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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034650127  76 DFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKCVKFGW 127
Cdd:cd22173     1 DFTTVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLWMPKCVKFGW 52

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127 821 IHDLSLFLFNDALLVSSRGTShtpfeRTSKTTYQFIASVALHRLLIENIPDSKYVKNAF-ILQGPKYKwICATEIEDDKF 899
Cdd:cd01226    25 IQKVHLFLLNDVLLIASWLPN-----RRGPVRYKFQALYPLEDLAVVNVKDLGPVKNAFkLLTFPETR-VFQCENAKIKK 98

                          90
                  ....*....|....*.
gi 1034650127 900 LWLSVLRNAIKSSMEK 915
Cdd:cd01226    99 EWLEKFEQAKRAKLAK 114

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  581 VVRELLQSERKYVQILEIVRDVYVAPLKAALSsnraILSAANIQIIFCDILQILSLNRQFLDNLRDRLQEWGPAHC-VGE 659
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVErIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  660 IVTKFGSQLNTYTNFFNNYPVILKTIEKCREmIPAFRTFLKRHDKTIVTKMLSLPELLLYPSRRFEEYLNLLYAVRLHTP 739
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKK-NPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155

                          170       180
                   ....*....|....*....|....*
gi 1034650127  740 AEHVDRGDLTTAIDQIKKYKGYIDQ 764
Cdd:smart00325 156 EDHEDREDLKKALKAIKELANQVNE 180

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034650127  76 DFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKCVKFGW 127
Cdd:cd22173     1 DFTTVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLWMPKCVKFGW 52

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  577 KRARVVRELLQSERKYVQILEIVRDVYVAPlkaaLSSNRAILSAANIQII---FCDILQILSLNRQFLDNLRDRlQEWGP 653
Cdd:COG5422    484 KRQEAIYEVIYTERDFVKDLEYLRDTWIKP----LEESNIIPENARRNFIkhvFANINEIYAVNSKLLKALTNR-QCLSP 558

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  654 -AHCVGEIVTKFGSQLNTYTNFFNNYPVILKTIEKCREMIPAFRTFLkrHDKTIVTKMLSLpELLLY---PSRRFEEYLN 729
Cdd:COG5422    559 iVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFD--HEVERLDESRKL-ELDGYltkPTTRLARYPL 635

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1034650127  730 LLYAVRLHTPAEHVDRGDLTTAIDQIKKYKGYIDQ 764
Cdd:COG5422    636 LLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNF 670

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127 821 IHDLSLFLFNDALLVSSRGTShtpfeRTSKTTYQFIASVALHRLLIENIPDSKYVKNAF-ILQGPKYKwICATEIEDDKF 899
Cdd:cd01226    25 IQKVHLFLLNDVLLIASWLPN-----RRGPVRYKFQALYPLEDLAVVNVKDLGPVKNAFkLLTFPETR-VFQCENAKIKK 98

                          90
                  ....*....|....*.
gi 1034650127 900 LWLSVLRNAIKSSMEK 915
Cdd:cd01226    99 EWLEKFEQAKRAKLAK 114

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  581 VVRELLQSERKYVQILEIVRDVYVAPLKAALSsnraILSAANIQIIFCDILQILSLNRQFLDNLRDRLQEWGPAHC-VGE 659
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVErIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127  660 IVTKFGSQLNTYTNFFNNYPVILKTIEKCREmIPAFRTFLKRHDKTIVTKMLSLPELLLYPSRRFEEYLNLLYAVRLHTP 739
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKK-NPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155

                          170       180
                   ....*....|....*....|....*
gi 1034650127  740 AEHVDRGDLTTAIDQIKKYKGYIDQ 764
Cdd:smart00325 156 EDHEDREDLKKALKAIKELANQVNE 180

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034650127  76 DFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKCVKFGW 127
Cdd:cd22173     1 DFTTVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLWMPKCVKFGW 52

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 1034650127  76 DFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKCVK 124
Cdd:cd22094     1 DFTRVLPRFLSLYIFSYLDPRSLCRAAQVSWYWKFLCESDELWLPKCLR 49

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034650127  58 QLRFVQDWFSERMQVakvDFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22133     1 QVRHMMQVIEPQFQR---DFISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLW 58

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

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:pfam12937   4 LPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLW 41

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127 821 IHDLSLFLFNDALLVSSRGTShtpfeRTSKTTYQFIASVALHRLLIENIPDSKYVKNAF-ILQGPKYKwICATEIEDDKF 899
Cdd:cd01226    25 IQKVHLFLLNDVLLIASWLPN-----RRGPVRYKFQALYPLEDLAVVNVKDLGPVKNAFkLLTFPETR-VFQCENAKIKK 98

                          90
                  ....*....|....*.
gi 1034650127 900 LWLSVLRNAIKSSMEK 915
Cdd:cd01226    99 EWLEKFEQAKRAKLAK 114

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 1034650127  77 FSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22148     1 FISLLPEHLALKILSYLSPKELLIASQVSKTWRRLASSNELW 42

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 1034650127  79 TVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22118     2 SSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

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
                  ....*....|....*....|....*....|....*...
gi 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22124     4 LPRKAALKIFSYLDLRDLARCAQVCRSWKVITQSSSLW 41

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 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKC 122
Cdd:cd22085     6 LPIDLQLYILSFLSPHDLCQLGLTSHYWHTLVRDPLLWRYFL 47

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127 826 LFLFNDALLVSSRGTShtpfertskTTYQFIA--SVALHRLLIENIPDSKYVKNAFILQGPKYKWICATEIEDDKFLWLS 903
Cdd:cd01220    27 FFLFSDVLLYTSRSPT---------PSLQFKVhgQLPLRGLMVEESEPEWGVAHCFTIYGGNRALTVAASSEEEKERWLE 97

                  ....*.
gi 1034650127 904 VLRNAI 909
Cdd:cd01220    98 DLQRAI 103

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034650127 828 LFNDALlVSSRGTSHTPFertskttyqfiasvALHRLLIENIPDSKYVKNAFILQGPKYKWICATEIEDDKFLWLSVLRN 907
Cdd:cd13269    34 LFNDAL-VHAQFSTHHIF--------------PLATLWVEPIPDEDSGQNALKITTPEESFTLVASTPQEKAEWLRAINQ 98

                  ....*...
gi 1034650127 908 AIKSSMEK 915
Cdd:cd13269    99 AIDQALNG 106

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 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKC 122
Cdd:cd22137     3 LPDLPMLRIFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNLC 44

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
                  ....*....|....*....|....*....|....*...
gi 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22138     4 LPVECQLKIFSFLSEVDKCLAATVCRSWSELIRSPRLW 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
                  ....*....|....*....|....*....|....*...
gi 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLW 118
Cdd:cd22115     7 LPKELLLRIFSFLDVVTLCRCAQVSKYWNVLALDGSNW 44

F-box domain found in F-box/WD repeat-containing protein 10 (FBXW10) and similar proteins; FBXW10, also called F-box and WD-40 domain-containing protein 10, or ubiquitin ligase-specificity factor, is a probable substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Its overexpression leads to degradation of CBX5 and CBX1. FBXW10 is negatively regulated in transcription and expression levels by protein O-GlcNAcylation. 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 1034650127  81 LPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQ 114
Cdd:cd22136     5 LPVHLSKYILSMLDKKSLNNCLCVSQHWRALTEE 38