RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18079262   7 VDIREEVTCPICLELLTEPLSIDCGHSFCQACITPNGRESVIgQEGERSCPVCQTSYQPGNLRPNRHLANIVR 79
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262  131 FLVEEVAQEYQEKFQeslKKLKNEEQEAEKLTafiREKKTSWKNQMEPERCRIQTEFNQLRNILDRVEQRELKKLEQEEK 210
Cdd:PRK12704  27 KIAEAKIKEAEEEAK---RILEEAKKEAEAIK---KEALLEAKEEIHKLRNEFEKELRERRNELQKLEKRLLQKEENLDR 100

                         90       100       110
                 ....*....|....*....|....*....|..
gi 18079262  211 KgLRIIEEAENDLVHQTQSLRELISDLERRCQ 242
Cdd:PRK12704 101 K-LELLEKREEELEKKEKELEQKQQELEKKEE 131

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18079262   7 VDIREEVTCPICLELLTEPLSIDCGHSFCQACITPNGRESVIgQEGERSCPVCQTSYQPGNLRPNRHLANIVR 79
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM5, TRIM6, TRIM22, TRIM34, TRIM38 and similar proteins; The family includes TRIM5, TRIM6, TRIM22, TRIM34, and TRIM38, all of which belong 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM5, also termed RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also termed RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also termed 50 kDa-stimulated trans-acting factor (Staf-50), or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also termed interferon-responsive finger protein 1, or RING finger protein 21 (RNF21), may function as an antiviral protein that contributes to the defense against retroviral infections. 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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 18079262  96 LCADHGEKLQLFCQEDGKVICWLCERSQEHRGHHTFLVE 134
Cdd:cd19761   2 HCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLLE 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 18079262    15 CPICLELLTEPLsIDCGHSFCQACItpngRESVIGQEGERSCP 57
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECL----EEMSQKKGGKFKCP 38

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)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 18079262     15 CPICLE-LLTEPLSIDCGHSFCQACITPngresvIGQEGERSCPVC 59
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRK------WLESGNNTCPIC 40

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262     4 PVLVDIREEVTCPICLELLTEPLSIDCGHSFCQACITPNGREsvigqegERSCPVCQTSYQPGNLRPNRHLANIV---RR 80
Cdd:TIGR00599  18 PSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSN-------QPKCPLCRAEDQESKLRSNWLVSEIVesfKN 90

                  ....*.
gi 18079262    81 LREVVL 86
Cdd:TIGR00599  91 LRPSLL 96

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18079262    6 LVDIREEVTCPICLELLTEPLSIDCGHSFCQACI------TPNGRESVIGQEGERS---CPVCQTSYQPGNLRP 70
Cdd:PLN03208  12 LVDSGGDFDCNICLDQVRDPVVTLCGHLFCWPCIhkwtyaSNNSRQRVDQYDHKREppkCPVCKSDVSEATLVP 85

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 18079262    96 LCADHG-EKLQLFCQEDGKVICWLCERSqEHRGHHT 130
Cdd:pfam00643   5 LCPEHEeEPLTLYCNDCQELLCEECSVG-EHRGHTV 39

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262   121 RSQEHRGHHTFLVEEVAQEYQEKFQESLKKlKNEEQEAEKLTAFI-REKKTSWKNQMEPERCRIQTEfnqlrnILDRVEQ 199
Cdd:pfam13904  74 AQKEEREKEEQEAELRKRLAKEKYQEWLQR-KARQQTKKREESHKqKAAESASKSLAKPERKVSQEE------AKEVLQE 146

                          90       100
                  ....*....|....*....|.
gi 18079262   200 RELKKLEQEEKKGLRIIEEAE 220
Cdd:pfam13904 147 WERKKLEQQQRKREEEQREQL 167

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, amplifying these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 302 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCS--NSLGPT 379
Cdd:cd15810   1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCShkRSDAMT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 380 FSFNHFAQNHSAYSRYQPQSGYWVIGLQHNHEYRAYEDSS----PSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFP 455
Cdd:cd15810  81 KSNANQINHQNVYSRYQPQYGYWVIGLQNESEYNAFEDSSsfnpHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVTNHGSL 160

                       170       180
                ....*....|....*....|....*....
gi 18079262 456 IYTFSKYYFPTTLCPYFNPCNCVIPMTLR 484
Cdd:cd15810 161 IYKFSKCCFSTTVCPYFNPWNCPVPMTLC 189

PRY/SPRY domain in tripartite motif-containing protein 22 (TRIM22), also known as RING finger protein 94 (RNF94) or Stimulated trans-acting factor of 50 kDa (STAF50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM22, also known as RING finger protein 94 (RNF94) or STAF50 (Stimulated trans-acting factor of 50 kDa). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM22 is an interferon-induced protein, predominantly expressed in peripheral blood leukocytes, in lymphoid tissue such as spleen and thymus, and in the ovary.TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 inhibits influenza A virus (IAV) infection by targeting the viral nucleoprotein for degradation; it represents a novel restriction factor up-regulated upon IAV infection that curtails its replicative capacity in epithelial cells. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. A large number of high-risk non-synonymous (ns)SNPs have been identified in the highly polymorphic TRIM22 gene, most of which are located in the SPRY domain and could possibly alter critical regions of the SPRY structural and functional residues, including several sites that undergo post-translational modification. TRIM22 is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. It is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines; p53 dysfunction may be one of the mechanisms for its down-regulation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 299 YWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGP 378
Cdd:cd15824   1 YWVDVMLNPVNAVSNVVVSADQRQVTVVHICMFRNSNPCDFSAFDVLGCQYFSSGKYYWEVDVSGKIAWILGVYSKRNNL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 379 T------FSFNHFAQNHSAYSRYQPQSGYWVIGLQHNHEYRAYEDSSPS----LLLSMTVPPRRVGVFLDYEAGTVSFYN 448
Cdd:cd15824  81 NkrkssgFAFDPNVNHPNVYSRYRPQNGYWVIGLQNESEYNAFEDSSSSdpkvLTLSMAVPPHRVGVFLDYEAGTVSFFN 160

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18079262 449 VTNHGFPIYTFSKYYFPTTLCPYFNPCNCVIPMTLRRP 486
Cdd:cd15824 161 VTNHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCPP 198

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 302 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSlgptf 380
Cdd:cd13733   1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCvCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARES----- 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 381 sfnhfaQNHSAYSRYQPQSGYWVIGLQHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGFPIYTFS 460
Cdd:cd13733  76 ------VNRKGKITLSPENGYWTVGLRNGNEYKAL--TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDD-GSHIYTFT 146

                       170
                ....*....|....*
gi 18079262 461 KyYFPTTLCPYFNPC 475
Cdd:cd13733 147 D-CFTEKLYPYFSPC 160

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 293 LTDVQSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGV 371
Cdd:cd15813   1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCiIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 372 CSNSLgptfsfnhfaqNHSAYSRYQPQSGYWVIGLQHNHEYRAyeDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTN 451
Cdd:cd15813  81 CKASV-----------SRKGSMTLSPENGYWVVMMTKRNEYQA--STSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTA 147

                       170       180
                ....*....|....*....|....
gi 18079262 452 HGFpIYTFSKYYFPTTLCPYFNPC 475
Cdd:cd15813 148 KSH-IYTFTSFSSSGPLQPIFSPG 170

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 301 VDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK--HYDCsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSL-- 376
Cdd:cd15819   2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERfdSLPC-VLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVmr 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 377 --GPTFSfnhfaqnhsaysryqPQSGYWVIGLqHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGF 454
Cdd:cd15819  81 kgRVTLS---------------PENGFWAIRL-YGNEYWAL--TSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTD-GS 141

                       170
                ....*....|....*...
gi 18079262 455 PIYTFSKYYFPTTLCPYF 472
Cdd:cd15819 142 HIYTFPQTAFSGPLRPFF 159

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 303 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK-HYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLgptfs 381
Cdd:cd15818  15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERfDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESI----- 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 382 fnhfaqNHSAYSRYQPQSGYWVIGLQHNHEYRAYEdsSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVT--NHgfpIYTF 459
Cdd:cd15818  90 ------NRKGNCPLSPEDGFWLLRLRNQNELKALD--VPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANtmSH---IYTF 158

                       170
                ....*....|....*.
gi 18079262 460 SKyYFPTTLCPYFNPC 475
Cdd:cd15818 159 SD-TFTEKIYPYFCPC 173

PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM38 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3). The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 282 DLKRMLRvcreltdvqSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVD 360
Cdd:cd15815   3 DVKKMLR---------RHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLpCVLGCEGFTSGRHYFEVD 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 361 VAKKTAWILGVCSNSLGPTFSfnhfaqnhsaySRYQPQSGYWVIGLQHNHEYRAYEDSSPSLLLSMTvpPRRVGVFLDYE 440
Cdd:cd15815  74 VGEGTGWDVGVCLENVQRGFG-----------MKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREK--PLVVGVFLDYE 140

                       170       180       190
                ....*....|....*....|....*....|..
gi 18079262 441 AGTVSFYNVTNhGFPIYTFSKYYFPTTLCPYF 472
Cdd:cd15815 141 AGLVSFYNMTT-GSHIFTFPKASFSDTLRPYF 171

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 296 VQSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPScLEKHYDCS--VLGSQHFSSGKHYWEVDVAKKTAWILGVCS 373
Cdd:cd15829  14 IKKFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPD-SPKRFTVNpvVLGFPGFHSGRHFWEVEVGDKPEWAVGVCK 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 374 NSLgptfsfnhfaqnhSAYSRYQP--QSGYWVIGLQhNHEYRAyEDSSPSLLLSmTVPPRRVGVFLDYEAGTVSFYNVTN 451
Cdd:cd15829  93 DSL-------------STKARRPPsgQQGCWRIQLQ-GGDYDA-PGAVPPPLLL-EVKPRGIGVFLDYELGEISFYNMPE 156

                       170       180
                ....*....|....*....|...
gi 18079262 452 --HgfpIYTFSKyYFPTTLCPYF 472
Cdd:cd15829 157 ksH---IHTFTD-TFSGPLRPYF 175

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 296 VQSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGVCSN 374
Cdd:cd15828   5 IKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCpAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQD 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 375 SLgptfsfnhfaqnhsAYSRYQP---QSGYWVIGLQHNHEYRAYEDSSPSLLlsMTVPPRRVGVFLDYEAGTVSFYNVtN 451
Cdd:cd15828  85 CL--------------PRNWSNQpsvQDGLWAIGRYSESNYVALGPKKIQLL--PKVRPSKIGIFLDYELGEVSFYNM-N 147

                       170       180
                ....*....|....*....|.
gi 18079262 452 HGFPIYTFSKyYFPTTLCPYF 472
Cdd:cd15828 148 DRSLLYTFSD-SFTGTLWPYF 167

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 302 DVTLNPHTANLNLVLAKNRRQVR--FVGAKVSGPSCLEKHYDCsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGpt 379
Cdd:cd15816   1 DVKLDPATAHPSLLLTADLRSVQdgELWRDVPGNPERFDTWPC-VLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAP-- 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 380 fsfnhfAQNHSAYSryqPQSGYWVIGLQHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTnHGFPIYTF 459
Cdd:cd15816  78 ------RKGETTPS---PENGVWAVWLLKGNEYMVL--ASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVT-AGSHIYTF 145

                       170       180
                ....*....|....*....|....
gi 18079262 460 SKyYFPTTLCPYFNPCNCViPMTL 483
Cdd:cd15816 146 RQ-LFSGILRPYFFVCDTT-PLTL 167

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 303 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK-HYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGPTFS 381
Cdd:cd12893   2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERfDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 382 FNHFaqnhsaysryqPQSGYWVIGLQHNhEYRAYEDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGfPIYTFsK 461
Cdd:cd12893  82 FTLS-----------PESGFWTIGFSEG-KYSARTSPEPRTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNT-HIHTF-T 147

                       170       180
                ....*....|....*....|..
gi 18079262 462 YYFPTTLCPYFNPCNCVIPMTL 483
Cdd:cd12893 148 HTFTERVFPYFYTGCKSEPLRI 169

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 301 VDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKH--YDCsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLgp 378
Cdd:cd15814   2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFnlFPC-VLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSV-- 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 379 tfsfnhfAQNHSAYSryQPQSGYWVIGLQHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIYT 458
Cdd:cd15814  79 -------CRKGGVTS--APQNGFWAVSLWYGKEYWAL--TSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCH-TFT 146

                       170
                ....*....|....*
gi 18079262 459 FSKYYFPTTLCPYFN 473
Cdd:cd15814 147 FSHATFCGPVRPYFS 161

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 303 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGPtfsf 382
Cdd:cd12891   1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIER---- 76

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18079262 383 nhfaQNHSAYSRYQPQSgyWviGLQ-HNHEYRAYEDSSPSLLLSmtVPPRRVGVFLDYEAGTVSFYNVTNHGFPIYTF 459
Cdd:cd12891  77 ----KGDESRIGRNDKS--W--CLEwQDKSFSAWHNNEETPLPS--VSSRRLGVYLDYEAGRLSFYELSDPIRHLHTF 144

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18079262 302 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK-HYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNS----- 375
Cdd:cd13741   1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRfSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESthhke 80