PIN (PilT N terminus) domain: Superfamily; The PIN (PilT N terminus) domain belongs to a large nuclease superfamily, and were originally named for their sequence similarity to the N-terminal domain of an annotated pili biogenesis protein, PilT, a domain fusion between a PIN-domain and a PilT ATPase domain. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. The PIN domain superfamily includes: the FEN-like PIN domain family such as the PIN domains of Flap endonuclease-1 (FEN1), exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), and Xeroderma pigmentosum complementation group G (XPG) nuclease, 5'-3' exonucleases of DNA polymerase I and bacteriophage T4- and T5-5' nucleases; the VapC-like PIN domain family which includes toxins of prokaryotic toxin/antitoxin operons FitAB and VapBC, as well as eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1; the LabA-like PIN domain family which includes the PIN domains of Synechococcus elongatus LabA (low-amplitude and bright); the PRORP-Zc3h12a-like PIN domain family which includes the PIN domains of RNase P (PRORP), ribonuclease Zc3h12a; and Bacillus subtilis YacP/Rae1-like PIN domains. It also includes the Mut7-C PIN domain family, which is not represented here as it is a shortened version of the PIN fold and lacks a core strand and helix (H3 and S3). The Mut7-C PIN domain family includes the C-terminus of Caenorhabditis elegans exonuclease Mut-7.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 483 IVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVMDGKR 562
Cdd:cd18728     1 IVIDGSNVAMVHGLQHFFSCRGIAIAVEYFWKRGHRNITVFVPQWRTKRDPNVTEQHFLTQLQELGILSLTPSRMVLGKR 80

                  ....*..
gi 2217296893 563 ISSYDDR 569
Cdd:cd18728    81 IASHDDR 87

first type I K homology (KH) RNA-binding domain found in the family of NEDD4-binding protein 1 (N4BP1); The N4BP1 family includes N4BP1, NYN domain and retroviral integrase catalytic domain-containing protein (NYNRIN) and KH and NYN domain-containing protein (KHNYN). These proteins are probably of retroviral origin. N4BP1 interacts with and is a substrate of NEDD4 ubiquitin ligase (neural precursor cell expressed, developmentally downregulated 4, E3 ubiquitin protein ligase). It is also an inhibitor of the E3 ubiquitin-protein ligase ITCH, a NEDD4 structurally related E3. N4BP1 acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates. NYNRIN, also known as CGIN1/Cousin of GIN1, may contribute to retroviral resistance in mammals by regulating the ubiquitination of viral proteins. KHNYN acts as a novel cofactor for zinc finger antiviral protein (ZAP) to target CpG-containing retroviral RNA for degradation. Members of this family contains two type I K homology (KH) RNA-binding domain. The model corresponds to the first one. The KH1 domain is a divergent KH domain that lacks the RNA-binding GXXG motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217296893  55 DRFAVSAEAENKVREQQPHVERIFSVGVSVLPKDC--PDNPHIWLQLEGPKENASRAKEYLKGLC 117
Cdd:cd09032     1 DEFVVPAEKVPLLERSRPRIERLFGVKVSLLEELSkpKDGGKQWVQLEGDEEDVRKAKEYIKALC 65

PRORP-like PIN domain of NEDD4 binding protein 1 and related proteins; NEDD4-binding partner-1 (N4BP1) interacts with and is a substrate of NEDD4 ubiquitin ligase (neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase). It is also an inhibitor of the E3 ubiquitin-protein ligase ITCH, a NEDD4 structurally related E3. This subfamily additionally includes NYNRIN (NYN domain and retroviral integrase containing, also known as CGIN1/Cousin of GIN1), and KHNYN (KH and NYN domain containing) protein. N4BP1, CGIN1, and KHNYN proteins are probably of retroviral origin. This subfamily belongs to the Zc3h12a-N4BP1-like PIN subfamily of the PRORP-Zc3h12a-like PIN family, the latter of which additionally includes human PRORP, also known as proteinaceous RNase P and mitochondrial RNase P protein subunit 3 (MRPP3), and Arabidopsis thaliana PRORP1-3. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 483 IVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVMDGKR 562
Cdd:cd18728     1 IVIDGSNVAMVHGLQHFFSCRGIAIAVEYFWKRGHRNITVFVPQWRTKRDPNVTEQHFLTQLQELGILSLTPSRMVLGKR 80

                  ....*..
gi 2217296893 563 ISSYDDR 569
Cdd:cd18728    81 IASHDDR 87

Zc3h12a-like Ribonuclease NYN domain; This domain is found in the Zc3h12a protein which has shown to be a ribonuclease that controls the stability of a set of inflammatory genes. It has been suggested that this domain belongs to the PIN domain superfamily. This domain has also been identified as part of the NYN domain family.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 479 DLRHIVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVM 558
Cdd:pfam11977   1 GLRPIVIDGSNVAMSHGRQKKFSVRGLAIAVDYFVKRGHEEITVFVPQWRKEADEKITDQHELLELERLGLIVFTPSRTL 80

                          90
                  ....*....|.
gi 2217296893 559 DGKRISSYDDR 569
Cdd:pfam11977  81 DGKRIVSYDDR 91

PRORP-like PIN domain of NEDD4 binding protein 1 and related proteins; NEDD4-binding partner-1 (N4BP1) interacts with and is a substrate of NEDD4 ubiquitin ligase (neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase). It is also an inhibitor of the E3 ubiquitin-protein ligase ITCH, a NEDD4 structurally related E3. This subfamily additionally includes NYNRIN (NYN domain and retroviral integrase containing, also known as CGIN1/Cousin of GIN1), and KHNYN (KH and NYN domain containing) protein. N4BP1, CGIN1, and KHNYN proteins are probably of retroviral origin. This subfamily belongs to the Zc3h12a-N4BP1-like PIN subfamily of the PRORP-Zc3h12a-like PIN family, the latter of which additionally includes human PRORP, also known as proteinaceous RNase P and mitochondrial RNase P protein subunit 3 (MRPP3), and Arabidopsis thaliana PRORP1-3. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 483 IVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVMDGKR 562
Cdd:cd18728     1 IVIDGSNVAMVHGLQHFFSCRGIAIAVEYFWKRGHRNITVFVPQWRTKRDPNVTEQHFLTQLQELGILSLTPSRMVLGKR 80

                  ....*..
gi 2217296893 563 ISSYDDR 569
Cdd:cd18728    81 IASHDDR 87

Zc3h12a-like Ribonuclease NYN domain; This domain is found in the Zc3h12a protein which has shown to be a ribonuclease that controls the stability of a set of inflammatory genes. It has been suggested that this domain belongs to the PIN domain superfamily. This domain has also been identified as part of the NYN domain family.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 479 DLRHIVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVM 558
Cdd:pfam11977   1 GLRPIVIDGSNVAMSHGRQKKFSVRGLAIAVDYFVKRGHEEITVFVPQWRKEADEKITDQHELLELERLGLIVFTPSRTL 80

                          90
                  ....*....|.
gi 2217296893 559 DGKRISSYDDR 569
Cdd:pfam11977  81 DGKRIVSYDDR 91

PRORP-like PIN domain of ribonuclease Zc3h12a, NEDD4-binding partner-1, and related proteins; Zc3h12a (zinc finger CCCH-type containing 12A, also known as MCPIP1/MCP induced protein 1 and Regnase-1) is a critical regulator of inflammatory response, with additional roles in defense against viruses and various stresses, cellular differentiation, and apoptosis. This subfamily also includes Caenorhabditis elegans REGE-1 (REGnasE-1), which also functions as a cytoplasmic endonuclease. Additionally, it includes three less-studied mammalian homologs: Zc3h12b-d/Regnase-2-4, as well as N4BP1 (NEDD4-binding partner-1), NYNRIN (NYN domain and retroviral integrase containing, also known as CGIN1/Cousin of GIN1), and KHNYN (KH and NYN domain containing) protein. N4BP1, CGIN1, and KHNYN proteins are probably of retroviral origin. This subfamily belongs to the PRORP-Zc3h12a-like PIN family which in addition includes human PRORP, also known as proteinaceous RNase P and mitochondrial RNase P protein subunit 3 (MRPP3), and Arabidopsis thaliana PRORP1-3. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 483 IVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHrDITVFVPQWRFSK-DAKVRESHFLQKLYSLSLLSLTPSRVMDGK 561
Cdd:cd18719     1 VVIDGSNVAMSHGNGKVFSCKGIQICVRYFLERGH-EVTAFVPQFRLESpNPNSTDQDILEELERLGILVFTPSRRVPGK 79

                  ....*...
gi 2217296893 562 RISSYDDR 569
Cdd:cd18719    80 RISSYDDR 87

first type I K homology (KH) RNA-binding domain found in the family of NEDD4-binding protein 1 (N4BP1); The N4BP1 family includes N4BP1, NYN domain and retroviral integrase catalytic domain-containing protein (NYNRIN) and KH and NYN domain-containing protein (KHNYN). These proteins are probably of retroviral origin. N4BP1 interacts with and is a substrate of NEDD4 ubiquitin ligase (neural precursor cell expressed, developmentally downregulated 4, E3 ubiquitin protein ligase). It is also an inhibitor of the E3 ubiquitin-protein ligase ITCH, a NEDD4 structurally related E3. N4BP1 acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates. NYNRIN, also known as CGIN1/Cousin of GIN1, may contribute to retroviral resistance in mammals by regulating the ubiquitination of viral proteins. KHNYN acts as a novel cofactor for zinc finger antiviral protein (ZAP) to target CpG-containing retroviral RNA for degradation. Members of this family contains two type I K homology (KH) RNA-binding domain. The model corresponds to the first one. The KH1 domain is a divergent KH domain that lacks the RNA-binding GXXG motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217296893  55 DRFAVSAEAENKVREQQPHVERIFSVGVSVLPKDC--PDNPHIWLQLEGPKENASRAKEYLKGLC 117
Cdd:cd09032     1 DEFVVPAEKVPLLERSRPRIERLFGVKVSLLEELSkpKDGGKQWVQLEGDEEDVRKAKEYIKALC 65

PIN domain of protein-only RNase P (PRORP), ribonuclease Zc3h12a, and related proteins; PRORPs catalyze the maturation of the 5' end of precursor tRNAs in eukaryotes. This family includes human PRORP, also known as proteinaceous RNase P and mitochondrial RNase P protein subunit 3 (MRPP3), and Arabidopsis thaliana PRORP1-3, PRORP1 localizes to the chloroplast and the mitochondria, and PRORP2 and PRORP3 localize to the nucleus. Zc3h12a (zinc finger CCCH-type containing 12A, also known as MCPIP1/MCP induced protein 1 and Regnase-1) is a critical regulator of inflammatory response, with additional roles in defense against viruses and various stresses, cellular differentiation, and apoptosis. This PIN_PRORP-Zc3h12a-like family also includes Caenorhabditis elegans REGE-1 (REGnasE-1), which also functions as a cytoplasmic endonuclease. Additionally, it includes three less-studied mammalian homologs: Zc3h12b-d/Regnase-2-4, as well as N4BP1 (NEDD4-binding partner-1), NYNRIN (NYN domain and retroviral integrase containing, also known as CGIN1/Cousin of GIN1), and KHNYN (KH and NYN domain containing) protein. N4BP1, CGIN1, and KHNYN proteins are probably of retroviral origin. The PIN (PilT N terminus) domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217296893 483 IVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGH--RDITVFVPQWRFSKDAKV--RESHFLQKLYSLSLLSLTPSrvm 558
Cdd:cd18671     1 AVIDGANVGLSHQNKESFSCRQLLLAVNWFLERSHnnTDPLVFLHKWRVEQPRPVppTDRHLLEEWEKKGILYATPP--- 77

                          90
                  ....*....|.
gi 2217296893 559 dgkriSSYDDR 569
Cdd:cd18671    78 -----GSNDDW 83