E3 ubiquitin-protein ligase RNF128 (EC 2.3.2.27) (Gene related to anergy in lymphocytes protein) (GRAIL) (RING finger protein 128) (RING-type E3 ubiquitin transferase RNF128)
1_MGPPP 6_ GAGVS 11_ CRGGC 16_ GFSRL 21_ LAWCF 26_ LLALS 31_ PQAPG 36_ SRGAE 41_ AVWTA 46_ YLNVS 51_ WRVPH 56_ TGVNR 61_ TVWEL 66_ SEEGV 71_ YGQDS 76_ PLEPV 81_ AGVLV 86_ PPDGP 91_ GALNA 96_ CNPHT 101_ NFTVP 106_ TVWGS 111_ TVQVS 116_ WLALI 121_ QRGGG 126_ CTFAD 131_ KIHLA 136_ YERGA 141_ SGAVI 146_ FNFPG 151_ TRNEV 156_ IPMSH 161_ PGAVD 166_ IVAIM 171_ IGNLK 176_ GTKIL 181_ QSIQR 186_ GIQVT 191_ MVIEV 196_ GKKHG 201_ PWVNH 206_ YSIFF 211_ VSVSF 216_ FIITA 221_ ATVGY 226_ FIFYS 231_ ARRLR 236_ NARAQ 241_ SRKQR 246_ QLKAD 251_ AKKAI 256_ GRLQL 261_ RTLKQ 266_ GDKEI 271_ GPDGD 276_ SCAVC 281_ IELYK 286_ PNDLV 291_ RILTC 296_ NHIFH 301_ KTCVD 306_ PWLLE 311_ HRTCP 316_ MCKCD 321_ ILKAL 326_ GIEVD 331_ VEDGS 336_ VSLQV 341_ PVSNE 346_ ISNSA 351_ SSHEE 356_ DNRSE 361_ TASSG 366_ YASVQ 371_ GTDEP 376_ PLEEH 381_ VQSTN 386_ ESLQL 391_ VNHEA 396_ NSVAV 401_ DVIPH 406_ VDNPT 411_ FEEDE 416_ TPNQE 421_TAVRE
1: E3 ubiquitin-protein ligase that catalyzes 'Lys-27', 'Lys-48'- or 'Lys-63'-linked polyubiquitin chains formation and plays a role in different biological processes such as modulation of immune response, cytoskeletal dynamics or protein homeostasis. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production (PubMed:12705856). Ubiquitinates ARPC5 with 'Lys-48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytoskeletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse (PubMed:22016387). Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals. Plays a positive role in innate immune response by promoting 'Lys-63'-linked ubiquitination of TBK1 after RNA- or DNA-virus infection (PubMed:27776110). Regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-kappa-B activation, hence decreasing pro-inflammatory cytokines (PubMed:37344492). Negatively regulates the IL-3/STAT5 signaling pathway by facilitating 'Lys-27'-linked polyubiquitination of IL3RA leading to its degradation via lysosomal pathway (PubMed:38702781). Directly regulates the N-glycosylation process in the endoplasmic reticulum by targeting the glycosyl-transferase RPN1 for ubiquitination and degradation (PubMed:39567208). Other substrates targeted for degradation by RNF128 include transmembrane proteins CD40L, CD83 or the tetraspanin CD151 (PubMed:18713730, PubMed:19542455)