heptad repeat 1-heptad repeat 2 region (ectodomain) of the transmembrane subunit of human T-cell leukemia virus type 1 (HTLV-1), and related domains; This domain subfamily spans both heptad repeats of the glycoprotein (gp)/transmembrane(TM) subunit of various endogenous retroviruses (ERVs) and infectious retroviruses, including HTLV-1, HTLV -2, primate Mason-Pfizer monkey virus, Moloney murine leukemia virus, simian T-cell lymphotropic virus, feline leukemia virus (FeLV), bovine leukemia virus, and various human endogenous retroviruses (HERVs), including, HERV-H1_c2q24.3, HERV-H2_3q26, HERV-F(c)1_cXq21.33, HERV-T_19q13.11, Syncytin-1 (HERV-W_c7q21.2/ ERVWE1), Syncytin-2 (HERV-FRD_6p24.1), and related domains. This domain includes an N-terminal heptad repeat, a CKS17-like immunosuppressive region, a CX6C motif that forms an intrasubunit disulfide bond, and a C-terminal heptad repeat. N-terminal to HR1-HR2 region is a fusion peptide (FP), and C-terminal, is a membrane-spanning region (MSR). Viral infection involves the formation of a trimer-of-hairpins structure (three HR1s helices, buttressed by three HR2 helices lying in antiparallel orientation). In this structure, the FP (inserted in the host cell membrane) and MSR (inserted in the viral membrane) are in close proximity. ERVs are likely to originate from ancient germ-line infections by active retroviruses. Some modern ERVs, those that integrated into the host genome post-speciation, have a currently active exogenous counterpart, such as FeLV. Some ERVs play specific roles in the host, including placental development, protection of the host from infection by related pathogenic and exogenous retroviruses, and genome plasticity. Syncytin-1 and Syncytin-2 are expressed in the placenta, and are fusogenic, although they have a different cell specificity for fusion. Syncytin-2, but not Syncytin-1, is immunosuppressive; its immunosuppressive domain may protect the fetus from the mother's immune system. Syncytin-1 may participate in the formation of the placental trophoblast; it is also implicated in cell fusions between cancer and host cells and between cancer cell, and in human osteclast fusion. This subfamily also contains a mouse envelope protein encoded by the Fv-4 env gene, that blocks infection by exogenous MuLV.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 37544404 345 QFYYKLSQELNGDMERVADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVNQSGIVTEKVKEIR 422
Cdd:cd09851   1 QSYKSLSHALDADIQRLAQSISKLQKQLTSLAEVVLQNRRGLDLLTLEQGGLCAALQEECCFYANQSGLVRDSIAKLR 78

heptad repeat 1-heptad repeat 2 region (ectodomain) of the transmembrane subunit of human T-cell leukemia virus type 1 (HTLV-1), and related domains; This domain subfamily spans both heptad repeats of the glycoprotein (gp)/transmembrane(TM) subunit of various endogenous retroviruses (ERVs) and infectious retroviruses, including HTLV-1, HTLV -2, primate Mason-Pfizer monkey virus, Moloney murine leukemia virus, simian T-cell lymphotropic virus, feline leukemia virus (FeLV), bovine leukemia virus, and various human endogenous retroviruses (HERVs), including, HERV-H1_c2q24.3, HERV-H2_3q26, HERV-F(c)1_cXq21.33, HERV-T_19q13.11, Syncytin-1 (HERV-W_c7q21.2/ ERVWE1), Syncytin-2 (HERV-FRD_6p24.1), and related domains. This domain includes an N-terminal heptad repeat, a CKS17-like immunosuppressive region, a CX6C motif that forms an intrasubunit disulfide bond, and a C-terminal heptad repeat. N-terminal to HR1-HR2 region is a fusion peptide (FP), and C-terminal, is a membrane-spanning region (MSR). Viral infection involves the formation of a trimer-of-hairpins structure (three HR1s helices, buttressed by three HR2 helices lying in antiparallel orientation). In this structure, the FP (inserted in the host cell membrane) and MSR (inserted in the viral membrane) are in close proximity. ERVs are likely to originate from ancient germ-line infections by active retroviruses. Some modern ERVs, those that integrated into the host genome post-speciation, have a currently active exogenous counterpart, such as FeLV. Some ERVs play specific roles in the host, including placental development, protection of the host from infection by related pathogenic and exogenous retroviruses, and genome plasticity. Syncytin-1 and Syncytin-2 are expressed in the placenta, and are fusogenic, although they have a different cell specificity for fusion. Syncytin-2, but not Syncytin-1, is immunosuppressive; its immunosuppressive domain may protect the fetus from the mother's immune system. Syncytin-1 may participate in the formation of the placental trophoblast; it is also implicated in cell fusions between cancer and host cells and between cancer cell, and in human osteclast fusion. This subfamily also contains a mouse envelope protein encoded by the Fv-4 env gene, that blocks infection by exogenous MuLV.

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gi 37544404 345 QFYYKLSQELNGDMERVADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVNQSGIVTEKVKEIR 422
Cdd:cd09851   1 QSYKSLSHALDADIQRLAQSISKLQKQLTSLAEVVLQNRRGLDLLTLEQGGLCAALQEECCFYANQSGLVRDSIAKLR 78

heptad repeat 1-heptad repeat 2 region of the transmembrane subunit of various endogenous retroviruses (ERVs) and infectious retroviruses, including Ebola virus and Rous sarcoma virus; This domain family spans both heptad repeats of the glycoprotein (gp)/transmembrane subunit of endogenous retroviruses (ERVs) and infectious retroviruses, including Ebola virus gp2, Rous sarcoma virus gp37, and the envelope proteins of various ERVs. This domain includes an N-terminal heptad repeat, a CKS17-like immunosuppressive region, a CX6C motif that forms an intra-subunit disulfide bond, and a C-terminal heptad repeat. N-terminal to HR1-HR2 region is a fusion peptide (FP), while C-terminal, is a membrane-spanning region (MSR). Viral infection involves the formation of a trimer-of-hairpins structure (three HR1s helices, buttressed by three HR2 helices lying in antiparallel orientation). In this structure, the FP (inserted in the host cell membrane) and MSR (inserted in the viral membrane) are in close proximity. ERVs are likely to originate from ancient germ-line infections by active retroviruses. Some modern ERVs, those that integrated into the host genome post-speciation, have a currently active exogenous counterpart, such as Jaagsiekte sheep retrovirus (JSRV), feline leukemia virus (FeLV), and avian leukemia virus (ALV). Some ERVs play specific roles in the host, including placental development, protection of the host from infection by related pathogenic and exogenous retroviruses, and genome plasticity. Human ERVs (HERVs) belonging to this family include Syncytin-1 (HERV-W_c7q21.2/ ERVWE1), and Syncytin-2 (HERV-FRD_6p24.1) which are expressed in the placenta, and are fusogenic, although they have a different cell specificity for fusion. Syncytin-2, but not Syncytin-1, is immunosuppressive. Its immunosuppressive domain may protect the fetus from the mother's immune system. Syncytin-1 may participate in the formation of the placental trophoblast. It is also implicated in cell fusions between cancer and host cells and between cancer cells, and in human osteclast fusion. This family also contains human HERV-R_c7q21.2 (ERV-3), which is also expressed in the placenta, but is not fusogenic, has an immunosuppressive domain, but lacks a fusion peptide. It is unclear whether ERV-3 has a critical biological role.

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gi 37544404 353 ELNGDMERVADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVN-QSGIVTEKVKEIRD 423
Cdd:cd09948   1 GLEQDANETTQALQLFLRNVTSLRTVVLQNRRALDFLLAREGGTCHIINEDCCCFLNdQSRITDKIDQLIEQ 72

heptad repeat 1-heptad repeat 2 region (ectodomain) of the transmembrane subunit of various endogenous retroviruses (ERVs) and infectious retroviruses, including Ebola virus and human immunodeficiency virus type 1 (HIV-1); This domain superfamily spans both heptad repeats of the glycoprotein (gp)/transmembrane subunit of various endogenous retroviruses (ERVs) and infectious retroviruses, including Ebola virus gp2, Rous sarcoma virus gp37, human immunodeficiency virus type 1 (HIV-1) gp41, and the envelope proteins of various ERVs. In the HR1-HR2 region of Ebola virus and RSV, the linker region between the two repeats includes a CKS17-like immunosuppressive region and a CX6C motif that forms an intra-subunit disulfide bond; MMTV, HIV-1, HERV-K endogenous retroviruses and related sequences lack a canonical CSK17-like sequence, and CX6C motif. N-terminal to the HR1-HR2 region is a fusion peptide (FP), and C-terminal, is a membrane-spanning region (MSR). Viral infection involves the formation of a trimer-of-hairpins structure (three HR1 helices, buttressed by three HR2 helices lying in antiparallel orientation). In this structure, the FP (inserted in the host cell membrane) and MSR (inserted in the viral membrane) are in close proximity. ERVs are likely to originate from ancient germ-line infections by active retroviruses. Some modern ERVs, those that integrated into the host genome post-speciation, have a currently active exogenous counterpart, such as Jaagsiekte sheep retrovirus (JSRV), feline leukemia virus (FeLV), and avian leukemia virus (ALV). Some ERVs play specific roles in the host, including placental development, protection of the host from infection by related pathogenic and exogenous retroviruses, and genome plasticity. Human ERVs (HERVs) belonging to this superfamily include Syncytin-1 (HERV-W_c7q21.2/ ERVWE1), and Syncytin-2 (HERV-FRD_6p24.1) which are expressed in the placenta, and are fusogenic, although they have a different cell specificity for fusion. Syncytin-2, but not Syncytin-1, is immunosuppressive; its immunosuppressive domain may protect the fetus from the mother's immune system. Syncytin-1 may participate in the formation of the placental trophoblast; it is also implicated in cell fusions between cancer and host cells and between cancer cell, and in human osteclast fusion. This superfamily also contains human HERV-R_c7q21.2 (ERV-3), which is also expressed in the placenta, but is not fusogenic, and has an immunosuppressive domain, but lacks a fusion peptide. It is unclear whether ERV-3 has a critical biological role. Included in this superfamily are ERVs from domestic sheep that are related to JSRV, the agent of transmissible lung cancer in sheep; for example, enJSRV-26 that retains an intact genome. These endogenous JSRVs protect the sheep against JSRV infection and are required for sheep placental development.

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gi 37544404 353 ELNGDMERVADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVN-QSGIVTEKVKEIRDR 424
Cdd:cd09947   1 RLQQLLRLTTQAIKNLHTNLTAIAKYLAQNRRGLDWLAARRGGTCVALTEVCCPFLSiTNKWWQDWIRKLDFL 73

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

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gi 37544404 177 EVSAQNPTNCwICLPLNFRPYVSIPVPEQWNNFSTEINTTSVLVgplvSNLEIT-----HTSNLTC-VKFSNTTYTTN 248
Cdd:cd20987  16 TLTCSVPDNC-PALSPEFSWLGAALTPLPPVLGRLEEEGTTTHS----SVLTFTprpedHGTNLTCqVKFPGATVTTE 88