Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   412 DPPLSSCGIFQSRIAGDALldSGIRISSVFASPALRCVQTAKLILEELKLEkkikIRVEPGIFEWT--KWEaGKTTPTLM 489
Cdd:pfam00300  22 DSPLTELGREQAEALAERL--AGEPFDAIYSSPLKRARQTAEIIAEALGLP----VEIDPRLREIDfgDWE-GLTFEEIA 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   490 S-LEELKEANFNIDTDYRPAfplsalmPAESYQEYMDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRE 568
Cdd:pfam00300  95 ErYPEEYDAWLADPADYRPP-------GGESLADVRARVRAALEELAARHPGKT--VLVVSHGGVIRALLAHLLGLPLEA 165

                  ....*.
gi 49640014   569 CGDFAQ 574
Cdd:pfam00300 166 LRRFPL 171

RNA 2',3'-cyclic phosphodiesterase (2'-5' RNA ligase) [Translation, ribosomal structure and biogenesis];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  76 LFLC--PTGPLLEKLQEFWRESKRQCAKNRAHEVFPHVTLCDFFTCEDQKVECLYEALKRAGDRL---------LGSFPT 144
Cdd:COG1514   3 LFIAlpPPEELREALAALRARLKAAPGGRWVRPENLHLTLAFLGEVDEERLEALAEALARAAAGAppfelrldgLGAFPR 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014 145 AVPLALhssisYLGffVSGSPAdvirefAMTFATE-ASLLADCSVKPCTKQL--HLTLAHKfyPHHQRTLEQLARAIPLG 221
Cdd:COG1514  83 PRPRVL-----WLG--VEPSPE------LLALHRRlRAALARAGLPPERRPFvpHVTLARG--KRPAPPLAPALAELRDF 147

                       170       180
                ....*....|....*....|....*...
gi 49640014 222 HSCQWTA---ALYSRDMRF--VHYQTLR 244
Cdd:COG1514 148 EFPEFTVdefVLYESELTPdgPRYEVLA 175

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   412 DPPLSSCGIFQSRIAGDALldSGIRISSVFASPALRCVQTAKLILEELKLEkkikIRVEPGIFEWT--KWEaGKTTPTLM 489
Cdd:pfam00300  22 DSPLTELGREQAEALAERL--AGEPFDAIYSSPLKRARQTAEIIAEALGLP----VEIDPRLREIDfgDWE-GLTFEEIA 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   490 S-LEELKEANFNIDTDYRPAfplsalmPAESYQEYMDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRE 568
Cdd:pfam00300  95 ErYPEEYDAWLADPADYRPP-------GGESLADVRARVRAALEELAARHPGKT--VLVVSHGGVIRALLAHLLGLPLEA 165

                  ....*.
gi 49640014   569 CGDFAQ 574
Cdd:pfam00300 166 LRRFPL 171

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 49640014 360 VLVVRHGERVDQIFGkawlqqcstpdgkyyrpdlnfpcslprRSRGIKDfendPPLSSCGIFQSRIAGDALLDSGIRISS 439
Cdd:cd07067   2 LYLVRHGESEWNAEG---------------------------RFQGWTD----VPLTEKGREQARALGKRLKELGIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014 440 VFASPALRCVQTAKLILEELkleKKIKIRVEPGIFEwtkweagkttptlmsleelkeanfnidtdyrpafplsalmpaes 519
Cdd:cd07067  51 IYSSPLKRAIQTAEIILEEL---PGLPVEVDPRLRE-------------------------------------------- 83

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 49640014 520 yqeymDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRECGDF 572
Cdd:cd07067  84 -----ARVLPALEELIAPHDGKN--VLIVSHGGVLRALLAYLLGLSDEDILRL 129

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 49640014    411 NDPPLSSCGIFQSRIAGDALLD-SGIRISSVFASPALRCVQTAKLILEELKLEKKIKIrvEPGIFEwtkweaGKTTPTLM 489
Cdd:smart00855  22 TDVPLTELGRAQAEALGRLLASlLLPRFDVVYSSPLKRARQTAEALAIALGLPGLRER--DFGAWE------GLTWDEIA 93

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 49640014    490 slEELKEANFNIDTDYRPAFPlSALMPAESYQEYMDRCTASMVQIVNTCPQDTGVILIVSHGSTL 554
Cdd:smart00855  94 --AKYPEEYLAAWRDPYDPAP-PAPPGGESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 49640014   245 ALFQYKPQNVDELTLSPGDYIFVDPtqqdEASEGWVIGisQRTGCRGFLPENYTD 299
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIE----ESEDGWWEG--INTGRTGLVPANYVE 49

bifunctional RNase H/acid phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  396 PCSLPRRSRGIkdfeNDPPLSSCGIFQSRIAGDALLDSGiRISSVFASPALRCVQTAKLILEELKLEkkikIRVEPGIFE 475
Cdd:PRK07238 183 ELSVQRRYSGR----GNPELTEVGRRQAAAAARYLAARG-GIDAVVSSPLQRARDTAAAAAKALGLD----VTVDDDLIE 253

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  476 -----W---TKWEAGKTTPtlmsleELKEANFNiDTDYRPafplsalmPA-ESYQEYMDRCTASMVQIVNTCPQDTgvIL 546
Cdd:PRK07238 254 tdfgaWeglTFAEAAERDP------ELHRAWLA-DTSVAP--------PGgESFDAVARRVRRARDRLIAEYPGAT--VL 316

                        170       180
                 ....*....|....*....|
gi 49640014  547 IVSHGSTLDSCTRPLLGLPP 566
Cdd:PRK07238 317 VVSHVTPIKTLLRLALDAGP 336

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  332 RCSGEFLPQTARSLSSLQALQATvarKSVLVVRHGERVDqifgkawlqqcSTPDgkYYRPDLNfPCSLPRRsrgikdfen 411
Cdd:PRK06193  20 GSGEEAASDEADDKTLLESLQKG---GYVIYFRHAATDR-----------SQAD--QDTSDMD-DCSTQRN--------- 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 49640014  412 dppLSSCGIFQSRIAGDALLDSGIRISSVFASPALRCVQTAKLILEELKLEKK 464
Cdd:PRK06193  74 ---LSEEGREQARAIGEAFRALAIPVGKVISSPYCRAWETAQLAFGRHEKEIR 123

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They 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. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. 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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVDPTQQDEASEGWVIGISQRTGCRGFLPENYTDR 300
Cdd:cd11791   1 VLRVLYPYTPQEEDELELVPGDYIYVSPEELDSSSDGWVEGTSWLTGCSGLLPENYTEK 59

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   412 DPPLSSCGIFQSRIAGDALldSGIRISSVFASPALRCVQTAKLILEELKLEkkikIRVEPGIFEWT--KWEaGKTTPTLM 489
Cdd:pfam00300  22 DSPLTELGREQAEALAERL--AGEPFDAIYSSPLKRARQTAEIIAEALGLP----VEIDPRLREIDfgDWE-GLTFEEIA 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   490 S-LEELKEANFNIDTDYRPAfplsalmPAESYQEYMDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRE 568
Cdd:pfam00300  95 ErYPEEYDAWLADPADYRPP-------GGESLADVRARVRAALEELAARHPGKT--VLVVSHGGVIRALLAHLLGLPLEA 165

                  ....*.
gi 49640014   569 CGDFAQ 574
Cdd:pfam00300 166 LRRFPL 171

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 49640014 360 VLVVRHGERVDQIFGkawlqqcstpdgkyyrpdlnfpcslprRSRGIKDfendPPLSSCGIFQSRIAGDALLDSGIRISS 439
Cdd:cd07067   2 LYLVRHGESEWNAEG---------------------------RFQGWTD----VPLTEKGREQARALGKRLKELGIKFDR 50

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014 440 VFASPALRCVQTAKLILEELkleKKIKIRVEPGIFEwtkweagkttptlmsleelkeanfnidtdyrpafplsalmpaes 519
Cdd:cd07067  51 IYSSPLKRAIQTAEIILEEL---PGLPVEVDPRLRE-------------------------------------------- 83

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 49640014 520 yqeymDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRECGDF 572
Cdd:cd07067  84 -----ARVLPALEELIAPHDGKN--VLIVSHGGVLRALLAYLLGLSDEDILRL 129

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 49640014    411 NDPPLSSCGIFQSRIAGDALLD-SGIRISSVFASPALRCVQTAKLILEELKLEKKIKIrvEPGIFEwtkweaGKTTPTLM 489
Cdd:smart00855  22 TDVPLTELGRAQAEALGRLLASlLLPRFDVVYSSPLKRARQTAEALAIALGLPGLRER--DFGAWE------GLTWDEIA 93

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 49640014    490 slEELKEANFNIDTDYRPAFPlSALMPAESYQEYMDRCTASMVQIVNTCPQDTGVILIVSHGSTL 554
Cdd:smart00855  94 --AKYPEEYLAAWRDPYDPAP-PAPPGGESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVDPTQ-QDEASEGWVIGISQRTGCRGFLPENYTDR 300
Cdd:cd11790   4 KVRATHDYTAEDTDELTFEKGDVILVIPFDdPEEQDEGWLMGVKESTGCRGVFPENFTER 63

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 49640014   412 DPPLSSCGIFQSRIAGDALldSGIRISSVFASPALRCVQTAKLILEELKLekkiKIRVEPGIFE--WTKWEagkttptLM 489
Cdd:TIGR03162  21 DVPLAESGEEQAAALREKL--ADVPFDAVYSSPLSRCRELAEILAERRGL----PIIKDDRLREmdFGDWE-------GR 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014   490 SLEELKEANFNIDtdYRPAFPLSALMP-AESYQEYMDRCTASMVQIVNTCPQDTgvILIVSHGSTLDSCTRPLLGLPPRE 568
Cdd:TIGR03162  88 SWDEIPEAYPELD--AWAADWQHARPPgGESFADFYQRVSEFLEELLKAHEGDN--VLIVTHGGVIRALLAHLLGLPLEQ 163

                  ....*.
gi 49640014   569 CGDFAQ 574
Cdd:TIGR03162 164 WWSFAV 169

Phosphohistidine phosphatase SixA [Signal transduction mechanisms];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 49640014 402 RSRGIKDFenDPPLSSCGIFQSRIAGDALLDSGIRISSVFASPALRCVQTAKLILEELKLEKkiKIRVEPGIFE 475
Cdd:COG2062  12 RAPGGDDF--DRPLTERGRRQARAMARWLAALGLKPDRILSSPALRARQTAEILAEALGLPP--KVEVEDELYD 81

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 49640014  22 PSLLEPLLAMGFPVHTALKALAATGRKTAEEALAWLHDHCNDPSLD 67
Cdd:cd14385   2 AEALAQLLGMGFPEVRCKKALLATGNSDAEAAMNWLFEHMDDPDID 47

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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIfVDPTQQDEaseGWVIGISQRTGCRGFLPENY 297
Cdd:cd11789   1 RYRAMYDYAAADDDEVSFQEGDVI-INVEIIDD---GWMEGTVQRTGQSGMLPANY 52

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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVdptqQDEASEGWVIGISQRTGCRGFLPENY 297
Cdd:cd11916   3 SYQALYSYAPQNDDELELRDGDIVDV----MEKCDDGWFVGTSRRTKQFGTFPGNY 54

Src Homology 3 domain of Bridging integrator 1 (Bin1), also called Amphiphysin-2; Bin1 isoforms are localized in many different tissues and may function in intracellular vesicle trafficking. It plays a role in the organization and maintenance of the T-tubule network in skeletal muscle. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Bin1 contains an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR) and a C-terminal SH3 domain. The SH3 domain of Bin1 forms transient complexes with actin, myosin filaments, and CDK5, to facilitate sarcomere organization and myofiber maturation. It also binds dynamin and prevents its self-assembly. 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 49640014 243 LRALFQYKPQNVDELTLSPGDYIFVDPTQQ-DEASEGWVIGISQR--------TGCRGFLPENYTDR 300
Cdd:cd12139   5 VQAQHDYTATDTDELQLKAGDVVLVIPFQNpEEQDEGWLMGVKESdwnqhkklEKCRGVFPENFTER 71

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014 241 QTLRALFQYKPQNVDELTLSPGDYIFVdptqQDEASEGWVIGISQRTGCRGFLPENYTDR 300
Cdd:cd11917   5 EPFQALYNYMPRNEDELELREGDVIDV----MEKCDDGWFVGTSRRTKFFGTFPGNYVKR 60

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super 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 49640014 241 QTLRALFQYKPQNVDELTLSPGDYIfVDPTQQDEaseGWVIGISQRTGCRGFLPENYTD 299
Cdd:cd11933   2 KSFRAMYDYRAADDDEVSFKDGDTI-VNVQTIDE---GWMYGTVQRTGKTGMLPANYVE 56

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 49640014 244 RALFQYKPQNVDELTLSPGDYIFVDptQQDEASEGWVIGisQRTGCRGFLPENYTDR 300
Cdd:cd11836   3 RALYAFEARNPDEISFQPGDIIQVD--ESQVAEPGWLAG--ELKGKTGWFPANYVEK 55

Third 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 third SH3 domain, located in the middle 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 49640014 245 ALFQYKPQNVDELTLSPGDYIFVDPTQQDeaseGWVIGISQRTGCRGFLPENY 297
Cdd:cd11783   4 ALYPYKPQKPDELELRKGEMYTVTEKCQD----GWFKGTSLRTGQSGVFPGNY 52

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) 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. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. 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 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 49640014 244 RALFQYKPQNVDELTLSPGDYIFVDPTQQDEAseGWVIGisQRTGCRGFLPENYTDR 300
Cdd:cd11987   3 RALYPFEARSHDEITIQPGDIVMVDESQTGEP--GWLGG--ELKGKTGWFPANYAEK 55

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. 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 49640014 244 RALFQYKPQNVDELTLSPGDYIFVdpTQQDeASEGWVIGISQRtGCRGFLPENY 297
Cdd:cd11763   3 RALYDFDSQPSGELSLRAGEVLTI--TRQD-VGDGWLEGRNSR-GEVGLFPSSY 52

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 49640014 244 RALFQYKPQNVDELTLSPGDYIFVdpTQQDEASEGWVIGisQRTGCRGFLPENY 297
Cdd:cd12142   3 RVLFDYNPVAPDELALKKGDVIEV--ISKETEDEGWWEG--ELNGRRGFFPDNF 52

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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVDPTQQDEAseGWVIGISQrtGCRGFLPENYTDR 300
Cdd:cd11988   3 NYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEP--GWLYGSFQ--GNFGWFPCNYVEK 57

Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; JNK-interacting proteins (JIPs) function as scaffolding proteins for c-Jun N-terminal kinase (JNK) signaling pathways. They bind to components of Mitogen-activated protein kinase (MAPK) pathways such as JNK, MKK, and several MAP3Ks such as MLK and DLK. There are four JIPs (JIP1-4); all contain a JNK binding domain. JIP1 and JIP2 also contain SH3 and Phosphotyrosine-binding (PTB) domains. Both are highly expressed in the brain and pancreatic beta-cells. JIP1 functions as an adaptor linking motor to cargo during axonal transport and also is involved in regulating insulin secretion. JIP2 form complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. The SH3 domain of JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. 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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVdptqQDEASEGWVIGISQRTGCRGFLPENY 297
Cdd:cd11801   1 THRALHKFIPRHEDEIELDIGDPVYV----EQEADDLWCEGTNLRTGQRGIFPAAY 52

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 49640014 242 TLRALFQYKPQNVDELTLSPGDYIFVdpTQQDEASeGWVIGisQRTGCRGFLPENY 297
Cdd:cd11778   1 YVEALYDYEAQGDDEISIRVGDRIAV--IRGDDGS-GWTYG--EINGVKGLFPTSY 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 49640014 244 RALFQYKPQNVDELTLSPGDYIFVDPTQQDeaseGWVIGISQRTGCRGFLPENYTD 299
Cdd:cd11785   3 RVIVPYPPQSEAELELKEGDIVFVHKKRED----GWFKGTLQRTGKTGLFPGSFVE 54

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. 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 49640014 244 RALFQYKPQNVDELTLSPGDYIfvdpTQQDEASEGWVIGISqRTGCRGFLPENY 297
Cdd:cd11819   3 KALYDYQAAEDNEISFVEGDII----TQIEQIDEGWWLGVN-AKGQKGLFPANY 51

UBA1 domain found in ubiquitin carboxyl-terminal hydrolase UBP5, UBP13 and similar proteins; 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. UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13, is an ortholog of UBP5. It has similar domain architecture, but functions differently from USP5 in cellular deubiquitination processes. It exhibits a weak deubiquitinating activity preferring to Lys63-linked polyubiquitin in a non-activation manner. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 49640014  22 PSLLEPLLAMGFPVHTALKALAATGRKTAEEALAWLHDHCNDP 64
Cdd:cd14294   1 EAVVSQLAEMGFPLEACRKAVYHTNNSGLEAAMNWIMEHMDDP 43

bifunctional RNase H/acid phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  396 PCSLPRRSRGIkdfeNDPPLSSCGIFQSRIAGDALLDSGiRISSVFASPALRCVQTAKLILEELKLEkkikIRVEPGIFE 475
Cdd:PRK07238 183 ELSVQRRYSGR----GNPELTEVGRRQAAAAARYLAARG-GIDAVVSSPLQRARDTAAAAAKALGLD----VTVDDDLIE 253

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49640014  476 -----W---TKWEAGKTTPtlmsleELKEANFNiDTDYRPafplsalmPA-ESYQEYMDRCTASMVQIVNTCPQDTgvIL 546
Cdd:PRK07238 254 tdfgaWeglTFAEAAERDP------ELHRAWLA-DTSVAP--------PGgESFDAVARRVRRARDRLIAEYPGAT--VL 316

                        170       180
                 ....*....|....*....|
gi 49640014  547 IVSHGSTLDSCTRPLLGLPP 566
Cdd:PRK07238 317 VVSHVTPIKTLLRLALDAGP 336

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 49640014 243 LRALFQYKPQNVDELTLSPGDYIFVdptQQDEASEGWVIGISQRTGCRGFLPENY 297
Cdd:cd11878   2 IRALYDYRAQTPGELSFSKGDFFHV---IGEEDQGEWYEATNPVTGKRGLVPKSY 53