Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   12 LCFLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARN 91
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 254675181   92 CVGMICCSASLEVQ 105
Cdd:cd20951    81 IHGEASSSASVVVE 94

Alpha-kinase family; This family is a novel family of eukaryotic protein kinase catalytic domains, which have no detectable similarity to conventional kinases. The family contains myosin heavy chain kinases and Elongation Factor-2 kinase and a bifunctional ion channel. This family is known as the alpha-kinase family. The structure of the kinase domain revealed unexpected similarity to eukaryotic protein kinases in the catalytic core as well as to metabolic enzymes with ATP-grasp domains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   1879 NDSYFGDHLRGQIstEELHFGEGVHRKAFRSKVMQGlmpvFQPGHACVLKVHNavahgTRNNDELVQRNYKlaaqECYVQ 1958
Cdd:smart00811    2 SGKWTVSETGVKI--ELKPFAKGAMRVAFRVKDLSE----DGSGTECVAKYFK-----KEYKNTVEDRYFE----DVEMQ 66

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   1959 NTARYYAKIYAAeaqpLEGFGEVPEIIPIFLIHRPENNIPY-ATVEEELIGEFVKYSIRDGKEINFLRRDSeagqKCCTF 2037
Cdd:smart00811   67 MVAKKFAEEFNQ----LKPSPKKIEFLPSYVLELPDRSIPYlFTVEPFLEGEFVKYNSNNGWVNDEARSTE----APQAF 138

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 254675181   2038 QHWVYQKTSGCLLVTDMQGVGMKLTDVGIATlARGYKGFKGNCSMTFIDQFRALHQCNKYC 2098
Cdd:smart00811  139 SHFTYERSGGSLLVVDLQGVGDLLTDPQIHT-EDGFGFGPGNLGEEGIEKFFATHKCNSIC 198

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   12 LCFLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARN 91
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 254675181   92 CVGMICCSASLEVQ 105
Cdd:cd20951    81 IHGEASSSASVVVE 94

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181     20 SQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQaiDLGGTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARNCVGMICCS 99
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGG--KLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                    ....*
gi 254675181    100 ASLEV 104
Cdd:smart00410   81 TTLTV 85

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1759 PVLLKRIQAEMAPEHSGNIKLSCQFsEIHEDSTVCWTKDSKSIAqakkSAGDNSSVS-----LAIVQAGQKDQGLYYCCL 1833
Cdd:cd05760     1 PVVLKHPASAAEIQPSSRVTLRCHI-DGHPRPTYQWFRDGTPLS----DGQGNYSVSskertLTLRSAGPDDSGLYYCCA 75

                          90
                  ....*....|....
gi 254675181 1834 KNSYGKVTAEFNLT 1847
Cdd:cd05760    76 HNAFGSVCSSQNFT 89

Alpha-kinase domain of alpha-protein kinases 2 and 3; Alpha-protein kinases 2 (ALPK2) and 3 (ALPK3) are also called heart alpha-protein kinase (HAK) and muscle alpha-protein kinase (MAK), respectively. They both contain a C-terminal alpha-kinase domain and two immunoglobulin (Ig)-like domains. Loss of function mutations in ALPK3 can cause early-onset and familial cardiomyopathy in humans. The ALPK2 gene may also be a novel candidate gene for inherited hypertension in Dahl rats. Alpha-kinase is an atypical protein kinase catalytic domain with no detectable similarity to conventional protein serine/threonine kinases. The alpha-kinase family was named after the unique mode of substrate recognition by its initial members, the Dictyostelium heavy chain kinases, which targeted protein sequences that adopt an alpha-helical conformation. More recently, alpha-kinases were found to also target residues in non-helical regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1861 RGCEEIEFSQLIFKEDVFNDSYFGDHLRGQISTEELHFGEGVHRKAFRSKVMQGLMPVFQPGHACVLKVHNAVAHGTRNN 1940
Cdd:cd16966     2 EVGEEIEMSPLIFAKDLLDSGYWGDKLFGRIATEELHFGEGVLRKASRSKVIYGLMPIFKSGHTCIIKVHNAIAYGTRNE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1941 DELVQRNYKLAAQECYVQNTARYYAKIYAAEAQPLEGFGEVPEIIPIFLIHRPENNIPYATVEEELIGEFVKYSIRDGKE 2020
Cdd:cd16966    82 DSLIQRNYKLTAQECKVQNTAREYAKIFAAEARPLEGFGEVPEIIPLFLIYRPANNIPYATVEEELIGPFVKYSIRDGKE 161

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 254675181 2021 INFLRRDSEAGQKCCTFQHWVYQKTSGCLLVTDMQGVGMKLTDVGIATLARGYKGFKGNCSMTFIDQFRALHQCNKYC 2098
Cdd:cd16966   162 INFLRSESEAGQKCCTFQHWVYQWTNGCLLVTDLQGVGMKLTDVGIATLAKGYQGLKGNCSMTFIDQFAALHQCNKYC 239

Alpha-kinase family; This family is a novel family of eukaryotic protein kinase catalytic domains, which have no detectable similarity to conventional kinases. The family contains myosin heavy chain kinases and Elongation Factor-2 kinase and a bifunctional ion channel. This family is known as the alpha-kinase family. The structure of the kinase domain revealed unexpected similarity to eukaryotic protein kinases in the catalytic core as well as to metabolic enzymes with ATP-grasp domains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   1879 NDSYFGDHLRGQIstEELHFGEGVHRKAFRSKVMQGlmpvFQPGHACVLKVHNavahgTRNNDELVQRNYKlaaqECYVQ 1958
Cdd:smart00811    2 SGKWTVSETGVKI--ELKPFAKGAMRVAFRVKDLSE----DGSGTECVAKYFK-----KEYKNTVEDRYFE----DVEMQ 66

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   1959 NTARYYAKIYAAeaqpLEGFGEVPEIIPIFLIHRPENNIPY-ATVEEELIGEFVKYSIRDGKEINFLRRDSeagqKCCTF 2037
Cdd:smart00811   67 MVAKKFAEEFNQ----LKPSPKKIEFLPSYVLELPDRSIPYlFTVEPFLEGEFVKYNSNNGWVNDEARSTE----APQAF 138

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 254675181   2038 QHWVYQKTSGCLLVTDMQGVGMKLTDVGIATlARGYKGFKGNCSMTFIDQFRALHQCNKYC 2098
Cdd:smart00811  139 SHFTYERSGGSLLVVDLQGVGDLLTDPQIHT-EDGFGFGPGNLGEEGIEKFFATHKCNSIC 198

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   12 LCFLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARN 91
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 254675181   92 CVGMICCSASLEVQ 105
Cdd:cd20951    81 IHGEASSSASVVVE 94

Alpha-kinase domain of channel kinase 1, also called transient receptor potential cation channel subfamily M member 7; Channel kinase 1 (ChaK1), also called transient receptor potential cation channel subfamily M member 7 (TRMP7) or long transient receptor potential channel 7 (LTrpC7), is a fusion protein containing a transmembrane ion pore or channel and a C-terminal alpha-kinase domain, both of which are functional. It is ubiquitously expressed and is a cation-selective channel that preferentially permeates Zn2+, Mg2+, and Ca2+ ions. It is a central regulator of Mg2+ and Ca2+ homeostasis. TRPM7 plays a role in cancer proliferation, stroke, hydrogen peroxide dependent neurodegeneration, and heavy metal toxicity. Alpha-kinase is an atypical protein kinase catalytic domain with no detectable similarity to conventional protein serine/threonine kinases. The alpha-kinase family was named after the unique mode of substrate recognition by its initial members, the Dictyostelium heavy chain kinases, which targeted protein sequences that adopt an alpha-helical conformation. More recently, alpha-kinases were found to also target residues in non-helical regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1982 PEIIPIFLIHRPENNIPYAtVEEELIGEFVKYSIRDGKEI---NFLRRDSEAgqkcctFQHWVYQKTSGCLLVTDMQGVG 2058
Cdd:cd16971   121 PRFLEVFLLYCHSAGQWFA-VEECMTGEFRKYNNNNGDEIiptNMLEETMLA------FSHWTYEYTRGELLVLDLQGVG 193

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 254675181 2059 MKLTDVGIATlargyKGFKGNCSMTF---------IDQFRALHQCNKYCK 2099
Cdd:cd16971   194 ENLTDPSVIK-----AGEKRSYDMVFgpanlgedaIKNFRAKHHCNSCCR 238

Alpha-kinase domain of myosin heavy chain kinase and similar domains; This group is composed of alpha-kinase domains of Dictyostelium discoideum myosin heavy chain kinases A-D (MHCKA, MHCKB, MHCKC, MHCKD), alpha-protein kinase 1 (AK1), and similar proteins. The myosin heavy chain kinases are involved in regulating myosin II filament assembly in Dictyostelium discoideum. They phosphorylate target threonine residues located in the carboxyl-terminal portion of the myosin II heavy chain (MHC) tail, resulting in filament disassembly. The different MHCK isoforms display different spatial regulation, indicating specific roles for each isoform in fine tuning the Dictyostelium actomyosin cytoskeleton. They all contain an alpha-kinase domain as well as WD40 repeats at the C-terminus. AK1 contains an N-terminal Arf-GAP domain and a central alpha-kinase domain. Alpha-kinase is an atypical protein kinase catalytic domain with no detectable similarity to conventional protein serine/threonine kinases. The alpha-kinase family was named after the unique mode of substrate recognition by its initial members, the Dictyostelium heavy chain kinases, which targeted protein sequences that adopt an alpha-helical conformation. More recently, alpha-kinases were found to also target residues in non-helical regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1891 ISTEELHFGEGVHRKAFRSKVMQGLmpvfQPGHACVLKVhnavahgTRNNDELVQRNYklaaQECYVQNTARYYAKIYAA 1970
Cdd:cd16968    21 VKIDPKPFAEGALREAYHLKDLSAP----GPSTLFVAKL-------SKDPNESRETYF----EDVEMQMVCKKWAEKFNA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1971 EAQPLEgfgevPEIIPIF---LIHRPenNIPYATVEEELIGEFVKYSIrdgkeiNFLRRDSEAGQKCCTFQHWVYQKTSG 2047
Cdd:cd16968    86 KNPPKK-----VEFLPAWvleLVDRP--PPPLCGVEPFIEGEYVKHNN------NFGYVDEDERNTPQAFSHFTYEASGH 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 254675181 2048 CLLVTDMQGVGMKLTDVGIATLARgyKGF-KGNCSMTFIDQFRALHQCNKYC 2098
Cdd:cd16968   153 QLLVVDIQGVGDLYTDPQIHTIDG--KGFgKGNLGQKGIEKFLETHKCNAIC 202

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181    14 FLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIdlgGTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARNCV 93
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL---RSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 254675181    94 GMICCSASLEV 104
Cdd:pfam07679   80 GEAEASAELTV 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   14 FLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEffENQYIHLLHLSCCTQSDAAVYQVSARNCV 93
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLV--RENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 254675181   94 GMICCSASLEV 104
Cdd:cd05744    81 GENSFNAELVV 91

Alpha-kinase domain of Dictyostelium discoideum VwkA and similar domains; Dictyostelium discoideum alpha-protein kinase VwkA is also called von Willebrand factor A alpha-kinase or vWF kinase. It influences myosin II abundance and assembly behavior as vWKA gene disruption leads to significant myosin II overassembly. VwkA also serves a critical conserved role in the periodic contractions of the contractile vacuole through its regulation of the myosin II cortical cytoskeleton. It contains a vWFa domain (named after its homology to von Willebrand factor A, a plasma glycoprotein essential for proper blood clotting) and a C-terminal alpha-kinase domain. Alpha-kinase is an atypical protein kinase catalytic domain with no detectable similarity to conventional protein serine/threonine kinases. The alpha-kinase family was named after the unique mode of substrate recognition by its initial members, the Dictyostelium heavy chain kinases, which targeted protein sequences that adopt an alpha-helical conformation. More recently, alpha-kinases were found to also target residues in non-helical regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1999 YATVEEELIGEFVKYSIRDGkeiNFLRRDSEAGQkccTFQHWVYQKTSGCLLVTDMQGV-----GMKLTDVGI--ATLAR 2071
Cdd:cd16970   130 YYTMESFLEGEYKKFNNNVG---VVNEDEVEILQ---AFSHWTYEASKGYLMVVDLQGVrtdddGFLLTDPAIhcTDVLR 203

                          90       100       110
                  ....*....|....*....|....*....|...
gi 254675181 2072 ------GYKGfkgncsmtfIDQFRALHQCNKYC 2098
Cdd:cd16970   204 fgrtnlGKEG---------IDKFFATHKCNQHC 227

Alpha kinase family; uncharacterized subgroup; The alpha kinase family is a novel family of eukaryotic protein kinase catalytic domains, which have no detectable similarity to conventional serine/threonine protein kinases. The family contains myosin heavy chain kinases, elongation factor-2 kinases, and bifunctional ion channel kinases. These kinases are implicated in a large variety of cellular processes such as protein translation, Mg2+/Ca2+ homeostasis, intracellular transport, cell migration, adhesion, and proliferation. The alpha-kinase family was named after the unique mode of substrate recognition by its initial members, the Dictyostelium heavy chain kinases, which targeted protein sequences that adopt an alpha-helical conformation. More recently, alpha-kinases were found to also target residues in non-helical regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1891 ISTEELHFGEGVHRKAFRSKVMQglmpvfqpghaCVLKVHNAVAHGTRnndeLVQRNYKLAAQE----------CYVQNT 1960
Cdd:cd17508    19 IAVRKLPFGEGAERNVFRCTEIS-----------KEGGTKTATKIGPR----LVAKESRHAEDEsfdikfhkkfCKTQST 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1961 ARYYAKIYAAEAQPLEGfGEVPEI--IPIFLIHRPENNIPYAT---VEEELIGEFVKY---------SIRDGKEINFLRR 2026
Cdd:cd17508    84 AQELAERFNKRLRALPG-GPAPRVkfLPCHVYKTKDVSYRGRAwvlVEKELEGKFTKWntnaggvkkSIESVGEGRGESN 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 2027 DSEAGQKCCT--FQHWVYQKTSGCLLVTDMQGV------GMKLTDVGIAT-------LARGYKGFKGncsmtfIDQFRAL 2091
Cdd:cd17508   163 SSRLRVDDVPqaFSHFTYEHSGGRFLVCDLQGVwnatpdGFLLTDPVIHHvsgkrhrFGATDKGLEG------IRNFLRT 236

                  ....*..
gi 254675181 2092 HQCNKYC 2098
Cdd:cd17508   237 HKCSPLC 243

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   13 CFLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGT-VSSYEffENQYIHLLHLSCCTQSDAAVYQVSARN 91
Cdd:cd05892     2 MFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDrISLYQ--DNCGRICLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 254675181   92 CVGMICCSASLEV 104
Cdd:cd05892    80 EAGVVSCNARLDV 92

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   14 FLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAI-----------DLGGTVSsyeffenqyihlLHLSCCTQSDA 82
Cdd:cd05893     3 FEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQIspksdhytiqrDLDGTCS------------LHTTASTLDDD 70

                          90       100
                  ....*....|....*....|..
gi 254675181   83 AVYQVSARNCVGMICCSASLEV 104
Cdd:cd05893    71 GNYTIMAANPQGRISCTGRLMV 92

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   14 FLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDlggTVSSYEFFENQYIHLLHLSCCTQSDAAVYQVSARNCV 93
Cdd:cd20972     4 FIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQ---NSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 254675181   94 GMICCSASLEV 104
Cdd:cd20972    81 GSDTTSAEIFV 91

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   17 TLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIdlggtVSSYEF---FENQYIHLLHLSCCTQSDAAVYQVSARNCV 93
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPI-----VESRRFqidQDEDGLCSLIISDVCGDDSGKYTCKAVNSL 77

                          90
                  ....*....|.
gi 254675181   94 GMICCSASLEV 104
Cdd:cd20973    78 GEATCSAELTV 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181    23 VPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDlggtvSSYEFFENQYihllhlsccTQSDAAVYQVSARNCVGMiCCSASL 102
Cdd:pfam13895   11 VTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS-----SSPNFFTLSV---------SAEDSGTYTCVARNGRGG-KVSNPV 75

                   ...
gi 254675181   103 EVQ 105
Cdd:pfam13895   76 ELT 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   23 VPEKSDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEfFENQYIHLLhLSCCTQSDAAVYQVSARNCVGMICCSASL 102
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYK-VRNQHWSLI-MESVVPSDKGNYTCVVENEYGSINHTYHL 93

                  ..
gi 254675181  103 EV 104
Cdd:cd05857    94 DV 95

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 254675181   26 KSDVVLRCMIAGQPKPEVTWYKNGQAIDLGG---TVSSYEffenqyiHLLHLSCCTQSDAAVYQVSARNCVGMICCS 99
Cdd:cd05760    16 SSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQgnySVSSKE-------RTLTLRSAGPDDSGLYYCCAHNAFGSVCSS 85

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 254675181   27 SDVVLRCMIAGQPKPEVTWYKNGQAIDLGGTVSSYEFFENQYIhllhLSCCTQSDAAVYQVSARNCVGMICCSASLEV 104
Cdd:cd04978    15 ETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLI----FSNLQPNDTAVYQCNASNVHGYLLANAFLHV 88

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181   14 FLSTLLSQKVPEKSDVVLRCMIAGQPKPEVTWYKNGQAIdlggTVSSYEFFENQYIHL--LHLSCCTQSDAAVYQVSARN 91
Cdd:cd20975     3 FKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPV----RPDQRRFAEEAEGGLcrLRILAAERGDAGFYTCKAVN 78

                          90
                  ....*....|...
gi 254675181   92 CVGMICCSASLEV 104
Cdd:cd20975    79 EYGARQCEARLEV 91

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 254675181 1759 PVLLKRIQAEMAPEHSGNIKLSCQFsEIHEDSTVCWTKDSKSIAqakkSAGDNSSVS-----LAIVQAGQKDQGLYYCCL 1833
Cdd:cd05760     1 PVVLKHPASAAEIQPSSRVTLRCHI-DGHPRPTYQWFRDGTPLS----DGQGNYSVSskertLTLRSAGPDDSGLYYCCA 75

                          90
                  ....*....|....
gi 254675181 1834 KNSYGKVTAEFNLT 1847
Cdd:cd05760    76 HNAFGSVCSSQNFT 89