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 47551329    4 MFLTVYLSNNDQHFSEVPITAETVCADVLQLCREPGEnSSCYLSEVWRGSERVVGENEKMMDLLLQWGQQRPEVRFFLRH 83
Cdd:cd17225    1 MFLTVYLSNNEQHFTEVPITPETTCRDVVELCKEPGE-TDCHLAEVWRGSERPVADNERMLDVLQQWGAQRNEVRFFLRH 79

                 .
gi 47551329   84 G 84
Cdd:cd17225   80 E 80

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  883 DPSQPNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQVCKFLVESGAAVFAMTYSDMqTAA 962
Cdd:COG0666  145 DVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGK-TAL 223

                 .
gi 47551329  963 D 963
Cdd:COG0666  224 D 224

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   320 PLPPDgqAPPQTPGSRVaavgPYIQSSTMPRGP------DRQDLPIKHNYPEftATAGHQDRSAQPGAGLHSGKASSKLA 393
Cdd:PHA03247 2554 PLPPA--APPAAPDRSV----PPPRPAPRPSEPavtsraRRPDAPPQSARPR--APVDDRGDPRGPAPPSPLPPDTHAPD 2625

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   394 NWSLANAKSGNnhvtsSLPRMVSQASKSQDNTDVQKRDPRVRPVSMFESTDLPAAALRKNQSSEDlvRDAQSAVKTIVKV 473
Cdd:PHA03247 2626 PPPPSPSPAAN-----EPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRR--RAARPTVGSLTSL 2698

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   474 PPPVPSKPKQANFPSGGLMGLGKNTGTYPGKSASPQPPAGPQTGTLPSKLEAP--------PAATVHPFSPDPPGAKDTG 545
Cdd:PHA03247 2699 ADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPggparparPPTTAGPPAPAPPAAPAAG 2778

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   546 GQMLLKPQTVTASSIYSMYTQQPSSGKATQQSIQGAlsraqtrtghfisvygkpvTSAGQPSQTPHPENPyldPPSVSET 625
Cdd:PHA03247 2779 PPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAP-------------------AAALPPAASPAGPLP---PPTSAQP 2836

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   626 LTDHSPAEPISETPETERIPRPLSPTKLLPfisnPYRHQSDLDLEALRKKLYNAPRPLKKRSSITEPEGPGGPNIQKlly 705
Cdd:PHA03247 2837 TAPPPPPGPPPPSLPLGGSVAPGGDVRRRP----PSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPP--- 2909

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 47551329   706 qkttlaametvSPPGEEEKETLAKPQGYDAETPEVPEETLPEFPIAPEVEAEDVPPPPPPHPAPKIDA 773
Cdd:PHA03247 2910 -----------QPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGA 2966

Ras-associating (RA) domain found in apoptosis-stimulating protein of p53 protein 2 (ASPP2); ASPP2, also termed Bcl2-binding protein (Bbp), or renal carcinoma antigen NY-REN-51, or tumor suppressor p53-binding protein 2 (53BP2), or p53-binding protein 2 (p53BP2), is a member of ASPP protein family and it functions as a tumor suppressor. ASPP2 binds to p53 and enhances p53-mediated transcription of proapoptotic genes. ASSP2 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. All p53 amino acids that are important for ASPP2 binding are mutated in human cancer, and ASPP2 is frequently downregulated in these tumor cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329    4 MFLTVYLSNNDQHFSEVPITAETVCADVLQLCREPGEnSSCYLSEVWRGSERVVGENEKMMDLLLQWGQQRPEVRFFLRH 83
Cdd:cd17225    1 MFLTVYLSNNEQHFTEVPITPETTCRDVVELCKEPGE-TDCHLAEVWRGSERPVADNERMLDVLQQWGAQRNEVRFFLRH 79

                 .
gi 47551329   84 G 84
Cdd:cd17225   80 E 80

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  883 DPSQPNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQVCKFLVESGAAVFAMTYSDMqTAA 962
Cdd:COG0666  145 DVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGK-TAL 223

                 .
gi 47551329  963 D 963
Cdd:COG0666  224 D 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 47551329     994 VYGLWDYEAAQEDECSFREGDCMSVIRREDEletDWWWV-CCGGAEGYVPRN 1044
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDD---GWWKGrLGRGKEGLFPSN 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 47551329    997 LWDYEAAQEDECSFREGDCMSVIRREDEletDWWWVCC-GGAEGYVP 1042
Cdd:pfam00018    3 LYDYTAQEPDELSFKKGDIIIVLEKSED---GWWKGRNkGGKEGLIP 46

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   168 KKLLQLRETLEQQEAQLKMVRALKGQVEQKRLSNGKLVEQVEQMNNLLHQKQKELVVAVAKVEELSKQLETLKSGQMDAm 247
Cdd:PRK03918  214 SELPELREELEKLEKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKA- 292

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 47551329   248 nsnhSSVAELDRLYRELQMRKNlNVEQN-AKLQQQRENLNKRNQEVANMDKRVSELPER---LWKKKAALQQKENL 319
Cdd:PRK03918  293 ----EEYIKLSEFYEEYLDELR-EIEKRlSRLEEEINGIEERIKELEEKEERLEELKKKlkeLEKRLEELEERHEL 363

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329    167 QKKLLQLRETLEQQEAQLKMVRALKGQVEQKRLSNGKLVEQVEQMNNL----LHQKQKELVVAVAKVEELSKQLETLKSG 242
Cdd:TIGR02168  287 QKELYALANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDElaeeLAELEEKLEELKEELESLEAELEELEAE 366

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 47551329    243 QMDAMNSNHSSVAELDRLYREL-QMRKNLNVeQNAKLQQQRENLNKRNQEVANMDKRVSELPERLWKKKAALQQKE 317
Cdd:TIGR02168  367 LEELESRLEELEEQLETLRSKVaQLELQIAS-LNNEIERLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAE 441

HOOK protein coiled-coil region; This family consists of several HOOK1, 2 and 3 proteins from different eukaryotic organizms. The different members of the human gene family are HOOK1, HOOK2 and HOOK3. Different domains have been identified in the three human HOOK proteins, and it was demonstrated that the highly conserved NH2-domain mediates attachment to microtubules, whereas this central coiled-coil motif mediates homodimerization and the more divergent C-terminal domains are involved in binding to specific organelles (organelle-binding domains). It has been demonstrated that endogenous HOOK3 binds to Golgi membranes, whereas both HOOK1 and HOOK2 are localized to discrete but unidentified cellular structures. In mice the Hook1 gene is predominantly expressed in the testis. Hook1 function is necessary for the correct positioning of microtubular structures within the haploid germ cell. Disruption of Hook1 function in mice causes abnormal sperm head shape and fragile attachment of the flagellum to the sperm head. This entry includes the central coiled-coiled domain and the divergent C-terminal domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329    171 LQLRETLEQQEAQLKMVRAlkGQVEQKRLSNGKLVEQVEQMNNLLHQKQKELVVAVAKVEELSKQLETLKSGQMDAMNSN 250
Cdd:pfam05622  278 AEIREKLIRLQHENKMLRL--GQEGSYRERLTELQQLLEDANRRKNELETQNRLANQRILELQQQVEELQKALQEQGSKA 355

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 47551329    251 HSSVAeldrLYRELQMRKNLNVEQNAKLQQQRENLNKRNQEV-ANMDKRVSELPERLWKKKAALQQKE 317
Cdd:pfam05622  356 EDSSL----LKQKLEEHLEKLHEAQSELQKKKEQIEELEPKQdSNLAQKIDELQEALRKKDEDMKAME 419

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329      3 PMFLTVYLSNNDQHFSEVPI------TAETVCADVLQ---LCREPgENSSCYLSEVWRGSERVVGENEKMMDLLLQWGQQ 73
Cdd:pfam00788    2 DGVLKVYTEDGKPGTTYKTIlvssstTAEEVIEALLEkfgLEDDP-RDYVLVEVLERGGGERRLPDDECPLQIQLQWPRD 80

                           90
                   ....*....|
gi 47551329     74 RPEVRFFLRH 83
Cdd:pfam00788   81 ASDSRFLLRK 90

calmodulin binding domain found in unconventional myosin-VI and similar proteins; Myosins, which are actin-based motor molecules with ATPase activity, include unconventional myosins that serve in intracellular movements. Myosin-VI, also called unconventional myosin-6 (MYO6), is a reverse-direction motor protein that moves towards the minus-end of actin filaments. It is required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Myosin-VI appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. It modulates RNA polymerase II-dependent transcription. As part of the DISP (DOCK7-Induced Septin disPlacement) complex, Myosin-VI may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. Myosin-VI is encoded by gene MYO6, the human homolog of the gene responsible for deafness in Snell's waltzer mice. It is mutated in autosomal dominant non-syndromic hearing loss. This family also includes Drosophila melanogaster unconventional myosin VI Jaguar (Jar; also called myosin heavy chain 95F (Mhc95F), or 95F MHC), which is a motor protein necessary for the morphogenesis of epithelial tissues during Drosophila development. Jar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. It contributes to synaptic transmission and development at the Drosophila neuromuscular junction. Together with CLIP-190 (CAP-Gly domain-containing/cytoplasmic linker protein 190), Jar may coordinate the interaction between the actin and microtubule cytoskeleton. Jar may link endocytic vesicles to microtubules and possibly be involved in transport in the early embryo and in the dynamic process of dorsal closure; its function is believed to change during the life cycle. This model corresponds to the calmodulin (CaM) binding domain (CBD), which consists of three subdomains: a unique insert (Insert 2 or Ins2), an IQ motif, and a proximal tail domain (PTD, also known as lever arm extension or LAE).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  203 KLVEQVEQMNNLLHQKQKELVVAVAKVEELSKQLETL-KSGQMDAMNSNhssvAELDRLYRELQMRKNlnvEQNAKLQQQ 281
Cdd:cd21759   76 ALEKQLKEMEEIASQLKKDKDKWTKQVKELKKEIDALiKKIKTNDMITR----KEIDKLYNALVKKVD---KQLAELQKK 148

Ras-associating (RA) domain found in apoptosis-stimulating protein of p53 protein 2 (ASPP2); ASPP2, also termed Bcl2-binding protein (Bbp), or renal carcinoma antigen NY-REN-51, or tumor suppressor p53-binding protein 2 (53BP2), or p53-binding protein 2 (p53BP2), is a member of ASPP protein family and it functions as a tumor suppressor. ASPP2 binds to p53 and enhances p53-mediated transcription of proapoptotic genes. ASSP2 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. All p53 amino acids that are important for ASPP2 binding are mutated in human cancer, and ASPP2 is frequently downregulated in these tumor cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329    4 MFLTVYLSNNDQHFSEVPITAETVCADVLQLCREPGEnSSCYLSEVWRGSERVVGENEKMMDLLLQWGQQRPEVRFFLRH 83
Cdd:cd17225    1 MFLTVYLSNNEQHFTEVPITPETTCRDVVELCKEPGE-TDCHLAEVWRGSERPVADNERMLDVLQQWGAQRNEVRFFLRH 79

                 .
gi 47551329   84 G 84
Cdd:cd17225   80 E 80

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 47551329    2 MPMFLTVYLSNNDQHFSEVPITAETVCADVLQLCREPGEnSSCYLSEVWRGSERVVGENEKMMDLLLQWGQQRPEVRFFL 81
Cdd:cd17224    1 MPMILTVFLSNNEQILTEVPITPETTCRDVVEFCKEPGE-TGCHLAEVWRGNERPIPYDHMMYEHLQKWGPRREEVKFFL 79

                 ..
gi 47551329   82 RH 83
Cdd:cd17224   80 RH 81

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 47551329  992 GVVYGLWDYEAAQEDECSFREGDCMSVIRREDELETDWWWVCCGGAEGYVPRNLLGL 1048
Cdd:cd11807    1 GVVYALFDYEAENGDELSFREGDELTVLRKGDDDETEWWWARLNDKEGYVPRNLLGL 57

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  883 DPSQPNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQVCKFLVESGAAVFAMTYSDMqTAA 962
Cdd:COG0666  145 DVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGK-TAL 223

                 .
gi 47551329  963 D 963
Cdd:COG0666  224 D 224

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  860 ALLLDSSLEGEFDLVQRVIYEVEDPSQPNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQV 939
Cdd:COG0666   89 TLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEI 168

                         90
                 ....*....|.
gi 47551329  940 CKFLVESGAAV 950
Cdd:COG0666  169 VKLLLEAGADV 179

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  857 NPLALLLDSSLEGEFDLVQRVIYEVEDPSQPNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNN 936
Cdd:COG0666   53 LGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGN 132

                         90
                 ....*....|....
gi 47551329  937 VQVCKFLVESGAAV 950
Cdd:COG0666  133 LEIVKLLLEAGADV 146

Ankyrin repeats (many copies);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 47551329    893 TALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQVCKFLV 944
Cdd:pfam13637    3 TALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54

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 47551329     994 VYGLWDYEAAQEDECSFREGDCMSVIRREDEletDWWWV-CCGGAEGYVPRN 1044
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDD---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 47551329  993 VVYGLWDYEAAQEDECSFREGDCMSVIrreDELETDWWWVCCGGAEGYVPRN 1044
Cdd:cd11772    1 VFRALYDYEAQHPDELSFEEGDLLYIS---DKSDPNWWKATCGGKTGLIPSN 49

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329    5 FLTVYLS--NNDQHFSEVPITAETVCADVLQLCREP---GENSSCY-LSEVW--RGSERVVGENEKMMDLLLQWGQQRPE 76
Cdd:cd17043    1 VLKVYDDdlAPGSAYKSILVSSTTTAREVVQLLLEKyglEEDPEDYsLYEVSekQETERVLHDDECPLLIQLEWGPQGTE 80

                 ....*..
gi 47551329   77 VRFFLRH 83
Cdd:cd17043   81 FRFVLKR 87

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general 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 site. 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 47551329  996 GLWDYEAAQEDECSFREGDCMSVIRREDeletDWWWVC----CGG--AEGYVPRNLL 1046
Cdd:cd11847    4 ALWDFKARGDEELSFQAGDQFRIAERSG----DWWTALkldrAGGvvAQGFVPNNYL 56

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  167 QKKLLQLRETLEQQEAQLkmvRALKGQVEQKRLSNGKLVEQVEQMNNLLHQKQKELVVAVAKVEELSKQLETLKSGQMDA 246
Cdd:COG4372   44 QEELEQLREELEQAREEL---EQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEEL 120

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 47551329  247 MNSNHSSVAELDRLYRELQMRKNLNVEQNAKLQQQRENLNKRNQEVANMDKRVSELP-ERLWKKKAALQQKEN 318
Cdd:COG4372  121 QKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSeAEAEQALDELLKEAN 193

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. 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 47551329  997 LWDYEAAQEDECSFREGDcmsVIRREDELETDWWWVCCGGAEGYVP 1042
Cdd:cd11828    5 LWDHVTMDPEELGFKAGD---VIEVLDMSDKDWWWGSIRDEEGWFP 47

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 47551329   887 PNDEGITALHNAVCAGHTEIVKFLVQYGVNVNAADSDGWTPLHCAASCNNVQVCKFLVESGAAVFAM 953
Cdd:PHA03100  188 KDVYGFTPLHYAVYNNNPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPSIKTI 254

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
                 ....*....|....*....|....*....|....*....|....*...
gi 47551329  999 DYEAAQEDECSFREGDCMSVIRREDEletDWWWVCCGGAEGYVPRNLL 1046
Cdd:cd11856    7 DYEAQGDDEISLQEGEVVEVLEKNDS---GWWYVRKGDKEGWVPASYL 51

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 47551329  994 VYGLWDYEAAQEDECSFREGDCMSVIrreDELETDWWWVCCGGAE-GYVPRN 1044
Cdd:cd11774    2 AKALYDYDKQTEEELSFNEGDTLDVY---DDSDSDWILVGFNGTQfGFVPAN 50

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   320 PLPPDgqAPPQTPGSRVaavgPYIQSSTMPRGP------DRQDLPIKHNYPEftATAGHQDRSAQPGAGLHSGKASSKLA 393
Cdd:PHA03247 2554 PLPPA--APPAAPDRSV----PPPRPAPRPSEPavtsraRRPDAPPQSARPR--APVDDRGDPRGPAPPSPLPPDTHAPD 2625

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   394 NWSLANAKSGNnhvtsSLPRMVSQASKSQDNTDVQKRDPRVRPVSMFESTDLPAAALRKNQSSEDlvRDAQSAVKTIVKV 473
Cdd:PHA03247 2626 PPPPSPSPAAN-----EPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRR--RAARPTVGSLTSL 2698

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   474 PPPVPSKPKQANFPSGGLMGLGKNTGTYPGKSASPQPPAGPQTGTLPSKLEAP--------PAATVHPFSPDPPGAKDTG 545
Cdd:PHA03247 2699 ADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPggparparPPTTAGPPAPAPPAAPAAG 2778

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   546 GQMLLKPQTVTASSIYSMYTQQPSSGKATQQSIQGAlsraqtrtghfisvygkpvTSAGQPSQTPHPENPyldPPSVSET 625
Cdd:PHA03247 2779 PPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAP-------------------AAALPPAASPAGPLP---PPTSAQP 2836

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329   626 LTDHSPAEPISETPETERIPRPLSPTKLLPfisnPYRHQSDLDLEALRKKLYNAPRPLKKRSSITEPEGPGGPNIQKlly 705
Cdd:PHA03247 2837 TAPPPPPGPPPPSLPLGGSVAPGGDVRRRP----PSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPP--- 2909

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 47551329   706 qkttlaametvSPPGEEEKETLAKPQGYDAETPEVPEETLPEFPIAPEVEAEDVPPPPPPHPAPKIDA 773
Cdd:PHA03247 2910 -----------QPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGA 2966

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It 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. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein 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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 47551329  996 GLWDYEAAQEDECSFREGDCMSVIRREDeletDWWWVCCGGAEGYVPRNLL 1046
Cdd:cd11947    4 GKFDFTASGEDELSFKKGDVLKILSSDD----IWFKAELNGEEGYVPKNFV 50

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. 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 47551329  994 VYGLWDYEAAQEDECSFREGDCMSVIRREDEletDWWWVCCGGAEGYVPRN 1044
Cdd:cd11826    2 VVALYDYTADKDDELSFQEGDIIYVTKKNDD---GWYEGVLNGVTGLFPGN 49

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 47551329    890 EGITALHNAVC-AGHTEIVKFLVQYGVNVNAAD 921
Cdd:pfam00023    1 DGNTPLHLAAGrRGNLEIVKLLLSKGADVNARD 33

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  167 QKKLLQLRETLEQQEAQLKMVRALKGQVEQK-------RLSNGklVEQVEQMNNLLHQKQKELVVAVAKVEELSKQLETL 239
Cdd:COG4913  294 EAELEELRAELARLEAELERLEARLDALREEldeleaqIRGNG--GDRLEQLEREIERLERELEERERRRARLEALLAAL 371

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47551329  240 K---SGQMDAMNSNHSSVAELDRLYRELQMRKNLNV-EQNAKLQQQRENLNKRNQEVANMDKRVSELPERLWKKKAALqq 315
Cdd:COG4913  372 GlplPASAEEFAALRAEAAALLEALEEELEALEEALaEAEAALRDLRRELRELEAEIASLERRKSNIPARLLALRDAL-- 449

                 ....*....
gi 47551329  316 KENLPLPPD 324
Cdd:COG4913  450 AEALGLDEA 458