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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 173
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 767929763 531 LSLSGCYQITDHGLRVLTLGggLPYLEHLNLSGCLTITGAGLQDLVSACPSL 582
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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 173
Cdd:cd22118    1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 767929763   136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 176
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFKL 41

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 767929763  284 PNLEHLDLTQTDISDsafdsWSWLGCCQSLRHLDLSGCEKITDV 327
Cdd:pfam12799   1 PNLEVLDLSNNQITD-----IPPLAKLPNLETLDLSGNNKITDL 39

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 767929763    8 VDVFTAPHWRMKQLVGLYCDKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLME--YFTYEELKDIKK----- 80
Cdd:pfam01814   3 IELLDAEHRRLRELLALLRALADALGDSHLRKLAELLDELVDELEAHHAAEEELLFPALERrsPGGEAPIEVLRKehdei 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 767929763   81 --------KVIAQHCSQKDTAELLRGL--SLWNH-AEERQKFF 112
Cdd:pfam01814  83 relleeleALLKGAEPGAAFAELLEALaeWLREHiAKEEEVLF 125

Leucine-rich repeat (LRR) protein [Transcription];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767929763 280 LELCPNLEHLDLTQTDISDSAfdswSWLGCCQSLRHLDLSGCeKITDvalekISRALGILTS 341
Cdd:COG4886  178 LGNLTNLKELDLSNNQITDLP----EPLGNLTNLEELDLSGN-QLTD-----LPEPLANLTN 229

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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 173
Cdd:cd22118    1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 174
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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 176
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 767929763 135 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 174
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 767929763 134 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTK 168
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 767929763 136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 173
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 767929763 135 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLYPVHW 181
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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTK-TGSLWKHL 176
Cdd:cd22113    1 IELLPPEMSLRIFSQLDVQSLCRASQTCKTWNDLIEnSDYLWRPH 45

F-box domain found in epithelial cell-transforming sequence 2 oncogene-like (ECT2L) and similar proteins; ECT2L, also called lung-specific F-box and DH domain-containing protein, or putative guanine nucleotide exchange factor LFDH, may act as a guanine nucleotide exchange factor (GEF). 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 767929763 134 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 173
Cdd:cd22173    4 TVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLW 43

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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 176
Cdd:cd22141    1 IGNLPFEISLKIFNYLQFEDLLNSLGVSKKWNKIIRNTALWKKL 44

F-box domain found in F-box/LRR-repeat protein 12 (FBXL12) and similar proteins; FBXL12, also called F-box and leucine-rich repeat protein 12, or F-box protein FBL12, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the polyubiquitination and proteasomal degradation of calcium/calmodulin dependent protein kinase I (CAMK1) leading to disruption of cyclin D1/CDK4 complex assembly, which results in G1 cell cycle arrest in lung epithelia. It regulates T-cell differentiation in a cell-autonomous manner. 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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 174
Cdd:cd22123    1 LDQLPENVLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42

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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKW 163
Cdd:cd22131    3 LKLLPLELSFYLLSFLDPESLLTCCLVSKQW 33

F-box domain found in F-box only protein 4 (FBXO4) and similar proteins; FBXO4, also called FBX4, is a specific substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. It recognizes TERF1 and promotes its ubiquitination together with UBE2D1. 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 767929763 132 GITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 176
Cdd:cd22085    2 LLNHLPIDLQLYILSFLSPHDLCQLGLTSHYWHTLVRDPLLWRYF 46

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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 177
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 767929763 282 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 336
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 767929763 268 SSAVSSKMVRQILELCPNLEHLDLTQTDISDSAFDSWSWlGCCQSLRHLDLSGCEKITDVALEKI 332
Cdd:cd09293  117 GHLITDVSLSALGKNCTFLQTVGFAGCDVTDKGVWELAS-GCSKSLERLSLNNCRNLTDQSIPAI 180

F-box domain found in F-box/WD repeat-containing protein 4 (FBXW4) and similar proteins; FBXW4, also called dactylin, or F-box and WD-40 domain-containing protein 4, probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It is likely to be involved in key signaling pathways crucial for normal limb development. It may participate in Wnt signaling and act as a novel tumor suppressor that regulates important cellular processes. 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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 174
Cdd:cd20090    2 LLDLPDDLLFLIFSYLDPASLGRLSQVCRRLYRLISRDAVWR 43

F-box domain found in F-box only protein 13 (FBXO13) and similar proteins; FBXO13, also called FBX13, F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of 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 767929763 132 GITHLPPEVMLSIFSYLNPQELCR-CSQVSMKWSQLTKTGSLWKHL 176
Cdd:cd22092    1 NINQLPDSILLKIFSYLSLQERCLsASLVCKYWRDLCLDSQFWKQI 46

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

                           10        20
                   ....*....|....*....|....*
gi 767929763   310 CQSLRHLDLSGCEKITDVALEKISR 334
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 767929763 257 GTSVKTLVLAYSSAVSSKMVRQILELCPNLEHLDLTQTD-ISDSAFDSWSwlGCCQSLRHLDLS---GCEKITDVALEKI 332
Cdd:cd09293   51 CNKLKKLILPGSKLIDDEGLIALAQSCPNLQVLDLRACEnITDSGIVALA--TNCPKLQTINLGrhrNGHLITDVSLSAL 128

                 ..
gi 767929763 333 SR 334
Cdd:cd09293  129 GK 130

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 767929763 531 LSLSGCYQITDHGLRVLTLGggLPYLEHLNLSGCLTITGAGLQDLVSACPSL 582
Cdd:cd09293   57 LILPGSKLIDDEGLIALAQS--CPNLQVLDLRACENITDSGIVALATNCPKL 106

F-box domain found in F-box only protein 7 (FBXO7) and similar proteins; FBXO7, also called FBX7, 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 recognizes BIRC2 and DLGAP5. FBXO7 plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. It promotes MFN1 ubiquitination. FBXO7 acts as a cell cycle regulator by enhancing cyclin D/cyclin-dependent kinase 6 (Cdk6) complex formation and stabilizing levels of p27, a cyclin-dependent kinase inhibitor. Mutations in the FBXO7 (PARK15) gene have been implicated in a juvenile form of parkinsonism called parkinsonian pyramidal syndrome (PPS), characterized by Parkinsonian symptoms and pyramidal tract signs. 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 767929763 136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 177
Cdd:cd22087    4 LPPEIKLRILSLLDVRSLLSLSQVCRDLNSATNDQLLWRFLL 45

F-box domain found in the early mitotic inhibitor (EMI) family of F-box proteins; The EMI family includes FBX5 (EMI1) and FBX43 (EMI2), which are anaphase-promoting complex/cyclosome (APC/C) inhibitors that bind APC/C-CCD20 (Cell division cycle protein 20) and/or APC/C-CDH1 (CDC20 homologue 1) complexes. 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 767929763 144 IFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 177
Cdd:cd22086   15 ILSYLSPEDLCRVSCVSKTWRQICLSDPKANRRR 48

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 767929763 136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 177
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 767929763 136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLT 167
Cdd:cd22111    4 LPSRVLEVIFSYLDLPDLRNCSLVCKSWYRLL 35

F-box domain found in F-box/LRR-repeat protein 6 (FBXL6) and similar proteins; FBXL6, also called F-box and leucine-rich repeat protein 6, or F-box protein FBL6 (FBL6A), is 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 767929763 133 ITHLPPEVMLSIFSYLNPQE-----LCRCSQVSMKWSQLTKTGSLWK 174
Cdd:cd22119    1 GQRLPPEILVKIFQFAVATEgavplLCRLSRVCRLWREVALDPSLWT 47

Hemerythrin-like domain; Hemerythrin (Hr) like domains have the same four alpha helix bundle and a similar, but slightly different active site structure than hemerythrin. They are non-heme diiron binding proteins mainly found in bacteria and eukaryotes. Like Hr, they may be involved in oxygen transport or like human FBXL5 (F-box and leucine-rich repeat protein 5), a member of this group, play a role in cellular iron homeostasis.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 767929763  32 EQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQP 64
Cdd:cd12108   98 GDAEDAEELAAALEALRTALREHLDEEEEELFP 130

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 767929763 136 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 177
Cdd:cd22117    4 LPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELN 45

F-box domain found in Saccharomyces cerevisiae mitochondrial distribution and morphology protein 30 (ScMDM30) and similar proteins; ScMDM30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. It 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. ScMDM30 recognizes FZO1 and regulates the amount of FZO1. It acts as a regulatory factor for the mitochondrial fusion machinery and is required for mitochondrial DNA maintenance. 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 767929763 133 ITHLPPEVMLSIFSYLNPQELCRCSQVSmKWSQLTKTGSLWKHL 176
Cdd:cd22143    2 FDSLPDEILSIIFSHLPQSDLYNLLFVN-KHFYSLALPELWRSI 44