SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892   1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTVW 644
Cdd:cd12892  81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                       170
                ....*....|....*..
gi 12621082 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892 161 NKCLTILTGLPIPDHLD 177

B-box-type 1 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. MID1 heterodimerizes in vitro with its paralog MID2.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 12621082 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836   1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

B-box-type 2 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. It heterodimerizes in vitro with its paralog MID2. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 12621082 168 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSE 214
Cdd:cd19822   1 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSD 47

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 381 APNPPTIREelctASYDTITVHWT--SDDEFSVVSYELQYTIftgqanvvslcNSADSWMIV--PNIKQNHYTVHGLQSG 456
Cdd:cd00063   3 PPTNLRVTD----VTSTSVTLSWTppEDDGGPITGYVVEYRE-----------KGSGDWKEVevTPGSETSYTLTGLKPG 67

                        90       100
                ....*....|....*....|....*.
gi 12621082 457 TKYIFMVKAINQAG-SRSSEPGKLKT 481
Cdd:cd00063  68 TEYEFRVRAVNGGGeSPPSESVTVTT 93

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892   1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTVW 644
Cdd:cd12892  81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                       170
                ....*....|....*..
gi 12621082 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892 161 NKCLTILTGLPIPDHLD 177

B-box-type 1 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. MID1 heterodimerizes in vitro with its paralog MID2.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 12621082 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836   1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 12621082   323 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 374
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

B-box-type 2 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. It heterodimerizes in vitro with its paralog MID2. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 12621082 168 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSE 214
Cdd:cd19822   1 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSD 47

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 381 APNPPTIREelctASYDTITVHWT--SDDEFSVVSYELQYTIftgqanvvslcNSADSWMIV--PNIKQNHYTVHGLQSG 456
Cdd:cd00063   3 PPTNLRVTD----VTSTSVTLSWTppEDDGGPITGYVVEYRE-----------KGSGDWKEVevTPGSETSYTLTGLKPG 67

                        90       100
                ....*....|....*....|....*.
gi 12621082 457 TKYIFMVKAINQAG-SRSSEPGKLKT 481
Cdd:cd00063  68 TEYEFRVRAVNGGGeSPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 380 TAPNPPTireELcTASYDT---ITVHWTSDDEFSVVSYELQYTIftgqanvvslcNSADSWMIVPNIKQNHYTVHGLQSG 456
Cdd:COG3401 231 TPPSAPT---GL-TATADTpgsVTLSWDPVTESDATGYRVYRSN-----------SGDGPFTKVATVTTTSYTDTGLTNG 295

                        90       100       110
                ....*....|....*....|....*....|.
gi 12621082 457 TKYIFMVKAINQAGSRS--SEPGKLKTNSQP 485
Cdd:COG3401 296 TTYYYRVTAVDAAGNESapSNVVSVTTDLTP 326

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082   381 APNPPTIREelctASYDTITVHWTSDDEFS--VVSYELQYtiftgqanvvSLCNSADSW--MIVPNIkQNHYTVHGLQSG 456
Cdd:pfam00041   2 APSNLTVTD----VTSTSLTVSWTPPPDGNgpITGYEVEY----------RPKNSGEPWneITVPGT-TTSVTLTGLKPG 66

                          90
                  ....*....|....
gi 12621082   457 TKYIFMVKAINQAG 470
Cdd:pfam00041  67 TEYEVRVQAVNGGG 80

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 12621082   174 MCLEHEDEKVNMYCVTDDQLICALCkLVGRHRDHQVAAL 212
Cdd:pfam00643   5 LCPEHEEEPLTLYCNDCQELLCEEC-SVGEHRGHTVVPL 42

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 12621082     10 CPICLELF-EDPLLLPCAHSLCFNCAHRILVSHCATnepvesinafqCPTC 59
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGNNT-----------CPIC 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 12621082    114 AEKVLCQFCDQdpaQDAVKTCVTCEVSYCDECLKATHpnkkpfTGHR 160
Cdd:smart00336   1 QRAPKCDSHGD---EPAEFFCEECGALLCRTCDEAEH------RGHT 38

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892   1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTVW 644
Cdd:cd12892  81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                       170
                ....*....|....*..
gi 12621082 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892 161 NKCLTILTGLPIPDHLD 177

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 486 FKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKH 565
Cdd:cd13734   1 FKLDPKTAHRKLRLSNDNLTVEYDPEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 566 EWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTVWN 645
Cdd:cd13734  81 EDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAVWN 160

                ....*
gi 12621082 646 KCLTI 650
Cdd:cd13734 161 GSLTL 165

RING finger, HC subclass, found in midline-2 (MID2) and similar proteins; MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is a probable E3 ubiquitin-protein ligase and is highly related to MID1 that associates with cytoplasmic microtubules along their length and throughout the cell cycle. Like MID1, MID2 associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. MID2 can also substitute for MID1 to control exocytosis of lytic granules in cytotoxic T cells. Loss-of-function mutations in MID2 lead to the human X-linked intellectual disability (XLID). MID2 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxy-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID2 hetero-dimerizes in vitro with its paralog MID1.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082   1 METLESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSHCATNEPVESINAFQCPTCRHVITLSQRGL 70
Cdd:cd16754   1 METLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILTSGCASGESIEPPSAFQCPTCRYVISLNHRGL 70

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 486 FKLDPKSAHRKLKVshDNLTVERDESSSK------------KSHTP----------------------ERFTSQgSYGVA 531
Cdd:cd12901   1 FKLDASSSHQNLKV--EDLSVEWDATGGKvlqkikgrendgRSRTAsprnssarcqspkrmpsarggrDRFTAE-SYTVL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 532 GNVFIDSGRHYWEVVIS-GSTWYAIGLAYKSAPKHEWIGKNSASWalCRCNNNWV-----VRHNSKEIPIEpAPHPRRVG 605
Cdd:cd12901  78 GDTLIDGGQHYWEVRAQkDSKAFSVGVAYRSLGKFDQLGKTNASW--CLHVNNWLqnsfaAKHNNKAKTLD-VPVPDRIG 154

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 12621082 606 ILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTVWNKCLTIITGLPIPD 658
Cdd:cd12901 155 VYCDFDEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVPS 207

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd13733   1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDT--CVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 12621082 565 HEWIGKNSAS--WALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTF 641
Cdd:cd13733  79 KGKITLSPENgyWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF 157

B-box-type 1 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. MID1 heterodimerizes in vitro with its paralog MID2.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 12621082 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836   1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082    538 SGRHYWEVVISGSTWYAIGLAYKSAPKHE--WIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSI 615
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYfaLLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 12621082    616 AFYDALNSIHLYTF-DVALAQPVCPTFTVWNKCLTIITGLPI 656
Cdd:smart00449  81 SFYKNGKYLHGLAFfDVKFSGPLYPAFSLGSGNSVRLNFGPL 122

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 12621082   323 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 374
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

PRY/SPRY domain containing protein 4 (SPRYD4); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain and is encoded by the SPRYD4 gene. SPRYD4 (SPRY containing domain 4) is ubiquitously expressed in many human tissues, most strongly in kidney, bladder, brain, thymus and stomach. Subcellular localization demonstrates that SPRYD4 protein is localized in the nucleus when overexpressed in COS-7 green monkey cell. It has remained uncharacterized thus far.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 486 FKLDPKSAHRKLK-------VSHDNLTVErdesSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGLA 558
Cdd:cd12903   1 FKLDERTAHSSLDlfkkdtgVIYRMLGVD----PTKVPQNPERFRDWAV--VLGDTPVTSGRHYWEVTVKRSQEFRIGVA 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 559 YKSAPKHEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVC 638
Cdd:cd12903  75 DVDMSRDECIGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVV 154

                ....*..
gi 12621082 639 PTFTVWN 645
Cdd:cd12903 155 PAFALWD 161

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76)-like; This domain is similar to the distinct PRY/SPRY subdomain found at the C-terminus of TRIM76, a Class I TRIM protein. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5 or myospryn or SPRYD2) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It has been suggested that TRIM76 is involved in two distinct processes, protein kinase A signaling and vesicular trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 486 FKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPE---RFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSA 562
Cdd:cd12899   2 FHLNEDTAHPLLSISEDGFTVVYGEEELPARDLSFsdnSFTR--CVAVMGSLIPVRGKHYWEVEVDEQTEYRVGVAFEDT 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 563 PKHEWIGKNSASWA----LCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVC 638
Cdd:cd12899  80 QRNGYLGANNTSWCmrhiITPSRHKYEFLHNGWTPDIRITVPPKKIGILLDYDSGRLSFFNVDLAQHLYTFSCQFQHFVH 159

                       170
                ....*....|....*..
gi 12621082 639 PTFTVWNK-CLTIITGL 654
Cdd:cd12899 160 PCFSLEKPgALKVHNGI 176

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082   540 RHYWEVVISG--STWYAIGLAYKSAP--KHEWIGKNSASWALCRCNNN--WVVRHNSKEIPIEPAPhpRRVGILLDYDNG 613
Cdd:pfam00622   1 RHYFEVEIFGqdGGGWRVGWATKSVPrkGERFLGDESGSWGYDGWTGKkyWASTSPLTGLPLFEPG--DVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 12621082   614 SIAFYDAlNSIHLYTF-DVALAQPVCPTFTV-WNKCLTIITGLP 655
Cdd:pfam00622  79 TISFTKN-GKSLGYAFrDVPFAGPLFPAVSLgAGEGLKFNFGLR 121

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTwyaiglayksapkhew 567
Cdd:cd15819   6 LDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPC--VLGQEGFTSGRHYWEVEVGDRT---------------- 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 568 igknsaSWALCRCNNN---------------WVVR-HN-------SKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSI 624
Cdd:cd15819  68 ------SWDLGVCRDNvmrkgrvtlspengfWAIRlYGneywaltSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGS 141

                       170       180       190
                ....*....|....*....|....*....|
gi 12621082 625 HLYTFD-VALAQPVCPTFTVWN---KCLTI 650
Cdd:cd15819 142 HIYTFPqTAFSGPLRPFFRLWSsdsGPLTI 171

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKHEW 567
Cdd:cd13741   4 LDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSA--DCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKEK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 568 IGKNSASWALCRCNNN---------------------WVVRHNSK---------EIPIEPAPHPRRVGILLDYDNGSIAF 617
Cdd:cd13741  82 VGSGGSSVSSGDASSSrhhhrrrrlhlpqqpllqrevWCVGTNGKryqaqssteQTLLSPSEKPRRFGVYLDYEAGRLGF 161

                       170       180       190
                ....*....|....*....|....*....|
gi 12621082 618 YDALNSIHLYTFDVA-LAQPVCPTFTVWNK 646
Cdd:cd13741 162 YNAETLAHVHTFSAAfLGERVFPFFRVLSK 191

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGLAyKSAPKHEW 567
Cdd:cd15817   4 LDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPA--VLGSEGFDSGRHFWEVEVGGKGEWILGVC-KDSLPRNA 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 12621082 568 IGKNSAS---WALCRCNNNWVVrHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCPTFTV 643
Cdd:cd15817  81 QDPPSPLggcWQIGRYMSGYVA-SGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYV 158

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 487 KLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKHe 566
Cdd:cd15816   3 KLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPC--VLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRK- 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 567 wiGKNSAS-----WALcrcnnnWVVRHN------SKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQ 635
Cdd:cd15816  80 --GETTPSpengvWAV------WLLKGNeymvlaSPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSG 151

                ....*...
gi 12621082 636 PVCPTFTV 643
Cdd:cd15816 152 ILRPYFFV 159

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFtsqgsY---GVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd15828  14 LDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRF-----YlcpAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPR 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 565 hEWigKNSAS-----WALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTFDVALAQPVCP 639
Cdd:cd15828  89 -NW--SNQPSvqdglWAIGRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTLWP 165

                ..
gi 12621082 640 TF 641
Cdd:cd15828 166 YF 167

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12621082 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKHEW 567
Cdd:cd15821   8 LDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDD--ALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQGP 85

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 12621082 568 IGKNSAS--WALCRCNNNWVVRHNSKEIPIEPAPHPRRVGILLDYDNGSIAFYDALNSIHLYTF-DVALAQPVCPTF 641
Cdd:cd15821  86 IELSPEHgfWTVSLRDGSVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFtKISAEEPLRPFF 162