first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   55 NTLVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPMGPGVP 134
Cdd:cd17176     1 NTLVIRIIIPDLQQTKCIRFNPDATVWVAKQRILCTLNQSLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPVNKGVP 80

                  ....*...
gi 568952722  135 SLEFRYKK 142
Cdd:cd17176    81 SLEFRYKK 88

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568952722 1836 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1901
Cdd:cd09506     1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 66

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568952722  586 RLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECV 637
Cdd:cd11983     1 RHFVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARGHVGWFPAECV 52

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 2 (SHANK2); SHANK2, also termed cortactin-binding protein 1 (CortBP1), or proline-rich synapse-associated protein 1, is a postsynaptic density (PSD)-associated scaffolding proteins at the excitatory synapse that interconnects neurotransmitter receptors and cell adhesion molecules by direct and indirect interactions with numerous other PSD-associated proteins. It is strongly expressed in the cerebellum. Moreover, SHANK2 acts as a component of the albumin endocytic pathway in podocytes, and regulates renal albumin endocytosis. It also associates with and regulates Na+/H+ exchanger 3 (NHE3) and is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity. Mutations in the SHANK2 synaptic scaffolding gene may lead to autism spectrum disorder and mental retardation. SHANK2 contains an N-terminal F0 domain of FERM (Band 4.1, ezrin, radixin, moesin), six ankyrin (ANK) repeats, one SH3 (Src homology 3) domain, one PDZ (PSD-95, Dlg, and ZO-1/2, also termed DHR or GLGF) domain, and a C-terminal SAM (sterile alpha motif) domain. This family corresponds to the F0 domain that adopts a ubiquitin-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   55 NTLVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPMGPGVP 134
Cdd:cd17176     1 NTLVIRIIIPDLQQTKCIRFNPDATVWVAKQRILCTLNQSLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPVNKGVP 80

                  ....*...
gi 568952722  135 SLEFRYKK 142
Cdd:cd17176    81 SLEFRYKK 88

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568952722 1836 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLL 1901
Cdd:cd09506     1 PVHEWTVDDVGDWLESLNLGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERALKKLL 66

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568952722  586 RLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECV 637
Cdd:cd11983     1 RHFVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARGHVGWFPAECV 52

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 568952722   1837 VHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNL-QKEDLIDLGVTRVGHRMNIERALKQLLDR 1903
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLtSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

ankyrin-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  164 LKKFMDHAQHRSVEKLAKLLDRGLDPNFHDlETGETPLT--LAAQLDDSMEVIKALRNGGAHLDFRSRDGMTALHKAARM 241
Cdd:PHA03095   15 LYDYLLNASNVTVEEVRRLLAAGADVNFRG-EYGKTPLHlyLHYSSEKVKDIVRLLLEAGADVNAPERCGFTPLHLYLYN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  242 RNQVA-LKTLLELGASPDYKDSYGLTPLyHTAIVGG--DPYCCELLLHEHASVCCKDENGWHEIHQACRYGH--VQHLEH 316
Cdd:PHA03095   94 ATTLDvIKLLIKAGADVNAKDKVGRTPL-HVYLSGFniNPKVIRLLLRKGADVNALDLYGMTPLAVLLKSRNanVELLRL 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568952722  317 LLFYGADMSAQNASGNTALHICALYNQDS--CARVLLFRGGNKELKNYNSQTPFQVA 371
Cdd:PHA03095  173 LIDAGADVYAVDDRFRSLLHHHLQSFKPRarIVRELIRAGCDPAATDMLGNTPLHSM 229

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 568952722    584 PGRLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEG-SARGHIGWFPAECVE 638
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYVE 56

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  198 ETPLTLAAQLDDSMEVIKALRNggAHLDFRSRDGM--TALHKAARMRNQVALKTLLE----LGASPDYKDSY-GLTPLyH 270
Cdd:cd22192    18 ESPLLLAAKENDVQAIKKLLKC--PSCDLFQRGALgeTALHVAALYDNLEAAVVLMEaapeLVNEPMTSDLYqGETAL-H 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  271 TAIVGGDPYCCELLLHEHASV--------------CCKDENGWHEIHQACRYGHVQHLEHLLFYGADMSAQNASGNTALH 336
Cdd:cd22192    95 IAVVNQNLNLVRELIARGADVvspratgtffrpgpKNLIYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQDSLGNTVLH 174

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568952722  337 ICALYNQD--SCARVLLFRGGNKE--------LKNYNSQTPFQVAIIAGNFELAEYIKNHKET 389
Cdd:cd22192   175 ILVLQPNKtfACQMYDLILSYDKEddlqpldlVPNNQGLTPFKLAAKEGNIVMFQHLVQKRRH 237

N-terminal or F0 domain of Talin-head FERM; FERM_f0 forms a stable globular structure. The fold is an ubiquitin-like fold joined to the f1 domain in a novel fixed orientation by an extensive charged interface. It is required for maximal integrin-activation, by interacting with other FA components, No binding partner has yet been found for it.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722    57 LVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYP 126
Cdd:pfam16511    1 LSLKISIVGSNVTKTMQFDPSTTVYDACRLIREKIPEGGLNASEYGLFLADEDPKKGRWLEPGRTLEYYD 70

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   197 GETPLTLAAQLDDSMEVIKALRNggahLDFRSRDGMTALHKAA-RMRNQVALKTLLELGASPD----------YKDSY-- 263
Cdd:TIGR00870   52 GRSALFVAAIENENLELTELLLN----LSCRGAVGDTLLHAISlEYVDAVEAILLHLLAAFRKsgplelandqYTSEFtp 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   264 GLTPLyHTAIVGGDPYCCELLLHEHASV---CCKDENGWHEIHQACRYGhvqhlEHLL-FY---------------GADM 324
Cdd:TIGR00870  128 GITAL-HLAAHRQNYEIVKLLLERGASVparACGDFFVKSQGVDSFYHG-----ESPLnAAaclgspsivallsedPADI 201

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568952722   325 SAQNASGNTALHICALYN-------------QDSCARVLLFRGGNKELK---NYNSQTPFQVAIIAGNFELAEYI 383
Cdd:TIGR00870  202 LTADSLGNTLLHLLVMENefkaeyeelscqmYNFALSLLDKLRDSKELEvilNHQGLTPLKLAAKEGRIVLFRLK 276

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 2 (SHANK2); SHANK2, also termed cortactin-binding protein 1 (CortBP1), or proline-rich synapse-associated protein 1, is a postsynaptic density (PSD)-associated scaffolding proteins at the excitatory synapse that interconnects neurotransmitter receptors and cell adhesion molecules by direct and indirect interactions with numerous other PSD-associated proteins. It is strongly expressed in the cerebellum. Moreover, SHANK2 acts as a component of the albumin endocytic pathway in podocytes, and regulates renal albumin endocytosis. It also associates with and regulates Na+/H+ exchanger 3 (NHE3) and is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity. Mutations in the SHANK2 synaptic scaffolding gene may lead to autism spectrum disorder and mental retardation. SHANK2 contains an N-terminal F0 domain of FERM (Band 4.1, ezrin, radixin, moesin), six ankyrin (ANK) repeats, one SH3 (Src homology 3) domain, one PDZ (PSD-95, Dlg, and ZO-1/2, also termed DHR or GLGF) domain, and a C-terminal SAM (sterile alpha motif) domain. This family corresponds to the F0 domain that adopts a ubiquitin-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   55 NTLVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPMGPGVP 134
Cdd:cd17176     1 NTLVIRIIIPDLQQTKCIRFNPDATVWVAKQRILCTLNQSLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPVNKGVP 80

                  ....*...
gi 568952722  135 SLEFRYKK 142
Cdd:cd17176    81 SLEFRYKK 88

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 3 (SHANK3); SHANK3, also termed proline-rich synapse-associated protein 2 (ProSAP2), is a postsynaptic density (PSD)-associated scaffolding protein at the excitatory synapse that interconnects neurotransmitter receptors and cell adhesion molecules by direct and indirect interactions with numerous other PSD-associated proteins. It is critical for synaptic plasticity and the trans-synaptic coupling between the reliability of presynaptic neurotransmitter release and postsynaptic responsiveness. It is a key component of a zinc-sensitive signaling system that regulates excitatory synaptic strength. Mutations in the SHANK3 synaptic scaffolding gene may lead to autism spectrum disorder and mental retardation, and the cause of human Phelan-McDermid syndrome (22q13.3 deletion syndrome) has been isolated to loss of function of one copy of the SHANK3 gene. SHANK3 contains an N-terminal F0 domain of FERM (Band 4.1, ezrin, radixin, moesin), six ankyrin (ANK) repeats, one SH3 (Src homology 3) domain, one PDZ (PSD-95, Dlg, and ZO-1/2, also known as DHR or GLGF) domain, and a C-terminal SAM (sterile alpha motif) domain. This family corresponds to the F0 domain that adopts a ubiquitin-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   56 TLVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPMGPGVPS 135
Cdd:cd17177     1 ALVVRIGIPDLQQTKCLRLNPDAPVWASKQRILCTLNHSLKDVLNYGLFQPAFNGRAGKFLDEERLLREYPLPLDTPVPY 80

                  ....*..
gi 568952722  136 LEFRYKK 142
Cdd:cd17177    81 LEFRYKR 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains proteins, SHANK1, SHANK2, and SHANK3; SHANK proteins (SHANK1, SHANK2, and SHANK3) are core components of the postsynaptic density (PSD) of excitatory synapses. They act as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin cytoskeleton. They play important roles in proper excitatory synapse and circuit function. Mutations in SHANK genes, especially in SHANK3 and SHANK2, may lead to neuropsychiatric disorders, such as autism spectrum disorder (ASD). SHANK proteins contain an N-terminal F0 domain of FERM (Band 4.1, ezrin, radixin, moesin), six ankyrin (ANK) repeats, one SH3 (Src homology 3) domain, one PDZ (PSD-95, Dlg, and ZO-1/2, also termed DHR or GLGF) domain, and a C-terminal SAM (sterile alpha motif) domain. This family corresponds to the F0 domain that adopts a ubiquitin-like fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   57 LVIRVVIQDLQQTKCIRFNPDATVWVAKQRILCTLNQGLKDVLNYGLFQPASNGRDGKFLDEERLLREYPQPmGPgVPSL 136
Cdd:cd17091     1 IVLRISIPDLNLQKCLKFNPDDTVWDAKQQVLEKLAKDLKDALNYGLFLPPTNGKAGKFLDEERLLREYPLD-GP-VGYL 78

                  ....*.
gi 568952722  137 EFRYKK 142
Cdd:cd17091    79 EFKYKR 84

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  149 NLDEKQLARLHTKTNLKKFMDHAQHRSVEKLAKLLDRGLDPNFHDLETgeTPLTLAAQLDDSMEVIKALRNGGAHLDFRS 228
Cdd:COG0666     7 LLLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALG--ALLLLAAALAGDLLVALLLLAAGADINAKD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  229 RDGMTALHKAARMRNQVALKTLLELGASPDYKDSYGLTPLyHTAIVGGDPYCCELLLHEHASVCCKDENGWHEIHQACRY 308
Cdd:COG0666    85 DGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPL-HLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAAN 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  309 GHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCARVLLFRGGNKELKNYNSQTPFQVAIIAGNFELAEYIKNHKE 388
Cdd:COG0666   164 GNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGA 243

                         250       260
                  ....*....|....*....|..
gi 568952722  389 TDIVPLAPTRRPISGAPPCSHR 410
Cdd:COG0666   244 DLNAKDKDGLTALLLAAAAGAA 265

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568952722  586 RLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECV 637
Cdd:cd11983     1 RHFVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARGHVGWFPAECV 52

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568952722  587 LFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAEC 636
Cdd:cd11832     1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPSDC 50

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568952722  586 RLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECV 637
Cdd:cd11982     1 RTFMAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52

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 568952722   1837 VHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNL-QKEDLIDLGVTRVGHRMNIERALKQLLDR 1903
Cdd:smart00454    1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLtSEEDLKELGITKLGHRKKILKAIQKLKEQ 68

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568952722 1836 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1900
Cdd:cd09507     1 PVTNWTTEEVGAWLESLQLGEYRDIFARNDIRGSELLHLERRDLKDLGITKVGHVKRILQAIKDL 65

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  214 IKALRNGGAHLDFRSRDGMTALHKAARMRNQVALKTLLELGASPDYKDSYGLTPLYHTAIVGGDPYCCELLLHEHASVCC 293
Cdd:COG0666     3 LLLLLLLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  294 KDENGWHEIHQACRYGHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCARVLLFRGGNKELKNYNSQTPFQVAII 373
Cdd:COG0666    83 KDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAA 162

                  ....*....
gi 568952722  374 AGNFELAEY 382
Cdd:COG0666   163 NGNLEIVKL 171

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 568952722 1844 DVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALK 1898
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55

SAM domain of Ste11_fungal subfamily; SAM (sterile alpha motif) domain of Ste11 subfamily is a protein-protein interaction domain. Proteins of this subfamily have SAM domain at the N-terminus and protein kinase domain at the C-terminus. They participate in regulation of mating pheromone response, invasive growth and high osmolarity growth response. MAP triple kinase Ste11 from S.cerevisia is known to interact with Ste20 kinase and Ste50 regulator. These kinases are able to form homodimers interacting through their SAM domains as well as heterodimers or heterogenous complexes when either SAM domain of monomeric or homodimeric form of Ste11 interacts with Ste50 regulator.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568952722 1840 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1900
Cdd:cd09534     1 WDEEFVEEWLNELNCGQYLDIFEKNLITGDLLLELDKEALKELGITKVGDRIRLLRAIKSL 61

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722  684 VVLQKKDNEGFGFVLRGakaDTPIeeftptpafpalqYLESVDEGGVAWQAGLRTGDFLIEVNNENVVKVGHRQVVNMIR 763
Cdd:cd06744     1 TVRVYRGNGSFGFTLRG---HAPV-------------YIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQ 64

                          90
                  ....*....|
gi 568952722  764 QGGNHLILKV 773
Cdd:cd06744    65 GSGSMPTLVV 74

SAM domain of WDSUB1 proteins; SAM (sterile alpha motif) domain of WDSUB1 subfamily proteins is a putative protein-protein interaction domain. Proteins of this group contain multiple domains: SAM, one or more WD40 repeats and U-box (derived version of the RING-finger domain). Apparently the WDSUB1 subfamily proteins participate in protein degradation through ubiquitination, since U-box domain are known as a member of E3 ubiquitin ligase family, while SAM and WD40 domains most probably are responsible for an E2 ubiquitin-conjugating enzyme binding and a target protein binding.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568952722 1840 WTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLI-DLGVTRVGHRMNIERALKQLLDR 1903
Cdd:cd09505     5 WSEEDVCTWLRSIGLEQYVEVFRANNIDGKELLNLTKESLSkDLKIESLGHRNKILRKIEELKMK 69

SAM domain of diacylglycerol kinase eta; SAM (sterile alpha motif) domain of DGK-eta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases. The SAM domain is located at the C-terminus of two out of three isoforms of DGK-eta protein. DGK-eta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DCK-eta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-delta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it is responsible for sustained endosomal localization of the protein and resulted in negative regulation of DCK-eta catalytic activity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568952722 1836 PVHLWTKPDVADWLESLNLGEHKETFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQL 1900
Cdd:cd09576     1 PVQKWGTDEVAAWLDLLSLGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568952722   302 IHQACRYGHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCARVLLfRGGNKELKNYNsQTPFQVAIIAGNFELAE 381
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLL-EHADVNLKDNG-RTALHYAARSGHLEIVK 78

                   ....*
gi 568952722   382 YIKNH 386
Cdd:pfam12796   79 LLLEK 83

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 568952722    584 PGRLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEG-SARGHIGWFPAECVE 638
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYVE 56