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 1034648089   4 KKGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAF 83
Cdd:cd12909    38 RDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAF 117

                          90       100
                  ....*....|....*....|....*..
gi 1034648089  84 TDLPP-NLYPTVGLQTPGEVVDANFGQ 109
Cdd:cd12909   118 RDIKKgNLYPTVGLRTPGEHVEANFGQ 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 1034648089 181 SIKNRQRIQKLVLAGRMGEAIETTQQLYPSLLERNPNLLFTLKVRQFIEMVNGTD 235
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 1034648089   4 KKGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAF 83
Cdd:cd12909    38 RDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAF 117

                          90       100
                  ....*....|....*....|....*..
gi 1034648089  84 TDLPP-NLYPTVGLQTPGEVVDANFGQ 109
Cdd:cd12909   118 RDIKKgNLYPTVGLRTPGEHVEANFGQ 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 1034648089   5 KGYMGIGLSAQGVNM--NRLPGWDKHSYGYHGDDGHSFCSSgTGQPYG-PTFTTGDVIGCCVNLINNTCFYTKNGHSLGI 81
Cdd:pfam00622  13 GGGWRVGWATKSVPRkgERFLGDESGSWGYDGWTGKKYWAS-TSPLTGlPLFEPGDVIGCFLDYEAGTISFTKNGKSLGY 91

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034648089  82 AFTDLP--PNLYPTVGLQtPGEVVDANFGQH 110
Cdd:pfam00622  92 AFRDVPfaGPLFPAVSLG-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 1034648089 181 SIKNRQRIQKLVLAGRMGEAIETTQQLYPSLLERNPNLLFTLKVRQFIEMVNGTD 235
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSGK 55

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        30
                   ....*....|....*....|....*....|....
gi 1034648089  142 EWQTMIQKMVSSYLVHHGYCATAEAFARSTDQTV 175
Cdd:smart00667   1 ISRSELNRLILEYLLRNGYEETAETLQKESGLSL 34

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 1034648089   4 KKGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAF 83
Cdd:cd12909    38 RDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTGKPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAF 117

                          90       100
                  ....*....|....*....|....*..
gi 1034648089  84 TDLPP-NLYPTVGLQTPGEVVDANFGQ 109
Cdd:cd12909   118 RDIKKgNLYPTVGLRTPGEHVEANFGQ 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 1034648089    4 KKGYMGIGLSAQGVN--MNRLPGWDKHSYGYHGDDGHSFCSSgTGQPYGPTFT-TGDVIGCCVNLINNTCFYTKNGHSLG 80
Cdd:smart00449  12 DGGHWRVGVATKSVPrgYFALLGEDKGSWGYDGDGGKKYHNS-TGPEYGLPLQePGDVIGCFLDLEAGTISFYKNGKYLH 90

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1034648089   81 I-AFTDLPPN--LYPTVGLQtPGEVVDANFGQ 109
Cdd:smart00449  91 GlAFFDVKFSgpLYPAFSLG-SGNSVRLNFGP 121

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 1034648089   4 KKGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINN--------------- 68
Cdd:cd12908    49 VRCYIAIGLAPQDYPLDRHPGWNPGSVAYHADDGKLFKGSGVGDQFGPRCTKGDRMGCGIRFPRDydtdsedqgdeeegr 128

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1034648089  69 --TCFYTKNGHSLGIAFTDLPPN-LYPTVGLQTPGEVV 103
Cdd:cd12908   129 tvQVFFTRNGKEVGRTEVPLPPGgFYPAVGMHSEGEKV 166

SPRY domain in SSH4 and similar proteins; This family includes SPRY domain in SSH4 (suppressor of SHR3 null mutation protein 4) and similar proteins. SSH4 is a component of the endosome-vacuole trafficking pathway that regulates nutrient transport and may be involved in processes determining whether plasma membrane proteins are degraded or routed to the plasma membrane. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. In yeast, SSH4 and the homologous protein EAR1 (endosomal adapter of RSP5) recruit Rsp5p, an essential ubiquitin ligase of the Nedd4 family, and assist it in its function at multivesicular bodies by directing the ubiquitylation of specific cargoes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648089   9 GIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCS-SGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLP 87
Cdd:cd12910    75 AIGFATKPYPPFRLPGWHRGSLAVHSDDGHRYINdPFGGKDFTPPFREGDTIGIGYRFSSGTIFFTRNGKRLGGWDLGEE 154

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1034648089  88 P--------------NLYPTVGL-QTPGEVVdANFGQ 109
Cdd:cd12910   155 LdaeddgvtglegfhDLYAAIGVfGGECEVH-VNPGQ 190

SPRY domain; 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 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). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648089   6 GYMGIGLSAQGVNMN--RLPGWDKHSYGYHGDDGHSfCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAF 83
Cdd:cd11709    15 GLIQVGWATKSFSLDgeGGVGDDEESWGYDGSRLRK-GHGGSSGPGGRPWKSGDVVGCLLDLDEGTLSFSLNGKDLGVAF 93

                          90       100
                  ....*....|....*....|....*.
gi 1034648089  84 TDL---PPNLYPTVGLqTPGEVVDAN 106
Cdd:cd11709    94 TNLflkGGGLYPAVSL-GSGQGVTIN 118

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034648089  181 SIKNRQRIQKLVLAGRMGEAIETTQQLYPSLLERNPNLLFTLKVRQFIEMVNGTDSE 237
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 1034648089  24 GWDKHSYGYhGDDGhSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTC--FYTKNGHSLGIAFT----DLPPN-LYPTVgl 96
Cdd:cd12884    86 GEEEFSYGY-GSTG-KKSTNCKFEDYGEPFGENDVIGCYLDFESEPVeiSFSKNGKDLGVAFKiskeELGGKaLFPHV-- 161

                          90
                  ....*....|....*
gi 1034648089  97 QTPGEVVDANFGQHP 111
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 1034648089   6 GYMGIGL-SAQGVNMNRLPGWDKHSYGYHG--DDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLG-- 80
Cdd:cd12886    16 TYAGIGVaNAAATGNNGLNGIELSSIGYSLgvYSGNKLSNGSSVATYGAGFTAGDVIGVALDLDAGKIWFYKNGVWQGgg 95

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1034648089  81 -IAFTDLPPNL----YPTVGLQ-TPGEVVDANFG 108
Cdd:cd12886    96 dPAPGTNPAFAgtamYPAVTGGsSTGGSFTANFG 129

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        30
                   ....*....|....*....|....*....|....
gi 1034648089  142 EWQTMIQKMVSSYLVHHGYCATAEAFARSTDQTV 175
Cdd:smart00667   1 ISRSELNRLILEYLLRNGYEETAETLQKESGLSL 34

SPRY domain 2 (SPRY2) of ryanodine receptor (RyR); This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034648089   6 GYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFcsSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGH----SLG- 80
Cdd:cd12878    26 GYMRVGWARPGFRPDLELGSDDLSYAFDGFLARKW--HQGSESFGKQWQPGDVVGCMLDLVDRTISFTLNGEllidSSGs 103

                  ....*...
gi 1034648089  81 -IAFTDLP 87
Cdd:cd12878   104 eVAFKDIE 111

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 1034648089  51 PTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPPN-LYPTVGLQTPG 100
Cdd:cd12881   102 SKFHQGDYITVVLDMEEGTLSFGKNGEEPGVAFEDVDATeLYPCVMFYSSG 152