PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 307 HFFLDGRWGASRERLAISKDQRAVRSIPGLPLLLAAERLLTGCHLSVDVVLGDVAVTQGRSYWACAVDPASYLVKVGVGL 386
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 387 ESKLQESFQGAPDVISPRYDPDSGHDSGAEDAAVEAlPPFAFLTIGMGKILLGSGASSNAGLTGRDGPTASCTVPLPPRL 466
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDATVES-PPFAFLTMGMGKIYLPSSVSSGHGLTGRDGPPAGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907151098 467 GICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAFCFIGGGAVQLQEP 516
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907151098 148 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 197
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098   45 LKDKLTKSLAYILGNQDTVQTQICELEETIRHTEVSGQQAKEEVSQLVRGLGAVLEEKRASLLQAIEECQQERLSRLSAQ 124
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1907151098  125 IHEHQSLLDG-SGLVGYAQEVLKETDQPCFVQAAKQLHNRIARATEA 170
Cdd:smart00502  81 LESLTQKQEKlSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 307 HFFLDGRWGASRERLAISKDQRAVRSIPGLPLLLAAERLLTGCHLSVDVVLGDVAVTQGRSYWACAVDPASYLVKVGVGL 386
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 387 ESKLQESFQGAPDVISPRYDPDSGHDSGAEDAAVEAlPPFAFLTIGMGKILLGSGASSNAGLTGRDGPTASCTVPLPPRL 466
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDATVES-PPFAFLTMGMGKIYLPSSVSSGHGLTGRDGPPAGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907151098 467 GICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAFCFIGGGAVQLQEP 516
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907151098 148 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 197
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 219 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpgPTRWQR--REEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSED 295
Cdd:cd00063    15 TSVTLSWTPPEDDGgPITGYVVEYREKG------SGDWKEveVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSES 88

                  ....*
gi 1907151098 296 VHLHT 300
Cdd:cd00063    89 VTVTT 93

B-Box-type zinc finger;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1907151098    1 MCPDHKEEVTH-YCKTCQRLVCQLCRvRRTHSGHKITPV 38
Cdd:smart00336   5 KCDSHGDEPAEfFCEECGALLCRTCD-EAEHRGHTVVLL 42

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907151098 219 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpGPTRWQRREEVRGT-SALLENPDTGSVYVLRVRGCNKAGYGEYS 293
Cdd:pfam00041  14 TSLTVSWTPPPDGNgPITGYEVEYRPKN-----SGEPWNEITVPGTTtSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 85

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1907151098  465 RLGICLDYERGRVSFLDAVSFRGLLECP-LDCSGPVCPAFCFIGGGAVQL 513
Cdd:smart00449  68 VIGCFLDLEAGTISFYKNGKYLHGLAFFdVKFSGPLYPAFSLGSGNSVRL 117

PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 307 HFFLDGRWGASRERLAISKDQRAVRSIPGLPLLLAAERLLTGCHLSVDVVLGDVAVTQGRSYWACAVDPASYLVKVGVGL 386
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 387 ESKLQESFQGAPDVISPRYDPDSGHDSGAEDAAVEAlPPFAFLTIGMGKILLGSGASSNAGLTGRDGPTASCTVPLPPRL 466
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDATVES-PPFAFLTMGMGKIYLPSSVSSGHGLTGRDGPPAGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907151098 467 GICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAFCFIGGGAVQLQEP 516
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); 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 TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. 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 1907151098 308 FFLDGRWgASRErLAISKDQRAVRSIPGLPLLLAAerLLTGCHLSVDVVLGDVAVTQGRSYWACAVDPaSYLVKVGVGLE 387
Cdd:cd13734     1 FKLDPKT-AHRK-LRLSNDNLTVEYDPEGSKDQAA--VLPRRFTGSPAVLGDVAISSGRHYWEVSVSR-STSYRVGVAYK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 388 SKLQesfqgapdvispryDPDSGHDSGAEDAAVEAlppFAFLTIGMGKILLGSgassnagltgrdgptascTVPLPPRLG 467
Cdd:cd13734    76 SAPR--------------DEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLR------------------VTGHPARIG 120

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1907151098 468 ICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAFCFiGGGAVQLQ 514
Cdd:cd13734   121 VLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAV-WNGSLTLH 166

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907151098 148 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 197
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

B-box-type 2 zinc finger found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation through interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 belongs to the C-I 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 RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAY 42
Cdd:cd19778     2 MCPEHEMEkVNMYCEACRRPVCHLCKLGGSHANHRVTSMSSAY 44

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVrRTHSGHKITPV 38
Cdd:pfam00643   5 LCPEHEEEpLTLYCNDCQELLCEECSV-GEHRGHTVVPL 42

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 219 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpgPTRWQR--REEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSED 295
Cdd:cd00063    15 TSVTLSWTPPEDDGgPITGYVVEYREKG------SGDWKEveVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSES 88

                  ....*
gi 1907151098 296 VHLHT 300
Cdd:cd00063    89 VTVTT 93

B-box-type 2 zinc finger found in tripartite motif-containing protein 44 (TRIM44) and similar proteins; TRIM44, also termed protein DIPB, functions as a critical regulator in tumor metastasis and progression. TRIM44 belongs to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. It contains a Bbox2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKI 35
Cdd:cd19784     3 CPEHGQELSLYCKEDEKIICVLCAVIGAHRQHQL 36

B-box-type 2 zinc finger 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 nuclear 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, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKI 35
Cdd:cd19763     4 CPQHDAYRLYHCEAEQVAVCEYCCYEGTHQGHSI 37

B-box-type 2 zinc finger found in tripartite motif-containing protein 37 (TRIM37) and similar proteins; TRIM37, also known as Mulibrey nanism protein, is a peroxisomal E3 ubiquitin-protein ligase that is involved in the tumorigenesis of several cancer types, including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), breast cancer, and sporadic fibrothecoma. It mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. Moreover, TRIM37 possesses anti-HIV-1 activity, and interferes with viral DNA synthesis. Mutations in the human TRIM37 gene (also known as MUL) cause Mulibrey (muscle-liver-brain-eye) nanism, a rare growth disorder of prenatal onset characterized by dysmorphic features, pericardial constriction, and hepatomegaly. TRIM37 belongs to the C-VIII 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 RING finger, Bbox2, and a coiled coil region, as well as a MATH (meprin and TRAF-C homology) domain positioned C-terminal to the RBCC domain. Its MATH domain has been shown to interact with the TRAF (TNF-Receptor-Associated Factor) domain of six known TRAFs in vitro. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1907151098   1 MCPDHKEEVTHYCKTCQRLVCQLCRV-RRTHSGHKITPV 38
Cdd:cd19779     2 KCETHNEKLSVYCWTCKKCICHQCALwGGTHSGHTFKPL 40

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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 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. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19787     3 CPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

PRY/SPRY domain containing protein 4 (SPRYD4); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain and is encoded by the SPRYD4 gene. SPRYD4 (SPRY containing domain 4) is ubiquitously expressed in many human tissues, most strongly in kidney, bladder, brain, thymus and stomach. Subcellular localization demonstrates that SPRYD4 protein is localized in the nucleus when overexpressed in COS-7 green monkey cell. It has remained uncharacterized thus far.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907151098 355 VVLGDVAVTQGRSYWACAVDPASYLvKVGVGLESKLQESFQGApdvisprydpdsghdsgAEDAAVealppFAFLTigmg 434
Cdd:cd12903    45 VVLGDTPVTSGRHYWEVTVKRSQEF-RIGVADVDMSRDECIGT-----------------NESSWV-----FAYAQ---- 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907151098 435 killgsgASSNAGLTGRDGPTASctVPLPPRLGICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAF 503
Cdd:cd12903    98 -------RKWYAMVANETVPVPL--VGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAF 157

B-box-type 2 zinc finger found in midline (MID) family; The MID family includes MID1 and MID2. MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is highly related to MID1. It associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. They also play a central role in the regulation of granule exocytosis, and functional redundancy exists between MID1 and MID2 in cytotoxic lymphocytes (CTL). Both MID1 and MID2 belong to the C-I 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 RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and 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.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19758     2 MCSEHEEEkVNMYCLTDDQLICSLCKLVGKHKDHEVAAL 40

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM16, TRIM29, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, such as TRIM16, TRIM29 and TRIM47. TRIM16, also termed estrogen-responsive B box protein (EBBP), is a regulator that may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM29, also termed ataxia telangiectasia group D-associated protein (ATDC), plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. TRIM16 and TRIM29 belong to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. TRIM47 belongs to the C-IV subclass of TRIM 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, Bbox1 and Bbox2, and two coiled coil domains, 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.

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gi 1907151098   1 MCPDHKEEVTHYCKTCQRLVCQLCRvRRTHSGHKITPV 38
Cdd:cd19769     2 VCPIHKKPLELFCRTDQMCICELCA-KEEHRGHDVVTV 38

B-box-type 2 zinc finger found in B box and SPRY domain-containing protein (BSPRY) and similar proteins; BSPRY is a regulatory protein for maintaining calcium homeostasis. It may regulate epithelial calcium transport by inhibiting TRPV5 activity. BSPRY is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The B-box motif shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19834     3 CPDHELELDWFCSTERRLVCAQCASLGTCRGHRVTPL 39

B-box-type 2 zinc finger found in tripartite motif-containing protein 65 (TRIM65), B box and SPRY domain-containing protein (BSPRY) and similar proteins; The family includes TRIM65 and BSPRY. 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 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. BSPRY is a regulatory protein for maintaining calcium homeostasis. It may regulate epithelial calcium transport by inhibiting TRPV5 activity. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19793     3 CPEHGRELELYCRTEKRCVCAQCASKGECRGHRVTLL 39

B-box-type 2 zinc finger found in Drosophila melanogaster brain tumor protein (BRAT) and similar proteins; BRAT is a NHL-domain family protein that functions as a translational repressor to inhibit cell proliferation. This family also contains Caenorhabditis elegans B-box type zinc finger protein ncl-1, a C. elegans Brat homolog which functions as a translational repressor that inhibits protein synthesis. BRAT contains Bbox1 and Bbox2 zinc fingers and NHL repeats. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   1 MCPDHKEEVTHY-CKTCQRLVCQLCRVRRTHSG-HKI 35
Cdd:cd19798     5 FCPKHPNEVLKFfCKTCNIPICKDCTLLDHNKGlHDY 41

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM9, TRIM67 and similar proteins; This family includes a group of tripartite motif-containing proteins including TRIM9 and TRIM67, both of which belong to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and 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. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. It plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also termed TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H (also known as glucosidase II beta), a protein kinase C substrate. It negatively regulates Ras signaling in cell proliferation via degradation of 80K-H, leading to neural differentiation including neuritogenesis.

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gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGH 33
Cdd:cd19764     1 TCSEHPDEaLSMYCLSCKVPVCYLCLEDGRHSNH 34

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

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gi 1907151098 461 PLPPRLGICLDYERGRVSFLDAVS 484
Cdd:cd12888   114 EVPRRIRVYLDYEGGQVAFFDADN 137

B-box-type 2 zinc finger found in muscle-specific RING finger protein 3 (MuRF-3) and similar proteins; MuRF-3, also known as tripartite motif-containing protein 54 (TRIM54), or RING finger protein 30 (RNF30), is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, and is developmentally upregulated, associates with microtubules, the sarcomeric M-line and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI). MuRF-3 belongs to the C-II 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 RING finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19833     2 MCEEHEEEkINIYCLSCEVPTCSLCKVFGAHKDCEVAPL 40

Fibronectin type III domain;

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gi 1907151098 219 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpGPTRWQRREEVRGT-SALLENPDTGSVYVLRVRGCNKAGYGEYS 293
Cdd:pfam00041  14 TSLTVSWTPPPDGNgPITGYEVEYRPKN-----SGEPWNEITVPGTTtSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 85

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong 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 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. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   2 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19765     3 CEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

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gi 1907151098  465 RLGICLDYERGRVSFLDAVSFRGLLECP-LDCSGPVCPAFCFIGGGAVQL 513
Cdd:smart00449  68 VIGCFLDLEAGTISFYKNGKYLHGLAFFdVKFSGPLYPAFSLGSGNSVRL 117

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM2, TRIM3, and similar proteins; TRIM2, also known as RING finger protein 86 (RNF86), is an E3 ubiquitin-protein ligase that ubiquitinates the neurofilament light chain, a component of the intermediate filament in axons. Loss of function of TRIM2 results in early-onset axonal neuropathy. TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It also plays an important role in the central nervous system (CNS). In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. Both TRIM2 and TRIM3 belong to the C-VII subclass of TRIM (tripartite motif)-NHL family that is 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 domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat 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.

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gi 1907151098   1 MCPDHKEEV-THYCKTCQRLVCQLCRVRRtHSGHKITP 37
Cdd:cd19759     3 VCPNHDGETlEFYCESCETAVCRECTAGE-HNEHRTVL 39

B-box-type 2 zinc finger found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II 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 RING finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1907151098   1 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPV 38
Cdd:cd19831     4 MCKEHEDEkINIYCLTCEVPTCSMCKVFGIHKACEVAPL 42

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

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gi 1907151098 460 VPLPPRLGICLDYERGRVSFLDAVSFRGLLECPLDCSGPVCPAF-CFIGGGAVQ--LQEP 516
Cdd:cd12901   147 VPVPDRIGVYCDFDEGQLSFYNARTKQLLHTFKMKFTQPVLPAFmVWCGGLSVStgLQVP 206

B-box-type 2 zinc finger found in transcription intermediary factor 1-alpha (TIF1-alpha); TIF1-alpha, also known as tripartite motif-containing protein 24 (TRIM24), E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the C-VI 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 RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TIF1-alpha interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta), and MOD2 (HP1gamma), as well as the vertebrate Kruppel-type (C2H2) zinc finger proteins that contain the transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of retinoic acid receptor (RAR) that interacts with multiple nuclear receptors in vitro via an LXXLL motif and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53, and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal PHD-Bromo region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development.

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gi 1907151098   2 CPDHK-EEVTHYCKTCQRLVCQLCRVRRtHSGHKITPVLSAYQALK 46
Cdd:cd19828     6 CPFHKkEQLKLYCETCDKLTCRDCQLLE-HKEHRYQFIEEAFQNQK 50

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

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gi 1907151098 451 RDGPTASCTVPL--------PPRLGICLDYERGRVSFLDaVSFRGLLECPLDC-SGPVCPAFC 504
Cdd:cd13745    99 RDGKYEALTSPPtplpvsvrPSRVGIFLDYEAGEVSFYN-VTDRSHLFTFTDTfSGTLRPYFY 160