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 13124388  31 LCADDECVYTISLASAQEDYNAPDCRFINVKKGQQIYVYSKLVKENGAGEFWAGSVYGD-GQDEMGVVGYFPRNLVKEQR 109
Cdd:cd11891   1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                ...
gi 13124388 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 13124388  31 LCADDECVYTISLASAQEDYNAPDCRFINVKKGQQIYVYSKLVKENGAGEFWAGSVYGD-GQDEMGVVGYFPRNLVKEQR 109
Cdd:cd11891   1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                ...
gi 13124388 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 13124388     46 AQEDYNAPDCRFINVKKGQQIYVYSKLVkengaGEFWAGSVyGDGQdemgvVGYFPRNLVK 106
Cdd:smart00326   7 ALYDYTAQDPDELSFKKGDIITVLEKSD-----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 13124388  31 LCADDECVYTISLASAQEDYNAPDCRFINVKKGQQIYVYSKLVKENGAGEFWAGSVYGD-GQDEMGVVGYFPRNLVKEQR 109
Cdd:cd11891   1 LCADEECVYAISLARAEDDYNAPDCRFINIKKGQLIYVYSKLVKENGAGEFWSGSVYSErYVDQMGIVGYFPSNLVKEQT 80

                ...
gi 13124388 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 13124388  29 KKLCADDECVYTISLASAQEDYNAPDCRFINVKKGQQIYVYSKLvkeNGAGE-FWAGSVYGDGQDEMGV-VGYFPRNLVK 106
Cdd:cd11890   1 KKLCADQECSHPISIAVALQDYMAPDCRFIPIQRGQVVYVFSKL---KGRGRlFWGGSVQGDYYGEQAArLGYFPSSIVQ 77

                        90       100
                ....*....|....*....|.
gi 13124388 107 EQRVYQEATKEVPTTDIDFFC 127
Cdd:cd11890  78 EDQYLKPGKVEVKTDKWDFYC 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 13124388  31 LCADDECVYTISLASAQEDYNAPDCRFINVKKGQQIYVYSKLVKenGAGEFWAGSVYGDgqdemgvVGYFPRNLVKEQRV 110
Cdd:cd11893   1 RCADEECSMLLCRGKAVKDFTGPDCRFLSFKKGETIYVYYKLSG--RRTDLWAGSVGFD-------FGYFPKDLLDVNHL 71

                .
gi 13124388 111 Y 111
Cdd:cd11893  72 Y 72

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). 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 13124388  44 ASAQEDYNAPDCRFINVKKGQQIYVYSKLvkenGAGEFWAGSVYGDgqdemgvVGYFPRNLVKE 107
Cdd:cd11830   2 AKARYDFCARDMRELSLKEGDVVKIYNKK----GQQGWWRGEINGR-------IGWFPSTYVEE 54

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13124388     46 AQEDYNAPDCRFINVKKGQQIYVYSKLVkengaGEFWAGSVyGDGQdemgvVGYFPRNLVK 106
Cdd:smart00326   7 ALYDYTAQDPDELSFKKGDIITVLEKSD-----DGWWKGRL-GRGK-----EGLFPSNYVE 56

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 13124388  43 LASAQEDYNAPDCRFINVKKGQQIYVYSKLvkenGAGEFWAGSVYGDgqdemgvVGYFPRNLVKEQ 108
Cdd:cd11978   2 IAIARYDFCARDMRELSLLKGDVVKIYTKM----STNGWWRGEVNGR-------VGWFPSTYVEED 56

C-type lysozyme inhibitor;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13124388    1 MARILLLFLPGLVAVCAVHGIFMDRLASKKL---CadDECVYTISLASAQEDYN-APDCRFINVKKG 63
Cdd:PRK11372   3 MKKLLIICLPVLLTGCSAYNQFVERMQTDTLeyqC--DEKPLTVKLNNPRQEVSfVYDNQLLHLKQG 67