SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   1 MGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLP 80
Cdd:cd12909   42 IGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIK 121

                         90       100
                 ....*....|....*....|...
gi 998074446  81 -ANLYPTVGLQTPGEIVDANFGQ 102
Cdd:cd12909  122 kGNLYPTVGLRTPGEHVEANFGQ 144

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 998074446  174 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTD 228
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSGK 55

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   1 MGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLP 80
Cdd:cd12909   42 IGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIK 121

                         90       100
                 ....*....|....*....|...
gi 998074446  81 -ANLYPTVGLQTPGEIVDANFGQ 102
Cdd:cd12909  122 kGNLYPTVGLRTPGEHVEANFGQ 144

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446    1 MGIGLSAQGVNM--NRLPGWDKHSYGYHGDDGHSFCSSgTGQPYG-PTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFT 77
Cdd:pfam00622  16 WRVGWATKSVPRkgERFLGDESGSWGYDGWTGKKYWAS-TSPLTGlPLFEPGDVIGCFLDYEAGTISFTKNGKSLGYAFR 94

                          90       100
                  ....*....|....*....|....*...
gi 998074446   78 DLPA--NLYPTVGLQtPGEIVDANFGQQ 103
Cdd:pfam00622  95 DVPFagPLFPAVSLG-AGEGLKFNFGLR 121

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 998074446  174 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTD 228
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSGK 55

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998074446  441 EYGK------NLAHTEMLQDAFSLLAYSDPWSC-PVGQQLDPIQREPVCAALNSAILESQNLPKQPPLMLALGQASECL 512
Cdd:pfam10607  61 EYARenlapfNEEHLKELEKLMGLLAFPDPTDSsPYKSLLSPSRWEKLASEFNRAILKLLGLSSESPLEILLKAGLSAL 139

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|...
gi 998074446  140 LQNMVSSYLVHHGYCATATAFAR 162
Cdd:pfam08513   2 LNRLIYDYLVKEGYEETAEAFEK 24

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   1 MGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLP 80
Cdd:cd12909   42 IGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIK 121

                         90       100
                 ....*....|....*....|...
gi 998074446  81 -ANLYPTVGLQTPGEIVDANFGQ 102
Cdd:cd12909  122 kGNLYPTVGLRTPGEHVEANFGQ 144

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        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446     1 MGIGLSAQGVN--MNRLPGWDKHSYGYHGDDGHsFCSSGTGQPYGPTFT-TGDVIGCCVNLINGTCFYTKNGHSLGI-AF 76
Cdd:smart00449  16 WRVGVATKSVPrgYFALLGEDKGSWGYDGDGGK-KYHNSTGPEYGLPLQePGDVIGCFLDLEAGTISFYKNGKYLHGlAF 94

                           90       100
                   ....*....|....*....|....*....
gi 998074446    77 TDLPAN--LYPTVGLQtPGEIVDANFGQQ 103
Cdd:smart00449  95 FDVKFSgpLYPAFSLG-SGNSVRLNFGPL 122

SPRY domain-containing protein 3; This family contains SPRY domain-containing protein 3 (SPRYD3). In humans, it is highly expressed in most tissues, including brain, kidney, heart, intestine, skeletal muscle, and testis. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   2 GIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLING-----------------TCF 64
Cdd:cd12908   54 AIGLAPQDYPLDRHPGWNPGSVAYHADDGKLFKGSGVGDQFGPRCTKGDRMGCGIRFPRDydtdsedqgdeeegrtvQVF 133

                         90       100       110
                 ....*....|....*....|....*....|...
gi 998074446  65 YTKNGHSLGIAFTDLPAN-LYPTVGLQTPGEIV 96
Cdd:cd12908  134 FTRNGKEVGRTEVPLPPGgFYPAVGMHSEGEKV 166

CT11-RanBPM; protein-protein interaction domain present in crown eukaryotes (plants, animals, fungi)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   420 ATERIILFGRELQAlseQLGREYGKNLahtEMLQDAFSLLAYSDP-WSCPVGQQLDPIQREPVCAALNSAILESQ-NLPK 497
Cdd:smart00757   2 KIEEALAYARELLA---PFAKEHEKFL---KELEKTMALLAYPDPtEPSPYKELLSPSQREKLAEELNSAILELLhGKSS 75

                           90       100
                   ....*....|....*....|
gi 998074446   498 QPPLMLALGQASECLRLMAR 517
Cdd:smart00757  76 ESPLEILLSAGLAALKTLLE 95

SPRY domain associated with DEAD box gene DDX1; This SPRY domain is associated with the DEAD box gene, DDX1, an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. It is suggested that DDX1 acts as a cellular cofactor by promoting oligomerization of Rev on the Rev response element (RRE). DDX1 RNA is overexpressed in breast cancer, data showing a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1, thus potentially serving as an effective prognostic biomarker for early recurrence in primary breast cancer. DDX1 also interacts with RelA and enhances nuclear factor kappaB-mediated transcription. DEAD-box proteins are associated with all levels of RNA metabolism and function, and have been implicated in translation initiation, transcription, RNA splicing, ribosome assembly, RNA transport, and RNA decay.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446  17 GWDKHSYGYHGDDGHSFCSSGTGqpYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFtDLPAN-----LYPTVGLQt 91
Cdd:cd12873   68 GTDKFGFGYGGTGKKSHGRQFDD--YGEPFGLGDVIGCYLDLDNGTISFSKNGKDLGKAF-DIPPHlrnsaLFPAVCLK- 143

                         90
                 ....*....|...
gi 998074446  92 pGEIVDANFGQQP 104
Cdd:cd12873  144 -NAEVEFNFGDKP 155

SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446  22 SYGYhgdDGHSFCS-SGTGQPYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLPAN----LYPTVGLQTpGEIV 96
Cdd:cd12882   48 SYAY---DGNRVRKwNVSTQKYGEPWVAGDVIGCCIDLDKGTISFYRNGRSLGVAFDNVRRGpglaYFPAVSLSF-GERL 123

                 ....*
gi 998074446  97 DANFG 101
Cdd:cd12882  124 ELNFG 128

C-terminal to LisH motif; Alpha-helical motif of unknown function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 998074446   174 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTDSE 230
Cdd:smart00668   1 EFDERKRIRELILKGDWDEALEWLSSLKPPLLERNSKLEFELRKQKFLELVRQGKLE 57

SPRY domain in heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1 (also known as HNRPUL1 ) which is a major constituent of nuclear matrix or scaffold and binds directly to DNA sequences through the N-terminal acidic region named serum amyloid P (SAP). Its function is specifically modulated by E1B-55kDa in adenovirus-infected cells. HNRPUL1 also participates in ATR protein kinase signaling pathways during adenovirus infection. Two transcript variants encoding different isoforms have been found for this gene. When associated with bromodomain-containing protein 7 (BRD7), it activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446  17 GWDKHSYGYhGDDGhSFCSSGTGQPYGPTFTTGDVIGCCVNLINGTC--FYTKNGHSLGIAFT----DL-PANLYPTVgl 89
Cdd:cd12884   86 GEEEFSYGY-GSTG-KKSTNCKFEDYGEPFGENDVIGCYLDFESEPVeiSFSKNGKDLGVAFKiskeELgGKALFPHV-- 161

                         90
                 ....*....|....*
gi 998074446  90 QTPGEIVDANFGQQP 104
Cdd:cd12884  162 LTKNCAVEVNFGQKE 176

SPRY domain-like in bacteria; This family contains SPRY-like domains that are found only in bacterial and are mostly uncharacterized. SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 eukaryotic protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074446   1 MGIGL-SAQGVNMNRLPGWDKHSYGYHG--DDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINGTCFYTKNGHSLG---I 74
Cdd:cd12886   18 AGIGVaNAAATGNNGLNGIELSSIGYSLgvYSGNKLSNGSSVATYGAGFTAGDVIGVALDLDAGKIWFYKNGVWQGggdP 97

                         90       100       110
                 ....*....|....*....|....*....|..
gi 998074446  75 AFTDLPANL----YPTVGLQTPGEI-VDANFG 101
Cdd:cd12886   98 APGTNPAFAgtamYPAVTGGSSTGGsFTANFG 129

SPRY domain in HERC1; This SPRY domain is found in the HERC1, a large protein related to chromosome condensation regulator RCC1. It is widely expressed in many tissues, playing an important role in intracellular membrane trafficking in the cytoplasm as well as Golgi apparatus. HERC1 also interacts with tuberous sclerosis 2 (TSC2, tuberin), which suppresses cell growth, and results in the destabilization of TSC2. However, the biological function of HERC1 has yet to be defined.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 998074446  44 PTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLPAN-LYPTVGLQTPGEI 95
Cdd:cd12881  102 SKFHQGDYITVVLDMEEGTLSFGKNGEEPGVAFEDVDATeLYPCVMFYSSGPG 154

SPRY domain in the F-box family Fbxo45; Fbxo45 is a novel synaptic E3 and ubiquitin ligase, related to the suppressor of cytokine signaling (SOCS) proteins and located N-terminal to a SPRY (SPla and the ryanodine receptor) domain. Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1, via the SPRY domain, thus playing an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. F-box motifs are found in proteins that function as the substrate recognition component of SCF E3 complexes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998074446  15 LPGWDKHSYGYHGDDGHSFCSSGTGQPY-----GPTFTTGDVIGCCVNLINGTCFYTKNGHSLGIAFTDLP-ANLYPTV 87
Cdd:cd12907   77 LLGSDDQSWGWNLVDNHLLHNGDSQGNYpqcnnAPKYQVGERIRVILDCEDNTLAFERGYEFLGVAFRGLPpTKLYPAV 155

Lissencephaly type-1-like homology motif; Alpha-helical motif present in Lis1, treacle, Nopp140, some katanin p60 subunits, muskelin, tonneau, LEUNIG and numerous WD40 repeat-containing proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly.

                           10        20
                   ....*....|....*....|....*...
gi 998074446   140 LQNMVSSYLVHHGYCATATAFARMTETP 167
Cdd:smart00667   6 LNRLILEYLLRNGYEETAETLQKESGLS 33

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|...
gi 998074446  140 LQNMVSSYLVHHGYCATATAFAR 162
Cdd:pfam08513   2 LNRLIYDYLVKEGYEETAEAFEK 24