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Conserved domains on  [gi|226498466|ref|NP_001140198|]
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T-cell immunoglobulin and mucin domain-containing protein 4 isoform 2 precursor [Homo sapiens]

Protein Classification

immunoglobulin domain-containing family protein( domain architecture ID 34076)

immunoglobulin (Ig) domain-containing family protein is a member of a large superfamily containing cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system, molecules involved in antigen presentation to lymphocytes, cell adhesion molecules, certain cytokine receptors and intracellular muscle proteins; immunoglobulin domains are typically divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 28-129 1.73e-39

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 cd20982:

Pssm-ID: 472250  Cd Length: 107  Bit Score: 135.28  E-value: 1.73e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  28 VTEVLGHRVTLPCLYS-SWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESD 106
Cdd:cd20982    3 YRAEVGHNAYLPCSYTtAAPGNLVPVCWGKGACPVSYCGNVLLRTDERDVTYQKSSRYQLKGDFSKGDVSLTIENVTLAD 82

                         90       100
                 ....*....|....*....|...
gi 226498466 107 SGVYCCRIEVPGWFNDVKINVRL 129
Cdd:cd20982   83 SGIYCCRIQIPGIMNDEKFNLKL 105
 
Name Accession Description Interval E-value
IgV_TIM-3_like cd20982
Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3) ...
 28-129 1.73e-39

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.


Pssm-ID: 409574  Cd Length: 107  Bit Score: 135.28  E-value: 1.73e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  28 VTEVLGHRVTLPCLYS-SWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESD 106
Cdd:cd20982    3 YRAEVGHNAYLPCSYTtAAPGNLVPVCWGKGACPVSYCGNVLLRTDERDVTYQKSSRYQLKGDFSKGDVSLTIENVTLAD 82

                         90       100
                 ....*....|....*....|...
gi 226498466 107 SGVYCCRIEVPGWFNDVKINVRL 129
Cdd:cd20982   83 SGIYCCRIQIPGIMNDEKFNLKL 105
V-set pfam07686
Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 ...
 23-128 6.74e-18

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


Pssm-ID: 462230  Cd Length: 109  Bit Score: 78.27  E-value: 6.74e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466   23 TSETVVTEVLGHRVTLPCLY-SSWSHNSNSMCWGKDQCPYsGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILN 101
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYsSSMSEASTSVYWYRQPPGK-GPTFLIAYYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQN 79

                          90       100       110
                  ....*....|....*....|....*....|
gi 226498466  102 PSESDSGVYCCRI---EVPGWFNDVKINVR 128
Cdd:pfam07686  80 LTLSDSGTYTCAVipsGEGVFGKGTRLTVL 109
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 27-115 6.60e-03

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 35.17  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466    27 VVTEVLGHRVTLPClySSWSHNSNSMCWgkdqcpysgckealIRTDGMRVTSRKsakyRLQGTIPRGDVSLTILNPSESD 106
Cdd:smart00410   3 SVTVKEGESVTLSC--EASGSPPPEVTW--------------YKQGGKLLAESG----RFSVSRSGSTSTLTISNVTPED 62


                   ....*....
gi 226498466   107 SGVYCCRIE 115
Cdd:smart00410  63 SGTYTCAAT 71
 
Name Accession Description Interval E-value
IgV_TIM-3_like cd20982
Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3) ...
 28-129 1.73e-39

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.


Pssm-ID: 409574  Cd Length: 107  Bit Score: 135.28  E-value: 1.73e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  28 VTEVLGHRVTLPCLYS-SWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESD 106
Cdd:cd20982    3 YRAEVGHNAYLPCSYTtAAPGNLVPVCWGKGACPVSYCGNVLLRTDERDVTYQKSSRYQLKGDFSKGDVSLTIENVTLAD 82

                         90       100
                 ....*....|....*....|...
gi 226498466 107 SGVYCCRIEVPGWFNDVKINVRL 129
Cdd:cd20982   83 SGIYCCRIQIPGIMNDEKFNLKL 105
V-set pfam07686
Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 ...
 23-128 6.74e-18

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


Pssm-ID: 462230  Cd Length: 109  Bit Score: 78.27  E-value: 6.74e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466   23 TSETVVTEVLGHRVTLPCLY-SSWSHNSNSMCWGKDQCPYsGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILN 101
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYsSSMSEASTSVYWYRQPPGK-GPTFLIAYYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQN 79

                          90       100       110
                  ....*....|....*....|....*....|
gi 226498466  102 PSESDSGVYCCRI---EVPGWFNDVKINVR 128
Cdd:pfam07686  80 LTLSDSGTYTCAVipsGEGVFGKGTRLTVL 109
IgV_pIgR_like cd05716
Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The ...
 23-130 6.00e-06

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.


Pssm-ID: 409381  Cd Length: 100  Bit Score: 44.31  E-value: 6.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  23 TSETVVTEVLGHRVTLPCLYSSWSHNSN-SMC-WGKDQCpysgckEALIRTDGMRVTSRKSAkyRLQGTipRGDVSLTIL 100
Cdd:cd05716    2 VGPEVVTGVEGGSVTIQCPYPPKYASSRkYWCkWGSEGC------QTLVSSEGVVPGGRISL--TDDPD--NGVFTVTLN 71

                         90       100       110
                 ....*....|....*....|....*....|
gi 226498466 101 NPSESDSGVYCCRIEVPGWFnDVKINVRLN 130
Cdd:cd05716   72 QLRKEDAGWYWCGVGDDGDR-GLTVQVKLV 100
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 25-113 2.18e-04

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: 39.68  E-value: 2.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  25 ETVVTEVLGHRVTLPCLYS-------SWSHNsnsmcwGKdqcpysgckealirtdgmrvtsrksakyRLQGTIPRGDV-- 95
Cdd:cd20978    8 EKNVVVKGGQDVTLPCQVTgvpqpkiTWLHN------GK----------------------------PLQGPMERATVed 53

                         90
                 ....*....|....*....
gi 226498466  96 -SLTILNPSESDSGVYCCR 113
Cdd:cd20978   54 gTLTIINVQPEDTGYYGCV 72
IgV cd00099
Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin ...
 33-112 4.96e-04

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.


Pssm-ID: 409355 [Multi-domain]  Cd Length: 111  Bit Score: 39.24  E-value: 4.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  33 GHRVTLPCLYSSwSHNSNSMCW---GKDQCPysgckEALIRTDGMRVTSRKSAKYRLQGTIPRG-DVSLTILNPSESDSG 108
Cdd:cd00099   13 GESVTLSCEVSS-SFSSTYIYWyrqKPGQGP-----EFLIYLSSSKGKTKGGVPGRFSGSRDGTsSFSLTISNLQPEDSG 86


                 ....
gi 226498466 109 VYCC 112
Cdd:cd00099   87 TYYC 90
IgV_CAR_like cd20960
Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and ...
 23-114 7.20e-04

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other


Pssm-ID: 409552  Cd Length: 114  Bit Score: 38.97  E-value: 7.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  23 TSETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTS--RKSAKYRLQGTIP--RGDVSLT 98
Cdd:cd20960    5 SAQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNhyYPALKGRVAFTSNdlSGDASLN 84

                         90
                 ....*....|....*.
gi 226498466  99 ILNPSESDSGVYCCRI 114
Cdd:cd20960   85 ISNLKLSDTGTYQCKV 100
IgV_1_PVR_like cd05718
First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 ...
 21-114 2.14e-03

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).


Pssm-ID: 409383  Cd Length: 113  Bit Score: 37.43  E-value: 2.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466  21 PVTSETVVTEVLGHRVTLPCLYSswshNSNSM-----CWGKDQCPYSGCKEALIRTDGMRVtsRKSAKYRLQGTIPR--- 92
Cdd:cd05718    2 RVQVPTEVTGFLGGSVTLPCSLT----SPGTTkitqvTWMKIGAGSSQNVAVFHPQYGPSV--PNPYAERVEFLAARlgl 75

                         90       100
                 ....*....|....*....|..
gi 226498466  93 GDVSLTILNPSESDSGVYCCRI 114
Cdd:cd05718   76 RNATLRIRNLRVEDEGNYICEF 97
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 27-115 6.60e-03

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


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 35.17  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226498466    27 VVTEVLGHRVTLPClySSWSHNSNSMCWgkdqcpysgckealIRTDGMRVTSRKsakyRLQGTIPRGDVSLTILNPSESD 106
Cdd:smart00410   3 SVTVKEGESVTLSC--EASGSPPPEVTW--------------YKQGGKLLAESG----RFSVSRSGSTSTLTISNVTPED 62


                   ....*....
gi 226498466   107 SGVYCCRIE 115
Cdd:smart00410  63 SGTYTCAAT 71
 
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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