ID ZY11B_HUMAN Reviewed; 744 AA. AC Q9C0D3; Q8N2X3; Q9H8L8; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 2. DT 27-MAR-2024, entry version 153. DE RecName: Full=Protein zyg-11 homolog B {ECO:0000305}; GN Name=ZYG11B {ECO:0000312|HGNC:HGNC:25820}; Synonyms=KIAA1730; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11214970; DOI=10.1093/dnares/7.6.347; RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 265-744 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH ELOC, IDENTIFICATION IN COMPLEX WITH ELOC AND CUL2, AND RP MUTAGENESIS OF LEU-18. RX PubMed=17304241; DOI=10.1038/sj.embor.7400895; RA Vasudevan S., Starostina N.G., Kipreos E.T.; RT "The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved RT family of CUL-2 complex components."; RL EMBO Rep. 8:279-286(2007). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [6] RP FUNCTION. RX PubMed=31273098; DOI=10.1126/science.aaw4912; RA Timms R.T., Zhang Z., Rhee D.Y., Harper J.W., Koren I., Elledge S.J.; RT "A glycine-specific N-degron pathway mediates the quality control of RT protein N-myristoylation."; RL Science 365:0-0(2019). RN [7] RP FUNCTION. RX PubMed=33093214; DOI=10.1126/science.aay2002; RA Robinson K.S., Teo D.E.T., Tan K.S., Toh G.A., Ong H.H., Lim C.K., Lay K., RA Au B.V., Lew T.S., Chu J.J.H., Chow V.T.K., Wang Y., Zhong F.L., RA Reversade B.; RT "Enteroviral 3C protease activates the human NLRP1 inflammasome in airway RT epithelia."; RL Science 0:0-0(2020). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND UBIQUITINATION (MICROBIAL INFECTION). RX PubMed=36933219; DOI=10.1016/j.celrep.2023.112278; RA Zhang J., Zhou E.C., He Y., Chai Z.L., Ji B.Z., Tu Y., Wang H.L., Wu W.Q., RA Liu Y., Zhang X.H., Liu Y.; RT "ZYG11B potentiates the antiviral innate immune response by enhancing cGAS- RT DNA binding and condensation."; RL Cell Rep. 42:112278-112278(2023). RN [9] {ECO:0007744|PDB:7EP0, ECO:0007744|PDB:7EP1, ECO:0007744|PDB:7EP2} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 485-728, FUNCTION, AND RP MUTAGENESIS OF ASP-526; ASN-567 AND GLU-570. RX PubMed=34214466; DOI=10.1016/j.molcel.2021.06.010; RA Yan X., Li Y., Wang G., Zhou Z., Song G., Feng Q., Zhao Y., Mi W., Ma Z., RA Dong C.; RT "Molecular basis for recognition of Gly/N-degrons by CRL2ZYG11B and RT CRL2ZER1."; RL Mol. Cell 81:3262-3274.e3(2021). RN [10] {ECO:0007744|PDB:7XV7} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 485-728, AND INTERACTION WITH RP SARS-COV-2 PROTEIN ORF10. RX PubMed=35636250; DOI=10.1016/j.bbrc.2022.05.069; RA Zhang B., Li Y., Feng Q., Song L., Dong C., Yan X.; RT "Structural insights into ORF10 recognition by ZYG11B."; RL Biochem. Biophys. Res. Commun. 616:14-18(2022). RN [11] {ECO:0007744|PDB:7XYV, ECO:0007744|PDB:7XYW, ECO:0007744|PDB:7XYX} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 485-728, FUNCTION, AND RP MUTAGENESIS OF TRP-522; ASN-523; ASP-526; ASN-567 AND GLU-570. RX PubMed=36496439; DOI=10.1038/s41467-022-35169-6; RA Li Y., Zhao Y., Yan X., Ye C., Weirich S., Zhang B., Wang X., Song L., RA Jiang C., Jeltsch A., Dong C., Mi W.; RT "CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation."; RL Nat. Commun. 13:7636-7636(2022). CC -!- FUNCTION: Serves as substrate adapter subunit in the E3 ubiquitin CC ligase complex ZYG11B-CUL2-Elongin BC. Acts to target substrates CC bearing N-terminal degrons for proteasomal degradation with the first CC four residues of substrates being the key recognition elements CC (PubMed:33093214, PubMed:34214466, PubMed:35636250). Prefers Nt-Gly but CC also has the capacity to recognize Nt-Ser, -Ala and -Cys CC (PubMed:36496439). Involved in the clearance of proteolytic fragments CC generated by caspase cleavage during apoptosis since N-terminal glycine CC degrons are strongly enriched at caspase cleavage sites. Also important CC in the quality control of protein N-myristoylation in which N-terminal CC glycine degrons are conditionally exposed after a failure of N- CC myristoylation (PubMed:31273098). In addition, plays a role in the CC amplification of cGAS to enhance innate immune response. CC Mechanistically, strengthens the processes of cGAS binding with dsDNA CC and assembling oligomers and also accelerates and stabilizes cGAS-DNA CC condensation, thereby enhancing production of antiviral IFNs and CC inflammatory cytokines (PubMed:36933219). {ECO:0000269|PubMed:31273098, CC ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:34214466, CC ECO:0000269|PubMed:35636250, ECO:0000269|PubMed:36496439, CC ECO:0000269|PubMed:36933219}. CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-COV-2 protein ORF10. CC {ECO:0000269|PubMed:35636250}. CC -!- SUBUNIT: Interacts with ELOC/Elongin C. Part of an E3 ubiquitin ligase CC complex including ZYG11B, CUL2 and Elongin BC. CC {ECO:0000269|PubMed:17304241}. CC -!- INTERACTION: CC Q9C0D3; Q13617: CUL2; NbExp=4; IntAct=EBI-1811414, EBI-456179; CC Q9C0D3; Q92538-3: GBF1; NbExp=3; IntAct=EBI-1811414, EBI-17724521; CC Q9C0D3; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1811414, EBI-748974; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:36933219}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9C0D3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9C0D3-2; Sequence=VSP_028224; CC -!- PTM: (Microbial infection) Ubiquitinated; leading to proteasomal CC degradation in the presence of herpes simplex virus 1/HHV-1. CC {ECO:0000269|PubMed:36933219}. CC -!- SIMILARITY: Belongs to the zyg-11 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB21821.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB051517; BAB21821.1; ALT_INIT; mRNA. DR EMBL; AK023518; BAB14596.1; -; mRNA. DR EMBL; BC029832; AAH29832.2; -; mRNA. DR CCDS; CCDS30717.1; -. [Q9C0D3-1] DR RefSeq; NP_078922.1; NM_024646.2. [Q9C0D3-1] DR PDB; 7EP0; X-ray; 2.16 A; A/B=480-728. DR PDB; 7EP1; X-ray; 1.85 A; A/B=485-728. DR PDB; 7EP2; X-ray; 2.38 A; A/B/C/D=443-728. DR PDB; 7XV7; X-ray; 2.60 A; A/B=485-728. DR PDB; 7XYV; X-ray; 2.52 A; A/B=485-728. DR PDB; 7XYW; X-ray; 2.50 A; A/B=485-728. DR PDB; 7XYX; X-ray; 2.87 A; A/B=485-728. DR PDB; 7YC2; X-ray; 2.90 A; A/B/C/D=490-728. DR PDBsum; 7EP0; -. DR PDBsum; 7EP1; -. DR PDBsum; 7EP2; -. DR PDBsum; 7XV7; -. DR PDBsum; 7XYV; -. DR PDBsum; 7XYW; -. DR PDBsum; 7XYX; -. DR PDBsum; 7YC2; -. DR AlphaFoldDB; Q9C0D3; -. DR SMR; Q9C0D3; -. DR BioGRID; 122820; 121. DR ComplexPortal; CPX-2220; ZYG11B-Elongin C-Elongin B E3 ubiquitin ligase complex. DR IntAct; Q9C0D3; 43. DR MINT; Q9C0D3; -. DR STRING; 9606.ENSP00000294353; -. DR GlyGen; Q9C0D3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9C0D3; -. DR PhosphoSitePlus; Q9C0D3; -. DR BioMuta; ZYG11B; -. DR DMDM; 158706479; -. DR EPD; Q9C0D3; -. DR jPOST; Q9C0D3; -. DR MassIVE; Q9C0D3; -. DR MaxQB; Q9C0D3; -. DR PaxDb; 9606-ENSP00000294353; -. DR PeptideAtlas; Q9C0D3; -. DR ProteomicsDB; 80011; -. [Q9C0D3-1] DR ProteomicsDB; 80012; -. [Q9C0D3-2] DR Pumba; Q9C0D3; -. DR Antibodypedia; 33029; 57 antibodies from 12 providers. DR DNASU; 79699; -. DR Ensembl; ENST00000294353.7; ENSP00000294353.6; ENSG00000162378.13. [Q9C0D3-1] DR GeneID; 79699; -. DR KEGG; hsa:79699; -. DR MANE-Select; ENST00000294353.7; ENSP00000294353.6; NM_024646.3; NP_078922.1. DR UCSC; uc001cuj.4; human. [Q9C0D3-1] DR AGR; HGNC:25820; -. DR CTD; 79699; -. DR DisGeNET; 79699; -. DR GeneCards; ZYG11B; -. DR HGNC; HGNC:25820; ZYG11B. DR HPA; ENSG00000162378; Tissue enhanced (skeletal muscle, tongue). DR MIM; 618673; gene. DR neXtProt; NX_Q9C0D3; -. DR OpenTargets; ENSG00000162378; -. DR PharmGKB; PA142670468; -. DR VEuPathDB; HostDB:ENSG00000162378; -. DR eggNOG; KOG3665; Eukaryota. DR GeneTree; ENSGT00530000063187; -. DR HOGENOM; CLU_011533_1_0_1; -. DR InParanoid; Q9C0D3; -. DR OMA; QAWTLSH; -. DR OrthoDB; 2909501at2759; -. DR PhylomeDB; Q9C0D3; -. DR TreeFam; TF313007; -. DR PathwayCommons; Q9C0D3; -. DR SignaLink; Q9C0D3; -. DR BioGRID-ORCS; 79699; 17 hits in 1199 CRISPR screens. DR ChiTaRS; ZYG11B; human. DR GenomeRNAi; 79699; -. DR Pharos; Q9C0D3; Tbio. DR PRO; PR:Q9C0D3; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9C0D3; Protein. DR Bgee; ENSG00000162378; Expressed in deltoid and 199 other cell types or tissues. DR ExpressionAtlas; Q9C0D3; baseline and differential. DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:UniProtKB. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR PANTHER; PTHR12904; -; 1. DR PANTHER; PTHR12904:SF21; PROTEIN ZYG-11 HOMOLOG B; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS51450; LRR; 1. DR Genevisible; Q9C0D3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Host-virus interaction; KW Leucine-rich repeat; Reference proteome; Repeat; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..744 FT /note="Protein zyg-11 homolog B" FT /id="PRO_0000305087" FT REPEAT 185..208 FT /note="LRR 1" FT REPEAT 216..236 FT /note="LRR 2" FT REPEAT 237..261 FT /note="LRR 3" FT VAR_SEQ 1..578 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_028224" FT MUTAGEN 18 FT /note="L->S: Abolishes interaction with ELOC." FT /evidence="ECO:0000269|PubMed:17304241" FT MUTAGEN 522 FT /note="W->A: Complete loss of N-degron binding." FT /evidence="ECO:0000269|PubMed:35636250" FT MUTAGEN 523 FT /note="N->A: Complete loss of N-degron binding." FT /evidence="ECO:0000269|PubMed:35636250" FT MUTAGEN 526 FT /note="D->A: Complete loss of N-degron binding." FT /evidence="ECO:0000269|PubMed:34214466, FT ECO:0000269|PubMed:35636250" FT MUTAGEN 567 FT /note="N->A: Complete loss of N-degron binding." FT /evidence="ECO:0000269|PubMed:34214466, FT ECO:0000269|PubMed:35636250" FT MUTAGEN 570 FT /note="E->A: Complete loss of N-degron binding." FT /evidence="ECO:0000269|PubMed:34214466, FT ECO:0000269|PubMed:35636250" FT CONFLICT 672 FT /note="W -> C (in Ref. 2; BAB14596)" FT /evidence="ECO:0000305" FT HELIX 447..457 FT /evidence="ECO:0007829|PDB:7EP2" FT HELIX 462..478 FT /evidence="ECO:0007829|PDB:7EP2" FT HELIX 485..506 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 512..524 FT /evidence="ECO:0007829|PDB:7EP1" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 529..537 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 540..550 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 555..569 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 572..578 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 581..591 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 596..611 FT /evidence="ECO:0007829|PDB:7EP1" FT TURN 614..616 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 621..637 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 652..654 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 655..658 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 664..680 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 682..691 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 694..703 FT /evidence="ECO:0007829|PDB:7EP1" FT HELIX 709..722 FT /evidence="ECO:0007829|PDB:7EP1" SQ SEQUENCE 744 AA; 83921 MW; 0D8C19251CA67573 CRC64; MPEDQAGAAM EEASPYSLLD ICLNFLTTHL EKFCSARQDG TLCLQEPGVF PQEVADRLLR TMAFHGLLND GTVGIFRGNQ MRLKRACIRK AKISAVAFRK AFCHHKLVEL DATGVNADIT ITDIISGLGS NKWIQQNLQC LVLNSLTLSL EDPYERCFSR LSGLRALSIT NVLFYNEDLA EVASLPRLES LDISNTSITD ITALLACKDR LKSLTMHHLK CLKMTTTQIL DVVRELKHLN HLDISDDKQF TSDIALRLLE QKDILPNLVS LDVSGRKHVT DKAVEAFIQQ RPSMQFVGLL ATDAGYSEFL TGEGHLKVSG EANETQIAEA LKRYSERAFF VREALFHLFS LTHVMEKTKP EILKLVVTGM RNHPMNLPVQ LAASACVFNL TKQDLAAGMP VRLLADVTHL LLKAMEHFPN HQQLQKNCLL SLCSDRILQD VPFNRFEAAK LVMQWLCNHE DQNMQRMAVA IISILAAKLS TEQTAQLGTE LFIVRQLLQI VKQKTNQNSV DTTLKFTLSA LWNLTDESPT TCRHFIENQG LELFMRVLES FPTESSIQQK VLGLLNNIAE VQELHSELMW KDFIDHISSL LHSVEVEVSY FAAGIIAHLI SRGEQAWTLS RSQRNSLLDD LHSAILKWPT PECEMVAYRS FNPFFPLLGC FTTPGVQLWA VWAMQHVCSK NPSRYCSMLI EEGGLQHLYN IKDHEHTDPH VQQIAVAILD SLEKHIVRHG RPPPCKKQPQ ARLN //