCRSCVGDRLGNG---CP 52
 
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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