F-box domain found in F-box/LRR-repeat protein 5 (FBXL5) and similar proteins; FBXL5, also called F-box and leucine-rich repeat protein 5, F-box protein FBL4/FBL5, or p45SKP2-like protein, is the substrate-recognition component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22118     1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217350109 584 LSLSGCYQITDHGLRVLTLGggLPYLEHLNLSGCLTITGAGLQDLVSACPSL 635
Cdd:cd09293    57 LILPGSKLIDDEGLIALAQS--CPNLQVLDLRACENITDSGIVALATNCPKL 106

F-box domain found in F-box/LRR-repeat protein 5 (FBXL5) and similar proteins; FBXL5, also called F-box and leucine-rich repeat protein 5, F-box protein FBL4/FBL5, or p45SKP2-like protein, is the substrate-recognition component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22118     1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2217350109  189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 229
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFKL 41

Hemerythrin HHE cation binding domain; Iteration of the HHE family found it to be related to Hemerythrin. It also demonstrated that what has been described as a single domain in fact consists of two cation binding domains. Members of this family occur all across nature and are involved in a variety of processes. For instance, in Nereis diversicolor Swiss:P80255 binds Cadmium so as to protect the organizm from toxicity. However Hemerythrin is classically described as Oxygen-binding through two attached Fe2+ ions. And the bacterial Swiss:Q7WX96 is a regulator of response to NO, which suggests yet another set-up for its metal ligands. In Staphylococcus aureus P72360 has been noted to be important when the organizm switches to living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store or scavenger. This domain can bind oxygen (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217350109  18 NNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRS---QTIYNVHSD--NKLSEMLSLFEKGLKNVKNEYEqlnyakq 92
Cdd:pfam01814  29 DSHLRKLAELLDELVDELEAHHAAEEELLFPALERRSpggEAPIEVLRKehDEIRELLEELEALLKGAEPGAA------- 101

                          90       100
                  ....*....|....*....|....*..
gi 2217350109  93 LKERLEAFTRDFLPHMKEEEEVFQPML 119
Cdd:pfam01814 102 FAELLEALAEWLREHIAKEEEVLFPLL 128

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2217350109 337 PNLEHLDLTQTDISDsafdsWSWLGCCQSLRHLDLSGCEKITDV 380
Cdd:pfam12799   1 PNLEVLDLSNNQITD-----IPPLAKLPNLETLDLSGNNKITDL 39

Hemerythrin domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217350109  20 DFRALLQSLYAtFKEF--KMHEQIENEYIIGLLQQRSQTIYNV-------HsdNKLSEMLSLFEKGLKNVKNEyeQLNYA 90
Cdd:COG3945    35 DFELLRDILDY-IREFadRCHHPKEEDILFPRLEERGGEAAGPiavllaeH--EQGRQLTRELEEALEAYLAG--DVVAR 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2217350109  91 KQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDI 131
Cdd:COG3945   110 DELAAALRAYIALLRQHIAKEENVLFPLAERLLSDEDWEEL 150

Hemerythrin family; Hemerythrin (Hr) and related proteins are found in bacteria, archaea and eukaryotes. They are non-heme diiron oxygen transport proteins. In addition to oxygen transport, members are involved in cadmium fixation and host anti-bacterial defense. They have the same "four alpha helix bundle" motif and similar active site structures. Some members, like Hr, form oligomers, the octameric form being most prevalent, while others are monomeric.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217350109  22 RALLQSLYATFKEFKMHEQIENEYIIGLLQQRSQTIYNVHSDNKLSEMLSLFEKGLknvkneyeqlnyaKQLKERLEAFT 101
Cdd:cd00522    21 LSKAQSLYATFKEFK*HFQIENEYMIGLLQQRSQTIYNVHSDNHLSF*LSLFEKGL-------------KQLKERLEAFT 87

                          90
                  ....*....|....*.
gi 2217350109 102 RDFLPHMK-EEEEVFQ 116
Cdd:cd00522    88 RWLVNHIKsEDFEYKG 103

F-box-like; This is an F-box-like family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 230
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRLC 45

F-box domain found in F-box/LRR-repeat protein 2 (FBXL2), F-box/LRR-repeat protein 20 (FBXL20) and similar proteins; The family includes FBXL2 and FBXL30. FBXL2, also called F-box and leucine-rich repeat protein 2, or F-box protein FBL2/FBL3, is a calcium-activated substrate-recognition component of an SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. FBXL20, also called SCRAPPER, F-box and leucine-rich repeat protein 20, or F-box/LRR-repeat protein 2-like, is a component of a synapse-localized SCF-type E3 ubiquitin ligase which regulates neural transmission. It is widely expressed in the central nervous system and plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. It may also mediate the ubiquitin degradation of E-cadherin resulting in an increased invasive ability of malignant cells. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 227
Cdd:cd22115     4 NKKLPKELLLRIFSFLDVVTLCRCAQVSKYWNVLALDGSNWQ 45

F-box domain found in Schizosaccharomyces pombe Skp1-binding protein 1 (SpPof1) and similar proteins; SpPof1, also called F-box/WD repeat-containing protein pof1, probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It is required for the inactivation of zip1 via ubiquitination. This subfamily also includes Saccharomyces cerevisiae methionine-requiring protein 30 (ScMET30, also called E3 ubiquitin ligase complex SCF(Met30) subunit MET30), Aspergillus niger sulfur controller B (AnSCONB, also called sulfur metabolite repression control protein B) and Neurospora crassa sulfur controller 2 (NcSCON2, also called sulfur metabolite repression control protein 2). ScMET30 acts as a transcriptional inhibitor that negatively regulates the expression of sulfur amino acid biosynthesis genes. It controls cell cycle function (being required for the G1/S transition and M-phase but not the S-phase), sulfur metabolism, and methionine biosynthesis as part of the E3 ubiquitin ligase complex SCF(Met30). AnSCONB and NcSCON2 are components of the SCF (sconB/scon-2) E3 ubiquitin ligase complexes involved in the regulation of sulfur metabolite repression, probably by mediating the inactivation or degradation of the metR transcription factor. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 229
Cdd:cd22147     2 LSALPVELSLKILSYLDAKSLCRAAQVSKKWRNLADDDELWKRM 45

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 13 (FBXO13); The family corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 13 (FBXO13). FBXO13, also called FBX13, or F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2217350109 188 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 227
Cdd:cd22138     3 SLPVECQLKIFSFLSEVDKCLAATVCRSWSELIRSPRLWR 42

F-box domain superfamily; This short domain is commonly found at the N-terminus of various proteins, and typically co-occurs with one or more other conserved domains or motifs, such as leucine rich repeats, WD40 repeats, kelch, tub, spry, and others. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression. One of the best researched roles of F-box proteins is their participation in SCF (Skp1-Cul1-F-box protein), a multi-protein complex that functions as a ubiquitin E3 ligase, where the role of the F-box protein is to recruit target substrates. Gene families containing the F-box are found greatly expanded in narrow taxonomic lineages, such as flowering plants and nematodes. In this hierarchical classification, many of the subfamilies are named according to their domain architectures.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2217350109 187 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTK 221
Cdd:cd09917     1 SDLPDEILLKILSYLDPRDLLRLSLVCKRWRELAS 35

F-box domain found in F-box only protein 16 (FBXO16) and similar proteins; FBXO16, also called FBX16, is part of an SCF (SKP1-cullin-F-box) protein ligase complex. It probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It functions as a tumor suppressor by attenuating nuclear beta-catenin function. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22172     9 LPRVLSLYIFSFLDPRSLCRCAQVCWYWKYLTELDQLW 46

F-box domain found in F-box only protein 3 (FBXO3) and similar proteins; FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. It also promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2217350109 188 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLYPVHW 234
Cdd:cd22084     3 DLPSDPLLNILSFLDYRDLISCSQVCRRLNQLCSHDPLWKRLCKKYW 49

F-box domain found in F-box only protein 48 (FBXO48) and similar proteins; FBXO48, also called FBX48, is one of the paralogs of the F-box only protein 7 (FBXO7), which is the causative gene for PARK15 (also known as Parkinsonian-pyramidal disease, PPD). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTK-TGSLWKHL 229
Cdd:cd22113     1 IELLPPEMSLRIFSQLDVQSLCRASQTCKTWNDLIEnSDYLWRPH 45

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2217350109  189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 229
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFKL 41

F-box domain found in F-box/WD repeat-containing protein 8 (FBXW8) and similar proteins; FBXW8, also called F-box and WD-40 domain-containing protein 8, or F-box only protein 29 (FBXO29), is the substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as GORASP1, IRS1, MAP4K1/HPK1. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22134     7 LPRELALKIFQYLSVTDLCRCAQVSKSWKSLAEDELLW 44

F-box domain found in Saccharomyces cerevisiae cell division control protein 4 (ScCDC4) and similar proteins; ScCDC4 is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It is essential for initiation of DNA replication and separation of the spindle pole bodies to form the poles of the mitotic spindle. It also plays a role in bud development, fusion of zygotic nuclei after conjugation and various aspects of sporulation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 229
Cdd:cd22141     1 IGNLPFEISLKIFNYLQFEDLLNSLGVSKKWNKIIRNTALWKKL 44

F-box domain found in F-box/WD repeat-containing protein 2 (FBXW2) and similar proteins; FBXW2, also called F-box and WD-40 domain-containing protein 2, or protein MD6, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a tumor suppressor by promoting SKP2 degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKW 216
Cdd:cd22131     3 LKLLPLELSFYLLSFLDPESLLTCCLVSKQW 33

F-box domain found in F-box only protein 10 (FBXO10) and similar proteins; FBXO10, also called FBX10, or PRMT11, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF(FBXO10) complex mediates ubiquitination and degradation of BCL2, an anti-apoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. It also associates with the receptor for advanced glycation end products (RAGE) to mediate its ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKT--GSLWKHLY 230
Cdd:cd22090     2 VTGLPLELWRLILAYLPVRDLCRCCQVCRAWYELILSldSTRWKQLY 48

F-box domain found in F-box only protein 15 (FBXO15) and similar proteins; FBXO15, also called FBX15, has a novel dual molecular function by controlling transcriptional repression and being part of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligases, which is essential for stress response, gliotoxin production and virulence in the opportunistic human pathogen Aspergillus fumigatus. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 230
Cdd:cd22093     1 IERLPSEILLKILSYLDASSLLCISCVNKLFYQLANDNALWRKLY 45

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217350109 335 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 389
Cdd:cd09293    26 LHSGLEWLELYMCPISDPPLD---QLSNCNKLKKLILPGSKLIDDEGLIALAQSC 77

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217350109 321 SSAVSSKMVRQILELCPNLEHLDLTQTDISDSAFDSWSWlGCCQSLRHLDLSGCEKITDVALEKI 385
Cdd:cd09293   117 GHLITDVSLSALGKNCTFLQTVGFAGCDVTDKGVWELAS-GCSKSLERLSLNNCRNLTDQSIPAI 180

F-box domain found in F-box only protein 8 (FBXO8) and similar proteins; FBXO8, also called FBX8, or F-box/SEC7 protein FBS, is a novel component of F-box proteins which contains an F-box domain and a putative Sec7 domain. FBX8 was originally identified as a Skp1-binding protein. It is involved in the ubiquitin-dependent proteolytic pathway. It acts as a metastasis suppressor that functions through mTOR signaling pathway. FBXO8 may promote the activation of ADP-ribosylation factor (ARF) through replacement of GDP with GTP. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVsmkWSQLTKTGSLWKHL 229
Cdd:cd22088     7 LPPELSLTVLSHLNATDLCLASCV---WQDLANDELLWQGL 44

Hemerythrin HHE cation binding domain; Iteration of the HHE family found it to be related to Hemerythrin. It also demonstrated that what has been described as a single domain in fact consists of two cation binding domains. Members of this family occur all across nature and are involved in a variety of processes. For instance, in Nereis diversicolor Swiss:P80255 binds Cadmium so as to protect the organizm from toxicity. However Hemerythrin is classically described as Oxygen-binding through two attached Fe2+ ions. And the bacterial Swiss:Q7WX96 is a regulator of response to NO, which suggests yet another set-up for its metal ligands. In Staphylococcus aureus P72360 has been noted to be important when the organizm switches to living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store or scavenger. This domain can bind oxygen (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217350109  18 NNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRS---QTIYNVHSD--NKLSEMLSLFEKGLKNVKNEYEqlnyakq 92
Cdd:pfam01814  29 DSHLRKLAELLDELVDELEAHHAAEEELLFPALERRSpggEAPIEVLRKehDEIRELLEELEALLKGAEPGAA------- 101

                          90       100
                  ....*....|....*....|....*..
gi 2217350109  93 LKERLEAFTRDFLPHMKEEEEVFQPML 119
Cdd:pfam01814 102 FAELLEALAEWLREHIAKEEEVLFPLL 128

Leucine-rich repeat - CC (cysteine-containing) subfamily;

                           10        20
                   ....*....|....*....|....*
gi 2217350109  363 CQSLRHLDLSGCEKITDVALEKISR 387
Cdd:smart00367   1 CPNLRELDLSGCTNITDEGLQALAK 25

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217350109 310 GTSVKTLVLAYSSAVSSKMVRQILELCPNLEHLDLTQTD-ISDSAFDSWSwlGCCQSLRHLDLS---GCEKITDVALEKI 385
Cdd:cd09293    51 CNKLKKLILPGSKLIDDEGLIALAQSCPNLQVLDLRACEnITDSGIVALA--TNCPKLQTINLGrhrNGHLITDVSLSAL 128

                  ..
gi 2217350109 386 SR 387
Cdd:cd09293   129 GK 130

F-box domain found in F-box/LRR-repeat protein 1 (FBXL1) and similar proteins; FBXL1, also called S-phase kinase-associated protein 2, cyclin-A/CDK2-associated protein p45, F-box protein Skp2, or p45skp2, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. It specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22114     4 LPDELLLGIFSCLCLPDLLKVSQVCKRWYRLASDESLW 41

F-box domain found in F-box/WD repeat-containing protein 7 (FBXW7) and similar proteins; FBXW7, also called Archipelago homolog (Ago), F-box and WD-40 domain-containing protein 7, F-box protein FBX30, SEL-10, or Cdc4, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217350109 186 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 227
Cdd:cd22133    18 ISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWR 59

F-box domain found in Arabidopsis thaliana F-box protein GID2 and similar proteins; AtGID2, also called protein SLEEPY 1, is an essential component of the SCF-type E3 ligase complex, SCF(GID2), a complex that positively regulates the gibberellin signaling pathway. Upon gibberellin treatment, the SCF(GID2) complex mediates the ubiquitination and subsequent degradation of DELLA proteins (GAI, RGA and RGL2), some repressors of the gibberellin pathway, leading to the activation of the pathway. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 230
Cdd:cd22151     3 LPDDLLQEIFKRLDPKSLARAACVCRRWRAAARSESLWENAC 44

F-box domain found in F-box only protein 36 (FBXO36) and similar proteins; FBXO36, also called FBX36, likely functions as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 230
Cdd:cd22106     4 LPDKLLLYIISYLDLEDIARLSQTSKRFKKLCNSDELWEKIY 45

F-box domain found in F-box only protein 45 (FBXO45) and similar proteins; FBXO45, also called FBX45, or F-box/SPRY domain-containing protein 1, functions as the substrate-recognition component of E3 ubiquitin ligase complexes. It is critical for synaptogenesis, neuronal migration, and synaptic transmission. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLT 220
Cdd:cd22111     4 LPSRVLEVIFSYLDLPDLRNCSLVCKSWYRLL 35

F-box domain found in F-box only proteins FBXO6, FBXO44 and similar proteins; This subfamily includes FBXO6 and FBXO44. FBXO6, also called FBX6, F-box protein that recognizes sugar chains 2 (FBS2), or F-box/G-domain protein 2 (FBG2), is a substrate-recognition component of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. It is involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins, by recognizing and binding sugar chains on unfolded glycoproteins that are retro-translocated into the cytosol and promoting their ubiquitination and subsequent degradation. FBXO6 can recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. It also recognizes sulfated glycans. FBXO6 is involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. FBXO44, also called FBXO6A, FBX44, or F-box/G-domain protein 3 (FBG3), is a substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It interacts with SKP1 and CUL1. FBXO44 mediates BRCA1 ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217350109 184 TGITHLPPEVMLSIFSYLNPQEL-CRCSQVSMKWSQLTKTGSLWKH------LYPVHWARG--DWY 240
Cdd:cd22168     2 LTISDLPEDVLLEILSLVPARDLiLSCRLVCSRWRDLVDLPTLWKRkcqregFILKDWDGPpkDWK 67

Uncharacterized conserved protein, contains DUF2059 domain [Function unknown];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217350109  65 KLSEMLSLFEKGLKNV----KNEYEQLN--YAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDI 131
Cdd:COG3184    37 ELTGAEKMFDQMLPQLaeqlKQQLAQANpeLWKDLDEVVQEKALALAARRDELEDEMAPIYAKHFTEEELKAI 109

F-box domain found in F-box/LRR-repeat protein 4 (FBXL4) and similar proteins; FBXL4, also called F-box and leucine-rich repeat protein 4, or F-box protein FBL4/FBL5, is part of an SCF (SKP1-cullin-F-box) protein ligase complex. It serves as a clock output molecule that regulates sleep through promotion of rhythmic degradation of the GABA(A) receptor. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multi-system disease characterized by lactic acidemia, developmental delay, and hypotonia. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 230
Cdd:cd22117     4 LPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELN 45

F-box domain found in F-box/LRR-repeat protein 10 (FBXL10) and similar proteins; FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10, F-box protein FBL10, JmjC domain-containing histone demethylation protein 1B (JHDM1B), Jumonji domain-containing EMSY-interactor methyltransferase motif protein, protein JEMMA, protein-containing CXXC domain 2, [Histone-H3]-lysine-36 demethylase 1B, or NDY1. It is a histone demethylase that catalyzes the demethylation of H3K4me3 and H3K36me2, thereby playing a central role in the histone code. It preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. FBXL10 may also serve as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2217350109 189 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 226
Cdd:cd22180     6 MQREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 43