Nse1 non-SMC component of SMC5-6 complex; S. cerevisiae Nse1 forms part of a complex with SMC5-SMC6. This non-structural maintenance of chromosomes (SMC) complex plays an essential role in genomic stability, being involved in DNA repair and DNA metabolism. It is conserved in eukaryotes from yeast to human. This domain lies immediately up-stream of the DNA-binding zinc-finger domain, zf-RING-like pfam08746.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   10 RRFLQLLMTHGVLEEWDVKRLQTHCYKVHDR-------SATVDKLEDFINNINSVLESLYIEIKRGVTE-DDGRPIYALV 81
Cdd:pfam07574   1 RAFLQALLARGTLTEEEAKPILAAIFSADEGepvdpndDITQDDLNDYISTINVALSPLDYEIRSVRHQlGKERVYYALV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   82 NLATTSISKMATDFAENELDLFRKALELIIDS------ETGFASSTNILNLVDQLK---------------------GKK 134
Cdd:pfam07574  81 NTTSDPETQLATTFSPDEIAFIKRLLDAMFDTyntprmEVMAITSMQAIKLARILApprrnrwssygytagsgqlsqAAG 160

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 211826035  135 MRKKEAEQVLQKFVQNKWLiEK--EGEFTLHGRAILE 169
Cdd:pfam07574 161 LTHSEAEKLLTRLVEEGWL-ERsrEGFYGLSPRALLE 196

Nse1 non-SMC component of SMC5-6 complex; S. cerevisiae Nse1 forms part of a complex with SMC5-SMC6. This non-structural maintenance of chromosomes (SMC) complex plays an essential role in genomic stability, being involved in DNA repair and DNA metabolism. It is conserved in eukaryotes from yeast to human. This domain lies immediately up-stream of the DNA-binding zinc-finger domain, zf-RING-like pfam08746.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   10 RRFLQLLMTHGVLEEWDVKRLQTHCYKVHDR-------SATVDKLEDFINNINSVLESLYIEIKRGVTE-DDGRPIYALV 81
Cdd:pfam07574   1 RAFLQALLARGTLTEEEAKPILAAIFSADEGepvdpndDITQDDLNDYISTINVALSPLDYEIRSVRHQlGKERVYYALV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   82 NLATTSISKMATDFAENELDLFRKALELIIDS------ETGFASSTNILNLVDQLK---------------------GKK 134
Cdd:pfam07574  81 NTTSDPETQLATTFSPDEIAFIKRLLDAMFDTyntprmEVMAITSMQAIKLARILApprrnrwssygytagsgqlsqAAG 160

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 211826035  135 MRKKEAEQVLQKFVQNKWLiEK--EGEFTLHGRAILE 169
Cdd:pfam07574 161 LTHSEAEKLLTRLVEEGWL-ERsrEGFYGLSPRALLE 196

RING-like domain; This is a zinc finger domain that is related to the C3HC4 RING finger domain (pfam00097).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 211826035  185 CNICHSLLIQGQSC--ETCGIRMHLPCVAKYFQSNAEPRCPHC 225
Cdd:pfam08746   1 CEACKEIVTQGQRCpnEDCNVRLHDDCLRKYFRTRRSPKCPKC 43

Nse1 non-SMC component of SMC5-6 complex; S. cerevisiae Nse1 forms part of a complex with SMC5-SMC6. This non-structural maintenance of chromosomes (SMC) complex plays an essential role in genomic stability, being involved in DNA repair and DNA metabolism. It is conserved in eukaryotes from yeast to human. This domain lies immediately up-stream of the DNA-binding zinc-finger domain, zf-RING-like pfam08746.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   10 RRFLQLLMTHGVLEEWDVKRLQTHCYKVHDR-------SATVDKLEDFINNINSVLESLYIEIKRGVTE-DDGRPIYALV 81
Cdd:pfam07574   1 RAFLQALLARGTLTEEEAKPILAAIFSADEGepvdpndDITQDDLNDYISTINVALSPLDYEIRSVRHQlGKERVYYALV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 211826035   82 NLATTSISKMATDFAENELDLFRKALELIIDS------ETGFASSTNILNLVDQLK---------------------GKK 134
Cdd:pfam07574  81 NTTSDPETQLATTFSPDEIAFIKRLLDAMFDTyntprmEVMAITSMQAIKLARILApprrnrwssygytagsgqlsqAAG 160

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 211826035  135 MRKKEAEQVLQKFVQNKWLiEK--EGEFTLHGRAILE 169
Cdd:pfam07574 161 LTHSEAEKLLTRLVEEGWL-ERsrEGFYGLSPRALLE 196

RING-like domain; This is a zinc finger domain that is related to the C3HC4 RING finger domain (pfam00097).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 211826035  185 CNICHSLLIQGQSC--ETCGIRMHLPCVAKYFQSNAEPRCPHC 225
Cdd:pfam08746   1 CEACKEIVTQGQRCpnEDCNVRLHDDCLRKYFRTRRSPKCPKC 43

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 211826035 185 CNICHSLLIQGQ--SCETCGIRMHLPCVAKYFQSNaEPRCPHCN 226
Cdd:cd16448    1 CVICLEEFEEGDvvRLLPCGHVFHLACILRWLESG-NNTCPLCR 43

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 211826035 185 CNICHSLLIQGQ------SCETCGIRMHLPCVAKYFQSNAEPRCPHC 225
Cdd:cd16491    3 CPICYSVIHGSNhslpklKCKTCKNKFHSACLYKWFRSSNKSTCPLC 49

protein kinase C conserved region 1 (C1 domain) found in A- and C-Raf (Rapidly Accelerated Fibrosarcoma) kinases, and similar proteins; This group includes A-Raf and C-Raf, both of which are serine/threonine-protein kinases. A-Raf, also called proto-oncogene A-Raf or proto-oncogene A-Raf-1, cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. C-Raf, also known as proto-oncogene Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around mid-gestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. Both A- and C-Raf are mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 211826035 168 LEMEQYIRETYPdAVKICNICHSLLIQGQSCETCGIRMHLPCVAK 212
Cdd:cd20870    1 LTTHNFVRKTFL-KLAFCDICQKFLLNGFRCQTCGYKFHEHCSTK 44

protein kinase C conserved region 1 (C1 domain) found in B-Raf (Rapidly Accelerated Fibrosarcoma) kinase and similar proteins; Serine/threonine-protein kinase B-Raf, also called proto-oncogene B-Raf, p94, or v-Raf murine sarcoma viral oncogene homolog B1, activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 211826035 168 LEMEQYIRETYpDAVKICNICHSLLIQGQSCETCGIRMHLPC 209
Cdd:cd20871    3 LTTHNFVRKTF-FTLAFCDFCRKLLFQGFRCQTCGYKFHQRC 43