SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1847688216 304 EEGMERQLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELLD 368
Cdd:cd09523     1 EAGVDPQLVNLLNELSAEHYLPVFARHRITMETLSTMTDEDLKKIGIHEIGLRKEILRAAQELLL 65

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216   8 ERRLELGQREHTQLLQQSSSQKDEILQTVKEEQSRLEQglsehqrhLNAERQRLQEQLKQTEQNISSRIQKLLQDNQRQK 87
Cdd:COG1196   213 ERYRELKEELKELEAELLLLKLRELEAELEELEAELEE--------LEAELEELEAELAELEAELEELRLELEELELELE 284

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216  88 KSSEILKSLENERIRMEQLMSITQEETESLRRRDVASAMQQMLTESCKNRLIQMAYESQRQnlVQQACSSMAEMDERFQQ 167
Cdd:COG1196   285 EAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEE--LEEAEEELEEAEAELAE 362

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216 168 ILSWQQMDQNKAISQILQESAMQKAAFEALQVKKDLmHRQIRSQIKLIETELLQLTQLELKRKSLDTESLQEMISEQRWA 247
Cdd:COG1196   363 AEEALLEAEAELAEAEEELEELAEELLEALRAAAEL-AAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEE 441

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216 248 LSSLLQQLLKEKQQREEELREILTELEAKSETRQENYWLIQYQRLLNQKPLSLKLQEegMERQLVALLEELSAEHYLPIF 327
Cdd:COG1196   442 EALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLE--AEADYEGFLEGVKAALLLAGL 519

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216 328 AHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRvQELLDAARIQPELKPPMGEVVTPTAPQEPPESVRPSAPPAELEV 407
Cdd:COG1196   520 RGLAGAVAVLIGVEAAYEAALEAALAAALQNIVVE-DDEVAAAAIEYLKAAKAGRATFLPLDKIRARAALAAALARGAIG 598

                         410
                  ....*....|....*..
gi 1847688216 408 QASECVVCLEREAQMIF 424
Cdd:COG1196   599 AAVDLVASDLREADARY 615

SAM domain of TAL subfamily; SAM (sterile alpha motif) domain of TAL (Tsg101-associated ligase) proteins, also known as LRSAM1 (Leucine-rich repeat and sterile alpha motif-containing) proteins, is a putative protein-protein interaction domain. Proteins of this subfamily participate in the regulation of retrovirus budding and receptor endocytosis. They show E3 ubiquitin ligase activity. Human TAL protein interacts with Tsg101 and TAL's C-terminal ring finger domain is essential for the multiple monoubiquitylation of Tsg101.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1847688216 304 EEGMERQLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELLD 368
Cdd:cd09523     1 EAGVDPQLVNLLNELSAEHYLPVFARHRITMETLSTMTDEDLKKIGIHEIGLRKEILRAAQELLL 65

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1847688216 411 ECVVCLEREAQMIFLNCGHVCC----CQQCCQPLRTCPLCRQDIAQR 453
Cdd:pfam13920   4 LCVICLDRPRNVVLLPCGHLCLceecAERLLRKKKKCPICRQPIESV 50

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1847688216 315 LEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQEL 366
Cdd:pfam00536  12 LESIGLGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63

CagA protein; The Helicobacter pylori type IV secretion effector CagA is a major bacterial virulence determinant and critical for gastric carcinogenesis. X-ray crystallographic analysis of the N-terminal CagA fragment (residues 1-876) revealed that the region has a structure comprised of three discrete domains. Domain I constitutes a mobile CagA N terminus, while Domain II tethers CagA to the plasma membrane by interacting with membrane phosphatidylserine. Domain III interacts intramolecularly with the intrinsically disordered C-terminal region, and this interaction potentiates the pathogenic scaffold/hub function of CagA.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216   2 LEKlEFERRLEL--GQREHTQLLQQSSSQKDEILQTVKEEQSRLEQGLSeHQRHLNAERQRLQEQLKQTEQNISSRIQKL 79
Cdd:pfam18971 629 LEK-EVEKKLESksGNKNKMEAKAQANSQKDEIFALINKEANRDARAIA-YTQNLKGIKRELSDKLEKISKDLKDFSKSF 706

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216  80 LQ----DNQRQKKSSEILKSLEN---------ERIRMEQLMSITQEETESLRRRDVASAMQQM--LTESCKNRLIQMAYE 144
Cdd:pfam18971 707 DEfkngKNKDFSKAEETLKALKGsvkdlginpEWISKVENLNAALNEFKNGKNKDFSKVTQAKsdLENSVKDVIINQKVT 786

                         170       180
                  ....*....|....*....|....*..
gi 1847688216 145 SQRQNLVQQACSSMAEMD-ERFQQILS 170
Cdd:pfam18971 787 DKVDNLNQAVSVAKAMGDfSRVEQVLA 813

SAM domain of TAL subfamily; SAM (sterile alpha motif) domain of TAL (Tsg101-associated ligase) proteins, also known as LRSAM1 (Leucine-rich repeat and sterile alpha motif-containing) proteins, is a putative protein-protein interaction domain. Proteins of this subfamily participate in the regulation of retrovirus budding and receptor endocytosis. They show E3 ubiquitin ligase activity. Human TAL protein interacts with Tsg101 and TAL's C-terminal ring finger domain is essential for the multiple monoubiquitylation of Tsg101.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1847688216 304 EEGMERQLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELLD 368
Cdd:cd09523     1 EAGVDPQLVNLLNELSAEHYLPVFARHRITMETLSTMTDEDLKKIGIHEIGLRKEILRAAQELLL 65

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1847688216 410 SECVVCLEREAQMIFLNCGHV----CCCQQCCQPLRTCPLCRQDIAQRLRIY 457
Cdd:cd16647     2 SECVICYERPVDTVLYRCGHMcmcyDCALQLKRRGGSCPICRAPIKDVIKIY 53

RING finger, HC subclass, found in inhibitor of apoptosis proteins (IAPs); IAPs are frequently overexpressed in cancer and associated with tumor cell survival, chemoresistance, disease progression, and poor prognosis. They function primarily as negative regulators of cell death. They regulate caspases and apoptosis through the inhibition of specific members of the caspase family of cysteine proteases. In addition, IAPs has been implicated in a multitude of other cellular processes, including inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. IAPs in this family includes cellular inhibitor of apoptosis protein c-IAP1 (BIRC2) and c-IAP2 (BIRC3), XIAP (BIRC4), BIRC7, and BIRC8, all of which contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. The UBA domain is only absent in mammalian homologs of BIRC7. Moreover, c-IAPs contains an additional caspase activation and recruitment domain (CARD) between the UBA and C3HC4-type RING-HC domains. The CARD domain may serve as a protein interaction surface.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1847688216 412 CVVCLEREAQMIFLNCGHVCCCQQCCQPLRTCPLCRQ 448
Cdd:cd16510     4 CKICMDREVNIVFLPCGHLVTCAQCAASLRKCPICRT 40

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1847688216 408 QASECVVCLEREAQMIFLNCGHVCC----CQQCCQPLRTCPLCRQDIAQRLRIY 457
Cdd:cd23129     1 QRDECVVCMDAPRDAVCVPCGHVAGcmscLKALMQSSPLCPICRAPVRQVIKVY 54

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1847688216 310 QLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQE 365
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQR 56

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1847688216 411 ECVVCLEREAQMIFLNCGHVC-----CCQQCCQPLRTCPLCRQDIAQRLRI 456
Cdd:cd23128     5 ECVMCMEEERSVVFLPCAHQVvcsgcNDLHEKKGMRECPSCRGEIQERIRV 55

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1847688216 410 SECVVCLEREAQMIFlNCGHVCCCQQCCqPLRTCPLCRQDI 450
Cdd:cd16520     1 ILCPICMERKKNVVF-LCGHGTCQKCAE-KLKKCPICRKPI 39

SAM domain of tankyrase1,2 subfamily; SAM (sterile alpha motif) domain of Tankyrase1,2 subfamily is a protein-protein interaction domain. In addition to the SAM domain, proteins of this group have ankyrin repeats and a ADP- ribosyltransferase (poly-(ADP-ribose) synthase) domain. Tankyrases can polymerize through their SAM domains forming homoligomers and these complexes are disrupted by autoribosylation. Tankyrases apparently act as master scaffolding proteins and thus may interact simultaneously with multiple proteins, in particular with TRF1, NuMA, IRAP and Grb14 (ankyrin repeats are involved in these interactions). Tankyrases participate in a variety of cell signaling pathways as effector molecules. Their functions are different depending on the intracellular location: at telomeres they play a role in the regulation of telomere length via control of telomerase access to telomeres, at centrosomes they promote spindle assembly/disassembly, in Golgi vesicles they participate in the regulation of vesicle trafficking and Golgi dynamics. Tankyrase 1 may be of interest as new potential target for telomerase-directed cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1847688216 314 LLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELL 367
Cdd:cd09524    11 FLSSLGLEHLREIFEREQITLDVLAEMGHEELKEIGINAYGHRHKLIKGVERLI 64

RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins; XIAP, also known as baculoviral IAP repeat-containing protein 4 (BIRC4), IAP-like protein (ILP), inhibitor of apoptosis protein 3 (IAP-3), or X-linked inhibitor of apoptosis protein (X-linked IAP), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac). The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK), the nuclear factor-kappaB (NF-kappaB), and the transforming growth factor-beta (TGF-beta) pathways. Moreover, XIAP can regulate copper homeostasis by interacting with MURR1. BIRC8, also known as inhibitor of apoptosis-like protein 2, IAP-like protein 2, ILP-2, or testis-specific inhibitor of apoptosis, is a tissue-specific homolog of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a C3HC4-type RING-HC finger at the carboxyl terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1847688216 412 CVVCLEREAQMIFLNCGHVCCCQQCCQPLRTCPLCRQDIAQRLRIYHS 459
Cdd:cd16714    17 CKICMDRNISIVFIPCGHLVTCKQCAEALDKCPICCTVITFKQKIFMS 64

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1847688216 315 LEELSAEHYLPIFAHHRL-SLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQEL 366
Cdd:cd09488     9 LESIKMGRYKENFTAAGYtSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1847688216 410 SECVVCLEREAQMIFLNCGHVCCCQ--QCCQPLRTCPLCR 447
Cdd:cd16649     1 GLCVVCLENPASVLLLPCRHLCLCEvcAKGLRGKTCPICR 40

phosphodiesterase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216  27 SQKDEILQTVKEEQSRLEQGLSEHQRHLNAERQRLQEQLKQTEQNISSRIQKLLQDNQR---------------QKKSSE 91
Cdd:PRK12704   53 AIKKEALLEAKEEIHKLRNEFEKELRERRNELQKLEKRLLQKEENLDRKLELLEKREEElekkekeleqkqqelEKKEEE 132

                          90       100
                  ....*....|....*....|..
gi 1847688216  92 ILKSLENERIRMEQLMSITQEE 113
Cdd:PRK12704  133 LEELIEEQLQELERISGLTAEE 154

SAM domain (Sterile alpha motif);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1847688216 310 QLVALLEELSAEHYLPIFAHHRLS-LDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELL 367
Cdd:pfam07647   8 SVADWLRSIGLEQYTDNFRDQGITgAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

third RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the third RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1847688216 412 CVVCLEREAQMIFLnCGHVCCCQQCCQpLRTCPLCRQDIAQRLRIY 457
Cdd:cd16727     3 CPVCLDRLKNMIFL-CGHGTCQLCGDR-MSECPICRKAIEKRILLY 46

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1847688216    2 LEKLEFERRLELGQREHTQLLQQSSSQKDEILQTVKEEQsrlEQGLSEHQRHLNAERQRLQEQLKQTEQNISSRIQKLLQ 81
Cdd:PTZ00121  1661 IKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAE---EAKKAEELKKKEAEEKKKAEELKKAEEENKIKAEEAKK 1737

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1847688216   82 DNQRQKKSSEILKSLENERIRMEQLMSITQEETESLRRRDVASAMQQMLTESCKNRL 138
Cdd:PTZ00121  1738 EAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRM 1794

RING finger, HC subclass, found in Arabidopsis thaliana SP1-like protein 2 (SPL2) and similar proteins; SPL2, also known as RING-type E3 ubiquitin transferase SPL2, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. SPL2 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1847688216 401 PPAELevqaseCVVCLEREAQMIFLNCGHVCCCQQCCQPLRT-----CPLCRQ 448
Cdd:cd23145     1 PDGEL------CVVCLLRRRRVAFIECGHRVCCELCARRVTReanprCPVCRQ 47

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1847688216  308 ERQLVALLEELSAEHYLPIFAHHRLS-LDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELLD 368
Cdd:smart00454   6 PESVADWLESIGLEQYADNFRKNGIDgALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKE 67

second RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the second RING-HC finger.

                          10        20        30
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gi 1847688216 411 ECVVCLEREAQMIFLNCGHVCCCQQCCQPLRTCPLCR 447
Cdd:cd16725     2 ECVVCSDKKASVLFKPCGHMCACEGCAALMKKCVQCR 38

SAM domain of ANKS6 (or SamCystin) subfamily; SAM (sterile alpha motif) domain of ANKS6 (or SamCystin) subfamily is a potential protein-protein interaction domain. Proteins of this subfamily have N-terminal ankyrin repeats and a C-terminal SAM domain. They are able to form self-associated complexes and both (SAM and ANK) domains play a role in such interactions. Mutations in Anks6 gene are associated with polycystic kidney disease. They cause formation of renal cysts in rodent models. It was suggested that the ANKS6 protein can interact indirectly (through RNA and protein intermediates) with BICC1, another polycystic kidney disease-associated protein.

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gi 1847688216 308 ERQLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQEL 366
Cdd:cd09518     5 EDELSGILRKLSLEKYQPIFEEQEVDMEAFLTLTDGDLKELGIKTDGPRQQILAAISEL 63

second RING finger, HC subclass, found in mind bomb 2 (MIB2) and similar proteins; MIB2, also known as novel zinc finger protein (Novelzin), putative NF-kappa-B-activating protein 002N, skeletrophin, or zinc finger ZZ type with ankyrin repeat domain protein 1, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands. Especially, it promotes Delta ubiquitylation and endocytosis in Notch activation. Overexpression of MIB2, activates NF-kappaB and interferon-stimulated response element (ISRE) reporter activity. Moreover, MIB2 acts as a novel component of the activated B-cell CLL/lymphoma 10 (BCL10) complex and controls BCL10-dependent NF-kappaB activation. It also functions as a founder myoblast-specific protein that regulates myoblast fusion and muscle stability. MIB2 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of two C3HC4-type RING-HC fingers. This model corresponds to the second RING-HC finger.

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gi 1847688216 412 CVVCLEREAQMIFlNCGHvCCCQQCCQPLRTCPLCRQDIAQRLRIY 457
Cdd:cd16728     7 CPICIDNHIKLVF-QCGH-GSCIECSSALKACPICRQAIRERIQIF 50