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 170014686  37 DVVTVVLGQDAKLPCFYRGDPDEQVGQVAWARVDPNEGIRELALLHSKYGLHVNPAYEDRVEQPPPPrDPLDGSVLLRNA 116
Cdd:cd05888    1 DVVTVVLGQDAKLPCFYRGDSGEQVGQVAWARVDAGEGAQEIALLHSKYGLHVFPAYEGRVEQPPPP-RPADGSVLLRNA 79

                         90       100
                 ....*....|....*....|....*....
gi 170014686 117 VQADEGEYECRVSTFPAGSFQARMRLRVL 145
Cdd:cd05888   80 VQADEGEYECRVSTFPAGNFQAELRLRVL 108

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 265 ATLKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD------TLGFPPLTTEHSGVYVCHVSNELSSRDSQVT 328
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselgngTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  37 DVVTVVLGQDAKLPCFYRGDPDEQVGQVAWARVDPNEGIRELALLHSKYGLHVNPAYEDRVEQPPPPrDPLDGSVLLRNA 116
Cdd:cd05888    1 DVVTVVLGQDAKLPCFYRGDSGEQVGQVAWARVDAGEGAQEIALLHSKYGLHVFPAYEGRVEQPPPP-RPADGSVLLRNA 79

                         90       100
                 ....*....|....*....|....*....
gi 170014686 117 VQADEGEYECRVSTFPAGSFQARMRLRVL 145
Cdd:cd05888   80 VQADEGEYECRVSTFPAGNFQAELRLRVL 108

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686   34 ETSDVVTVVLGQDAKLPCFYRGDPDEQVGQVAWARVDPNEGIRELALLHSKYGlhVNPAYEDRVEQPPPPRDPlDGSVLL 113
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPTFLIAYYSNGS--EEGVKKGRFSGRGDPSNG-DGSLTI 77

                          90       100       110
                  ....*....|....*....|....*....|..
gi 170014686  114 RNAVQADEGEYECRVSTFPAGSFQARMRLRVL 145
Cdd:pfam07686  78 QNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 265 ATLKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD------TLGFPPLTTEHSGVYVCHVSNELSSRDSQVT 328
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselgngTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 170014686  255 QNLWQVGREG--ATLKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD------TLGFPPLTTEHSGVYVCHVSN 318
Cdd:pfam13927   7 SPSSVTVREGetVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlsgsnsTLTISNVTRSDAGTYTCVASN 78

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  37 DVVTVVLGQDAKLPCFYRGDPDEQVGQVAWARVDPNEGIRELALLHSKYGLHVNPAYEDRVEQPPPPrDPLDGSVLLRNA 116
Cdd:cd05888    1 DVVTVVLGQDAKLPCFYRGDSGEQVGQVAWARVDAGEGAQEIALLHSKYGLHVFPAYEGRVEQPPPP-RPADGSVLLRNA 79

                         90       100
                 ....*....|....*....|....*....
gi 170014686 117 VQADEGEYECRVSTFPAGSFQARMRLRVL 145
Cdd:cd05888   80 VQADEGEYECRVSTFPAGNFQAELRLRVL 108

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 148 PLPSLNPGPPLEEGQGLTLAASCTAE-GSPAPSVTWDTEVKGTQSSRSFTHP-RSAAVTSEFHLVPSRSMNGQPLTCVVS 225
Cdd:cd05719    1 PTNSLEGGPALLIGGEPTLVATCISAnGKPPASVTWETDLKGEASTTQVRGSnGTVTVTSRYRLVPSREADGQPLTCVVE 80

                         90
                 ....*....|....*.
gi 170014686 226 HPGLLQDRRITHTLQV 241
Cdd:cd05719   81 HPSLEKDQRISVTLNV 96

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  150 PSLNPGPPLEEGQGLTLAASC-TAEGSPAPSVTWDTEVKG----TQSSRSFTHPRSAAVTSEFHLVPSRSMNGQPLTCVV 224
Cdd:pfam08205   1 PTIEPPASLLEGEGPEVVATCsSAGGKPAPRITWYLDGKPleaaETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQV 80

                  ....*
gi 170014686  225 SHPGL 229
Cdd:pfam08205  81 SYGAL 85

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  39 VTVVLGQDAKLPCfyRGDPDEQVGQVAWARVDPNeGIRELALLHSKYGLHVNPAYEDRVEQPPPprDPLDGSVLLRNAVQ 118
Cdd:cd05887    9 VTAVWGKNVSLKC--LIEVNETITQISWEKIHGK-SSQTVAVHHPQYGISIQGEYQGRVSFKNY--SLNDATITLHNVGF 83

                         90       100
                 ....*....|....*....|....*..
gi 170014686 119 ADEGEYECRVSTFPAGSFQARMRLRVL 145
Cdd:cd05887   84 SDSGKYICKAVTFPLGNAQSSTTVTVL 110

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 157 PLEEGQGLTLAASC-TAEGSPAPSVTWDTEVKG--TQSSRSFTHPRSAAVTSEFHLVPSRSMNGQPLTCVVSHPGLLQDR 233
Cdd:cd07703    9 EVQAGGIPVPVARCvSANGRPPARISWSSTLNGnaNTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTCKVEHETLEEPQ 88

                 ....*...
gi 170014686 234 RITHTLQV 241
Cdd:cd07703   89 LLPVTLSV 96

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686   258 WQVGREG--ATLKCLSEGQPPPKYNWTRLDG-PLPSGVRVKGD------TLGFPPLTTEHSGVYVCHVSNELSSRDSQVT 328
Cdd:smart00410   3 SVTVKEGesVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSrsgstsTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 170014686   329 VEV 331
Cdd:smart00410  83 LTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 170014686  255 QNLWQVGREG--ATLKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD------TLGFPPLTTEHSGVYVCHVSN 318
Cdd:pfam13927   7 SPSSVTVREGetVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlsgsnsTLTISNVTRSDAGTYTCVASN 78

Second immunoglobulin (Ig) domain of nectin-1, and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1, or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectin-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 156 PPLEEGQGLT---LAASCT-AEGSPAPSVTWDTEVKGTQSSRSFTHPR-SAAVTSEFHLVPSRSMNGQPLTCVVSHpgll 230
Cdd:cd05890   10 AVLRAKKGQDdkvLVATCTsANGKPPSVVSWDTRLKGEAEFQEIRNPNgTVTVISRYRLVPSREAHQQSLACIVNY---- 85

                 ....*....
gi 170014686 231 QDRRITHTL 239
Cdd:cd05890   86 HMDRFTDSL 94

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170014686 252 LEDQNLwqvgregaTLKCLSEGQPPPKYNWTrldgpLPSGVRVKGDTLGFPPLTTEHSGVYVCHVSNELSSRD-SQVTV 329
Cdd:cd20948    8 LSGENL--------NLSCHAASNPPAQYSWT-----INGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNiSLVLS 73

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 MuSK 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 170014686 263 EGATLKCLSEGQPPPKYNWTRLDGPLPSG-----VRVKGDTLGFPPLTTEHSGVYVCHVSNELSSRDSQ-VTVEV 331
Cdd:cd20970   18 ENATFMCRAEGSPEPEISWTRNGNLIIEFntryiVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSVEKrITLQV 92

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 170014686 267 LKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD---TLGFPPLTTEHSGVYVCHVSNELSSRDSQVTVEV 331
Cdd:cd05731   15 LECIAEGLPTPDIRWIKLGGELPKGRTKFENfnkTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 157 PLEEGQGLTLaaSCTAEGS-PAPSVTW---DTEVKGTQSSRSFTHPRSAAVTSEFHLVPSRSMNGQPLTCVVSHPGLLQD 232
Cdd:cd05761   15 PVVEGDEITL--TCTTSGSkPAADIRWfknDKELKGVKEVQESGAGKTFTVTSTLRFRVDRDDDGVAVICRVDHESLTST 92

                 ....
gi 170014686 233 RRIT 236
Cdd:cd05761   93 PKQT 96

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. 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. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170014686 266 TLKCLSEGQPPPKYNWTRLDGPLPSGVRVKGD---TLGFPPLTTEHSGVYVCHVSNELSSRDSQVTVEV 331
Cdd:cd05876   14 VLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNhnkTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Unlike aggrecan which is widely distributed in connective tissue and extracellular matrices, neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  35 TSDVVTVVLGQDAKLPCFY----RGDPDEQVGQVAWARVDPNEGIRELALLHSKYG-LHVNPAYEDRVEQPPPPRDPLDG 109
Cdd:cd05902    3 TAPPVRRPLSSSVLLPCVFtlppSASSPPEGPRIKWTKLSTSGGQQQRPVLVARDNvVRVAKAFQGRVSLPGYPKNRYNA 82

                         90
                 ....*....|....*....
gi 170014686 110 SVLLRNAVQADEGEYECRV 128
Cdd:cd05902   83 SLVLSRLRYSDSGTYRCEV 101

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 170014686 266 TLKCLSEGQPPPKYNWTRLDGPLPS--GVRVKGDTLGFPPLTTEHSGVYVCHVSN 318
Cdd:cd04968   20 TLECFALGNPVPQIKWRKVDGSPSSqwEITTSEPVLEIPNVQFEDEGTYECEAEN 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686    38 VVTVVLGQDAKLPCFYRGDPDEqvgQVAWARVDPNEgirelallhskyglhvnPAYEDRVEqppPPRDPLDGSVLLRNAV 117
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPP---EVTWYKQGGKL-----------------LAESGRFS---VSRSGSTSTLTISNVT 59

                           90       100
                   ....*....|....*....|....*..
gi 170014686   118 QADEGEYECRVsTFPAGSFQARMRLRV 144
Cdd:smart00410  60 PEDSGTYTCAA-TNSSGSASSGTTLTV 85

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170014686 266 TLKCLSEGQPPPKYNWTrLDG-PLPSGVRVK--------GDTLGFPPLT---TEHSGVYVCHVSNELSS 322
Cdd:cd20956   20 SLKCVASGNPLPQITWT-LDGfPIPESPRFRvgdyvtsdGDVVSYVNISsvrVEDGGEYTCTATNDVGS 87

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  41 VVLGQDAKLPCFYRgDPDEQVG----------QVAWARVDPNEGIRELALLHSKygLHVNPAYEDRVEQPPPPRDPLDGS 110
Cdd:cd05900    9 VVLGSSLLIPCYFQ-DPIAKDPgaptvaplspRIKWSFISKEKESVLLVATEGK--VRVNTEYLDRVSLPNYPAIPSDAT 85

                         90
                 ....*....|....*...
gi 170014686 111 VLLRNAVQADEGEYECRV 128
Cdd:cd05900   86 LEITELRSNDSGTYRCEV 103

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 170014686 266 TLKCLSEGQPPPKYNWTRLDGPLPSG-----VRVKGDTLGFPPLTTEHSGVYVCHVSNELSSRDSQ--VTVEVLD 333
Cdd:cd05760   20 TLRCHIDGHPRPTYQWFRDGTPLSDGqgnysVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSqnFTLSIID 94

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  153 NPGPPLEEGQGLTLaaSCTA-EGSPAPSVTWdtEVKGTQSSRSFTHPRSAAVT--SEFHLVPSRSMNGQPLTCVVSHPGL 229
Cdd:pfam00047   3 PPTVTVLEGDSATL--TCSAsTGSPGPDVTW--SKEGGTLIESLKVKHDNGRTtqSSLLISNVTKEDAGTYTCVVNNPGG 78

                  ....*..
gi 170014686  230 LQDRRIT 236
Cdd:pfam00047  79 SATLSTS 85

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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 170014686  33 LETSDVVTVvLGQDAKLPCFYRGDPdeqVGQVAWarvdpnegirelallhSKYGLHVNPAYEDRVEQPPpprdplDGSVL 112
Cdd:cd05722    6 SEPSDIVAM-RGGPVVLNCSAESDP---PPKIEW----------------KKDGVLLNLVSDERRQQLP------NGSLL 59

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 170014686 113 LRNAV-----QADEGEYECRVSTFPAGSFQARmRLRVLV 146
Cdd:cd05722   60 ITSVVhskhnKPDEGFYQCVAQNESLGSIVSR-TARVTV 97

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 150 PSLNPGPPLEEGQGLTLaaSCTAEGS---PAPSVTWDTEVKGTQSSRSFTHPRSAAVT--SEFHLVPSRSMNGQPLTCVV 224
Cdd:cd20987    1 PNIHVPEELEAGQEVTL--TCSVPDNcpaLSPEFSWLGAALTPLPPVLGRLEEEGTTThsSVLTFTPRPEDHGTNLTCQV 78

                 ....
gi 170014686 225 SHPG 228
Cdd:cd20987   79 KFPG 82

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  32 ELETSDVVTVVLGQDAKLPC-FYRGDPDEQVGQVAWARVDPNEGIRELALLHSKYGLHVN--PAYEDRVEQPPPPrDPLD 108
Cdd:cd05715    2 EVYTPRELNVLNGSDVRLTCtFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKPYILkvGRFKDRVSWAGNP-SKKD 80

                         90       100
                 ....*....|....*....|....
gi 170014686 109 GSVLLRNAVQADEGEYECRVSTFP 132
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPP 104

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 170014686 162 QGLTLAASCTAEGS-PAPSVTW---DTEVKGtQSSRSFTHPRSAAVTSEFHLVPSRSMNGQPLTCVVSHPGL--LQDRR 234
Cdd:cd05883   18 EGEEIELNCTAMASkPAATIRWfkgNKELTG-KSEVEEWYSRMFTVTSQLMLKVTKEDDGVPVICLVDHPAVkdLQTQR 95

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 154 PGPPLEEGQGLTLaaSCTAEG-SPAP-SVTW---DTEVKGTQSSRSFTHPR--SAAVTSEFHLVPSRSMNGQPLTCVVSH 226
Cdd:cd00098    7 PSPEEKGGGKVTL--VCLVSGfYPKDiTVTWlknGVPLTSGVSTSSPVEPNdgTYSVTSSLTVPPSDWDEGATYTCVVTH 84

                         90
                 ....*....|.
gi 170014686 227 PGLLQDRRITH 237
Cdd:cd00098   85 ESLKSPLSKTW 95

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686  252 LEDQNLWQvgREGATLKCLSEGQPPPKYNWTRLDGPLPSgvrvkGDTLGFPPLTTEHSGVYVCHVSNELSSRDSQ-VTVE 330
Cdd:pfam13895   6 PSPTVVTE--GEPVTLTCSAPGNPPPSYTWYKDGSAISS-----SPNFFTLSVSAEDSGTYTCVARNGRGGKVSNpVELT 78

                  .
gi 170014686  331 V 331
Cdd:pfam13895  79 V 79

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170014686 253 EDQNLWQvgREGATLKCLSEGQPPPKYNWTRLDGPLPSGVRVK------GDTLGFPPLTTEHSGVYVCHVSNELSSRDSQ 326
Cdd:cd05762    9 EDMKVRA--GESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKientenSSKLTITEGQQEHCGCYTLEVENKLGSRQAQ 86

                         90
                 ....*....|.
gi 170014686 327 VTVEVLDPEDP 337
Cdd:cd05762   87 VNLTVVDKPDP 97