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Conserved domains on  [gi|209977117|ref|NP_543148|]
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netrin receptor UNC5D isoform 1 precursor [Homo sapiens]

Protein Classification

UPA and Death_UNC5D domain-containing protein( domain architecture ID 11668633)

protein containing domains TSP1, ZU5, UPA, and Death_UNC5D

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
UPA pfam17217
UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich ...
 687-826 3.24e-82

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.


:

Pssm-ID: 465384  Cd Length: 140  Bit Score: 261.53  E-value: 3.24e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  687 AVKQLKVAVFGCMSCNSLDYNLRVYCVDNTPCAFQEVVSDERHQGGQLLEEPKLLHFKGNTFSLQISVLDIPPFLWRIKP 766
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  767 FTACQEVPFSRVWCSNRQPLHCAFSLERYTPTTTQLSCKICIRQLKGHEQILQVQTSILE 826
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTLAE 140
Death_UNC5D cd08801
Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). ...
 853-950 1.28e-66

Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). UNC5D is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


:

Pssm-ID: 176779  Cd Length: 98  Bit Score: 217.62  E-value: 1.28e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08801    1 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSIDRNLSYFATQSSPSAVILSLWEARHQHDGDLDSLACALEEIGRTHSKQ 80

                         90
                 ....*....|....*...
gi 209977117 933 SNISESQLDEADFNYSRQ 950
Cdd:cd08801   81 STIAETLDRESDFNYSRQ 98
ZU5 pfam00791
ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.
 544-639 4.65e-40

ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.


:

Pssm-ID: 459941  Cd Length: 97  Bit Score: 142.67  E-value: 4.65e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  544 TTGVFGHLGGRLVMPNTGVSLLIPHGAIPEENSWEIYMSINQGEPSL-QSDGSEVLLSPEVTCGPPDMIVTTPFALTIPH 622
Cdd:pfam00791   1 VSGLVDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRpPLEEGETLLSPVVECGPPGLKFLKPVILEVPH 80

                          90
                  ....*....|....*..
gi 209977117  623 CADVSSEHWNIHLKKRT 639
Cdd:pfam00791  81 CASLRPEEWEIVLKRSD 97
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 163-249 2.32e-18

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 cd05724:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 87  Bit Score: 80.52  E-value: 2.32e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 163 QDPQGREVPIEGMIVLHCRPPEGVPAAEVEWLKNEEPIDsEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIVAKRRS 242
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80


                 ....*..
gi 209977117 243 LSATVVV 249
Cdd:cd05724   81 RAARLSV 87
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 255-306 2.78e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 70.69  E-value: 2.78e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 209977117   255 WSSWTEWSACNVRCGRGWQKRSRTCTNPAPLNGGAFCEGMSVQKITC-TSLCP 306
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGGGPCTGEDVETRACnEQPCP 53
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 311-359 6.17e-10

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


:

Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 55.67  E-value: 6.17e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 209977117   311 WEVWSEWSVCSPECEH---LRIRECTAPPPRNGGKFCEGLSQESENCTDGLC 359
Cdd:smart00209   1 WSEWSEWSPCSVTCGGgvqTRTRSCCSPPPQNGGGPCTGEDVETRACNEQPC 52
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 54-155 7.76e-04

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 cd07693:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 99  Bit Score: 39.84  E-value: 7.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  54 PHFIEEPDDAYIIKSNPIALRCKA--RPAMQIFFKCNGEWV--HQNEHVSEETLDESSGLKVREVFINVTRQQVEDFhgp 129
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAegRPTPTIQWLKNGQPLetDKDDPRSHRIVLPSGSLFFLRVVHGRKGRSDEGV--- 77

                         90       100
                 ....*....|....*....|....*.
gi 209977117 130 edYWCqcVAWSHLGTSKSRKASVRIA 155
Cdd:cd07693   78 --YVC--VAHNSLGEAVSRNASLEVA 99
 
Name Accession Description Interval E-value
UPA pfam17217
UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich ...
 687-826 3.24e-82

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.


Pssm-ID: 465384  Cd Length: 140  Bit Score: 261.53  E-value: 3.24e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  687 AVKQLKVAVFGCMSCNSLDYNLRVYCVDNTPCAFQEVVSDERHQGGQLLEEPKLLHFKGNTFSLQISVLDIPPFLWRIKP 766
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  767 FTACQEVPFSRVWCSNRQPLHCAFSLERYTPTTTQLSCKICIRQLKGHEQILQVQTSILE 826
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTLAE 140
Death_UNC5D cd08801
Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). ...
 853-950 1.28e-66

Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). UNC5D is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 176779  Cd Length: 98  Bit Score: 217.62  E-value: 1.28e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08801    1 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSIDRNLSYFATQSSPSAVILSLWEARHQHDGDLDSLACALEEIGRTHSKQ 80

                         90
                 ....*....|....*...
gi 209977117 933 SNISESQLDEADFNYSRQ 950
Cdd:cd08801   81 STIAETLDRESDFNYSRQ 98
ZU5 pfam00791
ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.
 544-639 4.65e-40

ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.


Pssm-ID: 459941  Cd Length: 97  Bit Score: 142.67  E-value: 4.65e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  544 TTGVFGHLGGRLVMPNTGVSLLIPHGAIPEENSWEIYMSINQGEPSL-QSDGSEVLLSPEVTCGPPDMIVTTPFALTIPH 622
Cdd:pfam00791   1 VSGLVDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRpPLEEGETLLSPVVECGPPGLKFLKPVILEVPH 80

                          90
                  ....*....|....*..
gi 209977117  623 CADVSSEHWNIHLKKRT 639
Cdd:pfam00791  81 CASLRPEEWEIVLKRSD 97
ZU5 smart00218
Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.
 546-642 2.63e-23

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.


Pssm-ID: 128514  Cd Length: 104  Bit Score: 95.50  E-value: 2.63e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117   546 GVFGHLGGRLVMPNTGVSLLIPHGAIPEENSWEIYMSINQGE---PSLQsdGSEVLLSPEVTCGPPDMIVTTPFALTIPH 622
Cdd:smart00218   7 GTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLstpPPLE--EGETLLSPVVECGPHGALFLRPVILEVPH 84

                           90       100
                   ....*....|....*....|
gi 209977117   623 CADVSSEHWNIHLKKRTQQG 642
Cdd:smart00218  85 CASLRPRDWEIVLLRSENGG 104
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 163-249 2.32e-18

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: 80.52  E-value: 2.32e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 163 QDPQGREVPIEGMIVLHCRPPEGVPAAEVEWLKNEEPIDsEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIVAKRRS 242
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80


                 ....*..
gi 209977117 243 LSATVVV 249
Cdd:cd05724   81 RAARLSV 87
Death pfam00531
Death domain;
858-929 9.32e-16

Death domain;


Pssm-ID: 459845 [Multi-domain]  Cd Length: 86  Bit Score: 73.17  E-value: 9.32e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209977117  858 RQRICATFDTPNAKGKDWQMLAQKNSINRN-LSYFATQS----SPSAVILNLWEARHQHDGDLDSLACALEEIGRTH 929
Cdd:pfam00531   1 RKQLDRLLDPPPPLGKDWRELARKLGLSENeIDEIESENprlrSQTYELLRLWEQREGKNATVGTLLEALRKLGRRD 77
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 255-306 2.78e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 70.69  E-value: 2.78e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 209977117   255 WSSWTEWSACNVRCGRGWQKRSRTCTNPAPLNGGAFCEGMSVQKITC-TSLCP 306
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGGGPCTGEDVETRACnEQPCP 53
I-set pfam07679
Immunoglobulin I-set domain;
161-249 7.50e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.19  E-value: 7.50e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  161 FEQDPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIDTRAD-HNLIIRQARLSDSGNYTCMAANIVAK 239
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSSDRFKVTYEGGtYTLTISNVQPDDSGKYTCVATNSAGE 81

                          90
                  ....*....|
gi 209977117  240 RRSlSATVVV 249
Cdd:pfam07679  82 AEA-SAELTV 90
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 311-359 6.17e-10

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 55.67  E-value: 6.17e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 209977117   311 WEVWSEWSVCSPECEH---LRIRECTAPPPRNGGKFCEGLSQESENCTDGLC 359
Cdd:smart00209   1 WSEWSEWSPCSVTCGGgvqTRTRSCCSPPPQNGGGPCTGEDVETRACNEQPC 52
TSP_1 pfam00090
Thrombospondin type 1 domain;
256-303 1.95e-08

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 51.26  E-value: 1.95e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 209977117  256 SSWTEWSACNVRCGRGWQKRSRTCTNPAPlnGGAFCEGMSVQKITCTS 303
Cdd:pfam00090   1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFP--GGEPCTGDDIETQACKM 46
DEATH smart00005
DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain ...
 857-929 4.21e-08

DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.


Pssm-ID: 214467 [Multi-domain]  Cd Length: 88  Bit Score: 51.64  E-value: 4.21e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209977117   857 IRQRICATFDTPnaKGKDWQMLAQKNSINRN-LSYFATQS-----SPSAVILNLWEARHQHDGDLDSLACALEEIGRTH 929
Cdd:smart00005   4 TRQKLAKLLDHP--LGLDWRELARKLGLSEAdIDQIRTEAprdlaEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDD 80
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 165-251 4.30e-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: 51.35  E-value: 4.30e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117   165 PQGREVPIEGMIVLHCRPPeGVPAAEVEWLKN-EEPIDSEQDENIDTRA-DHNLIIRQARLSDSGNYTCMAANivaKRRS 242
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAS-GSPPPEVTWYKQgGKLLAESGRFSVSRSGsTSTLTISNVTPEDSGTYTCAATN---SSGS 76


                   ....*....
gi 209977117   243 LSATVVVYV 251
Cdd:smart00410  77 ASSGTTLTV 85
TSP_1 pfam00090
Thrombospondin type 1 domain;
313-359 7.41e-05

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 41.25  E-value: 7.41e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 209977117  313 VWSEWSVCSPECE---HLRIRECTAPPPrnGGKFCEGLSQESENCTDGLC 359
Cdd:pfam00090   2 PWSPWSPCSVTCGkgiQVRQRTCKSPFP--GGEPCTGDDIETQACKMDKC 49
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 54-155 7.76e-04

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. 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, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 39.84  E-value: 7.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  54 PHFIEEPDDAYIIKSNPIALRCKA--RPAMQIFFKCNGEWV--HQNEHVSEETLDESSGLKVREVFINVTRQQVEDFhgp 129
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAegRPTPTIQWLKNGQPLetDKDDPRSHRIVLPSGSLFFLRVVHGRKGRSDEGV--- 77

                         90       100
                 ....*....|....*....|....*.
gi 209977117 130 edYWCqcVAWSHLGTSKSRKASVRIA 155
Cdd:cd07693   78 --YVC--VAHNSLGEAVSRNASLEVA 99
 
Name Accession Description Interval E-value
UPA pfam17217
UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich ...
 687-826 3.24e-82

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.


Pssm-ID: 465384  Cd Length: 140  Bit Score: 261.53  E-value: 3.24e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  687 AVKQLKVAVFGCMSCNSLDYNLRVYCVDNTPCAFQEVVSDERHQGGQLLEEPKLLHFKGNTFSLQISVLDIPPFLWRIKP 766
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQLLEEPKTLHFKDSTHNLRLSIHDIPPSLWKSKL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  767 FTACQEVPFSRVWCSNRQPLHCAFSLERYTPTTTQLSCKICIRQLKGHEQILQVQTSILE 826
Cdd:pfam17217  81 FAKYQEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQVEGEGQIFQLYTTLAE 140
Death_UNC5D cd08801
Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). ...
 853-950 1.28e-66

Death domain found in Uncoordinated-5D; Death Domain (DD) found in Uncoordinated-5D (UNC5D). UNC5D is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 176779  Cd Length: 98  Bit Score: 217.62  E-value: 1.28e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08801    1 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSIDRNLSYFATQSSPSAVILSLWEARHQHDGDLDSLACALEEIGRTHSKQ 80

                         90
                 ....*....|....*...
gi 209977117 933 SNISESQLDEADFNYSRQ 950
Cdd:cd08801   81 STIAETLDRESDFNYSRQ 98
ZU5 pfam00791
ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.
 544-639 4.65e-40

ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.


Pssm-ID: 459941  Cd Length: 97  Bit Score: 142.67  E-value: 4.65e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  544 TTGVFGHLGGRLVMPNTGVSLLIPHGAIPEENSWEIYMSINQGEPSL-QSDGSEVLLSPEVTCGPPDMIVTTPFALTIPH 622
Cdd:pfam00791   1 VSGLVDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRpPLEEGETLLSPVVECGPPGLKFLKPVILEVPH 80

                          90
                  ....*....|....*..
gi 209977117  623 CADVSSEHWNIHLKKRT 639
Cdd:pfam00791  81 CASLRPEEWEIVLKRSD 97
Death_UNC5-like cd08781
Death domain found in Uncoordinated-5 homolog family; Death Domain (DD) found in ...
 853-935 1.79e-39

Death domain found in Uncoordinated-5 homolog family; Death Domain (DD) found in Uncoordinated-5 (UNC-5) homolog family, which includes Unc5A, B, C and D in vertebrates. UNC5 proteins are receptors for secreted netrins (netrin-1, -3 and -4) that are involved in diverse processes like axonal guidance, neuronal migration, blood vessel patterning, and apoptosis. They are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260051  Cd Length: 83  Bit Score: 140.49  E-value: 1.79e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08781    1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKLSVDRYINYFATKPSPTEVILDLWEARNRDDGALNSLAAILREMGRHDAAT 80


                 ...
gi 209977117 933 SNI 935
Cdd:cd08781   81 ILE 83
Death_UNC5B cd08802
Death domain found in Uncoordinated-5B; Death Domain (DD) found in Uncoordinated-5B (UNC5B). ...
 853-928 2.73e-33

Death domain found in Uncoordinated-5B; Death Domain (DD) found in Uncoordinated-5B (UNC5B). UNC5B is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5B signaling is involved in the netrin-1-induced proliferation and migration of renal proximal tubular cells. It is also required for vascular patterning during embryonic development, and its activation inhibits sprouting angiogenesis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 176780  Cd Length: 84  Bit Score: 123.21  E-value: 2.73e-33
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRT 928
Cdd:cd08802    1 IPLSIRQKICNSLDAPNSRGNDWRLLAQKLSMDRYLNYFATKASPTGVILDLWEARHQDDGDLNSLASALEEMGKS 76
Death_UNC5C cd08799
Death domain found in Uncoordinated-5C; Death Domain (DD) found in Uncoordinated-5C (UNC5C). ...
 853-933 1.57e-27

Death domain found in Uncoordinated-5C; Death Domain (DD) found in Uncoordinated-5C (UNC5C). UNC5C is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5C plays a critical role in the development of spinal accessory motor neurons. Methylation of the UNC5C gene is associated with early stages of colorectal carcinogenesis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260064  Cd Length: 83  Bit Score: 106.63  E-value: 1.57e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08799    1 IPLSIRQKLCGSLDAPQTRGNDWRMLAHKLNLDRYLNYFATKSSPTGVILDLWEAQHFPDGNLSRLAAVLEEMGRHETVV 80


                 .
gi 209977117 933 S 933
Cdd:cd08799   81 S 81
Death_UNC5A cd08800
Death domain found in Uncoordinated-5A; Death Domain (DD) found in Uncoordinated-5A (UNC5A). ...
 853-936 3.13e-26

Death domain found in Uncoordinated-5A; Death Domain (DD) found in Uncoordinated-5A (UNC5A). UNC5A is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a critical role in neuronal development and differentiation, as well as axon-guidance. It also plays a role in regulating apoptosis in non-neuronal cells as a downstream target of p53. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260065  Cd Length: 84  Bit Score: 103.04  E-value: 3.13e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 853 IPYSIRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEARHQHDGDLDSLACALEEIGRTHTKL 932
Cdd:cd08800    1 IPFLIRQKIISSLDPPCPRGADWRTLAQKLNLDSHLSFFASKSSPTAMILNLWEAQHFPNGNLSQLAAVVAEIGKQDAML 80


                 ....
gi 209977117 933 SNIS 936
Cdd:cd08800   81 FLVS 84
ZU5 smart00218
Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.
 546-642 2.63e-23

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.


Pssm-ID: 128514  Cd Length: 104  Bit Score: 95.50  E-value: 2.63e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117   546 GVFGHLGGRLVMPNTGVSLLIPHGAIPEENSWEIYMSINQGE---PSLQsdGSEVLLSPEVTCGPPDMIVTTPFALTIPH 622
Cdd:smart00218   7 GTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLstpPPLE--EGETLLSPVVECGPHGALFLRPVILEVPH 84

                           90       100
                   ....*....|....*....|
gi 209977117   623 CADVSSEHWNIHLKKRTQQG 642
Cdd:smart00218  85 CASLRPRDWEIVLLRSENGG 104
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 163-249 2.32e-18

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: 80.52  E-value: 2.32e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 163 QDPQGREVPIEGMIVLHCRPPEGVPAAEVEWLKNEEPIDsEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIVAKRRS 242
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80


                 ....*..
gi 209977117 243 LSATVVV 249
Cdd:cd05724   81 RAARLSV 87
Death pfam00531
Death domain;
858-929 9.32e-16

Death domain;


Pssm-ID: 459845 [Multi-domain]  Cd Length: 86  Bit Score: 73.17  E-value: 9.32e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209977117  858 RQRICATFDTPNAKGKDWQMLAQKNSINRN-LSYFATQS----SPSAVILNLWEARHQHDGDLDSLACALEEIGRTH 929
Cdd:pfam00531   1 RKQLDRLLDPPPPLGKDWRELARKLGLSENeIDEIESENprlrSQTYELLRLWEQREGKNATVGTLLEALRKLGRRD 77
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 255-306 2.78e-15

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 70.69  E-value: 2.78e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 209977117   255 WSSWTEWSACNVRCGRGWQKRSRTCTNPAPLNGGAFCEGMSVQKITC-TSLCP 306
Cdd:smart00209   1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNGGGPCTGEDVETRACnEQPCP 53
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 176-245 6.49e-11

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: 58.88  E-value: 6.49e-11
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209977117 176 IVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIDTR-ADHNLIIRQARLSDSGNYTCMAANIVAKRRSLSA 245
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSElGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70
I-set pfam07679
Immunoglobulin I-set domain;
161-249 7.50e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.19  E-value: 7.50e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  161 FEQDPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIDTRAD-HNLIIRQARLSDSGNYTCMAANIVAK 239
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSSDRFKVTYEGGtYTLTISNVQPDDSGKYTCVATNSAGE 81

                          90
                  ....*....|
gi 209977117  240 RRSlSATVVV 249
Cdd:pfam07679  82 AEA-SAELTV 90
TSP1 smart00209
Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
 311-359 6.17e-10

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.


Pssm-ID: 214559 [Multi-domain]  Cd Length: 53  Bit Score: 55.67  E-value: 6.17e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 209977117   311 WEVWSEWSVCSPECEH---LRIRECTAPPPRNGGKFCEGLSQESENCTDGLC 359
Cdd:smart00209   1 WSEWSEWSPCSVTCGGgvqTRTRSCCSPPPQNGGGPCTGEDVETRACNEQPC 52
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 161-249 8.25e-10

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: 56.35  E-value: 8.25e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 161 FEQDPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIdSEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIVAKr 240
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQA-TGEPVPTISWLKDGVPL-LGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGE- 78


                 ....*....
gi 209977117 241 RSLSATVVV 249
Cdd:cd20952   79 ATWSAVLDV 87
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
 166-248 2.53e-09

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 54.96  E-value: 2.53e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 166 QGREVPIEGMIVLHCrppEGVPAAEVEWLKNEEPIDSEQDENIDTRAD-HNLIIRQARLSDSGNYTCMAANIVAKRRSLS 244
Cdd:cd05736   10 QAKEPGVEASLRCHA---EGIPLPRVQWLKNGMDINPKLSKQLTLIANgSELHISNVRYEDTGAYTCIAKNEGGVDEDIS 86


                 ....
gi 209977117 245 ATVV 248
Cdd:cd05736   87 SLFV 90
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 176-251 3.38e-09

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: 54.82  E-value: 3.38e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209977117 176 IVLHCRPPEGVPAAEVEWLKNEEPIDSEQDENI---DTRADHNLIIRQARLSDSGNYTCMAANIVAKRrslSATVVVYV 251
Cdd:cd05750   17 LVLKCEATSENPSPRYRWFKDGKELNRKRPKNIkirNKKKNSELQINKAKLEDSGEYTCVVENILGKD---TVTGNVTV 92
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 165-235 4.67e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 53.72  E-value: 4.67e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209977117  165 PQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIDTRADH-NLIIRQARLSDSGNYTCMAAN 235
Cdd:pfam13927   8 PSSVTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNsTLTISNVTRSDAGTYTCVASN 78
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 160-249 7.54e-09

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: 53.74  E-value: 7.54e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 160 NFEQDPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIDTRAD-HNLIIRQARLSDSGNYTCMAANIVA 238
Cdd:cd20972    3 QFIQKLRSQEVAEGSKVRLECRV-TGNPTPVVRWFCEGKELQNSPDIQIHQEGDlHSLIIAEAFEEDTGRYSCLATNSVG 81

                         90
                 ....*....|.
gi 209977117 239 kRRSLSATVVV 249
Cdd:cd20972   82 -SDTTSAEIFV 91
TSP_1 pfam00090
Thrombospondin type 1 domain;
256-303 1.95e-08

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 51.26  E-value: 1.95e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 209977117  256 SSWTEWSACNVRCGRGWQKRSRTCTNPAPlnGGAFCEGMSVQKITCTS 303
Cdd:pfam00090   1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFP--GGEPCTGDDIETQACKM 46
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 160-249 3.47e-08

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth 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.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 51.69  E-value: 3.47e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 160 NFEQDPQGREVPIE--GMIVLHCRPpEGVPAAEVEWLKNEEPIdsEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIV 237
Cdd:cd04969    2 DFELNPVKKKILAAkgGDVIIECKP-KASPKPTISWSKGTELL--TNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFF 78

                         90
                 ....*....|..
gi 209977117 238 AKRRSlSATVVV 249
Cdd:cd04969   79 GKANS-TGSLSV 89
DEATH smart00005
DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain ...
 857-929 4.21e-08

DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.


Pssm-ID: 214467 [Multi-domain]  Cd Length: 88  Bit Score: 51.64  E-value: 4.21e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209977117   857 IRQRICATFDTPnaKGKDWQMLAQKNSINRN-LSYFATQS-----SPSAVILNLWEARHQHDGDLDSLACALEEIGRTH 929
Cdd:smart00005   4 TRQKLAKLLDHP--LGLDWRELARKLGLSEAdIDQIRTEAprdlaEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDD 80
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 165-251 4.30e-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: 51.35  E-value: 4.30e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117   165 PQGREVPIEGMIVLHCRPPeGVPAAEVEWLKN-EEPIDSEQDENIDTRA-DHNLIIRQARLSDSGNYTCMAANivaKRRS 242
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAS-GSPPPEVTWYKQgGKLLAESGRFSVSRSGsTSTLTISNVTPEDSGTYTCAATN---SSGS 76


                   ....*....
gi 209977117   243 LSATVVVYV 251
Cdd:smart00410  77 ASSGTTLTV 85
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 185-251 1.24e-07

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: 49.90  E-value: 1.24e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 185 GVPAAEVEWLKNEEPIDSEQDENIDTRADHN-LIIRQARLSDSGNYTCMAANIVAKRrslSATVVVYV 251
Cdd:cd05748   18 GRPTPTVTWSKDGQPLKETGRVQIETTASSTsLVIKNAKRSDSGKYTLTLKNSAGEK---SATINVKV 82
TSP1_spondin pfam19028
Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an ...
 256-291 1.39e-07

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.


Pssm-ID: 465948  Cd Length: 52  Bit Score: 48.81  E-value: 1.39e-07
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 209977117  256 SSWTEWSACNVRCGRGWQKRSRTCTNPaPLNGGAFC 291
Cdd:pfam19028   4 SEWSEWSECSVTCGGGVQTRTRTVIVE-PQNGGRPC 38
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 173-249 1.82e-07

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


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 49.73  E-value: 1.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 173 EGM-IVLHCRPpEGVPAAEVEWLKNEEPIDSEQDE---NIDTRAD-HNLIIRQARLSDSGNYTCMAANIvAKRRSLSATV 247
Cdd:cd20951   14 EKSdAKLRVEV-QGKPDPEVKWYKNGVPIDPSSIPgkyKIESEYGvHVLHIRRVTVEDSAVYSAVAKNI-HGEASSSASV 91


                 ..
gi 209977117 248 VV 249
Cdd:cd20951   92 VV 93
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 163-235 3.43e-07

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: 48.73  E-value: 3.43e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209977117  163 QDPQGREVPIEGMIVLHCRPPEGVPAAEVEWLK-NEEPIDSEQD-ENIDTRADHNLIIRQARLSDSGNYTCMAAN 235
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKeGGTLIESLKVkHDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75
Death_MyD88 cd08312
Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of ...
 858-927 4.26e-07

Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260026  Cd Length: 79  Bit Score: 48.37  E-value: 4.26e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209977117 858 RQRICATFDTPNAKGKDWQMLAQK-----NSInRNlsyFATQSSPSAVILNLWEARHQHdGDLDSLACALEEIGR 927
Cdd:cd08312    2 RKKLSLYLNPEKVVANDWRGLAELmgfdyLEI-RN---FERQSSPTERLLEDWETRPPG-ATVGNLLEILEELER 71
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 176-235 1.16e-06

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third 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.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 47.62  E-value: 1.16e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 176 IVLHCrPPEGVPAAEVEWLKNEEPIDSEQDENIDTRADHNLIIRQARLSDSGNYTCMAAN 235
Cdd:cd05730   21 VTLAC-DADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAEN 79
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 165-249 2.22e-06

Third 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 third 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 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, 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, and 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 Slit2 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: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 46.62  E-value: 2.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 165 PQGREVPIEGMIVLHCRPpEGVPAAEVEWLKN--EEPIDSEQdenidTRADHNLIIRQARLSDSGNYTCMAANIVAKrRS 242
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEV-GGDPVPTVRWRKEdgELPKGRYE-----ILDDHSLKIRKVTAGDMGSYTCVAENMVGK-IE 76


                 ....*..
gi 209977117 243 LSATVVV 249
Cdd:cd05725   77 ASATLTV 83
Ig6_Contactin cd04970
Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth ...
 193-249 3.64e-06

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.


Pssm-ID: 409359  Cd Length: 102  Bit Score: 46.39  E-value: 3.64e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209977117 193 WLKNEEPIDSEQDENIDTR-----ADHNLIIRQARLSDSGNYTCMAANIVAKRRSlSATVVV 249
Cdd:cd04970   38 WSFNGVPIDLEKIEGHYRRrygkdSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSA-SATLVV 98
Death_DAPK1 cd08782
Death domain found in death-associated protein kinase 1; Death domain (DD) found in ...
 857-927 4.77e-06

Death domain found in death-associated protein kinase 1; Death domain (DD) found in death-associated protein kinase 1 (DAPK1). DAPK1 is composed of several functional domains, including a kinase domain, a CaM regulatory domain, ankyrin repeats, a cytoskeletal-binding domain and a C-terminal DD. It plays important roles in a diverse range of signal transduction pathways including apoptosis, growth factor signalling, and autophagy. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260052  Cd Length: 82  Bit Score: 45.41  E-value: 4.77e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209977117 857 IRQRICATFDTPNAKGKDWQMLAQKNSINRNLSYFAT----QSSPSAVILNLWEARhqHDGDLDSLACALEEIGR 927
Cdd:cd08782    2 TRRKLARLLDPPDPMGRDWCLLAVNLGLTDLVAKLDStsspLPSPTDRLLQEWTAR--PPSTIGALLRKLRELGR 74
IgI_VEGFR cd04976
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member ...
 185-249 5.03e-06

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: 45.67  E-value: 5.03e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 185 GVPAAEVEWLKNEEPIDseqdENIDTRADHNLIIRQARLSDSGNYTCMAANIVAK-RRSLSATVVV 249
Cdd:cd04976   29 AYPPPEVVWYKDGLPLT----EKARYLTRHSLIIKEVTEEDTGNYTILLSNKQSNvFKNLTATLVV 90
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 161-235 6.17e-06

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


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 45.56  E-value: 6.17e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 161 FEQDPQGREVpIEG-MIVLHCRPpEGVPAAEVEWLKNEEPI--DSEQDENIDTRADHNLIIRQARLSDSGNYTCMAAN 235
Cdd:cd05744    3 FLQAPGDLEV-QEGrLCRFDCKV-SGLPTPDLFWQLNGKPVrpDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARN 78
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 176-249 6.72e-06

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin 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 domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the 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: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 45.08  E-value: 6.72e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 209977117 176 IVLHCRPpEGVPAAEVEWLKNEEPIDSEQdENIdTRADHNLIIRQARLSDSGNYTCMAANIVAKRRSlSATVVV 249
Cdd:cd20978   19 VTLPCQV-TGVPQPKITWLHNGKPLQGPM-ERA-TVEDGTLTIINVQPEDTGYYGCVATNEIGDIYT-ETLLHV 88
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 170-249 1.74e-05

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 43.92  E-value: 1.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  170 VPIEGMIVLHCRPPeGVPAAEVEWLKNEEPIDSEQdenidtradhNLIIRQARLSDSGNYTCMAANIVAKRRSLSATVVV 249
Cdd:pfam13895  11 VTEGEPVTLTCSAP-GNPPPSYTWYKDGSAISSSP----------NFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 172-249 3.60e-05

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: 43.27  E-value: 3.60e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 172 IEG-MIVLHCRPpEGVPAAEVEWLKNEEPIDsEQDENIDTRAD-HNLIIRQARLSDSGNYTCMAANIVAKRRSLSATVVV 249
Cdd:cd20970   15 REGeNATFMCRA-EGSPEPEISWTRNGNLII-EFNTRYIVRENgTTLTIRNIRRSDMGIYLCIASNGVPGSVEKRITLQV 92
IgI_1_Contactin cd04967
First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; ...
 161-247 4.06e-05

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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.


Pssm-ID: 409356 [Multi-domain]  Cd Length: 96  Bit Score: 43.39  E-value: 4.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 161 FEQDPQGREVP---IEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIdTRADHNLIIRQ-ARLSDSGNYTCMAANI 236
Cdd:cd04967    4 FEEQPDDTIFPedsDEKKVALNCRA-RANPVPSYRWLMNGTEIDLESDYRY-SLVDGTLVISNpSKAKDAGHYQCLATNT 81

                         90
                 ....*....|.
gi 209977117 237 VAKRRSLSATV 247
Cdd:cd04967   82 VGSVLSREATL 92
IgI_1_Contactin-1 cd05849
First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; ...
 161-247 4.07e-05

First immunoglobulin (Ig) domain of contactin-1; 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-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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.


Pssm-ID: 409436 [Multi-domain]  Cd Length: 95  Bit Score: 43.40  E-value: 4.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 161 FEQDPQGREVP---IEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENidTRADHNLIIRQA-RLSDSGNYTCMAANI 236
Cdd:cd05849    4 FEEQPIDTIYPeesTEGKVSVNCRA-RANPFPIYKWRKNNLDIDLTNDRY--SMVGGNLVINNPdKYKDAGRYVCIVSNI 80

                         90
                 ....*....|.
gi 209977117 237 VAKRRSLSATV 247
Cdd:cd05849   81 YGKVRSREATL 91
TSP_1 pfam00090
Thrombospondin type 1 domain;
313-359 7.41e-05

Thrombospondin type 1 domain;


Pssm-ID: 459668 [Multi-domain]  Cd Length: 49  Bit Score: 41.25  E-value: 7.41e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 209977117  313 VWSEWSVCSPECE---HLRIRECTAPPPrnGGKFCEGLSQESENCTDGLC 359
Cdd:pfam00090   2 PWSPWSPCSVTCGkgiQVRQRTCKSPFP--GGEPCTGDDIETQACKMDKC 49
Death_NFkB-like cd08310
Death domain of Nuclear Factor-KappaB precursor proteins; Death Domain (DD) of Nuclear ...
 857-928 8.50e-05

Death domain of Nuclear Factor-KappaB precursor proteins; Death Domain (DD) of Nuclear Factor-KappaB (NF-kB) precursor proteins. The NF-kB family of transcription factors play a central role in cardiovascular growth, stress response, and inflammation by controlling the expression of a network of different genes. There are five NF-kB proteins, all containing an N-terminal REL Homology Domain (RHD). Two of these, NF-kB1 and NF-kB2 are produced from the processing of the precursor proteins p105 and p100, respectively. In addition to RHD, p105 and p100 contain ANK repeats and a C-terminal DD. NF-kBs are regulated by the Inhibitor of NF-kB (IkB) Kinase (IKK) complex through classical and non-canonical pathways, which differ in the IKK subunits involved and downstream targets. IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. The precursor proteins p105 and p100 function as IkBs and as NF-kB proteins after being processed by the proteasome. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260024  Cd Length: 72  Bit Score: 41.46  E-value: 8.50e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209977117 857 IRQRICATFDtpnaKGKDWQMLAQKNSINRNLSYFATQSSPSAVILNLWEarhQHDGDLDSLACALEEIGRT 928
Cdd:cd08310    1 TRLRLCKLLD----VGKDWRELAELLGLGHLVESIEQSSSPTKLLLDYYE---AQGGTLEKLREALRALGET 65
Ig2_Contactin-2-like cd05727
Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 176-237 1.09e-04

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 409392  Cd Length: 88  Bit Score: 41.78  E-value: 1.09e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 209977117 176 IVLHCRPPEGVPAAEVEWLKNEEPIDSEQDENI-DTRADHNLIIRQARLSDSGNYTCMAANIV 237
Cdd:cd05727   13 VVLFCDPPPHYPDLSYRWLLNEFPNFIPEDGRRfVSQTNGNLYIAKVEASDRGNYSCFVSSPS 75
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 170-235 1.46e-04

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 41.82  E-value: 1.46e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 170 VPIEGMIVLHCrPPEGVPAAEVEWLKNEEPIDSEQDENI-DTRADH-NLIIRQARLSDSGNYTCMAAN 235
Cdd:cd05729   16 LPAANKVRLEC-GAGGNPMPNITWLKDGKEFKKEHRIGGtKVEEKGwSLIIERAIPRDKGKYTCIVEN 82
IgI_1_Contactin-5 cd05848
First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; ...
 161-247 1.55e-04

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: 41.47  E-value: 1.55e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 161 FEQDPQGREVPI---EGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEQDENIdTRADHNLIIRQA-RLSDSGNYTCMAANI 236
Cdd:cd05848    4 FVQEPDDAIFPTdsdEKKVILNCEA-RGNPVPTYRWLRNGTEIDTESDYRY-SLIDGNLIISNPsEVKDSGRYQCLATNS 81

                         90
                 ....*....|.
gi 209977117 237 VAKRRSLSATV 247
Cdd:cd05848   82 IGSILSREALL 92
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 184-249 1.61e-04

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


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 41.41  E-value: 1.61e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 184 EGVPAAEVEWLKNEEPIDSEQDENIDTRADHN--LIIRQARLSDSGNYTCMAANiVAKRRSLSATVVV 249
Cdd:cd20973   22 EGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcsLIISDVCGDDSGKYTCKAVN-SLGEATCSAELTV 88
Ig_Sema3 cd05871
Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed ...
 178-233 1.92e-04

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.


Pssm-ID: 409455  Cd Length: 92  Bit Score: 41.18  E-value: 1.92e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 178 LHCRPPEgvPAAEVEWL--KNEEPIDSE--QDENIdTRADHNLIIRQARLSDSGNYTCMA 233
Cdd:cd05871   17 LECLPKS--PQATVKWLfqRGGDQRKEEvkSEERL-IVTDRGLLLRSLQRSDAGVYTCQA 73
Ig_Pro_neuregulin-1 cd05895
Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of ...
 168-249 1.93e-04

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.


Pssm-ID: 409476  Cd Length: 93  Bit Score: 41.13  E-value: 1.93e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 168 REVPIEGMIVLHCRPPEGVPAAEVEWLKNEEPIDSE-QDENIDTRAD---HNLIIRQARLSDSGNYTCMAANIVAKrRSL 243
Cdd:cd05895    9 QEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINRKnKPENIKIQKKkkkSELRINKASLADSGEYMCKVSSKLGN-DSA 87


                 ....*.
gi 209977117 244 SATVVV 249
Cdd:cd05895   88 SANVTI 93
TSP1_ADAMTS pfam19030
Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found ...
 259-292 1.96e-04

Thrombospondin type 1 domain; This subfamily of thrombospondin type 1 repeats are mainly found in ADAMTS proteins.


Pssm-ID: 465950 [Multi-domain]  Cd Length: 55  Bit Score: 40.13  E-value: 1.96e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 209977117  259 TEWSACNVRCGRGWQKRSRTCTNPAP--LNGGAFCE 292
Cdd:pfam19030   4 GPWGECSVTCGGGVQTRLVQCVQKGGgsIVPDSECS 39
IgI_2_RPTP_IIa_LAR_like cd05738
Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; ...
 185-249 2.12e-04

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.


Pssm-ID: 409400 [Multi-domain]  Cd Length: 91  Bit Score: 41.15  E-value: 2.12e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 185 GVPAAEVEWLKNEEPIDSEQ-DENIDTRADHNLIIRQARLSDSGNYTCMAANIVAKRRSLSATVVV 249
Cdd:cd05738   25 GNPDPEISWFKDFLPVDTATsNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSAPANLYV 90
IgI_2_L1-CAM_like cd05845
Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
 176-234 2.49e-04

Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins. 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 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: 409432  Cd Length: 91  Bit Score: 40.94  E-value: 2.49e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209977117 176 IVLHCRPPEGVPAAEVEWLKNE-EPIdsEQDENIDTRADHNLIIRQARLSDSGN-YTCMAA 234
Cdd:cd05845   15 VVLPCNPPKGAPPPRIYWMNSSlEHI--TQDERVSMGQNGDLYFSNVMEQDSHPdYICHAH 73
IgI_VEGFR-2 cd05864
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); ...
 185-247 2.66e-04

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); 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 2 (VEGFR-2). 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. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; 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. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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: 409450  Cd Length: 89  Bit Score: 40.68  E-value: 2.66e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 185 GVPAAEVEWLKNEEPIDSeqdeNIDTRADHNLIIRQARLSDSGNYTCMAANIVAK---RRSLSATV 247
Cdd:cd05864   28 GYPPPEIKWYKNGIPIES----NHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKekqRHTFSLVV 89
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 161-235 2.75e-04

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 40.66  E-value: 2.75e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209977117 161 FEQDPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSEqdENIDTRADhNLIIRQARLSDSGNYTCMAAN 235
Cdd:cd05728    2 WLKVISDTEADIGSSLRWECKA-SGNPRPAYRWLKNGQPLASE--NRIEVEAG-DLRITKLSLSDSGMYQCVAEN 72
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 178-249 2.76e-04

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. 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, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 41.00  E-value: 2.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 178 LHCRPpEGVPAAEVEWLKNEEPIDSEQDeniDTRADHNLII------------RQARlSDSGNYTCMAANIVAKRRSLSA 245
Cdd:cd07693   20 LNCKA-EGRPTPTIQWLKNGQPLETDKD---DPRSHRIVLPsgslfflrvvhgRKGR-SDEGVYVCVAHNSLGEAVSRNA 94


                 ....
gi 209977117 246 TVVV 249
Cdd:cd07693   95 SLEV 98
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
 170-235 2.90e-04

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


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 40.99  E-value: 2.90e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 170 VPIEGMIVLHCrPPEGVPAAEVEWLKNEEPIDSEQD-ENIDTRADH-NLIIRQARLSDSGNYTCMAAN 235
Cdd:cd05857   16 VPAANTVKFRC-PAAGNPTPTMRWLKNGKEFKQEHRiGGYKVRNQHwSLIMESVVPSDKGNYTCVVEN 82
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 172-251 4.80e-04

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 39.93  E-value: 4.80e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 172 IEGM-IVLHCrPPEGVPAAEVEWLKNEEPIDSEQDENIDTRADHNLIIRQARLSDSGNYTCMAANIVAkrrSLSATVVVY 250
Cdd:cd20976   14 VEGQdFVAQC-SARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG---QVSCSAWVT 89


                 .
gi 209977117 251 V 251
Cdd:cd20976   90 V 90
IgI_6_Dscam cd20959
Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 175-249 5.49e-04

Sixth 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 sixth 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: 409551  Cd Length: 94  Bit Score: 40.17  E-value: 5.49e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209977117 175 MIVLHCRPPEGVPAAEVEWLKNEEPIDSEQDENIdTRADHN---LIIRQARLSDSGNYTCMAANiVAKRRSLSATVVV 249
Cdd:cd20959   19 RAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITV-SRLGRRssiLSIDSLEASHAGNYTCHARN-SAGSASYTAPLTV 94
IgI_Lingo-1 cd20969
Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing ...
 176-235 6.06e-04

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409561  Cd Length: 92  Bit Score: 39.68  E-value: 6.06e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209977117 176 IVLHCRPpEGVPAAEVEWL-KNEEPIDSEQDENIDTRADHNLIIRQARLSDSGNYTCMAAN 235
Cdd:cd20969   20 VQFVCRA-DGDPPPAILWLsPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAAN 79
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 54-155 7.76e-04

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. 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, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 39.84  E-value: 7.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117  54 PHFIEEPDDAYIIKSNPIALRCKA--RPAMQIFFKCNGEWV--HQNEHVSEETLDESSGLKVREVFINVTRQQVEDFhgp 129
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAegRPTPTIQWLKNGQPLetDKDDPRSHRIVLPSGSLFFLRVVHGRKGRSDEGV--- 77

                         90       100
                 ....*....|....*....|....*.
gi 209977117 130 edYWCqcVAWSHLGTSKSRKASVRIA 155
Cdd:cd07693   78 --YVC--VAHNSLGEAVSRNASLEVA 99
IgI_2_JAM1 cd20950
Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF ...
 170-235 1.53e-03

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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: 409542  Cd Length: 97  Bit Score: 38.84  E-value: 1.53e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 209977117 170 VPIEGMIVLHCRPPEGVPAAEVEWLKN-----EEPIDSEQDENIDTRADHN---LIIRQARLSDSGNYTCMAAN 235
Cdd:cd20950    9 ATIGNRAVLTCSEPDGSPPSEYTWFKDgvvmpTNPKSTRAFSNSSYSLDPTtgeLVFDPLSASDTGEYSCEARN 82
Death cd01670
Death Domain: a protein-protein interaction domain; Death Domains (DDs) are protein-protein ...
 872-928 1.76e-03

Death Domain: a protein-protein interaction domain; Death Domains (DDs) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. Structural analysis of DD-DD complexes show that the domains interact with each other in many different ways. DD-containing proteins serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes. In mammals, they are prominent components of the programmed cell death (apoptosis) pathway and are found in a number of other signaling pathways. In invertebrates, they are involved in transcriptional regulation of zygotic patterning genes in insect embryogenesis, and are components of the ToII/NF-kappaB pathway, a conserved innate immune pathway in animal cells.


Pssm-ID: 260017 [Multi-domain]  Cd Length: 79  Bit Score: 38.03  E-value: 1.76e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 209977117 872 GKDWQMLAQKNSINRN-LSYFATQSSPSAV-----ILNLWEARHQHDGDLDSLACALEEIGRT 928
Cdd:cd01670   10 GRDWKKLARKLGLSEGdIDQIEEDNRDDLKeqayqMLERWREREGDEATLGRLIQALREIGRR 72
IgI_Perlecan_like cd05754
Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of ...
 163-235 2.24e-03

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412  Cd Length: 85  Bit Score: 37.92  E-value: 2.24e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 163 QDPQGREVPIEGMIVLHCRPPEGVPAAEVEWLKNEEPIDSeqdenidtRA-DHN--LIIRQARLSDSGNYTCMAAN 235
Cdd:cd05754    6 EEPRSQEVRPGADVSFICRAKSKSPAYTLVWTRVNGTLPS--------RAmDFNgiLTIRNVQLSDAGTYVCTGSN 73
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
 164-235 2.38e-03

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 38.30  E-value: 2.38e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209977117 164 DPQGREVPIEGMIVLHCrPPEGVPAAEVEWLKNeepidSEQDENIDTRADH-----------NLIIRQARLSDSGNYTCM 232
Cdd:cd05765    6 SPTHQTVKVGETASFHC-DVTGRPQPEITWEKQ-----VPGKENLIMRPNHvrgnvvvtnigQLVIYNAQPQDAGLYTCT 79


                 ...
gi 209977117 233 AAN 235
Cdd:cd05765   80 ARN 82
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 164-235 2.78e-03

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 37.90  E-value: 2.78e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209977117 164 DPQGREVPIEGMIVLHCRPpEGVPAAEVEWLKNEEPIDSeqDENIDTRADHNLIIRQARLSDSGNYTCMAAN 235
Cdd:cd20957    7 DPPVQTVDFGRTAVFNCSV-TGNPIHTVLWMKDGKPLGH--SSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75
Ig1_IL1R_like cd05756
First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; ...
 193-248 3.39e-03

First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.


Pssm-ID: 409414  Cd Length: 96  Bit Score: 37.79  E-value: 3.39e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 209977117 193 WLKN--EEPIDSEQDENIDTRADhNLIIRQARLSDSGNYTCMAANIV-AKRRSLSATVV 248
Cdd:cd05756   39 WYKNdsETPISFEPDSRIHQEKD-KLWFVPALLEDSGNYYCVVRNSTyCSKVSISLEVV 96
Death_p75NR cd08311
Death domain of p75 Neurotrophin Receptor; Death Domain (DD) found in p75 neurotrophin ...
 872-927 5.68e-03

Death domain of p75 Neurotrophin Receptor; Death Domain (DD) found in p75 neurotrophin receptor (p75NTR, NGFR, TNFRSF16). p75NTR binds members of the neurotrophin (NT) family including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT3, among others. It contains an NT-binding extracellular region that bears four cysteine-rich repeats, a transmembrane domain, and an intracellular DD. p75NTR plays roles in the immune, vascular, and nervous systems, and has been shown to promote cell death or survival, and to induce neurite outgrowth or collapse depending on its ligands and co-receptors. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.


Pssm-ID: 260025  Cd Length: 80  Bit Score: 36.50  E-value: 5.68e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 209977117 872 GKDWQMLAQKnsinrnLSY-------FATQSSPSAVILNLWEarHQHDGDLDSLACALEEIGR 927
Cdd:cd08311   18 GSDWRALAGE------LGYsaeeidsFAREADPCRALLTDWS--AQDGATLGVLLTALRKIGR 72
Ig2_FcgammaR_like cd05753
Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; ...
 176-251 6.09e-03

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second 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: 409411  Cd Length: 83  Bit Score: 36.51  E-value: 6.09e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209977117 176 IVLHCRPPEGVPAAEVEWLKNEEPIDSeqdenidTRADHNLIIRQARLSDSGNYTCmAANIVAKRRSlSATVVVYV 251
Cdd:cd05753   17 LTLRCHGWKDKKVHKVTYYKDGKALKF-------SYENSNFSIPQATLSDSGSYHC-SGTVRIKRRS-SESVNITV 83
 
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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