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Conserved domains on  [gi|77176454|ref|NP_001029181|]
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cell surface glycoprotein MUC18 isoform 2 precursor [Rattus norvegicus]

Protein Classification

C2-set_2 and Ig domain-containing protein( domain architecture ID 11173850)

protein containing domains C2-set_2, and Ig

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2-set_2 pfam08205
CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.
 141-236 2.95e-20

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


:

Pssm-ID: 400489  Cd Length: 89  Bit Score: 85.55  E-value: 2.95e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454   141 PTIQANVLGIhvDIQELKEVATCVGRNGYPIPQVIWYKNGRPLqeeenRVHIQSSQTVESSGLYTLKSVLSARLVKEDKD 220
Cdd:pfam08205   1 PTIEPPASLL--EGEGPEVVATCSSAGGKPAPRITWYLDGKPL-----EAAETSSEQDPESGLVTVTSELKLVPSRSDHG 73

                          90
                  ....*....|....*.
gi 77176454   221 AQFYCELSYRLPSGNR 236
Cdd:pfam08205  74 QSLTCQVSYGALRGSI 89
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 348-412 5.30e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


:

Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 53.34  E-value: 5.30e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454   348 VQVDPTAPEVQEGDSLTLTCKAESNQDLEFEWLRDKT---------GQLLGKGPILQLNNVKREAGGRYLCVAS 412
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 264-323 1.03e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


:

Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 46.79  E-value: 1.03e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77176454   264 LKEGDHVKIRCLTDGNPQPHFTI---NKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPTITWyknGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 452-508 4.95e-06

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.


The actual alignment was detected with superfamily member cd04978:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 89  Bit Score: 45.13  E-value: 4.95e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 452 LSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLNVLVTPEL--LETGA-ECTASNSLG 508
Cdd:cd04978  19 LICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLqpNDTAVyQCNASNVHG 78
CD19_double_Ig super family cl49627
CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, ...
 43-120 3.19e-03

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding.


The actual alignment was detected with superfamily member cd23998:

Pssm-ID: 483967  Cd Length: 95  Bit Score: 37.08  E-value: 3.19e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454  43 GNTALLKCGPAHPSGNFSQVEWFLIH-KERQIPIFRVHQGKGQsePGEYEHRLSLHGPGATLALSQVTPHDDRMFLCKS 120
Cdd:cd23998   8 GSTLWLSCGVPPDSGTRGPISWTHVHpKPSNTSLLSLELKEDR--PAREKWVLGTLRGGALLLLPRATAQDAGIYHCHL 84
 
Name Accession Description Interval E-value
C2-set_2 pfam08205
CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.
 141-236 2.95e-20

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


Pssm-ID: 400489  Cd Length: 89  Bit Score: 85.55  E-value: 2.95e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454   141 PTIQANVLGIhvDIQELKEVATCVGRNGYPIPQVIWYKNGRPLqeeenRVHIQSSQTVESSGLYTLKSVLSARLVKEDKD 220
Cdd:pfam08205   1 PTIEPPASLL--EGEGPEVVATCSSAGGKPAPRITWYLDGKPL-----EAAETSSEQDPESGLVTVTSELKLVPSRSDHG 73

                          90
                  ....*....|....*.
gi 77176454   221 AQFYCELSYRLPSGNR 236
Cdd:pfam08205  74 QSLTCQVSYGALRGSI 89
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 348-412 5.30e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 53.34  E-value: 5.30e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454   348 VQVDPTAPEVQEGDSLTLTCKAESNQDLEFEWLRDKT---------GQLLGKGPILQLNNVKREAGGRYLCVAS 412
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 356-415 1.83e-08

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.74  E-value: 1.83e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454    356 EVQEGDSLTLTCKAESNQDLEFEWLRDKTGQLLGKG----------PILQLNNVKREAGGRYLCVASVPS 415
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSS 74
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 264-323 1.03e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 46.79  E-value: 1.03e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77176454   264 LKEGDHVKIRCLTDGNPQPHFTI---NKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPTITWyknGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 452-508 4.95e-06

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.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 45.13  E-value: 4.95e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 452 LSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLNVLVTPEL--LETGA-ECTASNSLG 508
Cdd:cd04978  19 LICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLqpNDTAVyQCNASNVHG 78
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 437-505 4.71e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.78  E-value: 4.71e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77176454   437 AKERKVWAQENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLN-VLVTPELLETGA---ECTASN 505
Cdd:pfam13927   6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNsTLTISNVTRSDAgtyTCVASN 78
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 363-412 6.84e-05

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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 41.16  E-value: 6.84e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454 363 LTLTCKAESNQDLEFEWLRDKTGQLLGKGP---------ILQLNNVKREAGGRYLCVAS 412
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDsrrselgngTLTISNVTLEDSGTYTCVAS 59
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 270-323 8.58e-05

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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 41.16  E-value: 8.58e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454 270 VKIRCLTDGNPQPHFT---INKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:cd00096   1 VTLTCSASGNPPPTITwykNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 159-192 6.80e-04

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 38.92  E-value: 6.80e-04
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 77176454 159 EVAT--CVGRNGYPIPQVIWYKNGRPLQEEENRVHI 192
Cdd:cd05724  13 EMAVleCSPPRGHPEPTVSWRKDGQPLNLDNERVRI 48
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 260-323 1.94e-03

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 37.48  E-value: 1.94e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77176454    260 PVGLLKEGDHVKIRCLTDGNPQPHFTINKKNPSTEEMEE----ESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCA 69
CD19_protodomain_3_4 cd23998
CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 ...
 43-120 3.19e-03

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 and 4; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding. This group contains the protodomains 3 and 4 of the CD19 double Ig domain.


Pssm-ID: 467825  Cd Length: 95  Bit Score: 37.08  E-value: 3.19e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454  43 GNTALLKCGPAHPSGNFSQVEWFLIH-KERQIPIFRVHQGKGQsePGEYEHRLSLHGPGATLALSQVTPHDDRMFLCKS 120
Cdd:cd23998   8 GSTLWLSCGVPPDSGTRGPISWTHVHpKPSNTSLLSLELKEDR--PAREKWVLGTLRGGALLLLPRATAQDAGIYHCHL 84
 
Name Accession Description Interval E-value
C2-set_2 pfam08205
CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.
 141-236 2.95e-20

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


Pssm-ID: 400489  Cd Length: 89  Bit Score: 85.55  E-value: 2.95e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454   141 PTIQANVLGIhvDIQELKEVATCVGRNGYPIPQVIWYKNGRPLqeeenRVHIQSSQTVESSGLYTLKSVLSARLVKEDKD 220
Cdd:pfam08205   1 PTIEPPASLL--EGEGPEVVATCSSAGGKPAPRITWYLDGKPL-----EAAETSSEQDPESGLVTVTSELKLVPSRSDHG 73

                          90
                  ....*....|....*.
gi 77176454   221 AQFYCELSYRLPSGNR 236
Cdd:pfam08205  74 QSLTCQVSYGALRGSI 89
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 348-412 5.30e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 53.34  E-value: 5.30e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454   348 VQVDPTAPEVQEGDSLTLTCKAESNQDLEFEWLRDKT---------GQLLGKGPILQLNNVKREAGGRYLCVAS 412
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 356-415 1.83e-08

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.74  E-value: 1.83e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454    356 EVQEGDSLTLTCKAESNQDLEFEWLRDKTGQLLGKG----------PILQLNNVKREAGGRYLCVASVPS 415
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSS 74
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 351-427 3.87e-07

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 47.77  E-value: 3.87e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454   351 DPTAPEVQEGDSLTLTCKAESNQDLEFEWLRDktGQLLGKGPILQLNNVKREAGGRYLCVASVPSVPGLNRTRRVSV 427
Cdd:pfam13895   5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKD--GSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 264-323 1.03e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 46.79  E-value: 1.03e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77176454   264 LKEGDHVKIRCLTDGNPQPHFTI---NKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPTITWyknGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
I-set pfam07679
Immunoglobulin I-set domain;
356-415 3.26e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 45.71  E-value: 3.26e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454   356 EVQEGDSLTLTCKAESNQDLEFEWLRDktGQLLGKGPILQL-----------NNVKREAGGRYLCVASVPS 415
Cdd:pfam07679  11 EVQEGESARFTCTVTGTPDPEVSWFKD--GQPLRSSDRFKVtyeggtytltiSNVQPDDSGKYTCVATNSA 79
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 452-508 4.95e-06

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.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 45.13  E-value: 4.95e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 452 LSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLNVLVTPEL--LETGA-ECTASNSLG 508
Cdd:cd04978  19 LICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLqpNDTAVyQCNASNVHG 78
IgI_L1-CAM_like cd05733
Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; ...
 452-515 3.21e-05

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.


Pssm-ID: 409396 [Multi-domain]  Cd Length: 94  Bit Score: 42.78  E-value: 3.21e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77176454 452 LSCEASGHPQPTISWNINGsaTEWNP--DPQTVVS----TLNVLV---TPELLETGAECTASNSLG---SNTTVII 515
Cdd:cd05733  21 IKCEAKGNPQPTFRWTKDG--KFFDPakDPRVSMRrrsgTLVIDNhngGPEDYQGEYQCYASNELGtaiSNEIRLV 94
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 450-515 3.28e-05

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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 42.32  E-value: 3.28e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77176454 450 LNLSCEASGHPQPTISWNINGSATEWNPDP----QTVVSTLNVL-VTPEllETGA-ECTASNSLGSNTTVII 515
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDsrrsELGNGTLTISnVTLE--DSGTyTCVASNSAGGSASASV 70
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
 444-508 4.48e-05

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 42.51  E-value: 4.48e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77176454 444 AQENAMLNLSCEASGHPQPTISWNI---NGSATEWNPDPQTVV------STLNvLVTPELLETGA-ECTASNSLG 508
Cdd:cd05732  13 AVELEQITLTCEAEGDPIPEITWRRatrGISFEEGDLDGRIVVrgharvSSLT-LKDVQLTDAGRyDCEASNRIG 86
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 437-505 4.71e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.78  E-value: 4.71e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77176454   437 AKERKVWAQENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLN-VLVTPELLETGA---ECTASN 505
Cdd:pfam13927   6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNsTLTISNVTRSDAgtyTCVASN 78
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 350-427 4.94e-05

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.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.18  E-value: 4.94e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454   350 VDPTAPEVQEGDSLTLTCKAESNQDL-EFEWLRDKTGQLLG--KGPI--------LQLNNVKREAGGRYLCVAsvpSVPG 418
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGpDVTWSKEGGTLIESlkVKHDngrttqssLLISNVTKEDAGTYTCVV---NNPG 77


                  ....*....
gi 77176454   419 LNRTRRVSV 427
Cdd:pfam00047  78 GSATLSTSL 86
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 363-412 6.84e-05

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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 41.16  E-value: 6.84e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454 363 LTLTCKAESNQDLEFEWLRDKTGQLLGKGP---------ILQLNNVKREAGGRYLCVAS 412
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDsrrselgngTLTISNVTLEDSGTYTCVAS 59
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 270-323 8.58e-05

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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 41.16  E-value: 8.58e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454 270 VKIRCLTDGNPQPHFT---INKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:cd00096   1 VTLTCSASGNPPPTITwykNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgC2_CD22_d3 cd20937
Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 ...
 347-418 8.86e-05

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. 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. 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.


Pssm-ID: 409531  Cd Length: 88  Bit Score: 41.71  E-value: 8.86e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454 347 DVQVDPTAPEVQEGDSLTLTCKAESNQDL--EFEWLRDKTGQLLGKGPILQLNNVKREAGGRYLCVASVPSVPG 418
Cdd:cd20937   4 EIKVTPSDAIVREGDSVTMTCEVSSSNPEytTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPG 77
IgI_NrCAM cd05874
Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); ...
 452-514 1.35e-04

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.


Pssm-ID: 409458  Cd Length: 95  Bit Score: 41.12  E-value: 1.35e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454 452 LSCEASGHPQPTISWNINGSATEWNPDPQ--------TVVSTLNVLVTPELLETGAECTASNSLG---SNTTVI 514
Cdd:cd05874  21 IQCEAKGKPPPSFSWTRNGTHFDIDKDPKvtmkpntgTLVINIMNGEKAEAYEGVYQCTARNERGaavSNNIVI 94
Ig4_NrCAM cd05868
Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The ...
 451-508 1.75e-04

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.


Pssm-ID: 409454  Cd Length: 89  Bit Score: 40.73  E-value: 1.75e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454 451 NLSCEASGHPQPTISWNINGSATEWNP-DPQTVVSTLNVLVTPELLETGA--ECTASNSLG 508
Cdd:cd05868  18 TLICRANGNPKPSISWLTNGVPIEIAPtDPSRKVDGDTIIFSKVQERSSAvyQCNASNEYG 78
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 357-412 1.84e-04

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.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 40.57  E-value: 1.84e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454 357 VQEGDSLTLTCKAESNQDLEFEWLRDK-------TGQLL-GKGPILQLNNVKREAGGRYLCVAS 412
Cdd:cd20970  14 AREGENATFMCRAEGSPEPEISWTRNGnliiefnTRYIVrENGTTLTIRNIRRSDMGIYLCIAS 77
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 355-412 3.17e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 40.19  E-value: 3.17e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454 355 PEVQEGDSLTLTCKAES-NQDLEFEWLRDKTgQLLGKGPI------------LQLNNVKREAGGRYLCVAS 412
Cdd:cd05750   9 QTVQEGSKLVLKCEATSeNPSPRYRWFKDGK-ELNRKRPKnikirnkkknseLQINKAKLEDSGEYTCVVE 78
IgI_hCEACAM_2_4_6_like cd05740
Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion ...
 357-414 5.03e-04

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. 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. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.


Pssm-ID: 409402 [Multi-domain]  Cd Length: 89  Bit Score: 39.30  E-value: 5.03e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454 357 VQEGDSLTLTCKAEsNQDLEFEWLRDktGQLLGKGPILQL---------NNVKREAGGRYLCVASVP 414
Cdd:cd05740  12 VEDKDAVTLTCEPE-TQNTSYLWWFN--GQSLPVTPRLTLsngnrtltlLNVTREDAGAYQCEISNP 75
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 450-509 5.13e-04

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.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 39.47  E-value: 5.13e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454 450 LNLSCEASGHPQPTISWNINGSATEWNPDPQ---------TVVSTLNVL-VTPEllETGA-ECTASNSLGS 509
Cdd:cd20956  19 VSLKCVASGNPLPQITWTLDGFPIPESPRFRvgdyvtsdgDVVSYVNISsVRVE--DGGEyTCTATNDVGS 87
I-set pfam07679
Immunoglobulin I-set domain;
440-514 6.18e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 39.16  E-value: 6.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454   440 RKVWAQENAMLNLSCEASGHPQPTISWNINGSATewNPDPQTVVSTLNVLVTPELLETGAE------CTASNSLGSNTTV 513
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL--RSSDRFKVTYEGGTYTLTISNVQPDdsgkytCVATNSAGEAEAS 85


                  .
gi 77176454   514 I 514
Cdd:pfam07679  86 A 86
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 159-192 6.80e-04

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 38.92  E-value: 6.80e-04
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 77176454 159 EVAT--CVGRNGYPIPQVIWYKNGRPLQEEENRVHI 192
Cdd:cd05724  13 EMAVleCSPPRGHPEPTVSWRKDGQPLNLDNERVRI 48
IgI_1_Contactin-5 cd05848
First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; ...
 446-509 1.08e-03

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409435  Cd Length: 96  Bit Score: 38.77  E-value: 1.08e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454 446 ENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLNVLVT--PELLETGA-ECTASNSLGS 509
Cdd:cd05848  18 DEKKVILNCEARGNPVPTYRWLRNGTEIDTESDYRYSLIDGNLIISnpSEVKDSGRyQCLATNSIGS 84
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 350-415 1.26e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 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


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 38.25  E-value: 1.26e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77176454 350 VDPTAPEVQEGDSLTLTCKAESNQDLEFEWLRDKTgQLLGKGP--------ILQLNNVKREAGGRYLCVASVPS 415
Cdd:cd20952   4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGV-PLLGKDErittlengSLQIKGAEKSDTGEYTCVALNLS 76
IgI_NCAM-1 cd05869
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members ...
 450-511 1.45e-03

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 143277 [Multi-domain]  Cd Length: 97  Bit Score: 38.42  E-value: 1.45e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454 450 LNLSCEASGHPQPTISWNI---NGSATEWNPDPQTVVST---LNVLVTPELLETGAE---CTASNSLGSNT 511
Cdd:cd05869  20 ITLTCEASGDPIPSITWRTstrNISSEEKTLDGHIVVRSharVSSLTLKYIQYTDAGeylCTASNTIGQDS 90
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 446-513 1.48e-03

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 37.61  E-value: 1.48e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454 446 ENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVVS-TLNVLVTPELLETGAECTASNSLGSNTTV 513
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSgTLRISRVALHDQGQYECQAVNIVGSQRTV 69
IgI_hNeurofascin_like cd05875
Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig ...
 452-509 1.48e-03

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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 lacks a C" strand.


Pssm-ID: 409459  Cd Length: 95  Bit Score: 38.42  E-value: 1.48e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77176454 452 LSCEASGHPQPTISWNINGSATEWNPDPQ-TVVSTLNVLV-------TPELLETGAECTASNSLGS 509
Cdd:cd05875  21 IECEAKGNPVPTFHWTRNGKFFNVAKDPRvSMRRRSGTLVidfrgggRPEDYEGEYQCFARNKFGT 86
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 433-512 1.54e-03

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.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 37.95  E-value: 1.54e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 433 PWMAAKERKVWAQENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVV-STLNVLVTPELLE--TGA-ECTASNSLG 508
Cdd:cd20972   2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQeGDLHSLIIAEAFEedTGRySCLATNSVG 81


                ....
gi 77176454 509 SNTT 512
Cdd:cd20972  82 SDTT 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 260-323 1.94e-03

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 37.48  E-value: 1.94e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77176454    260 PVGLLKEGDHVKIRCLTDGNPQPHFTINKKNPSTEEMEE----ESTDENGLLSLEPAQKHHSGVYQCQ 323
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCA 69
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 444-505 2.31e-03

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.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 37.49  E-value: 2.31e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77176454 444 AQENAMLNLSCEASGHPQPTISWNINGSATEWNPDPQTVVSTLNVLVTPEL--LETGAE-CTASN 505
Cdd:cd20970  14 AREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIrrSDMGIYlCIASN 78
IgC2_CEACAM5-like cd20948
Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell ...
 359-427 2.75e-03

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.


Pssm-ID: 409540  Cd Length: 76  Bit Score: 37.09  E-value: 2.75e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77176454 359 EGDSLTLTCKAESNQDLEFEWLRDKTGQLLGKgpILQLNNVKREAGGRYLCVASvPSVPGLNRTRRVSV 427
Cdd:cd20948   9 SGENLNLSCHAASNPPAQYSWTINGTFQTSSQ--ELFLPAITENNEGTYTCSAH-NSLTGKNISLVLSV 74
IgI_VEGFR cd04976
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member ...
 168-206 2.81e-03

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. 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.


Pssm-ID: 409365  Cd Length: 90  Bit Score: 37.19  E-value: 2.81e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 77176454 168 GYPIPQVIWYKNGRPLqEEENRVHIQSSQTV-----ESSGLYTL 206
Cdd:cd04976  29 AYPPPEVVWYKDGLPL-TEKARYLTRHSLIIkevteEDTGNYTI 71
CD19_protodomain_3_4 cd23998
CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 ...
 43-120 3.19e-03

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 and 4; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding. This group contains the protodomains 3 and 4 of the CD19 double Ig domain.


Pssm-ID: 467825  Cd Length: 95  Bit Score: 37.08  E-value: 3.19e-03
                        10        20        30        40        50        60        70
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gi 77176454  43 GNTALLKCGPAHPSGNFSQVEWFLIH-KERQIPIFRVHQGKGQsePGEYEHRLSLHGPGATLALSQVTPHDDRMFLCKS 120
Cdd:cd23998   8 GSTLWLSCGVPPDSGTRGPISWTHVHpKPSNTSLLSLELKEDR--PAREKWVLGTLRGGALLLLPRATAQDAGIYHCHL 84
IgC2_D1_D2_LILR_KIR_like cd16843
Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer ...
 258-342 3.27e-03

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.


Pssm-ID: 409518 [Multi-domain]  Cd Length: 90  Bit Score: 36.97  E-value: 3.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 258 VEPVGLLKEGDHVKIRCltdGNPQPHFT----INKKNPSTEEMEEESTDENGLLSLEPAQKHHSGVYQCQSlDLETTVML 333
Cdd:cd16843   6 AEPSSVVPLGENVTIRC---QGPPEAVLfqlyKEGNSLSQGTVREKEPQNKAEFYIPHMDRNHAGRYRCRY-RSGTLWSE 81


                ....*....
gi 77176454 334 SSDPLELLV 342
Cdd:cd16843  82 PSDPLELVV 90
Ig4_L1-CAM_like cd05867
Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members ...
 452-508 4.42e-03

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.


Pssm-ID: 409453 [Multi-domain]  Cd Length: 89  Bit Score: 36.80  E-value: 4.42e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77176454 452 LSCEASGHPQPTISWNINGSATE-WNPDPQTVVSTlNVLVTPELLETGA---ECTASNSLG 508
Cdd:cd05867  19 LDCQVEGIPTPNITWSINGAPIEgTDPDPRRHVSS-GALILTDVQPSDTavyQCEARNRHG 78
CD19_double_Ig cd23997
CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, ...
 38-134 4.55e-03

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding.


Pssm-ID: 467824  Cd Length: 89  Bit Score: 36.55  E-value: 4.55e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454  38 VEVEVGNTALLKCGPAHPSGNFSQVEWFLIHKErqIPIFRVHQGkgqsEPGEYEHRLSLhgpGATLALSQVTPHDDRMFL 117
Cdd:cd23997   3 VTVAEGSTLWLPCLVPPSDGPRGPLTWSRGHPK--TPLLSLELG----SPGLWVLVGPL---GILLLLPNVSAQMGGFYL 73

                        90
                ....*....|....*..
gi 77176454 118 CKsKQPRPQDHYVQLQV 134
Cdd:cd23997  74 CE-LGNLSWTIGWTVSV 89
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 168-207 6.60e-03

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 36.03  E-value: 6.60e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 77176454 168 GYPIPQVIWYKNGRPLQEEEnRVHIQSSQTVES----------SGLYTLK 207
Cdd:cd05748  18 GRPTPTVTWSKDGQPLKETG-RVQIETTASSTSlviknakrsdSGKYTLT 66
Ig1_FcgammaR_like cd05752
First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; ...
 162-213 6.99e-03

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.


Pssm-ID: 409410 [Multi-domain]  Cd Length: 79  Bit Score: 35.80  E-value: 6.99e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 77176454 162 TCVGRNGYPIPQVIWYKNGRPLQEEENRVHIQSSqTVESSGLYTLKSVLSAR 213
Cdd:cd05752  21 TCQGFYSPEQNSTQWYHNGTLISSTSSSYRIVAA-TVNDSGEYRCQTQGSSL 71
IgI_2_Axl_Tyro3_like cd05749
Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); ...
 447-514 7.77e-03

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.


Pssm-ID: 409407  Cd Length: 82  Bit Score: 35.90  E-value: 7.77e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77176454 447 NAMLNLSCEASGHPQP-TISWNINGS--ATEWNPDPqtvvSTLNVlvtPELLETGA-ECTASNSLG---SNTTVI 514
Cdd:cd05749  14 NTPFNLTCQAVGPPEPvEILWWQGGSplGGPPAPSP----SVLNV---PGLNETTKfSCEAHNAKGltsSRTATV 81
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
 433-514 7.78e-03

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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.


Pssm-ID: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 35.91  E-value: 7.78e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77176454 433 PWMAAKERKVWAQENAMLNLSCEASGHPQPTISWNI-------NGSATEWNPDpqtvvSTLNVLVTpELLETGA-ECTAS 504
Cdd:cd05764   1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISpegklisNSSRTLVYDN-----GTLDILIT-TVKDTGAfTCIAS 74

                        90
                ....*....|
gi 77176454 505 NSLGSNTTVI 514
Cdd:cd05764  75 NPAGEATARV 84
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 449-512 9.26e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 35.45  E-value: 9.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77176454   449 MLNLSCEASGHPQPTISWNINGSATEWNPDpqtvvstlnvLVTPELLETGA---ECTASNSLGSNTT 512
Cdd:pfam13895  16 PVTLTCSAPGNPPPSYTWYKDGSAISSSPN----------FFTLSVSAEDSgtyTCVARNGRGGKVS 72
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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