Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24497612 256 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 317
Cdd:cd11936   1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction; Subgroup of the catalytic domain of a functionally diverse set of proteins, most of which are phosphatases. The conserved catalytic core of this domain contains a His residue which is phosphorylated in the reaction. This subgroup contains cofactor-dependent and cofactor-independent phosphoglycerate mutases (dPGM, and BPGM respectively), fructose-2,6-bisphosphatase (F26BP)ase, Sts-1, SixA, and related proteins. Functions include roles in metabolism, signaling, or regulation, for example, F26BPase affects glycolysis and gluconeogenesis through controlling the concentration of F26BP; BPGM controls the concentration of 2,3-BPG (the main allosteric effector of hemoglobin in human blood cells); human Sts-1 is a T-cell regulator; Escherichia coli Six A participates in the ArcB-dependent His-to-Asp phosphorelay signaling system. Deficiency and mutation in many of the human members result in disease, for example erythrocyte BPGM deficiency is a disease associated with a decrease in the concentration of 2,3-BPG.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 386 LFVCRHGERMdvvfgkywlsqcFDAKGRYIRtnlnmphslpqrsggfrdyEKDAPITVFGCMQARLVGEALLESNTIIDH 465
Cdd:cd07067   2 LYLVRHGESE------------WNAEGRFQG-------------------WTDVPLTEKGREQARALGKRLKELGIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 466 VYCSPSLRCVQTAHNILKGLqqeNHLKIRVEPGLFEwtkwvagstlpawippselaaanlsvdttyrphipisklvvses 545
Cdd:cd07067  51 IYSSPLKRAIQTAEIILEEL---PGLPVEVDPRLRE-------------------------------------------- 83

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 24497612 546 ydtyiSRSFQVTKEIISECKSKgnNILIVAHASSLEACTCQLQGLSPQNSKDF 598
Cdd:cd07067  84 -----ARVLPALEELIAPHDGK--NVLIVSHGGVLRALLAYLLGLSDEDILRL 129

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24497612 256 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 317
Cdd:cd11936   1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction; Subgroup of the catalytic domain of a functionally diverse set of proteins, most of which are phosphatases. The conserved catalytic core of this domain contains a His residue which is phosphorylated in the reaction. This subgroup contains cofactor-dependent and cofactor-independent phosphoglycerate mutases (dPGM, and BPGM respectively), fructose-2,6-bisphosphatase (F26BP)ase, Sts-1, SixA, and related proteins. Functions include roles in metabolism, signaling, or regulation, for example, F26BPase affects glycolysis and gluconeogenesis through controlling the concentration of F26BP; BPGM controls the concentration of 2,3-BPG (the main allosteric effector of hemoglobin in human blood cells); human Sts-1 is a T-cell regulator; Escherichia coli Six A participates in the ArcB-dependent His-to-Asp phosphorelay signaling system. Deficiency and mutation in many of the human members result in disease, for example erythrocyte BPGM deficiency is a disease associated with a decrease in the concentration of 2,3-BPG.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 386 LFVCRHGERMdvvfgkywlsqcFDAKGRYIRtnlnmphslpqrsggfrdyEKDAPITVFGCMQARLVGEALLESNTIIDH 465
Cdd:cd07067   2 LYLVRHGESE------------WNAEGRFQG-------------------WTDVPLTEKGREQARALGKRLKELGIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 466 VYCSPSLRCVQTAHNILKGLqqeNHLKIRVEPGLFEwtkwvagstlpawippselaaanlsvdttyrphipisklvvses 545
Cdd:cd07067  51 IYSSPLKRAIQTAEIILEEL---PGLPVEVDPRLRE-------------------------------------------- 83

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 24497612 546 ydtyiSRSFQVTKEIISECKSKgnNILIVAHASSLEACTCQLQGLSPQNSKDF 598
Cdd:cd07067  84 -----ARVLPALEELIAPHDGK--NVLIVSHGGVLRALLAYLLGLSDEDILRL 129

Broad specificity phosphatase PhoE [Carbohydrate transport and metabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 438 DAPITVFGCMQARLVGEALLESNtiIDHVYCSPSLRCVQTAHNILKGLqqenHLKIRVEPGLFEWtkwvagsTLPAW--I 515
Cdd:COG0406  25 DVPLTELGRAQARALAERLADIP--FDAVYSSPLQRARQTAEALAEAL----GLPVEVDPRLREI-------DFGDWegL 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 516 PPSELAAANLSVDTTYRPHIPISKLVVSESYDTYISRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQGLSPQNS 595
Cdd:COG0406  92 TFAELEARYPEALAAWLADPAEFRPPGGESLADVQARVRAALEELLA--RHPGGTVLVVTHGGVIRALLAHLLGLPLEAF 169

                ...
gi 24497612 596 KDF 598
Cdd:COG0406 170 WRL 172

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 24497612   261 VIYPYTPQNDDELELVPGDFIFMSPMeqtsTSEGWIYGTslTTGCSGLLPENYIT 315
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEE----SEDGWWEGI--NTGRTGLVPANYVE 49

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 24497612    257 ETLQVIYPYTPQNDDELELVPGDFIFMspMEQtsTSEGWIYGTsLTTGCSGLLPENYIT 315
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITV--LEK--SDDGWWKGR-LGRGKEGLFPSNYVE 56

phosphoglycerate mutase like-protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612  438 DAPITVFGCMQARLVGEALLESNTIIDHVYCSPSLRCVQTAHNILKGLQQ------------ENHLKIRvePGL--FEWT 503
Cdd:PTZ00123  12 DVPLSEKGVQEAREAGKLLKEKGFRFDVVYTSVLKRAIKTAWIVLEELGQlhvpvikswrlnERHYGAL--QGLnkSETA 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612  504 KWVAGSTLPAW-----IPPSELAAANL---SVDTTYRpHIPISKLVVSESYDTYISRSFQVTKEIISECKSKGNNILIVA 575
Cdd:PTZ00123  90 EKHGEEQVKIWrrsydIPPPPLEKSDErypGNDPVYK-DIPKDALPNTECLKDTVERVLPYWEDHIAPDILAGKKVLVAA 168

                        170
                 ....*....|....*...
gi 24497612  576 HASSLEACTCQLQGLSPQ 593
Cdd:PTZ00123 169 HGNSLRALVKYLDKMSEE 186

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24497612 256 HETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 317
Cdd:cd11936   1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 24497612 257 ETLQVIYPYTPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENY 313
Cdd:cd11937   1 QTLRALFQYKPQNIDELMLSPGDYIFVDPTQQSEASEGWVIGISHRTGCRGFLPENY 57

Histidine phosphatase domain found in phosphoglycerate mutases and related proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction; Subgroup of the catalytic domain of a functionally diverse set of proteins, most of which are phosphatases. The conserved catalytic core of this domain contains a His residue which is phosphorylated in the reaction. This subgroup contains cofactor-dependent and cofactor-independent phosphoglycerate mutases (dPGM, and BPGM respectively), fructose-2,6-bisphosphatase (F26BP)ase, Sts-1, SixA, and related proteins. Functions include roles in metabolism, signaling, or regulation, for example, F26BPase affects glycolysis and gluconeogenesis through controlling the concentration of F26BP; BPGM controls the concentration of 2,3-BPG (the main allosteric effector of hemoglobin in human blood cells); human Sts-1 is a T-cell regulator; Escherichia coli Six A participates in the ArcB-dependent His-to-Asp phosphorelay signaling system. Deficiency and mutation in many of the human members result in disease, for example erythrocyte BPGM deficiency is a disease associated with a decrease in the concentration of 2,3-BPG.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 386 LFVCRHGERMdvvfgkywlsqcFDAKGRYIRtnlnmphslpqrsggfrdyEKDAPITVFGCMQARLVGEALLESNTIIDH 465
Cdd:cd07067   2 LYLVRHGESE------------WNAEGRFQG-------------------WTDVPLTEKGREQARALGKRLKELGIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 466 VYCSPSLRCVQTAHNILKGLqqeNHLKIRVEPGLFEwtkwvagstlpawippselaaanlsvdttyrphipisklvvses 545
Cdd:cd07067  51 IYSSPLKRAIQTAEIILEEL---PGLPVEVDPRLRE-------------------------------------------- 83

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 24497612 546 ydtyiSRSFQVTKEIISECKSKgnNILIVAHASSLEACTCQLQGLSPQNSKDF 598
Cdd:cd07067  84 -----ARVLPALEELIAPHDGK--NVLIVSHGGVLRALLAYLLGLSDEDILRL 129

Histidine phosphatase domain found in a functionally diverse set of proteins, mostly phosphatases; contains a His residue which is phosphorylated during the reaction; Catalytic domain of a functionally diverse set of proteins, most of which are phosphatases. The conserved catalytic core of this domain contains a His residue which is phosphorylated in the reaction. This set of proteins includes cofactor-dependent and cofactor-independent phosphoglycerate mutases (dPGM, and BPGM respectively), fructose-2,6-bisphosphatase (F26BP)ase, Sts-1, SixA, histidine acid phosphatases, phytases, and related proteins. Functions include roles in metabolism, signaling, or regulation, for example F26BPase affects glycolysis and gluconeogenesis through controlling the concentration of F26BP; BPGM controls the concentration of 2,3-BPG (the main allosteric effector of hemoglobin in human blood cells); human Sts-1 is a T-cell regulator; Escherichia coli Six A participates in the ArcB-dependent His-to-Asp phosphorelay signaling system; phytases scavenge phosphate from extracellular sources. Deficiency and mutation in many of the human members result in disease, for example erythrocyte BPGM deficiency is a disease associated with a decrease in the concentration of 2,3-BPG. Clinical applications include the use of prostatic acid phosphatase (PAP) as a serum marker for prostate cancer. Agricultural applications include the addition of phytases to animal feed.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 386 LFVCRHGERMDVVFGKYWLsqcfdakgryirtnlnmphslpqrsggfrdyEKDAPITVFGCMQARLVGEALLESNTIIDH 465
Cdd:cd07040   2 LYLVRHGEREPNAEGRFTG-------------------------------WGDGPLTEKGRQQARELGKALRERYIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 466 VYCSPSLRCVQTAHNILKGLQQenHLKIRVEPGlfewtkwvagstlpawippselaaanlsvdttyrphipisklvvses 545
Cdd:cd07040  51 IYSSPLKRAIQTAEIILEGLFE--GLPVEVDPR----------------------------------------------- 81

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24497612 546 ydtyiSRSFQVTKEIISECKSKGNNILIVAHASSLEACTCQLQGLSPQNSKDFvqmvrKIPYLGFCSCEELGETGIWQL 624
Cdd:cd07040  82 -----ARVLNALLELLARHLLDGKNVLIVSHGGTIRALLAALLGLSDEEILSL-----NLPNGSILVLELDECGGKYVR 150

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. 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 24497612 260 QVIYPYTPQNDDELELVPGDFIFMspMEQtsTSEGWIYGTSLTTGCSGLLPENYITK 316
Cdd:cd11780   3 RALYSYTPQNEDELELREGDIVYV--MEK--CDDGWFVGTSERTGLFGTFPGNYVAR 55

Phosphoglycerate mutase family; Phosphoglycerate mutase (PGAM) and bisphosphoglycerate mutase (BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate... Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase activity). In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612    438 DAPITVFGCMQARLVGEALLESNTI-IDHVYCSPSLRCVQTAHNILKGLQQeNHLKIRvEPGLFEwtkwvaGSTLPAWI- 515
Cdd:smart00855  23 DVPLTELGRAQAEALGRLLASLLLPrFDVVYSSPLKRARQTAEALAIALGL-PGLRER-DFGAWE------GLTWDEIAa 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24497612    516 -PPSELAAANLSVDTTYRPHIPisklvVSESYDTYISRSFQVTKEIISECKSKGNNILIVAHASSL 580
Cdd:smart00855  95 kYPEEYLAAWRDPYDPAPPAPP-----GGESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

UBA1 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 24497612  38 GSALDVLLSMGFPRARAQKALASTGGRSVQAACDWLFSHVGDPFLD 83
Cdd:cd14385   2 AEALAQLLGMGFPEVRCKKALLATGNSDAEAAMNWLFEHMDDPDID 47

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. 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 24497612 258 TLQVIYPYTPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSLTTGCSGLLPENYI 314
Cdd:cd11916   3 SYQALYSYAPQNDDELELRDGDIV--DVMEK--CDDGWFVGTSRRTKQFGTFPGNYV 55

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide 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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612 258 TLQVIYPYTPQNDDELELVPGDFI----FMSPMEQtstSEGWIYGTSLTTGCSGLLPENY 313
Cdd:cd11790   4 KVRATHDYTAEDTDELTFEKGDVIlvipFDDPEEQ---DEGWLMGVKESTGCRGVFPENF 60

alpha-ribazole phosphatase; Members of this protein family include the known CobC protein of Salmonella and Eschichia coli species, and homologous proteins found in cobalamin biosynthesis regions in other bacteria. This protein is alpha-ribazole phosphatase (EC 3.1.3.73) and, like many phosphatases, can be closely related in sequence to other phosphatases with different functions. Close homologs excluded from this model include proteins with duplications, so this model is built in -g mode to suppress hits to those proteins. [Biosynthesis of cofactors, prosthetic groups, and carriers, Heme, porphyrin, and cobalamin]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612   438 DAPITVFGCMQARLVGEALleSNTIIDHVYCSPSLRCVQTAHNILKGLqqenHLKIRVEP-------GLFEWTKWvagST 510
Cdd:TIGR03162  21 DVPLAESGEEQAAALREKL--ADVPFDAVYSSPLSRCRELAEILAERR----GLPIIKDDrlremdfGDWEGRSW---DE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612   511 LPAWIPpsELAA-ANLSVdtTYRPHipisklvVSESYDTYISRSFQVTKEIISEckSKGNNILIVAHASSLEACTCQLQG 589
Cdd:TIGR03162  92 IPEAYP--ELDAwAADWQ--HARPP-------GGESFADFYQRVSEFLEELLKA--HEGDNVLIVTHGGVIRALLAHLLG 158

                  ....
gi 24497612   590 LSPQ 593
Cdd:TIGR03162 159 LPLE 162

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. 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 24497612 262 IYPYTPQNDDELELVPGDFIFmspmEQTSTSEGWIYGTSLTTGCSGLLPENYITK 316
Cdd:cd11789   5 MYDYAAADDDEVSFQEGDVII----NVEIIDDGWMEGTVQRTGQSGMLPANYVEL 55

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, 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        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24497612 258 TLQVIYPYTPQNDDELELVPGDFIF-MSPMEqtstsEGWIYGTSLTTGCSGLLPENYI 314
Cdd:cd11935   2 TYRAMYDYSAQDEDEVSFRDGDYIVnVQPID-----EGWMYGTVQRTGRTGMLPANYI 54

UBA domain found in plant AAA-type ATPase-like proteins; This family includes some uncharacterized AAA-type ATPase-like proteins found in plant. The AAA+ ATPases function as molecular chaperons, ATPase subunits of proteases, helicases, or nucleic-acid stimulated ATPases. Members in this family contains an N-terminal ubiquitin-association (UBA) domain, a AAA-type ATPase domain and a C-terminal MgsA AAA+ ATPase domain. This model corresponds to the UBA domain which show a high level of sequence similarity with mammalian ubiquitin-associated and SH3 domain-containing protein A (UBS3A).

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 24497612  41 LDVLLSMGFPRARAQKALASTGGRSVQAACDWLFSH 76
Cdd:cd14389   1 MEQLVDMGFSSDLAAEALAATGGKSTQKATEWILSH 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 5 (UBP5); UBP5, also called deubiquitinating enzyme 5, Isopeptidase T (IsoT), ubiquitin thioesterase 5, or ubiquitin-specific-processing protease 5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. ZnF domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin. This model corresponds to the UBA2 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 24497612  40 ALDVLLSMGFPRARAQKALASTGGrSVQAACDWLFSHVGD 79
Cdd:cd14386   5 AVAMLVSMGFTRDQAIKALKATDN-NVERAADWIFSHPDE 43

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. 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 24497612 260 QVIYPYTPQNDDELELVPGDFIFMSpmEQTSTSEGWIYGTslTTGCSGLLPENYITK 316
Cdd:cd11836   3 RALYAFEARNPDEISFQPGDIIQVD--ESQVAEPGWLAGE--LKGKTGWFPANYVEK 55

Second Src Homology 3 domain (SH3B) 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 second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A 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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24497612 260 QVIYPYTPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTslTTGCSGLLPENYI 314
Cdd:cd12054   4 KVLFEYVPQNEDELELKVGDIIDIN----EEVEEGWWSGT--LNGKSGLFPSNFV 52

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins 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, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24497612 260 QVIYPYTPQNDDELELVPGDFIFMSPMEqtstSEGWIYGTsLTTGCSGLLPENY 313
Cdd:cd00174   3 RALYDYEAQDDDELSFKKGDIITVLEKD----DDGWWEGE-LNGGREGLFPANY 51

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. 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 24497612 260 QVIYPYTPQNDDELELVPGDFIFMSPMEQtstsEGWIYGTSLTTGCSGLLPENYI 314
Cdd:cd11785   3 RVIVPYPPQSEAELELKEGDIVFVHKKRE----DGWFKGTLQRTGKTGLFPGSFV 53

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, 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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24497612 260 QVIYPYTPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSLTTGCSGLLPENYI 314
Cdd:cd11934   6 RAVYDYNAADEDEVSFQDGDTI----VNVQQIDDGWMYGTVERTGDTGMLPANYV 56

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. 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 24497612 261 VIYPYTPQNDDELELVPGDFIFMSPMEQtstsEGWIYGTSLTTGCSGLLPENYIT 315
Cdd:cd11784   4 ALHSYSAHRPEELELQKGEGVRVLGKFQ----EGWLRGLSLVTGRVGIFPSNYVS 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24497612 260 QVIYPYTPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTSLTTGCSGLLPENY 313
Cdd:cd11793   3 QCVHAYTAQQPDELTLEEGDVVNVL----RKMPDGWYEGERLRDGERGWFPSSY 52

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 24497612    257 ETLQVIYPYTPQNDDELELVPGDFIFMspMEQtsTSEGWIYGTsLTTGCSGLLPENYIT 315
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITV--LEK--SDDGWWKGR-LGRGKEGLFPSNYVE 56

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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24497612 261 VIYPYTPQNDDELELVPGDFIFMspMEQTSTSEGWIYGTslTTGCSGLLPENYIT 315
Cdd:cd11875   4 VLFDYEAENEDELTLREGDIVTI--LSKDCEDKGWWKGE--LNGKRGVFPDNFVE 54

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second 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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24497612 258 TLQVIYPYTPQNDDELELVPGDFIfmsPMEQTSTSEGWIYGTslTTGCSGLLPENY 313
Cdd:cd11778   1 YVEALYDYEAQGDDEISIRVGDRI---AVIRGDDGSGWTYGE--INGVKGLFPTSY 51

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. 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 24497612 258 TLQVIYPYTPQNDDELELVPGDFIFMSpmEQTSTSEGWIYGTslTTGCSGLLPENYITK 316
Cdd:cd11988   3 NYRALYPFEARNHDEMSFNAGDIIQVD--EKTVGEPGWLYGS--FQGNFGWFPCNYVEK 57

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 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        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24497612 260 QVIYPYTPQNDDELELVPGDFIFMspMEQTSTSEGWIYGTslTTGCSGLLPENYI 314
Cdd:cd12142   3 RVLFDYNPVAPDELALKKGDVIEV--ISKETEDEGWWEGE--LNGRRGFFPDNFV 53

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 24497612    39 SALDVLLSMGFPRARAQKALASTGGrSVQAACDWL 73
Cdd:pfam00627   4 EAIQRLVEMGFDREQVREALRATGN-NVERAAEYL 37

phosphoglycerate mutase like-protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612  438 DAPITVFGCMQARLVGEALLESNTIIDHVYCSPSLRCVQTAHNILKGLQQ------------ENHLKIRvePGL--FEWT 503
Cdd:PTZ00123  12 DVPLSEKGVQEAREAGKLLKEKGFRFDVVYTSVLKRAIKTAWIVLEELGQlhvpvikswrlnERHYGAL--QGLnkSETA 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24497612  504 KWVAGSTLPAW-----IPPSELAAANL---SVDTTYRpHIPISKLVVSESYDTYISRSFQVTKEIISECKSKGNNILIVA 575
Cdd:PTZ00123  90 EKHGEEQVKIWrrsydIPPPPLEKSDErypGNDPVYK-DIPKDALPNTECLKDTVERVLPYWEDHIAPDILAGKKVLVAA 168

                        170
                 ....*....|....*...
gi 24497612  576 HASSLEACTCQLQGLSPQ 593
Cdd:PTZ00123 169 HGNSLRALVKYLDKMSEE 186

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. 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 24497612 260 QVIYPYTPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSlTTGCSGLLPENYI 314
Cdd:cd11962   3 VVLYDYEKDEDNEIELVEGEIV----TNIEMVDEDWWMGTN-SKGESGLFPSNYV 52

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. 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 24497612 260 QVIYPYTPQNDDELELVPGDFIFMspMEqtSTSEGWIYGTSLttGCSGLLPENYITK 316
Cdd:cd11766   3 VVKFNYEAQREDELSLRKGDRVLV--LE--KSSDGWWRGECN--GQVGWFPSNYVTE 53