Melanoma Inhibitory Activity-Like protein; MIAL is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans. MIAL is a member of the recently identified family that also includes MIA, MIA2, and MIA3 (also called TANGO); MIA is the most studied member of the family. MIA is a single domain protein that adopts a Src Homology 3 (SH3) domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109092987  31 LCADDECVYTISLARAQEDYNAPDCRFINVKKGQQIYVYSKLVKENEAGEFWAGSVYGD-GQDEMGVVGYFPSNLVKEQR 109
Cdd:cd11891    1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                 ...
gi 109092987 110 VYQ 112
Cdd:cd11891   81 VYK 83

Melanoma Inhibitory Activity-Like protein; MIAL is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans. MIAL is a member of the recently identified family that also includes MIA, MIA2, and MIA3 (also called TANGO); MIA is the most studied member of the family. MIA is a single domain protein that adopts a Src Homology 3 (SH3) domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109092987  31 LCADDECVYTISLARAQEDYNAPDCRFINVKKGQQIYVYSKLVKENEAGEFWAGSVYGD-GQDEMGVVGYFPSNLVKEQR 109
Cdd:cd11891    1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                 ...
gi 109092987 110 VYQ 112
Cdd:cd11891   81 VYK 83

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 109092987    44 ARAQEDYNAPDCRFINVKKGQQIYVYSKLVkeneaGEFWAGSVyGDGQdemgvVGYFPSNLVK 106
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSD-----DGWWKGRL-GRGK-----EGLFPSNYVE 56

Melanoma Inhibitory Activity-Like protein; MIAL is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans. MIAL is a member of the recently identified family that also includes MIA, MIA2, and MIA3 (also called TANGO); MIA is the most studied member of the family. MIA is a single domain protein that adopts a Src Homology 3 (SH3) domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109092987  31 LCADDECVYTISLARAQEDYNAPDCRFINVKKGQQIYVYSKLVKENEAGEFWAGSVYGD-GQDEMGVVGYFPSNLVKEQR 109
Cdd:cd11891    1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                 ...
gi 109092987 110 VYQ 112
Cdd:cd11891   81 VYK 83

Melanoma Inhibitory Activity protein; MIA is a single domain protein that adopts a Src Homology 3 (SH3) domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. It binds peptide ligands with sequence similarity to type III human fibronectin repeats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109092987  29 KKLCADDECVYTISLARAQEDYNAPDCRFINVKKGQQIYVYSKLvkENEAGEFWAGSVYGDGQDEMGV-VGYFPSNLVKE 107
Cdd:cd11890    1 KKLCADQECSHPISIAVALQDYMAPDCRFIPIQRGQVVYVFSKL--KGRGRLFWGGSVQGDYYGEQAArLGYFPSSIVQE 78

                         90       100
                 ....*....|....*....|
gi 109092987 108 QRVYQEATKEVPTTDIDFFC 127
Cdd:cd11890   79 DQYLKPGKVEVKTDKWDFYC 98

Src Homology 3 domain of Melanoma Inhibitory Activity 3 protein; MIA3, also called TANGO or TANGO1, acts as a tumor suppressor of malignant melanoma. It is downregulated or lost in melanoma cells lines. Unlike other MIA family members, MIA3 is widely expressed except in hematopoietic cells. MIA3 is an ER resident transmembrane protein that is required for the loading of collagen VII into transport vesicles. SNPs in the MIA3 gene have been associated with coronary arterial disease and myocardial infarction. MIA3 contains an N-terminal SH3-like domain, similar to MIA. It is a member of the recently identified family that also includes MIA, MIAL, and MIA2. MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109092987  31 LCADDECVYTISLARAQEDYNAPDCRFINVKKGQQIYVYSKLVKENEagEFWAGSVYGDgqdemgvVGYFPSNLVKEQRV 110
Cdd:cd11893    1 RCADEECSMLLCRGKAVKDFTGPDCRFLSFKKGETIYVYYKLSGRRT--DLWAGSVGFD-------FGYFPKDLLDVNHL 71

                 .
gi 109092987 111 Y 111
Cdd:cd11893   72 Y 72

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 109092987    44 ARAQEDYNAPDCRFINVKKGQQIYVYSKLVkeneaGEFWAGSVyGDGQdemgvVGYFPSNLVK 106
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSD-----DGWWKGRL-GRGK-----EGLFPSNYVE 56

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. 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 109092987  45 RAQEDYNAPDCRFINVKKGQQIYVYSKlvkeNEAGeFWAGSVYGDGQDemGVVGYFPSN 103
Cdd:cd11883    3 VALYDFTPKSKNQLSFKAGDIIYVLNK----DPSG-WWDGVIISSSGK--VKRGWFPSN 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. 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 109092987  44 ARAQEDYNAPDCRFINVKKGQQIYVYSKlvkENEAGeFWAGSVYGDgqdemgvVGYFPSNLVKE 107
Cdd:cd11976    2 AKARYDFCARDRSELSLKEGDIIKILNK---KGQQG-WWRGEIYGR-------VGWFPANYVEE 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. 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 109092987  43 LARAQEDYNAPDCRFINVKKGQQIYVYSKLvkenEAGEFWAGSVYGDgqdemgvVGYFPSNLVKEQ 108
Cdd:cd11978    2 IAIARYDFCARDMRELSLLKGDVVKIYTKM----STNGWWRGEVNGR-------VGWFPSTYVEED 56

C-type lysozyme inhibitor;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 109092987   1 MARILLLFLPGLVAVCAVHGIFMDRLASKKL---CadDECVYTISLARAQEDYN-APDCRFINVKKG 63
Cdd:PRK11372   3 MKKLLIICLPVLLTGCSAYNQFVERMQTDTLeyqC--DEKPLTVKLNNPRQEVSfVYDNQLLHLKQG 67

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. 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 109092987  49 DYNAPDCRFINVKKGQQIYVyskLVKENEagEFWAGSVyGDGQDemgvvGYFPSNLV 105
Cdd:cd11812    7 DYTANRSDELTIHRGDIIRV---LYKDND--NWWFGSL-VNGQQ-----GYFPANYV 52