Cyclin box fold superfamily; The cyclin box is a protein binding domain that functions in cell-cycle and transcriptional control. It is about 100 amino acids in length, composed of five helices, and is present in cyclins, transcription initiation factor IIB (TFIIB), and retinoblastoma tumour suppressor protein (Rb). Cyclins consist of 8 classes of cell cycle regulators that function as regulatory subunits of cyclin-dependent kinases (CDKs), which are serine/threonine kinases. The catalytic activities of CDKs are modulated not only by their interactions with cyclins but also by CDK inhibitors (CKIs). CDKs, cyclins and CKIs play key roles in transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions, and spermatogenesis. TFIIB is a transcription factor that binds the TATA box. Members in this superfamily contain one or two copies of the cyclin box.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  75 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 154
Cdd:cd20578    1 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 80

                         90       100
                 ....*....|....*....|....*
gi 209862835 155 EVDCLRACQEQIEAALRESLREASQ 179
Cdd:cd20578   81 EVDCLRACQEQIEAALRESLREASQ 105

second cyclin box found in G1/S-specific cyclin-D3 (CCND3); CCND3 is a regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family, including RB1, and regulates the cell-cycle during G(1)/S transition. In skeletal muscle, CCND3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. CCND3 contains two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  75 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 154
Cdd:cd20578    1 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 80

                         90       100
                 ....*....|....*....|....*
gi 209862835 155 EVDCLRACQEQIEAALRESLREASQ 179
Cdd:cd20578   81 EVDCLRACQEQIEAALRESLREASQ 105

Cyclin, N-terminal domain; Cyclins regulate cyclin dependent kinases (CDKs). Swiss:P22674 is a Uracil-DNA glycosylase that is related to other cyclins. Cyclins contain two domains of similar all-alpha fold, of which this family corresponds with the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209862835    1 MNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWDLA 72
Cdd:pfam00134  56 VNYLDRFLSKKSVPKNKLQLVGVTCLFIAAKYEEIYPPTVEDLVYITDNAYTREEILRMERLILETLNFDLS 127

domain present in cyclins, TFIIB and Retinoblastoma; A helical domain present in cyclins and TFIIB (twice) and Retinoblastoma (once). A protein recognition domain functioning in cell-cycle and transcription control.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 209862835     1 MNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEkLCIYTdHAVSPRQLRDWEVLVL 64
Cdd:smart00385  21 VNLLDRFLSDYKFLKYSPSLIAAAALYLASKTEETPPWTKE-LVHYT-GYFTEEEILRMERLLL 82

second cyclin box found in G1/S-specific cyclin-D3 (CCND3); CCND3 is a regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family, including RB1, and regulates the cell-cycle during G(1)/S transition. In skeletal muscle, CCND3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. CCND3 contains two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  75 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 154
Cdd:cd20578    1 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 80

                         90       100
                 ....*....|....*....|....*
gi 209862835 155 EVDCLRACQEQIEAALRESLREASQ 179
Cdd:cd20578   81 EVDCLRACQEQIEAALRESLREASQ 105

second cyclin box found in G1/S-specific cyclin-D2 (CCND2); CCND2 is a regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family, including RB1, and regulates the cell-cycle during G(1)/S transition. It is a critical mediator of exercise-induced cardiac hypertrophy. It also acts as a regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. CCND2 contains two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  77 HDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGL----GACSMSGDELTELLAGIT 152
Cdd:cd20577    3 HDFIEHILRKLPLPKDKLPLIRKHAQTFIALCATDFKFAMYPPSMIATGSVGAAICGLqldrGDSSLSGDSLTELLAKIT 82

                         90       100
                 ....*....|....*....|...
gi 209862835 153 GTEVDCLRACQEQIEAALRESLR 175
Cdd:cd20577   83 NTDVDCLKACQEQIESVLVSNLR 105

second cyclin box found in cyclin-D (CCND) family; The CCND family includes three mitogen-induced D-type cyclins, CCND1, CCND2 and CCND3, which function as regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6, that drive progression through the G1 phase of the cell cycle. Members in this family contain two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  75 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSM-SGDELTELLAGITG 153
Cdd:cd20516    1 TPLDFLEHILHRLPLDSEDVDKVRKHAETFIALCATDYKFSSYPPSMIAAASILAALRGLLLHSGnSKEDLLEKLQQLTR 80

                         90
                 ....*....|....*...
gi 209862835 154 TEVDCLRACQEQIEAALR 171
Cdd:cd20516   81 IDEDLLRACQEQIEDLLE 98

second cyclin box found in G1/S-specific cyclin-D1 (CCND1); CCND1, also called B-cell lymphoma 1 protein (BCL-1), or BCL-1 oncogene, or PRAD1 oncogene, is a regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family, including RB1, and regulates the cell-cycle during G(1)/S transition. It is an important cell cycle regulatory protein involved in carcinogenesis of various human cancers. CCND1 contains two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  77 HDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACS----MSGDELTELLAGIT 152
Cdd:cd20576    3 HDFIEHFLSKMPLAEDTKQIIRKHAQTFVALCATDVKFISNPPSMIAAGSVAAAVQGLNLGNtnsfLSYQRLTRFLSQVI 82

                         90       100
                 ....*....|....*....|....*..
gi 209862835 153 GTEVDCLRACQEQIEAALRESLREASQ 179
Cdd:cd20576   83 KCDPDCLRACQEQIESLLESSLRQAQQ 109

Cyclin, N-terminal domain; Cyclins regulate cyclin dependent kinases (CDKs). Swiss:P22674 is a Uracil-DNA glycosylase that is related to other cyclins. Cyclins contain two domains of similar all-alpha fold, of which this family corresponds with the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 209862835    1 MNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWDLA 72
Cdd:pfam00134  56 VNYLDRFLSKKSVPKNKLQLVGVTCLFIAAKYEEIYPPTVEDLVYITDNAYTREEILRMERLILETLNFDLS 127

first cyclin box found in cyclin-A (CCNA) family; The CCNA family includes two A-type cyclins, CCNA1 and CCNA2. CCNA1 may primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells. CCNA2 controls both the G1/S and the G2/M transition phases of the cell cycle. Members in this family contain two cyclin boxes. The model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209862835   2 NYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLK 68
Cdd:cd20504   61 NYIDRFLSQMSVLRSKLQLVGTACMFIAAKYEEIYPPEVEEFVYITDDTYTKKQVLRMEHLVLKVLS 127

first cyclin box found in Arabidopsis thaliana A-type cyclins (CycAs) and similar proteins; Plant A-type cyclins (CycAs) correspond to a group of G2/mitotic-specific cyclins that are functionally linked to S- and M-phases of the mitotic cycle, which predicts their involvement also in meiosis. CycAs associate with their partner cyclin-dependent kinases (CDKs) to trigger the kinase activity. They contain two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209862835   2 NYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWD 70
Cdd:cd20562   68 SYIDRFLSGNYVNRQRLQLLGVSCMLIASKYEEICAPQVEEFCYITDNTYTKQEVLEMEIDVLNALQFE 136

first cyclin box found in G1/S-specific cyclin-E (CCNE) family; The CCNE family includes two E-type cyclins, CCNE1 and CCNE2. CCNE1 is essential for the control of the cell cycle at the G1/S (start) transition. It interacts with CDK2 protein kinase to form a serine/threonine kinase holoenzyme complex. CCNE2 is essential for the control of the cell cycle at the late G1 and early S phase. It interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein kinases to form a serine/threonine kinase holoenzyme complexes. Members of this family contain two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835   1 MNYLDRYLSCVP-TRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKW 69
Cdd:cd20519   62 VDFVDRYLSTQTnVPKTQLQLIGITCLFIAAKLEEIYPPKLSEFAYVTDGACTEDEILTMELIILKALNW 131

first cyclin box found in cyclin-A2 (CCNA2) and similar proteins; CCNA2 controls both the G1/S and the G2/M transition phases of the cell cycle. It is significantly over-expressed in various cancer types, and can be used as a prognostic biomarker for estrogen receptor positive (ER+) breast cancer and tamoxifen resistance. CCNA2 contains two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835   1 MNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWD 70
Cdd:cd20561   62 VNYIDRFLSSMSVLRGKLQLVGTAAMLLASKFEEIYPPEVAEFVYITDDTYTKKQVLRMEHLVLKVLTFD 131

first cyclin box found in G2/mitotic-specific cyclin-B1 (CCNB1); CCNB1 is essential for the control of the cell cycle at the G2/M (mitosis) transition. It is required for embryo development. Over-expression of human CCNB1 has been found in numerous cancers and has been associated with tumor aggressiveness. CCNB1 contains two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209862835   4 LDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKW 69
Cdd:cd20565   64 IDRFLQNNPVPKKMLQLVGVTAMFIASKYEEMYPPEIGDFAFVTDNTYTKHQIRQMEMKILRALDF 129

first cyclin box found in plant cyclin-delta family; This subfamily is composed of plant delta family cyclins, including a group of G1/S-specific D-type cyclins from Arabidopsis thaliana which may activate the cell cycle in the root apical meristem (RAM) and promote embryonic root (radicle) protrusion. Members of this family contain two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 209862835   1 MNYLDRYLSCVPTRKAQ---LQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAV-SPRQLRDWEVLVLGKLKW 69
Cdd:cd20543   27 VNYLDRFLSSYDLPKDKpwmLQLLAVACLSLAAKMEETDVPLLVDLQVEEPKYVfEAKTIQRMELLVLSTLEW 99

first cyclin box found in G2/mitotic-specific cyclin-B2 (CCNB2) and similar proteins; CCNB2 is essential for the control of the cell cycle at the G2/M (mitosis) transition. It is required for progression through meiosis. CCNB2 contains two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209862835   4 LDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKW 69
Cdd:cd20566   68 MDRFLQVQPVSRKKLQLVGVTALLLASKYEEMYSPEIGDFVYITDNAYTKAQIREMEMLILKELNF 133

first cyclin box found in G2/mitotic-specific cyclin-B3 (CCNB3) and similar proteins; CCNB3 is a mitotic B-type cyclin that promotes the metaphase-anaphase transition. It controls anaphase onset independent of spindle assembly checkpoint in meiotic oocytes. CCNB3 contains two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209862835   4 LDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWD 70
Cdd:cd20508   76 VDLYLSKKVVKKEKLQLLGATAILIASKFDERCPPCVDDFLYICDDAYTREELLKMEREILKTLDFD 142

Cyclin box fold superfamily; The cyclin box is a protein binding domain that functions in cell-cycle and transcriptional control. It is about 100 amino acids in length, composed of five helices, and is present in cyclins, transcription initiation factor IIB (TFIIB), and retinoblastoma tumour suppressor protein (Rb). Cyclins consist of 8 classes of cell cycle regulators that function as regulatory subunits of cyclin-dependent kinases (CDKs), which are serine/threonine kinases. The catalytic activities of CDKs are modulated not only by their interactions with cyclins but also by CDK inhibitors (CKIs). CDKs, cyclins and CKIs play key roles in transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions, and spermatogenesis. TFIIB is a transcription factor that binds the TATA box. Members in this superfamily contain one or two copies of the cyclin box.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835   1 MNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLREtTPLTIEKLCIYTDhaVSPRQLRDWE 60
Cdd:cd00043   24 IELLDRFLSKGLLLGRSPELIAAACLYLACKLEE-LPRTLKEIAKVSG--VSEKELRKAE 80

first cyclin box found in G1/S-specific cyclin-E2 (CCNE2); CCNE2 is essential for the control of the cell cycle at the late G1 and early S phase. It interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein kinases to form a serine/threonine kinase holoenzyme complexes. CCNE2 contains two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209862835   2 NYLDRY-LSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKW 69
Cdd:cd20580   69 DFFDRFmLTQKNINKSMLQLIGITSLFIASKLEEIYPPKLHEFAYVTDGACSEDDILDMELIILKALKW 137

cyclin box found in Saccharomyces cerevisiae G1/S-specific cyclins (ScCLNs) and similar proteins; ScCLNs, including ScCLN1-3, are essential for the control of the cell cycle at the G1/S (start) transition in Saccharomyces. ScCLN1 and ScCLN2 interact with the CDC28 protein kinase to form maturation promoting factor (MPF). ScCLN3 may be an upstream activator of the G1 cyclins that directly initiate G1/S transition. This family also includes Schizosaccharomyces pombe cyclin puc1, which contributes to negative regulation of the timing of sexual development in fission yeast, and functions at the transition between cycling and non-cycling cells. It interacts with protein kinase A. Members of this family contain one cyclin box. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209862835   2 NYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTP--LTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWD 70
Cdd:cd20559   25 NLIDRYCSKRIVLKKHYQLVGCTCLWIASKFWESKArvPLLSELSKMCCNSYGEELFIQMEMHILNTLNWD 95

second cyclin box found in viral cyclin (v-cyclin); v-Cyclin modulates host cell cycle progression and apoptotic signaling pathways. It forms an active kinase complex with cellular CDK6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins. v-Cyclin belongs to Cyclin D subfamily. It contains two cyclin boxes. This model corresponds to the second one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835  75 IAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGT 154
Cdd:cd20518    1 LATDVTSPLLLKLKGGSDQLDALHHAVNTLITKALVDPNTGSLPPSLISAAGCLLLVPANVTPQTHSGGVLPRLASILGC 80

                         90
                 ....*....|....*...
gi 209862835 155 EVDCLRACQEQIEAALRE 172
Cdd:cd20518   81 SVSTLQAAVEQVLTSLSD 98

first cyclin box found in cyclin-J (CCNJ) family; The CCNJ family includes two cyclins, CCNJ and CCNJ-like. CCNJ may regulate the cell cycle or transcription. Members of this family contain two cyclin boxes. This model corresponds to the first one. The cyclin box is a protein binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862835   3 YLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLT--IEKLCIYTD-HAVSPRQLRDWEVLVLGKLKW 69
Cdd:cd20528   34 LLDRFMDRYDISEDQLHLVALTCLLLAAKFEELDDNIpkISDLNRYLCnSVYSKQEYLQMELLILEFFQW 103