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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 258 VPSYDSATFVLENFSTLRQRADPVYSPPLQVSGLCWRLKVYPDGNGVVRGYYLSVFLELSAGLPETSKYEYRVEMVHQSc 337
Cdd:cd03773     1 IPPYDSATFTLENFSTLRQSADPVYSDPLNVDGLCWRLKVYPDGNGEVRGNFLSVFLELCSGLGEASKYEYRVEMVHQA- 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1768049529 338 nDPTKNIIREFASDFEVGECWGYNRFFRLDLLANEGYLNRQNDTVILRFQVRSP 391
Cdd:cd03773    80 -NPTKNIKREFASDFEVGECWGYNRFFRLDLLINEGYLLPENDTLILRFSVRPP 132

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        40
                  ....*....|....*....|....*....|....*....|
gi 1768049529  78 DKCENHHEKLSVFCWTCKKCICHQCALWGGMHGGHTFKPL 117
Cdd:cd19779     1 DKCETHNEKLSVYCWTCKKCICHQCALWGGTHSGHTFKPL 40

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 258 VPSYDSATFVLENFSTLRQRADPVYSPPLQVSGLCWRLKVYPDGNGVVRGYYLSVFLELSAGLPETSKYEYRVEMVHQSc 337
Cdd:cd03773     1 IPPYDSATFTLENFSTLRQSADPVYSDPLNVDGLCWRLKVYPDGNGEVRGNFLSVFLELCSGLGEASKYEYRVEMVHQA- 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1768049529 338 nDPTKNIIREFASDFEVGECWGYNRFFRLDLLANEGYLNRQNDTVILRFQVRSP 391
Cdd:cd03773    80 -NPTKNIKREFASDFEVGECWGYNRFFRLDLLINEGYLLPENDTLILRFSVRPP 132

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        40
                  ....*....|....*....|....*....|....*....|
gi 1768049529  78 DKCENHHEKLSVFCWTCKKCICHQCALWGGMHGGHTFKPL 117
Cdd:cd19779     1 DKCETHNEKLSVYCWTCKKCICHQCALWGGTHSGHTFKPL 40

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1768049529  75 NEKDKCENHH-EKLSVFCWTCKKCICHQCALwgGMHGGHTFKPL 117
Cdd:pfam00643   1 SKERLCPEHEeEPLTLYCNDCQELLCEECSV--GEHRGHTVVPL 42

MATH domain; This motif has been called the Meprin And TRAF-Homology (MATH) domain. This domain is hugely expanded in the nematode C. elegans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 270 NFSTLRQRaDPVYSPPLQVSGLCWRLKVYPDGNgvvrgyYLSVFL----ELSAGLPETSKYEYRVEMVHQSCNDPTKNII 345
Cdd:pfam00917   3 NFSKIKEG-ESYYSPVEERFNIPWRLQIYRKGG------FLGLYLhcdkEEELERGWSIETEFTLKLVSSNGKSVTKTDT 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1768049529 346 REFASDfevgECWGYNRFFRLDLLANEgYLNrqNDTVI 383
Cdd:pfam00917  76 HVFEKP----KGWGWGKFISWDDLEKD-YLV--DDSIT 106

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 117 LAEIYEQhVTKVNEEVAKLRRRLMELISLVQEV--ERN---------VEAVRNAKDER------VREIRNAVEMMIARLD 179
Cdd:COG1340    10 LEELEEK-IEELREEIEELKEKRDELNEELKELaeKRDelnaqvkelREEAQELREKRdelnekVKELKEERDELNEKLN 88

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1768049529 180 tQLKNKLITLMGQKTSLTQETELLESLLQEVEH 212
Cdd:COG1340    89 -ELREELDELRKELAELNKAGGSIDKLRKEIER 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 258 VPSYDSATFVLENFSTLRQRADPVYSPPLQVSGLCWRLKVYPDGNGVVRGYYLSVFLELSAGLPETSKYEYRVEMVHQSc 337
Cdd:cd03773     1 IPPYDSATFTLENFSTLRQSADPVYSDPLNVDGLCWRLKVYPDGNGEVRGNFLSVFLELCSGLGEASKYEYRVEMVHQA- 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1768049529 338 nDPTKNIIREFASDFEVGECWGYNRFFRLDLLANEGYLNRQNDTVILRFQVRSP 391
Cdd:cd03773    80 -NPTKNIKREFASDFEVGECWGYNRFFRLDLLINEGYLLPENDTLILRFSVRPP 132

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 265 TFVLENFSTLRQRADPVYSPPLQVSGLCWRLKVYPDGNGvVRGYYLSVFLELSAGLPETS----KYEYRVEMVHQscnDP 340
Cdd:cd00121     2 KHTWKIVNFSELEGESIYSPPFEVGGYKWRIRIYPNGDG-ESGDYLSLYLELDKGESDLEkwsvRAEFTLKLVNQ---NG 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1768049529 341 TKNIIREFASDF--EVGECWGYNRFFRLDLLANEGYLNrqNDTVILRFQVR 389
Cdd:cd00121    78 GKSLSKSFTHVFfsEKGSGWGFPKFISWDDLEDSYYLV--DDSLTIEVEVK 126

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529  269 ENFSTLRqRADPVYSPPLQVSGLCWRLKVYPDGNgvvrgyYLSVFLELSAGLPETSKY--EYRVEMVHQSCNDptKNIIR 346
Cdd:smart00061   7 KNVSRLE-EGESYFSPSEEHFNIPWRLKIYRKNG------FLSLYLHCEKEECDSRKWsiEAEFTLKLVSQNG--KSLSK 77

                           90
                   ....*....|....*...
gi 1768049529  347 EFASDFEVGECWGYNRFF 364
Cdd:smart00061  78 KDKHVFEKPSGWGFSKFI 95

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1768049529   76 EKDKCENHH-EKLSVFCWTCKKCICHQCALWggMHGGHTFKPL 117
Cdd:smart00336   2 RAPKCDSHGdEPAEFFCEECGALLCRTCDEA--EHRGHTVVLL 42

MATH domain; This motif has been called the Meprin And TRAF-Homology (MATH) domain. This domain is hugely expanded in the nematode C. elegans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 270 NFSTLRQRaDPVYSPPLQVSGLCWRLKVYPDGNgvvrgyYLSVFL----ELSAGLPETSKYEYRVEMVHQSCNDPTKNII 345
Cdd:pfam00917   3 NFSKIKEG-ESYYSPVEERFNIPWRLQIYRKGG------FLGLYLhcdkEEELERGWSIETEFTLKLVSSNGKSVTKTDT 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1768049529 346 REFASDfevgECWGYNRFFRLDLLANEgYLNrqNDTVI 383
Cdd:pfam00917  76 HVFEKP----KGWGWGKFISWDDLEKD-YLV--DDSIT 106

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1768049529  79 KCENHHEKLSVFCWTCKKCICHQCALwgGMHGGHTFKPLAE 119
Cdd:cd19769     2 VCPIHKKPLELFCRTDQMCICELCAK--EEHRGHDVVTVEE 40

B-box-type 2 zinc finger found in tripartite motif-containing protein 14 (TRIM14) and similar proteins; TRIM14 is a mitochondrial adaptor that facilitates innate immune signaling. It also plays a critical role in tumor development. TRIM14 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 zinc finger as well as a C-terminal SPRY/B30.2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1768049529  78 DKCENHHE-KLSVFCWTCKKCICHQCALWGGmHGGHTFKPLAEIY 121
Cdd:cd19768     1 RCCPEHKDrPLELFCKTCKRCVCALCPILGQ-HRGHDVRLIDEEA 44

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1768049529  79 KCENH-HEKLSVFCWTCKKCICHQCaLWGGMHGGHTFKPL 117
Cdd:cd19764     1 TCSEHpDEALSMYCLSCKVPVCYLC-LEDGRHSNHDVQAL 39

B-box-type 2 zinc finger found in Xenopus laevis nuclear factor 7 (xNF7) and similar proteins; xNF7 is a maternally expressed novel zinc finger nuclear phosphoprotein. It acts as a transcription factor that determines dorsal-ventral body axis. xNF7 harbors a B-box motif that 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1768049529  78 DKCENHHEKLSVFCWTCKKCICHQCALwGGMHGGHTFKPL 117
Cdd:cd19800     1 EVCSEHDEPLKLFCKDDKRLICVICRD-SRKHRGHRFLPV 39

Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) family, N-terminal MATH (TRAF-like) domain; composed of proteins similar to human HAUSP, an enzyme that specifically catalyzes the deubiquitylation of p53 and MDM2, hence playing an important role in the p53-MDM2 pathway. It contains an N-terminal TRAF-like domain and a C-terminal catalytic protease (C19 family) domain. The tumor suppressor p53 protein is a transcription factor that responds to many cellular stress signals and is regulated primarily through ubiquitylation and subsequent degradation. MDM2 is a RING-finger E3 ubiquitin ligase that promotes p53 ubiquitinylation. p53 and MDM2 bind to the same site in the N-terminal TRAF-like domain of HAUSP in a mutually exclusive manner. HAUSP also interacts with the Epstein-Barr nuclear antigen 1 (EBNA1) protein of the Epstein-Barr virus (EBV), which efficiently immortalizes infected cells predisposing the host to a variety of cancers. EBNA1 plays several important roles in EBV latent infection and cellular transformation. It binds the same pocket as p53 in the HAUSP TRAF-like domain. Through interactions with p53, MDM2 and EBNA1, HAUSP plays a role in cell proliferation, apoptosis and EBV-mediated immortalization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 266 FVLENFSTLRQRadpVYSPPLQVSGLCWRLKVYPDGNGVVRGYYLSV--FLELSaglPETSKYEYRV----EMVHQSCND 339
Cdd:cd03772     7 FTVERFSRLSES---VLSPPCFVRNLPWKIMVMPRNYPDRNPHQKSVgfFLQCN---AESDSTSWSChaqaVLRIINYKD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1768049529 340 PTKNIIREFASDFEVGEC-WGYNRFFRLDLLANE--GYLnrQNDTVILRFQV 388
Cdd:cd03772    81 DEPSFSRRISHLFFSKENdWGFSNFMTWSEVTDPekGFI--EDDTITLEVYV 130

B-box-type 2 zinc finger found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis via targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1768049529  78 DKCENHHEKLSVFCWTCKKCICHQCALWGGmHGGHTFKPLAE 119
Cdd:cd19797     1 GHCEEHLDPLSVYCEQDRALICGVCASLGK-HKGHNIITAAE 41

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768049529 117 LAEIYEQhVTKVNEEVAKLRRRLMELISLVQEV--ERN---------VEAVRNAKDER------VREIRNAVEMMIARLD 179
Cdd:COG1340    10 LEELEEK-IEELREEIEELKEKRDELNEELKELaeKRDelnaqvkelREEAQELREKRdelnekVKELKEERDELNEKLN 88

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1768049529 180 tQLKNKLITLMGQKTSLTQETELLESLLQEVEH 212
Cdd:COG1340    89 -ELREELDELRKELAELNKAGGSIDKLRKEIER 120

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 1768049529  80 CENHH-EKLSVFCWTCKKCICHQCALwGGMHGGHTFKPLAEIY 121
Cdd:cd19778     3 CPEHEmEKVNMYCEACRRPVCHLCKL-GGSHANHRVTSMSSAY 44

Speckle-type POZ protein (SPOP) family, MATH domain; composed of proteins with similarity to human SPOP. SPOP was isolated as a novel antigen recognized by serum from a scleroderma patient, whose overexpression in COS cells results in a discrete speckled pattern in the nuclei. It contains an N-terminal MATH domain and a C-terminal BTB (also called POZ) domain. Together with Cul3, SPOP constitutes an ubiquitin E3 ligase which is able to ubiquitinate the PcG protein BMI1, the variant histone macroH2A1 and the death domain-associated protein Daxx. Therefore, SPOP may be involved in the regulation of these proteins and may play a role in transcriptional regulation, apoptosis and X-chromosome inactivation. Cul3 binds to the BTB domain of SPOP whereas Daxx and the macroH2A1 nonhistone region have been shown to bind to the MATH domain. Both MATH and BTB domains are necessary for the nuclear speckled accumulation of SPOP. There are many proteins, mostly uncharacterized, containing both MATH and BTB domains from C. elegans and plants which are excluded from this family.

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gi 1768049529 268 LENFSTLRQRADPVYSPPLQVSG----LCWRLKVYPDGNGVVRGYYLSVFLELSAGLPETSKYEYRVEMVHqSCNDPTKN 343
Cdd:cd03774    11 ISNFSFCREEMGEVIKSSTFSSGandkLKWCLRVNPKGLDEESKDYLSLYLLLVSCPKSEVRAKFKFSILN-AKGEETKA 89

                          90       100
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gi 1768049529 344 IIREFASDFEVGECWGYNRFFRLDLLANE 372
Cdd:cd03774    90 MESQRAYRFVQGKDWGFKKFIRRDFLLDE 118

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM20 and similar proteins; TRIM20, also termed Pyrin, or Marenostrin (MEFV), is involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. TRIM20 belongs to unclassified TRIM 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 pyrin domain, a Bbox2 zinc finger, and a C-terminal SPRY/B30.2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1768049529  80 CENHHEKLSVFCWTCKKCICHQCALwGGMHGGHTFKPL 117
Cdd:cd19771     3 CKLHLEQLKLFCEDHREPICLICQL-SQEHQGHRVRPI 39