RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1698288618 1519 PCIICHEDMVPHETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVHI 1563
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1158 VLFGPTAVQVPQETRRSVAVNTELHERFEKQLGDINKMQKSIGSMEEQIEKISsgcekvdvEDLTDLKDEIQKITANIQV 1237
Cdd:COG3883      5 ALAAPTPAFADPQIQAKQKELSELQAELEAAQAELDALQAELEELNEEYNELQ--------AELEALQAEIDKLQAEIAE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1238 TNTELSLFQQKLEEEVKKDQKEKKA------------------NQEVLKSLKVKREQLMEEQKSLAHKLRETKANYDTVL 1299
Cdd:COG3883     77 AEAEIEERREELGERARALYRSGGSvsyldvllgsesfsdfldRLSALSKIADADADLLEELKADKAELEAKKAELEAKL 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1300 SDFLGSSNRIAAEKSSLEGKIQSCKTQL-SLATRRSHIAQTLYQENIDQEKSRRRITEQP 1358
Cdd:COG3883    157 AELEALKAELEAAKAELEAQQAEQEALLaQLSAEEAAAEAQLAELEAELAAAEAAAAAAA 216

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1698288618 1519 PCIICHEDMVPHETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVHI 1563
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

Tetratricopeptide (TPR) repeat [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   86 GNEYFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVCDGKRAILIEPFWPKGHYRYCEALFSLGEVQM 165
Cdd:COG0457     49 GLAYLRLGRYEEALADYEQALELDPDDAEALNNLGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYDE 128

                   ..
gi 1698288618  166 AI 167
Cdd:COG0457    129 AI 130

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|.
gi 1698288618  1520 CIICHEDMvPHETCVLDCRHSFHSQCIKPWLK-GHNTCPTC 1559
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   53 IKTMSSNVSAMLDSLKTIPSSYNMEKSEKMKEKGNEYFRKEQYEEAVKFYTQAInNCPDNHLIYGNRALCYIKSKKYLKA 132
Cdd:TIGR00990  101 VEPADELPEIDESSVANLSEEERKKYAAKLKEKGNKAYRNKDFNKAIKLYSKAI-ECKPDPVYYSNRAACHNALGDWEKV 179

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1698288618  133 VCDGKRAILIEPFWPKGHYRYCEALFSLGEVQMAI 167
Cdd:TIGR00990  180 VEDTTAALELDPDYSKALNRRANAYDGLGKYADAL 214

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1169 QETRRSVAVNTELHERFEKQL----GDINKMQKSIGSMEEQIEKIssgcekvdVEDLTDLKDEIQKITANIQVTN----- 1239
Cdd:TIGR02168  242 EELQEELKEAEEELEELTAELqeleEKLEELRLEVSELEEEIEEL--------QKELYALANEISRLEQQKQILRerlan 313

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1240 -----TELSLFQQKLEEEVKKDQKEKKANQEVLKSLKVKREQLMEEQKSLAHKLRETKANYDTVLSDFLGSSNRIAA--- 1311
Cdd:TIGR02168  314 lerqlEELEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQlel 393

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1698288618 1312 EKSSLEGKIQSCKTQLSLATRRshiAQTLYQENIDQEKS 1350
Cdd:TIGR02168  394 QIASLNNEIERLEARLERLEDR---RERLQQEIEELLKK 429

DNA double-strand break repair ATPase Rad50;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618 1180 ELHERFEKQLGDINKMQKSIGSMEEQIEKISSGCEKVD--VEDLTDLKDEIQKITANIQvtntelslfqqKLEEEVKKDQ 1257
Cdd:PRK03918   197 EKEKELEEVLREINEISSELPELREELEKLEKEVKELEelKEEIEELEKELESLEGSKR-----------KLEEKIRELE 265

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1698288618 1258 K---EKKANQEVLKSlKVKREQLMEEQKSLAHKLRETKANYDTVLsdflgssNRIAAEKSSLEGKIQSCKTQLS 1328
Cdd:PRK03918   266 ErieELKKEIEELEE-KVKELKELKEKAEEYIKLSEFYEEYLDEL-------REIEKRLSRLEEEINGIEERIK 331

Tetratricopeptide repeats; Repeats present in 4 or more copies in proteins. Contain a minimum of 34 amino acids each and self-associate via a "knobs and holes" mechanism.

                            10        20        30
                    ....*....|....*....|....*....|
gi 1698288618    83 KEKGNEYFRKEQYEEAVKFYTQAINNCPDN 112
Cdd:smart00028    5 YNLGNAYLKLGDYDEALEYYEKALELDPNN 34

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618  1176 AVNTELHERFEKQLGDINKMQKSIGSMEEQIEKISSgceKVDVEDLTDLKDEIQKITANIQVtntelslFQQKLEEEVKK 1255
Cdd:smart00935   18 AAQKQLEKEFKKRQAELEKLEKELQKLKEKLQKDAA---TLSEAAREKKEKELQKKVQEFQR-------KQQKLQQDLQK 87

                            90       100
                    ....*....|....*....|....*..
gi 1698288618  1256 DQKEkkANQEVLKSLKVKREQLMEEQK 1282
Cdd:smart00935   88 RQQE--ELQKILDKINKAIKEVAKKKG 112

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1698288618 1519 PCIICHEDMVPHETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVHI 1563
Cdd:cd16481      1 PCIICHDDLKPDQLAKLECGHIFHKECIKQWLKEQSTCPTCRVHV 45

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1698288618 1519 PCIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16454      1 TCAICLEEFKEGEKVrVLPCNHLFHKDCIDPWLEQHNTCPLCR 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 1698288618 1520 CIICHEDM-VPHETCVLDCRHSFHSQCIKPWLK-GHNTCPTCR 1560
Cdd:cd16448      1 CVICLEEFeEGDVVRLLPCGHVFHLACILRWLEsGNNTCPLCR 43

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1698288618 1517 EDPCIICHEDMVPHETcVLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16479      1 DNTCIICREEMTVGAK-KLPCGHIFHLSCLRSWLQRQQTCPTCR 43

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1698288618 1517 EDPCIICHEDmvPHETCVL---DCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:pfam12678   11 MEPCPECQAP--GDDECPVvwgECGHAFHLHCISRWLKTNNTCPLCR 55

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1698288618 1520 CIICHEDMVPHETC--VLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16461      2 CAICLSDYENGEELrrLPECKHAFHKECIDEWLKSNSTCPLCR 44

Tetratricopeptide (TPR) repeat [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   85 KGNEYFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVCDGKRAILIEPFWPKGHYRYCEALFSLGEVQ 164
Cdd:COG0457     82 LGLALQALGRYEEALEDYDKALELDPDDAEALYNLGLALLELGRYDEAIEAYERALELDPDDADALYNLGIALEKLGRYE 161

                   ...
gi 1698288618  165 MAI 167
Cdd:COG0457    162 EAL 164

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|.
gi 1698288618  1520 CIICHEDMvPHETCVLDCRHSFHSQCIKPWLK-GHNTCPTC 1559
Cdd:smart00184    1 CPICLEEY-LKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

Tetratricopeptide (TPR) repeat [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   85 KGNEYFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVCDGKRAILIEPFWPKGHYRYCEALFSLGEVQ 164
Cdd:COG0457     14 LGLAYRRLGRYEEAIEDYEKALELDPDDAEALYNLGLAYLRLGRYEEALADYEQALELDPDDAEALNNLGLALQALGRYE 93

                           90
                   ....*....|...
gi 1698288618  165 MAI--CANSLAIN 175
Cdd:COG0457     94 EALedYDKALELD 106

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1698288618 1518 DPCIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCRVHI 1563
Cdd:cd16469      1 DTCAVCLEEFKLKEELgVCPCGHAFHTKCLKKWLEVRNSCPICKSPV 47

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1698288618 1520 CIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16472      5 CVVCMCDYEKRQLLrVLPCSHEFHAKCIDKWLKTNRTCPICR 46

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1698288618 1520 CIICHEDMVPHETCV-LDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16669      2 CPICLLEFEEGETVKqLPCKHSFHSDCILPWLGKTNSCPLCR 43

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription, is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression is regulated by histone deacetylases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1698288618 1518 DPCIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCRVHIL 1564
Cdd:cd16802      1 DSCAVCIEPYKPNDVVrILTCNHLFHKNCIDPWLLEHRTCPMCKCDIL 48

RING finger, H2 subclass, found in RING finger proteins, RNF130, RNF149, RNF150 and similar proteins; This subfamily includes RING finger proteins, RNF130, RNF149 and RNF150, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence. RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128. It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property and controls the development of T cell clonal anergy by ubiquitination. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that induces the ubiquitination of wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and promotes its proteasome-dependent degradation. RNF150 polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. This subfamily also includes Drosophila melanogaster protein goliath (d-goliath), also known as protein g1, which is one of the founding members of the group. It was originally identified as a transcription factor involved in the embryo mesoderm formation.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1698288618 1520 CIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCRVHI 1563
Cdd:cd16668      2 CAVCIEPYKPSDVIrILPCKHIFHKSCVDPWLLEHRTCPMCKLDI 46

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1698288618 1519 PCIICHEDmvPHETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVhiLLQEDF 1569
Cdd:cd16561      4 ECSICLED--LNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRT--ELPDDF 50

Outer membrane protein chaperone/metalloprotease BepA/YfgC, contains M48 and TPR domains [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   85 KGNEYFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVCDGKRAILIEPFWPKGHYRYCEALFSLGEVQ 164
Cdd:COG4783     44 LGEILLQLGDLDEAIVLLHEALELDPDEPEARLNLGLALLKAGDYDEALALLEKALKLDPEHPEAYLRLARAYRALGRPD 123

                   ...
gi 1698288618  165 MAI 167
Cdd:COG4783    124 EAI 126

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1698288618 1520 CIICHEDMvpHETCVLDCRHSFHSQCIKPWLKGHN--TCPTCRVHI 1563
Cdd:cd16568      7 CIICHEYL--YEPMVTTCGHTYCYTCLNTWFKSNRslSCPDCRTKI 50

Type IV pilus assembly protein PilF/PilW [Cell motility, Extracellular structures];

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1698288618   89 YFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVcDGKRAILIEPFWPKGHYRYCEALFSLGEVQMAI 167
Cdd:COG3063      2 YLKLGDLEEAEEYYEKALELDPDNADALNNLGLLLLEQGRYDEAI-ALEKALKLDPNNAEALLNLAELLLELGDYDEAL 79

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1698288618 1520 CIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTC 1559
Cdd:cd16468      2 CVICMADFVVGDPIrYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1698288618 1520 CIICHEDMVPHETC-VLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16680     10 CVVCFSDFESRQLLrVLPCNHEFHTKCVDKWLKTNRTCPICR 51

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1698288618 1520 CIICHEDMVP-HETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVHIL 1564
Cdd:cd16798      6 CAICLEEFSEgQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNII 51

RING finger, H2 subclass, found in Arabidopsis thaliana NEP1-interacting protein-like 1 (NIPL1) and similar proteins; This subfamily includes Arabidopsis thaliana NIPL1 and MISFOLDED PROTEIN SENSING RING E3 LIGASE 1 (MPSR1). NIPL1, also called RING-H2 finger protein ATL27, may be involved in the early steps of the plant defense signaling pathway. MPSR1 is a cytoplasmic E3 ubiquitin-protein ligase involved in protein quality control (PQC) under proteotoxic stress. It is essential for plant survival under proteotoxic stress. It functions by removing damaged proteins before they form cytotoxic aggregates. It recognizes misfolded proteins selectively and tethers polyubiquitin chains to the proteins directly for subsequent degradation by the 26S proteasome pathway. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1698288618 1520 CIICHEDMVPHET--CVLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd23119      2 CTICLQDLQVGEIarSLPHCHHTFHLGCVDKWLGRHGSCPVCR 44

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   86 GNEYFRKEQYEEAVKFYTQAINNCPDNHLIYGNRALCYIKSKKYLKAVCDGKRAILIEPFWPKGHYRYCEALFSLGEVQM 165
Cdd:COG3914    119 GNLLLALGRLEEALAALRRALALNPDFAEAYLNLGEALRRLGRLEEAIAALRRALELDPDNAEALNNLGNALQDLGRLEE 198

                           90
                   ....*....|.
gi 1698288618  166 AICANSLAINL 176
Cdd:COG3914    199 AIAAYRRALEL 209

RING finger, H2 subclass, found in Arabidopsis thaliana MED25-binding RING-H2 protein (MBR) and similar proteins; This subfamily includes MBR1 and MBR2 (also called HAL3-interacting protein 1 or AtHIP1). They are E3 ubiquitin-protein ligases that function as regulators of MED25 stability by targeting MED25 for degradation in a RING-H2-dependent manner. Proteasome-dependent degradation of MED25 seems to activate its function as a positive regulator of FLOWERING LOCUS T (FT) and is important to induce the expression of FT, and consequently to promote flowering. MBR2 may also function downstream of HAL3 and be required for HAL3-regulated plant growth. Activation of MBR2 by HAL3 may lead to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. Both MBR1 and MBR2 contain a C3H2C3-type RING-H2 finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1698288618 1519 PCIICHEDMVP-HETCVLDCRHSFHSQCIKPWLKGHNTCPTCRVHIL 1564
Cdd:cd23113      4 KCCICQEEYEEgDELGTIECGHEYHSDCIKQWLVQKNLCPICKATAL 50

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1698288618 1520 CIICHEDMVP-HETCVLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16666      2 CAICLEEYEEgQELRVLPCQHEFHRKCVDPWLLQNHTCPLCL 43

mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1698288618   53 IKTMSSNVSAMLDSLKTIPSSYNMEKSEKMKEKGNEYFRKEQYEEAVKFYTQAInNCPDNHLIYGNRALCYIKSKKYLKA 132
Cdd:TIGR00990  101 VEPADELPEIDESSVANLSEEERKKYAAKLKEKGNKAYRNKDFNKAIKLYSKAI-ECKPDPVYYSNRAACHNALGDWEKV 179

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1698288618  133 VCDGKRAILIEPFWPKGHYRYCEALFSLGEVQMAI 167
Cdd:TIGR00990  180 VEDTTAALELDPDYSKALNRRANAYDGLGKYADAL 214

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1698288618 1518 DPCIICHEDMVPHETC-VLDCRHSFHSQCIKPWL-KGHNTCPTCR 1560
Cdd:cd16797      1 DVCAICLDEYEEGDKLrVLPCSHAYHSKCVDPWLtQTKKTCPVCK 45

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1698288618 1518 DPCIICHEDMVPHETcvLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16455      1 DDCAICWESMQSARK--LPCGHLFHNSCLRSWLEQDTSCPTCR 41

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1698288618 1520 CIIChedMVPHETCVLDCRHSFHSQCIKPWLKGHNTCPTCR 1560
Cdd:cd16545      3 CCIC---MDRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40