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 688593789   38 KTILTVFLSDNQQLLTEVPITPETLCKDVVEFCKEAGESGCHLAEVWKGKERAIPFDQMMFEHLQKWGQRRAEVKFYLRH 117
Cdd:cd17224     2 PMILTVFLSNNEQILTEVPITPETTCRDVVEFCKEPGETGCHLAEVWRGNERPIPYDHMMYEHLQKWGPRREEVKFFLRH 81

                  ....
gi 688593789  118 EECP 121
Cdd:cd17224    82 EDSP 85

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  918 LLLDASLEGEFDLVQRIIYEVENPSTPNDEGITPLHNSVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHLC 997
Cdd:COG0666   123 PLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIV 202

                          90       100
                  ....*....|....*....|...
gi 688593789  998 KLLVESGAAIFATTiSDVETAAD 1020
Cdd:COG0666   203 KLLLEAGADVNAKD-NDGKTALD 224

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  192 EQRLRYLKQQdpcQGQSASESDKLQRLRERVENQEAKLKKVRAMRGQVDYSKlinGNLSAEIEhvsslFQEKQAELQSAM 271
Cdd:COG4717    77 EEELKEAEEK---EEEYAELQEELEELEEELEELEAELEELREELEKLEKLL---QLLPLYQE-----LEALEAELAELP 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  272 LKVDQLTQQLDDLRQgrlnglqplggpvtsnAALELRKLYQEL-QIRNKLNQEQNSKLQQHKDMLNKRNMEVTMMDKRIG 350
Cdd:COG4717   146 ERLEELEERLEELRE----------------LEEELEELEAELaELQEELEELLEQLSLATEEELQDLAEELEELQQRLA 209

                         170
                  ....*....|....*
gi 688593789  351 DLRERLYKKKAELGR 365
Cdd:COG4717   210 ELEEELEEAQEELEE 224

Ras-associating (RA) domain found in apoptosis-stimulating protein of p53 protein 1 (ASPP1); ASPP1 is a member of the ASPP protein family (Apoptosi-Stimulating Protein of p53) that activates the p53-mediated apoptotic response. ASSP1 functions as a tumor suppressor and coordinates with p53 to protect hematopoietic stem cell (HSC) pool integrity, guarding against hematological malignancies. ASSP1 contains a RA domain at the N-terminus. The RA domain is a ubiquitin-like domain and RA domain-containing proteins are involved in several different functions ranging from tumor suppression to being oncoproteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789   38 KTILTVFLSDNQQLLTEVPITPETLCKDVVEFCKEAGESGCHLAEVWKGKERAIPFDQMMFEHLQKWGQRRAEVKFYLRH 117
Cdd:cd17224     2 PMILTVFLSNNEQILTEVPITPETTCRDVVEFCKEPGETGCHLAEVWRGNERPIPYDHMMYEHLQKWGPRREEVKFFLRH 81

                  ....
gi 688593789  118 EECP 121
Cdd:cd17224    82 EDSP 85

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  918 LLLDASLEGEFDLVQRIIYEVENPSTPNDEGITPLHNSVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHLC 997
Cdd:COG0666   123 PLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIV 202

                          90       100
                  ....*....|....*....|...
gi 688593789  998 KLLVESGAAIFATTiSDVETAAD 1020
Cdd:COG0666   203 KLLLEAGADVNAKD-NDGKTALD 224

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 688593789   1048 KGTVYALWDYEAQSADELSFREGDALTIMSRRDDsetEWWWAKVND-KEGYVPRN 1101
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDD---GWWKGRLGRgKEGLFPSN 53

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  929 DLVQRIIYEVENPSTPNDEGITPLHN--SVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHL--CKLLVESG 1004
Cdd:PHA03100   87 EIVKLLLEYGANVNAPDNNGITPLLYaiSKKSNSYSIVEYLLDNGANVNIKNSDGENLLHLYLESNKIDLkiLKLLIDKG 166

                  ....*..
gi 688593789 1005 AAIFATT 1011
Cdd:PHA03100  167 VDINAKN 173

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  192 EQRLRYLKQQdpcQGQSASESDKLQRLRERVENQEAKLKKVRAMRGQVDYSKlinGNLSAEIEhvsslFQEKQAELQSAM 271
Cdd:COG4717    77 EEELKEAEEK---EEEYAELQEELEELEEELEELEAELEELREELEKLEKLL---QLLPLYQE-----LEALEAELAELP 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  272 LKVDQLTQQLDDLRQgrlnglqplggpvtsnAALELRKLYQEL-QIRNKLNQEQNSKLQQHKDMLNKRNMEVTMMDKRIG 350
Cdd:COG4717   146 ERLEELEERLEELRE----------------LEEELEELEAELaELQEELEELLEQLSLATEEELQDLAEELEELQQRLA 209

                         170
                  ....*....|....*
gi 688593789  351 DLRERLYKKKAELGR 365
Cdd:COG4717   210 ELEEELEEAQEELEE 224

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789   182 IAKLSIVR-SEEQRLRYLKQQDPCQGQSASESDKLQRLRERVENQEAKLKKVRAMRGQVDYSKlinGNLSAEiEHVSSLF 260
Cdd:pfam15558    9 IAALMLARhKEEQRMRELQQQAALAWEELRRRDQKRQETLERERRLLLQQSQEQWQAEKEQRK---ARLGRE-ERRRADR 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789   261 QEKQAELQSamlkvDQLTQQLDD---LRQGRLNGLQPLGgpvtsnaalELRKLYQELQIRnklnqEQNSKLQQHKDMLNK 337
Cdd:pfam15558   85 REKQVIEKE-----SRWREQAEDqenQRQEKLERARQEA---------EQRKQCQEQRLK-----EKEEELQALREQNSL 145

                          170       180
                   ....*....|....*....|...
gi 688593789   338 RNMEVTMMDKRIGDLRERLYKKK 360
Cdd:pfam15558  146 QLQERLEEACHKRQLKEREEQKK 168

Spc7 kinetochore protein; This domain is found in cell division proteins which are required for kinetochore-spindle association.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789    248 NLSAEIEHVSSLFQEKQAELQSAMLKVDQLTQQLDDLRQGRLNGLQplggpvtsNAALELRKLYQELQIRNKLNQEQNSK 327
Cdd:smart00787  162 LLMKELELLNSIKPKLRDRKDALEEELRQLKQLEDELEDCDPTELD--------RAKEKLKKLLQEIMIKVKKLEELEEE 233

                            90       100       110
                    ....*....|....*....|....*....|...
gi 688593789    328 LQQHKDMLNKRNMEVTMMDKRIGDLRERLYKKK 360
Cdd:smart00787  234 LQELESKIEDLTNKKSELNTEIAEAEKKLEQCR 266

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  181 LIAKLSIVRSEEQRLRYLK--------QQDPCQGQSASESDKLQRLRERVENQEAKLKKVRAMRGQV--------DYSKL 244
Cdd:PRK03918  219 LREELEKLEKEVKELEELKeeieelekELESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELkelkekaeEYIKL 298

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  245 IN----------------GNLSAEIEHVsslfQEKQAELQSAMLKVDQLTQQLDDLRQgRLNGLQPlggpvtSNAALE-L 307
Cdd:PRK03918  299 SEfyeeyldelreiekrlSRLEEEINGI----EERIKELEEKEERLEELKKKLKELEK-RLEELEE------RHELYEeA 367

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 688593789  308 RKLYQELQ-IRNKLNQEQNSKLQQHKDMLNKRNMEVTMMDKRIGDLRERLYKKKAEL 363
Cdd:PRK03918  368 KAKKEELErLKKRLTGLTPEKLEKELEELEKAKEEIEEEISKITARIGELKKEIKEL 424

Coiled-coiled domain of autophagy-related 16 (Atg16) family proteins; The Atg16 family includes Saccharomyces cerevisiae Atg16 (also called cytoplasm to vacuole targeting protein 11, CVT11, or SAP18), human autophagy-related protein 16-1 (also called APG16-like 1, ATG16L1, or APG16L) and autophagy-related protein 16-2 (also called APG16-like 2, ATG16L2, WD repeat-containing protein 80 or WDR80), and similar proteins. Atg16 stabilizes the Atg5-Atg12 conjugate and mediates the formation of the 350 kDa complex, which is necessary for autophagy. The Atg5-Atg12/Atg16 complex is required for efficient promotion of Atg8-conjugation to phosphatidylethanolamine and Atg8 localization to the pre-autophagosomal structure (PAS). Similarly, human ATG16L1 plays an essential role in autophagy and acts as a molecular scaffold which mediates protein-protein interactions essential for autophagosome formation. ATG16L2, though structurally similar to ATG16L1 and able to form a complex with the autophagy proteins Atg5 and Atg12, is not essential for autophagy. Single-nucleotide polymorphisms in ATG16L1 is associated with an increased risk of developing Crohn disease. Saccharomyces cerevisiae Atg16 contains an N-terminal domain (NTD) that interacts with the Atg5-Atg12 protein conjugate and a coiled-coil domain (CCD) that dimerizes and mediates self-assembly. Human ATG16L1 and ATG16L2 also contains an N-terminal region that binds Atg5, a CCD homologous to the yeast CCD, and a WD40 domain that represents approximately 50% of the full-length protein. This model corresponds to the CCD of Atg16 family proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  262 EKQAELQSAMLKVDQLTQQLDDLRQgrlnglqplggpvtsnaalELRKLYQELQIRNKLNQEQNSKLQQHkdmlnkrNME 341
Cdd:cd22887     1 ELESELQELEKRLAELEAELASLEE-------------------EIKDLEEELKEKNKANEILNDELIAL-------QIE 54

                          90       100       110
                  ....*....|....*....|....*....|....
gi 688593789  342 VTMMDKRIGDLR-------ERLYKKKAELG-RMN 367
Cdd:cd22887    55 NNLLEEKLRKLQeendelvERWMAKKQQEAdKMN 88

Ras-associating (RA) domain found in apoptosis-stimulating protein of p53 protein 1 (ASPP1); ASPP1 is a member of the ASPP protein family (Apoptosi-Stimulating Protein of p53) that activates the p53-mediated apoptotic response. ASSP1 functions as a tumor suppressor and coordinates with p53 to protect hematopoietic stem cell (HSC) pool integrity, guarding against hematological malignancies. ASSP1 contains a RA domain at the N-terminus. The RA domain is a ubiquitin-like domain and RA domain-containing proteins are involved in several different functions ranging from tumor suppression to being oncoproteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789   38 KTILTVFLSDNQQLLTEVPITPETLCKDVVEFCKEAGESGCHLAEVWKGKERAIPFDQMMFEHLQKWGQRRAEVKFYLRH 117
Cdd:cd17224     2 PMILTVFLSNNEQILTEVPITPETTCRDVVEFCKEPGETGCHLAEVWRGNERPIPYDHMMYEHLQKWGPRREEVKFFLRH 81

                  ....
gi 688593789  118 EECP 121
Cdd:cd17224    82 EDSP 85

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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 688593789 1049 GTVYALWDYEAQSADELSFREGDALTIMSRRDDSETEWWWAKVNDKEGYVPRNLLGL 1105
Cdd:cd11954     1 GMVYALWDYEAQNADELSFQEGDAITILRRKDDSETEWWWARLNDKEGYVPKNLLGL 57

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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 688593789 1049 GTVYALWDYEAQSADELSFREGDALTIMSRRDDSETEWWWAKVNDKEGYVPRNLLGL 1105
Cdd:cd11807     1 GVVYALFDYEAENGDELSFREGDELTVLRKGDDDETEWWWARLNDKEGYVPRNLLGL 57

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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 688593789 1049 GTVYALWDYEAQSADELSFREGDALTIMsRRDDSETEWWWAKVNDKEGYVPRNLLGL 1105
Cdd:cd11952     1 GVVYALWDYSAEFPDELSFKEGDMVTVL-RKDGEGTDWWWASLCGREGYVPRNYFGL 56

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  917 ALLLDASLEGEFDLVQRIIYEVENPSTPNDEGITPLHNSVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHL 996
Cdd:COG0666    89 TLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEI 168

                          90
                  ....*....|.
gi 688593789  997 CKLLVESGAAI 1007
Cdd:COG0666   169 VKLLLEAGADV 179

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  914 NPLALLLDASLEGEFDLVQRIIYEVENPSTPNDEGITPLHNSVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNN 993
Cdd:COG0666    53 LGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGN 132

                          90
                  ....*....|....
gi 688593789  994 VHLCKLLVESGAAI 1007
Cdd:COG0666   133 LEIVKLLLEAGADV 146

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 688593789   1048 KGTVYALWDYEAQSADELSFREGDALTIMSRRDDsetEWWWAKVND-KEGYVPRN 1101
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDD---GWWKGRLGRgKEGLFPSN 53

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. 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 688593789 1051 VY-ALWDYEAQSADELSFREGDALTIMsrrDDSETEWWWAKVNDKEGYVPRN 1101
Cdd:cd11772     1 VFrALYDYEAQHPDELSFEEGDLLYIS---DKSDPNWWKATCGGKTGLIPSN 49

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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 688593789 1050 TVYALWDYEAQSADELSFREGDALTIMsrrDDSETEWWWAK--VNDKEGYVPRN 1101
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQIL---DDSDGDWWLARhlSTGKEGYIPSN 51

Ankyrin repeats (many copies);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 688593789   950 TPLHNSVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHLCKLLV 1001
Cdd:pfam13637    3 TALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 688593789 1052 YALWDYEAQSADELSFREGDALTIMsrrDDSETEWWWAKVNDKEGYVPRNLL 1103
Cdd:cd11856     3 VAIADYEAQGDDEISLQEGEVVEVL---EKNDSGWWYVRKGDKEGWVPASYL 51

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  929 DLVQRIIYEVENPSTPNDEGITPLHN--SVCAGHHHIVKFLLDFGVNVNAADSDGWTPLHCAASCNNVHL--CKLLVESG 1004
Cdd:PHA03100   87 EIVKLLLEYGANVNAPDNNGITPLLYaiSKKSNSYSIVEYLLDNGANVNIKNSDGENLLHLYLESNKIDLkiLKLLIDKG 166

                  ....*..
gi 688593789 1005 AAIFATT 1011
Cdd:PHA03100  167 VDINAKN 173

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. 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 688593789 1050 TVYALWDYEAQSADELSFREGDALTIMsrrDDSETEWWWAKVNDKE-GYVPRN 1101
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVY---DDSDSDWILVGFNGTQfGFVPAN 50

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. 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
                  ....*....|....*....|....*....|....*....|....*....
gi 688593789 1053 ALWDYEAQSADELSFREGDALTIMSRRDDSetEWWWAKVNDKEGYVPRN 1101
Cdd:cd11804     4 AKHDFKATAEDELSFKKGSILKVLNMEDDP--NWYKAELDGKEGLIPKN 50

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically 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 688593789 1050 TVYALWDYEAQSADELSFREGDALTIMsrrDDSETEWWWAKVNDKEGYVPRN 1101
Cdd:cd11949     1 YVQALFDFDPQEDGELGFRRGDFIEVM---DNSDPNWWKGACHGQTGMFPRN 49

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  369 PPSPQPTPGSSGRVAAVCPYIQVPVPGRKEGYTLPPEPLKPHSFSTVNHA-RSKSEEDRVRMPAGPWKVSDLDIIVDPLV 447
Cdd:PHA03247 2624 PDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAaQASSPPQRPRRRAARPTVGSLTSLADPPP 2703

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  448 PSSEPSNGPDSDCFSTNDAIWPSFSSNRVPLKPPDwkdanldhtsKMGTSDKEAPKLLGTVTALSKQPppiygtypsagh 527
Cdd:PHA03247 2704 PPPTPEPAPHALVSATPLPPGPAAARQASPALPAA----------PAPPAVPAGPATPGGPARPARPP------------ 2761

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  528 hSTVCATSSLPRSAPGTLGWQRAPPTSGSTSQQIQQRITVPPSPTPGSALFPHGERTEPPLAVAVRPFIPDRGSRPQSPR 607
Cdd:PHA03247 2762 -TTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPP 2840

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688593789  608 KGPATMNSSSIYNMYL-----------QQPTAKNYSGSSRTAVKAVyGKPVLPGSTSPSPVPLYQQsstdETDREAAQEN 676
Cdd:PHA03247 2841 PPPGPPPPSLPLGGSVapggdvrrrppSRSPAAKPAAPARPPVRRL-ARPAVSRSTESFALPPDQP----ERPPQPQAPP 2915

                         330       340       350
                  ....*....|....*....|....*....|...
gi 688593789  677 HPLPPSSVENIPRPLSPTKLTPVAHSPLRYQSD 709
Cdd:PHA03247 2916 PPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTD 2948

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. 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 688593789 1052 YALWDYEAQSADELSFREGDALTIMSRRDDS-ETEWWWAKVNDKEGYVPRNLLG 1104
Cdd:cd12141     3 YAVYTFKARSPNELSVSANQRVRILEFSDLTgNKEWWLAEANGQKGYVPSNYIR 56

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). 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
                  ....*....|....*....|....*....|....*....|....*....
gi 688593789 1053 ALWDYEAQSADELSFREGDALTIMsRRDDSetEWWWAKVNDKEGYVPRN 1101
Cdd:cd11827     4 ALYAYDAQDTDELSFNEGDIIEIL-KEDPS--GWWTGRLRGKEGLFPGN 49

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. 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
                  ....*....|....*....|....*....|....*....|....*....
gi 688593789 1053 ALWDYEAQSADELSFREGDALTIMSrRDDSETEWWWAKVNDKEGYVPRN 1101
Cdd:cd11875     4 VLFDYEAENEDELTLREGDIVTILS-KDCEDKGWWKGELNGKRGVFPDN 51

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. 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 688593789 1053 ALWDYEAQSADELSFREGDALTIMSRRDDSETeWWWAKVNDKEGYVPRNLL 1103
Cdd:cd11866     4 GLWDCSGNEPDELSFKRGDLIYIISKEYDSFG-WWVGELNGKVGLVPKDYL 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. 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
                  ....*....|....*....|....*....|....*....|....*....
gi 688593789 1053 ALWDYEAQSADELSFREGDALTIMSrRDDSETEWWWAKVNDKEGYVPRN 1101
Cdd:cd12056     6 ALFHYEGTNEDELDFKEGEIILIIS-KDTGEPGWWKGELNGKEGVFPDN 53

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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
                  ....*....|....*....|....*....|....*....|....*..
gi 688593789 1053 ALWDYEAQSADELSFREGDALTIMSRRDDsetEWWWAKVNDKEGYVP 1099
Cdd:cd11809     4 AQFDYTGRSERELSFKKGDSLTLYRQVSD---DWWRGQLNGQDGLVP 47