eukaryotic translation initiation factor 3 subunit H isoform 4 [Mus musculus]
Protein Classification
eukaryotic translation initiation factor 3 subunit H( domain architecture ID 10169158)
eukaryotic translation initiation factor 3 subunit H is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| MPN_eIF3h | cd08065 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; ... |
37-250 | 6.16e-104 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; Eukaryotic translation initiation factor 3 (eIF3) subunit h (eIF3h; eIF3 subunit 3; eIF3S3; eIF3-gamma; eIF3-p40) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.Together with eIF3e and eIF3f, eIF3h stabilizes the eIF3 complex. Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. For example, EIF3h gene amplification is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease. It has been shown that coamplification of MYC, a well characterized oncogene involved in cell growth, differentiation, and apoptosis, and EIF3h in patients with non-small cell lung cancer (NSCLC) improves survival if treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), Gefitinib. Plant eIF3h is implicated in translation of specific mRNAs. : Pssm-ID: 163696 [Multi-domain] Cd Length: 266 Bit Score: 304.19 E-value: 6.16e-104
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| Name | Accession | Description | Interval | E-value | |||||
| MPN_eIF3h | cd08065 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; ... |
37-250 | 6.16e-104 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; Eukaryotic translation initiation factor 3 (eIF3) subunit h (eIF3h; eIF3 subunit 3; eIF3S3; eIF3-gamma; eIF3-p40) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.Together with eIF3e and eIF3f, eIF3h stabilizes the eIF3 complex. Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. For example, EIF3h gene amplification is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease. It has been shown that coamplification of MYC, a well characterized oncogene involved in cell growth, differentiation, and apoptosis, and EIF3h in patients with non-small cell lung cancer (NSCLC) improves survival if treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), Gefitinib. Plant eIF3h is implicated in translation of specific mRNAs. Pssm-ID: 163696 [Multi-domain] Cd Length: 266 Bit Score: 304.19 E-value: 6.16e-104
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| eIF3h_C | pfam19445 | C-terminal region of eIF3h; This entry represents a C-terminal helical region present in ... |
157-302 | 8.73e-72 | |||||
C-terminal region of eIF3h; This entry represents a C-terminal helical region present in eukaryotic initiation factor 3 chain H. This protein is part of the eIF3 complex that is involved in eukaryotic translation initiation. eIF3 is a large and structurally complex molecular assembly that, in the majority of eukaryotes, consists of 11-13 subunits (eIF3a-IF3m) with a molecular weight of 600-800 kDa. Pssm-ID: 466087 Cd Length: 196 Bit Score: 220.03 E-value: 8.73e-72
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| JAB_MPN | smart00232 | JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ... |
38-172 | 1.21e-41 | |||||
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function. Pssm-ID: 214573 Cd Length: 135 Bit Score: 140.59 E-value: 1.21e-41
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| PLN03246 | PLN03246 | 26S proteasome regulatory subunit; Provisional |
38-123 | 5.11e-07 | |||||
26S proteasome regulatory subunit; Provisional Pssm-ID: 215645 [Multi-domain] Cd Length: 303 Bit Score: 50.12 E-value: 5.11e-07
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| Name | Accession | Description | Interval | E-value | |||||
| MPN_eIF3h | cd08065 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; ... |
37-250 | 6.16e-104 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; Eukaryotic translation initiation factor 3 (eIF3) subunit h (eIF3h; eIF3 subunit 3; eIF3S3; eIF3-gamma; eIF3-p40) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.Together with eIF3e and eIF3f, eIF3h stabilizes the eIF3 complex. Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. For example, EIF3h gene amplification is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease. It has been shown that coamplification of MYC, a well characterized oncogene involved in cell growth, differentiation, and apoptosis, and EIF3h in patients with non-small cell lung cancer (NSCLC) improves survival if treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), Gefitinib. Plant eIF3h is implicated in translation of specific mRNAs. Pssm-ID: 163696 [Multi-domain] Cd Length: 266 Bit Score: 304.19 E-value: 6.16e-104
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| eIF3h_C | pfam19445 | C-terminal region of eIF3h; This entry represents a C-terminal helical region present in ... |
157-302 | 8.73e-72 | |||||
C-terminal region of eIF3h; This entry represents a C-terminal helical region present in eukaryotic initiation factor 3 chain H. This protein is part of the eIF3 complex that is involved in eukaryotic translation initiation. eIF3 is a large and structurally complex molecular assembly that, in the majority of eukaryotes, consists of 11-13 subunits (eIF3a-IF3m) with a molecular weight of 600-800 kDa. Pssm-ID: 466087 Cd Length: 196 Bit Score: 220.03 E-value: 8.73e-72
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| JAB_MPN | smart00232 | JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ... |
38-172 | 1.21e-41 | |||||
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function. Pssm-ID: 214573 Cd Length: 135 Bit Score: 140.59 E-value: 1.21e-41
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| MPN_euk_non_mb | cd08057 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non ... |
39-182 | 1.27e-37 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non metal-binding); eukaryotic; This family contains MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains variants lacking key residues in the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Rpn7/PSMD7, Rpn8/PSMD8, CSN6, Prp8p, and the translation initiation factor 3 subunits f and h do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function. Rpn7 is known to be critical for the integrity of the 26S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. CSN6 is a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. It cleaves ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. EIF3f s a potent inhibitor of HIV-1 replication as well as an important negative regulator of cell growth and proliferation. EIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. Pssm-ID: 163688 [Multi-domain] Cd Length: 157 Bit Score: 131.03 E-value: 1.27e-37
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| JAB | pfam01398 | JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ... |
34-146 | 1.33e-35 | |||||
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. This family is also known as the MPN domain and PAD-1-like domain, JABP1 domain or JAMM domain. These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are shown to have a similar role, and the archael protein from Haloferax volcanii is found to cleave ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates. Pssm-ID: 396120 Cd Length: 117 Bit Score: 124.38 E-value: 1.33e-35
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| MPN_eIF3f | cd08064 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; ... |
44-120 | 2.15e-11 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; Eukaryotic translation initiation factor 3 (eIF3) subunit F (eIF3F; EIF3S5; eIF3-p47; eukaryotic translation initiation factor 3, subunit 5 epsilon, 47kDa; Mov34/MPN/PAD-1 family protein) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity. It has been shown that eIF3f mRNA expression is significantly decreased in many human tumors including pancreatic cancer and melanoma. EIF3f is a potent inhibitor of HIV-1 replication; it mediates restriction of HIV-1 expression through several factors including the serine/arginine-rich (SR) protein 9G8, and cyclin-dependent kinase 11 (CDK11). EIF3f phosphorylation by CDK11 is important in regulating its function in translation and apoptosis. It enhances its association with the core eIF3 subunits during apoptosis, suggesting that eIF3f may inhibit translation by increasing the binding to the eIF3 complex during apoptosis. Thus, eIF3f may be an important negative regulator of cell growth and proliferation. Pssm-ID: 163695 [Multi-domain] Cd Length: 265 Bit Score: 62.99 E-value: 2.15e-11
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| MPN_RPN11_CSN5 | cd08069 | Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit ... |
37-172 | 1.51e-09 | |||||
Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit CSN5; This family contains proteasomal regulatory protein Rpn11 (26S proteasome regulatory subunit rpn11; PAD1; POH1; RPN11; PSMD14; Rpn11 subunit of the 19S-proteasome; regulatory particle number 11) and signalosomal CSN5 (COP9 signalosome complex subunit 5; COP9 complex homolog subunit 5; c-Jun activation domain-binding protein-1; CSN5/JAB1; JAB1). COP9 signalosome (CSN) and the proteasome lid are paralogous complexes and their respective subunits CSN5 and Rpn11 are most closely related between the two complexes, both containing the conserved JAMM (JAB1/MPN/Mov34 metalloenzyme) motif involved in zinc ion coordination and providing the active site for isopeptidase activity. Rpn11 is responsible for substrate deubiquitination during proteasomal degradation. It is essential for maintaining a correct cell cycle and normal mitochondrial morphology and physiology; mutations in Rpn11 cause cell cycle and mitochondrial defects, temperature sensitivity and sensitivity to DNA damaging reagents such as UV. It has been shown that the C-terminal region of Rpn11 is involved in the regulation of the mitochondrial fission and tubulation processes. CSN5, one of the eight subunits of CSN, is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Its MPN+ domain is critical for the physical interaction of RUNX3 and Jab1. It has been suggested that the direct interaction of CSN5/JAB1 with p27 provides p27 with a leucine-rich nuclear export signal (NES), which is required for binding to chromosomal region maintenance 1 (CRM1), and facilitates nuclear export. The over-expression of CSN5/JAB1 also has been implicated in cancer initiation and progression, including cancer of the lung, pancreas, mouth, thyroid, and breast, suggesting that the oncogenic activity of CSN5 is associated with the down-regulation of RUNX3. Pssm-ID: 163700 [Multi-domain] Cd Length: 268 Bit Score: 57.65 E-value: 1.51e-09
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| MPN_RPN7_8 | cd08062 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ... |
37-122 | 3.63e-07 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S proteasomal subunits Rpn7 and Rpn8; This family includes lid subunits of the 26 S proteasome regulatory particles, Rpn7 (PSMD7; proteasome 26S non-ATPase subunit 7; p44), and Rpn8 (PSMD8; proteasome 26S non-ATPase subunit 8; p40; Mov34). Rpn7 is known to be critical for the integrity of the 26 S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. Rpn7 and Rpn8 are ATP-independent components of the 19S regulator subunit, and contain the MPN structural motif on its N-terminal region. However, while they show a typical MPN metalloprotease fold, they lack the canonical JAMM motif, and therefore do not show catalytic isopeptidase activity. It is suggested that Rpn7 function is primarily structural. Pssm-ID: 163693 [Multi-domain] Cd Length: 280 Bit Score: 50.66 E-value: 3.63e-07
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| PLN03246 | PLN03246 | 26S proteasome regulatory subunit; Provisional |
38-123 | 5.11e-07 | |||||
26S proteasome regulatory subunit; Provisional Pssm-ID: 215645 [Multi-domain] Cd Length: 303 Bit Score: 50.12 E-value: 5.11e-07
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| MPN | cd07767 | Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ... |
47-167 | 5.02e-03 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains are found in the N-terminal termini of proteins with a variety of functions; they are components of the proteasome regulatory subunits, the signalosome (CSN), eukaryotic translation initiation factor 3 (eIF3) complexes, and regulators of transcription factors. These domains are isopeptidases that release ubiquitin from ubiquitinated proteins (thus having deubiquitinating (DUB) activity) that are tagged for degradation. Catalytically active MPN domains contain a metalloprotease signature known as the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif. For example, Rpn11 (also known as POH1 or PSMD14), a subunit of the 19S proteasome lid is involved in the ATP-dependent degradation of ubiquitinated proteins, contains the conserved JAMM motif involved in zinc ion coordination. Poh1 is a regulator of c-Jun, an important regulator of cell proliferation, differentiation, survival and death. JAB1 is a component of the COP9 signalosome (CSN), a regulatory particle of the ubiquitin (Ub)/26S proteasome system occurring in all eukaryotic cells; it cleaves the ubiquitin-like protein NEDD8 from the cullin subunit of the SCF (Skp1, Cullins, F-box proteins) family of E3 ubiquitin ligases. AMSH (associated molecule with the SH3 domain of STAM, also known as STAMBP), a member of JAMM/MPN+ deubiquitinases (DUBs), specifically cleaves Lys 63-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. Similarly, BRCC36, part of the nuclear complex that includes BRCA1 protein and is targeted to DNA damage foci after irradiation, specifically disassembles K63-linked polyUb. BRCC36 is aberrantly expressed in sporadic breast tumors, indicative of a potential role in the pathogenesis of the disease. Some variants of the JAB1/MPN domains lack key residues in their JAMM motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Mov34/PSMD7, Rpn8, CSN6, Prp8p, and the translation initiation factor 3 subunits f (p47) and h (p40) do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function. Pssm-ID: 163686 [Multi-domain] Cd Length: 116 Bit Score: 36.34 E-value: 5.02e-03
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| MPN_euk_mb | cd08058 | Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); ... |
47-170 | 5.65e-03 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); eukaryotic; This family contains eukaryotic MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains found in proteins with a variety of functions, including AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM), H2A-DUB (histone H2A deubiquitinase), BRCC36 (BRCA1/BRCA2-containing complex subunit 36), as well as Rpn11 (regulatory particle number 11) and CSN5 (COP9 signalosome complex subunit 5). These domains contain the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, EXnHS/THX7SXXD, which is involved in zinc ion coordination and provides the active site for isopeptidase activity. Rpn11 is responsible for substrate deubiquitination during proteasomal degradation. It is essential for maintaining a correct cell cycle and normal mitochondrial morphology and physiology. CSN5 is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Over-expression of CSN5 has been implicated in cancer initiation and progression. AMSH specifically cleaves Lys 63 and not Lys48-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. It is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity; it is targeted to DNA damage foci after irradiation. 2A-DUB is specific for monoubiquitinated H2A (uH2A), regulating transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. It is a positive regulator of androgen receptor (AR) transactivation activity on a reporter gene and serves as a marker in prostate tumors. Pssm-ID: 163689 Cd Length: 119 Bit Score: 36.02 E-value: 5.65e-03
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