Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129689   7 EVDVFTAPHWRMKQLVGLYCDK-----------------SLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 65
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKlgrtdfsdpqdlaalleSLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129689  66 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 143
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

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 302129689 337 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 391
Cdd:cd09293   26 LHSGLEWLELYMCPISDPPLD---QLSNCNKLKKLILPGSKLIDDEGLIALAQSC 77

Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129689   7 EVDVFTAPHWRMKQLVGLYCDK-----------------SLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 65
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKlgrtdfsdpqdlaalleSLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129689  66 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 143
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 302129689  188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRLC 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 302129689 337 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 391
Cdd:cd09293   26 LHSGLEWLELYMCPISDPPLD---QLSNCNKLKKLILPGSKLIDDEGLIALAQSC 77

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

                           10        20
                   ....*....|....*....|....*
gi 302129689   365 CQSLRHLDLSGCEKITDVALEKISR 389
Cdd:smart00367   1 CPNLRELDLSGCTNITDEGLQALAK 25

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 302129689    8 VDVFTAPHWRMKQLVGLYCD--------------KSLYATFKEFKMHEQIENEYIIGLLQQRS---QTIYNVHSD--NKL 68
Cdd:pfam01814   3 IELLDAEHRRLRELLALLRAladalgdshlrklaELLDELVDELEAHHAAEEELLFPALERRSpggEAPIEVLRKehDEI 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 302129689   69 SEMLSLFEKGLKNVKNEYEqlnyakqLKERLEAFTRDFLPHMKEEEEVFQPML 121
Cdd:pfam01814  83 RELLEELEALLKGAEPGAA-------FAELLEALAEWLREHIAKEEEVLFPLL 128

Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129689   7 EVDVFTAPHWRMKQLVGLYCDK-----------------SLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 65
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKlgrtdfsdpqdlaalleSLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129689  66 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 143
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 228
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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22115    4 NKKLPKELLLRIFSFLDVVTLCRCAQVSKYWNVLALDGSNWQ 45

F-box domain found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11, also called FBX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1), 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 DTL/CDT2, BCL6 and PRDM1/BLIMP1. 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 302129689 190 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:cd22091    3 ELPDEVLLKIFSYLLEQDLCRAAQVCKRFNTLANDPELWKRLY 45

F-box domain found in F-box/LRR-repeat protein 13 (FBXL13) and similar proteins; FBXL13, also called F-box and leucine-rich repeat protein 13, or dynein regulatory complex subunit 6, is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. It is also 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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 228
Cdd:cd22124    1 ISLLPRKAALKIFSYLDLRDLARCAQVCRSWKVITQSSSLW 41

F-box domain; This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; pfam00560 and pfam07723) and the WD repeat (pfam00400). 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 302129689  188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKH 230
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in the JmjC domain-containing histone demethylation protein (JHDM) family; The JHDM family includes F-box/LRR-repeat proteins FBXL10, FBXL11 and FBXL19. FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10 (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. FBXL11, also called KDM2A, CXXC8, F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. FBXL19, also called F-box and leucine-rich repeat protein 19, is the substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It acts as a CpG island-binding protein in mouse embryonic stem (ES) cells and has been shown to associate with the CDK-Mediator complex. It promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with RNF20. 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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKH 230
Cdd:cd22122    4 LPREVWLPVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWKR 43

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 3 (FBXO3); This subfamily corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 3 (FBXO3). FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, that 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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 231
Cdd:cd22139    4 LPDELWLHIFSFLSPKDLCQVALVCRRFNRLASDESLWKQI 44

F-box domain found in F-box only protein 16 (FBXO16), epithelial cell-transforming sequence 2 oncogene-like (ECT2L) and similar proteins; This family includes FBXO16 and ECT2L. 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. 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 302129689 189 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22094    4 RVLPRFLSLYIFSYLDPRSLCRAAQVSWYWKFLCESDELWL 44

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 302129689 189 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 228
Cdd:cd22173    4 TVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLW 43

F-box domain found in Dictyostelium discoideum Rho GTPase-activating protein gacFF (DdgacFF) and similar proteins; DdgacFF, also called GTPase activating factor for raC protein FF, is a Rho GTPase-activating protein involved in the signal transduction 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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22148    2 ISLLPEHLALKILSYLSPKELLIASQVSKTWRRLASSNELWK 43

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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22123    1 LDQLPENVLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42

F-box domain found in F-box/WD repeat-containing protein 12 (FBXW12) and similar proteins; FBXW12, also called F-box and WD-40 domain-containing protein 12, or F-box only protein 35 (FBXO35), is the substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It functions as an epithelial growth suppressor. 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 302129689 190 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 231
Cdd:cd22137    2 QLPDLPMLRIFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNL 43

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 302129689 187 GITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 231
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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:cd22093    1 IERLPSEILLKILSYLDASSLLCISCVNKLFYQLANDNALWRKLY 45

F-box domain found in F-box/WD repeat-containing protein 5 (FBXW5) and similar proteins; FBXW5, also called F-box and WD-40 domain-containing protein 5, is the substrate-recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase 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        40
                 ....*....|....*....|....*....|....*....|....
gi 302129689 189 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:cd22132    2 PLLPDSLLLHIFSYLSPKDLLAAGQVCKQWYRVSRDEFLWKELF 45

F-box domain found in Drosophila melanogaster S-phase kinase-associated protein 2 (DmSKP2) and similar proteins; DmSKP2 is a Drosophila F-box protein that regulates cell proliferation by targeting Dacapo (Dap) for ubiquitination and proteasome-mediated degradation. It plays a role in maintaining diploidy of mitotic cells during development. 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 302129689 190 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22149    3 RLSDEIILSIFKWLPKKTLARCARVCRRWKRLCFDESLWR 42

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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd20090    2 LLDLPDDLLFLIFSYLDPASLGRLSQVCRRLYRLISRDAVWR 43

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 302129689  339 PNLEHLDLTQTDISDsafdsWSWLGCCQSLRHLDLSGCEKITDV 382
Cdd:pfam12799   1 PNLEVLDLSNNQITD-----IPPLAKLPNLETLDLSGNNKITDL 39

F-box domain found in F-box/LRR-repeat protein 7 (FBXL7) and similar proteins; FBXL7, also called F-box and leucine-rich repeat protein 7, or F-box protein FBL6/FBL7, 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 Aurora kinase A (AURKA) during mitosis, causing mitotic arrest. 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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 228
Cdd:cd22120    4 LPDDVILQIFSHLPTNQLCRCARVCRRWYNLAWDPRLW 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129689 312 GTSVKTLVLAYSSAVSSKMVRQILELCPNLEHLDLTQTD-ISDSAFDSWSwlGCCQSLRHLDLS---GCEKITDVALEKI 387
Cdd:cd09293   51 CNKLKKLILPGSKLIDDEGLIALAQSCPNLQVLDLRACEnITDSGIVALA--TNCPKLQTINLGrhrNGHLITDVSLSAL 128

                 ..
gi 302129689 388 SR 389
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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 228
Cdd:cd22114    4 LPDELLLGIFSCLCLPDLLKVSQVCKRWYRLASDESLW 41

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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:cd22087    4 LPPEIKLRILSLLDVRSLLSLSQVCRDLNSATNDQLLWRFLL 45

F-box domain found in F-box only protein 31 (FBXO31) and similar proteins; FBXO31, also called FBX31, or FBXO14, is a component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. It specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. FBXO31 may act as a tumor suppressor. 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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22102    1 ILDLPPELLVEIFSSLPGTDLPSLAQVCKKFREILNTDTIWQ 42

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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 232
Cdd:cd22151    3 LPDDLLQEIFKRLDPKSLARAACVCRRWRAAARSESLWENAC 44

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 302129689 191 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLT 222
Cdd:cd22111    4 LPSRVLEVIFSYLDLPDLRNCSLVCKSWYRLL 35

F-box domain found in F-box only protein 17 (FBXO17), F-box only protein 27 (FBXO27) and similar proteins; This subfamily includes FBXO17 and FBXO27. FBXO17 is also called FBX17, F-box only protein 26 (FBX26/FBXO26), or FBG4, while FBXO27 is also called FBX27, or F-box/G-domain protein 5. FBXO17 and FBXO27 are the substrate-recognition components of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. They can recognize and bind denatured glycoproteins, which are modified with complex-type oligosaccharides. FBXO17 also recognizes sulfated glycans but does not bind high-mannose glycoproteins. 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 302129689 188 ITHLPPEVMLSIFSYLNPQELC-RCSQVSMKWSQLTKTGSLWK 229
Cdd:cd22169    1 LSLLPEELLLLVLSHVPARTLVtRCRLVCRDWRDLVDGPTLWK 43

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 302129689  67 KLSEMLSLFEKGLKNV----KNEYEQLN--YAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDI 133
Cdd:COG3184   37 ELTGAEKMFDQMLPQLaeqlKQQLAQANpeLWKDLDEVVQEKALALAARRDELEDEMAPIYAKHFTEEELKAI 109

F-box domain found in F-box only protein 42 (FBXO42) and similar proteins; FBXO42, also called FBX42, or just one F-box and Kelch domain-containing protein (JFK), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It specifically recognizes p53/TP53, promoting its ubiquitination and degradation. FBXO42 is also involved in the ubiquitin-proteasome system that may play a role in the pathogenesis of Parkinson's disease (PD). 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 302129689 188 ITHLPPEVMLSIFSYLNP-QELCRCSQVSMKWSQLTKT 224
Cdd:cd22110    1 INDLPEEILEYILSYLSPyGDLKSAALVCKRWHRIIKG 38

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 302129689 188 ITHLPPEVMLSIFSYLNPQELCRCSQVSmKWSQLTKTGSLWKHL 231
Cdd:cd22143    2 FDSLPDEILSIIFSHLPQSDLYNLLFVN-KHFYSLALPELWRSI 44