CYLD_MOUSE
ID CYLD_MOUSE Reviewed; 952 AA.
AC Q80TQ2; Q80VB3; Q8BXZ3; Q8BYL9; Q8CGB0;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase CYLD;
DE EC=3.4.19.12 {ECO:0000269|PubMed:32424362};
DE AltName: Full=Deubiquitinating enzyme CYLD;
DE AltName: Full=Ubiquitin thioesterase CYLD;
DE AltName: Full=Ubiquitin-specific-processing protease CYLD;
GN Name=Cyld; Synonyms=Cyld1, Kiaa0849;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-620 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Hypothalamus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH BCL3, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16713561; DOI=10.1016/j.cell.2006.03.041;
RA Massoumi R., Chmielarska K., Hennecke K., Pfeifer A., Fassler R.;
RT "Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-
RT kappaB signaling.";
RL Cell 125:665-677(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16501569; DOI=10.1038/ni1315;
RA Reiley W.W., Zhang M., Jin W., Losiewicz M., Donohue K.B., Norbury C.C.,
RA Sun S.C.;
RT "Regulation of T cell development by the deubiquitinating enzyme CYLD.";
RL Nat. Immunol. 7:411-417(2006).
RN [6]
RP FUNCTION, INTERACTION WITH MAP3K7, AND DISRUPTION PHENOTYPE.
RX PubMed=17548520; DOI=10.1084/jem.20062694;
RA Reiley W.W., Jin W., Lee A.J., Wright A., Wu X., Tewalt E.F., Leonard T.O.,
RA Norbury C.C., Fitzpatrick L., Zhang M., Sun S.C.;
RT "Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent
RT kinase Tak1 and prevents abnormal T cell responses.";
RL J. Exp. Med. 204:1475-1485(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18643924; DOI=10.1111/j.1462-5822.2008.01204.x;
RA Lim J.H., Ha U.H., Woo C.H., Xu H., Li J.D.;
RT "CYLD is a crucial negative regulator of innate immune response in
RT Escherichia coli pneumonia.";
RL Cell. Microbiol. 10:2247-2256(2008).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH SQSTM1, IDENTIFICATION IN
RP A COMPLEX WITH TRAF6 AND SQSTM1, AND INDUCTION.
RX PubMed=18382763; DOI=10.1172/jci34257;
RA Jin W., Chang M., Paul E.M., Babu G., Lee A.J., Reiley W., Wright A.,
RA Zhang M., You J., Sun S.C.;
RT "Deubiquitinating enzyme CYLD negatively regulates RANK signaling and
RT osteoclastogenesis in mice.";
RL J. Clin. Invest. 118:1858-1866(2008).
RN [9]
RP FUNCTION.
RX PubMed=20194890; DOI=10.1182/blood-2009-10-248526;
RA Gao J., Sun L., Huo L., Liu M., Li D., Zhou J.;
RT "CYLD regulates angiogenesis by mediating vascular endothelial cell
RT migration.";
RL Blood 115:4130-4137(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP FUNCTION, INTERACTION WITH HDAC6, BCL3 AND MICROTUBULES, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19893491; DOI=10.1038/emboj.2009.317;
RA Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R.;
RT "CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and
RT increasing the levels of acetylated tubulin.";
RL EMBO J. 29:131-144(2010).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25134987; DOI=10.1038/ncomms5585;
RA Eguether T., Ermolaeva M.A., Zhao Y., Bonnet M.C., Jain A., Pasparakis M.,
RA Courtois G., Tassin A.M.;
RT "The deubiquitinating enzyme CYLD controls apical docking of basal bodies
RT in ciliated epithelial cells.";
RL Nat. Commun. 5:4585-4585(2014).
RN [13]
RP FUNCTION.
RX PubMed=28701375; DOI=10.1101/gad.299776.117;
RA Wei R., Xu L.W., Liu J., Li Y., Zhang P., Shan B., Lu X., Qian L., Wu Z.,
RA Dong K., Zhu H., Pan L., Yuan J., Pan H.;
RT "SPATA2 regulates the activation of RIPK1 by modulating linear
RT ubiquitination.";
RL Genes Dev. 31:1162-1176(2017).
RN [14]
RP FUNCTION, UBIQUITINATION, AND DISRUPTION PHENOTYPE.
RX PubMed=29291351; DOI=10.1038/nm.4461;
RA Ji Y.X., Huang Z., Yang X., Wang X., Zhao L.P., Wang P.X., Zhang X.J.,
RA Alves-Bezerra M., Cai L., Zhang P., Lu Y.X., Bai L., Gao M.M., Zhao H.,
RA Tian S., Wang Y., Huang Z.X., Zhu X.Y., Zhang Y., Gong J., She Z.G., Li F.,
RA Cohen D.E., Li H.;
RT "The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic
RT steatohepatitis.";
RL Nat. Med. 24:213-223(2018).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF ASP-677 AND MET-715.
RX PubMed=32185393; DOI=10.1093/brain/awaa039;
RA Dobson-Stone C., Hallupp M., Shahheydari H., Ragagnin A.M.G.,
RA Chatterton Z., Carew-Jones F., Shepherd C.E., Stefen H., Paric E., Fath T.,
RA Thompson E.M., Blumbergs P., Short C.L., Field C.D., Panegyres P.K.,
RA Hecker J., Nicholson G., Shaw A.D., Fullerton J.M., Luty A.A.,
RA Schofield P.R., Brooks W.S., Rajan N., Bennett M.F., Bahlo M.,
RA Landers J.E., Piguet O., Hodges J.R., Halliday G.M., Topp S.D., Smith B.N.,
RA Shaw C.E., McCann E., Fifita J.A., Williams K.L., Atkin J.D., Blair I.P.,
RA Kwok J.B.;
RT "CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral
RT sclerosis.";
RL Brain 143:783-799(2020).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, ACTIVE SITE, AND
RP MUTAGENESIS OF CYS-597.
RX PubMed=32424362; DOI=10.1038/s41590-020-0681-x;
RA Mukherjee S., Kumar R., Tsakem Lenou E., Basrur V., Kontoyiannis D.L.,
RA Ioakeimidis F., Mosialos G., Theiss A.L., Flavell R.A., Venuprasad K.;
RT "Deubiquitination of NLRP6 inflammasome by Cyld critically regulates
RT intestinal inflammation.";
RL Nat. Immunol. 21:626-635(2020).
CC -!- FUNCTION: Deubiquitinase that specifically cleaves 'Lys-63'- and linear
CC 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B
CC activation and TNF-alpha-induced necroptosis (PubMed:17548520,
CC PubMed:28701375, PubMed:29291351, PubMed:32185393, PubMed:32424362).
CC Negatively regulates NF-kappa-B activation by deubiquitinating upstream
CC signaling factors (PubMed:16713561). Contributes to the regulation of
CC cell survival, proliferation and differentiation via its effects on NF-
CC kappa-B activation (PubMed:16713561). Negative regulator of Wnt
CC signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-
CC tubulin and stabilization of microtubules (PubMed:19893491). Plays a
CC role in the regulation of microtubule dynamics, and thereby contributes
CC to the regulation of cell proliferation, cell polarization, cell
CC migration, and angiogenesis (PubMed:16713561, PubMed:20194890,
CC PubMed:19893491). Required for normal cell cycle progress and normal
CC cytokinesis (PubMed:19893491). Inhibits nuclear translocation of NF-
CC kappa-B (By similarity). Plays a role in the regulation of inflammation
CC and the innate immune response, via its effects on NF-kappa-B
CC activation (By similarity). Dispensable for the maturation of
CC intrathymic natural killer cells, but required for the continued
CC survival of immature natural killer cells (PubMed:16501569,
CC PubMed:18643924). Negatively regulates TNFRSF11A signaling and
CC osteoclastogenesis (PubMed:18382763). Involved in the regulation of
CC ciliogenesis, allowing ciliary basal bodies to migrate and dock to the
CC plasma membrane; this process does not depend on NF-kappa-B activation
CC (PubMed:25134987). Ability to remove linear ('Met-1'-linked)
CC polyubiquitin chains regulates innate immunity and TNF-alpha-induced
CC necroptosis: recruited to the LUBAC complex via interaction with SPATA2
CC and restricts linear polyubiquitin formation on target proteins
CC (PubMed:28701375). Regulates innate immunity by restricting linear
CC polyubiquitin formation on RIPK2 in response to NOD2 stimulation (By
CC similarity). Involved in TNF-alpha-induced necroptosis by removing
CC linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby
CC regulating the kinase activity of RIPK1 (PubMed:28701375). Negatively
CC regulates intestinal inflammation by removing 'Lys-63' linked
CC polyubiquitin chain of NLRP6, thereby reducing the interaction between
CC NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome
CC (PubMed:32424362). Removes 'Lys-63' linked polyubiquitin chain of
CC MAP3K7, which inhibits phosphorylation and blocks downstream activation
CC of the JNK-p38 kinase cascades (PubMed:17548520, PubMed:29291351).
CC {ECO:0000250|UniProtKB:Q9NQC7, ECO:0000269|PubMed:16501569,
CC ECO:0000269|PubMed:16713561, ECO:0000269|PubMed:17548520,
CC ECO:0000269|PubMed:18382763, ECO:0000269|PubMed:18643924,
CC ECO:0000269|PubMed:19893491, ECO:0000269|PubMed:20194890,
CC ECO:0000269|PubMed:25134987, ECO:0000269|PubMed:28701375,
CC ECO:0000269|PubMed:29291351, ECO:0000269|PubMed:32185393,
CC ECO:0000269|PubMed:32424362}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:32424362};
CC -!- SUBUNIT: Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-
CC rich C-terminal region) (By similarity). Interacts with TRAF2 and TRIP
CC (By similarity). Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and
CC DDX58 (By similarity). Interacts (via CAP-Gly domain) with microtubules
CC (PubMed:19893491). Interacts with HDAC6 and BCL3 (PubMed:16713561,
CC PubMed:19893491). Interacts with MAP3K7 (PubMed:17548520). Identified
CC in a complex with TRAF6 and SQSTM1 (PubMed:18382763). Interacts with
CC OPTN and SQSTM1 (By similarity). Interacts with CEP350 (By similarity).
CC Interacts with RNF31; the interaction is indirect and is mediated via
CC SPATA2 (By similarity). Interacts with SPATA2 (via the PUB domain); the
CC interaction is direct and recruits CYLD to the LUBAC complex, thereby
CC regulating TNF-alpha-induced necroptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q9NQC7, ECO:0000269|PubMed:16713561,
CC ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:18382763,
CC ECO:0000269|PubMed:19893491}.
CC -!- INTERACTION:
CC Q80TQ2; Q9Z2F6: Bcl3; NbExp=5; IntAct=EBI-943859, EBI-943884;
CC Q80TQ2; Q9Z2V5: Hdac6; NbExp=3; IntAct=EBI-943859, EBI-1009256;
CC Q80TQ2; Q8C863: Itch; NbExp=2; IntAct=EBI-943859, EBI-851782;
CC Q80TQ2; P68369: Tuba1a; NbExp=5; IntAct=EBI-943859, EBI-400542;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC Cytoplasm, cytoskeleton. Cell membrane {ECO:0000250|UniProtKB:Q9NQC7};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9NQC7}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:25134987}. Note=Detected at the microtubule
CC cytoskeleton during interphase (By similarity). Detected at the midbody
CC during telophase (By similarity). During metaphase, it remains
CC localized to the centrosome but is also present along the spindle (By
CC similarity). {ECO:0000250|UniProtKB:Q9NQC7,
CC ECO:0000269|PubMed:25134987}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2;
CC IsoId=Q80TQ2-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q80TQ2-2; Sequence=VSP_011278;
CC Name=3;
CC IsoId=Q80TQ2-3; Sequence=VSP_011279, VSP_011280;
CC -!- INDUCTION: Up-regulated by TNFRSF11A. {ECO:0000269|PubMed:18382763}.
CC -!- PTM: Phosphorylated on several serine residues by IKKA and/or IKKB in
CC response to immune stimuli. Phosphorylation requires IKBKG.
CC Phosphorylation abolishes TRAF2 deubiquitination, interferes with the
CC activation of Jun kinases, and strongly reduces CD40-dependent gene
CC activation by NF-kappa-B (By similarity).
CC {ECO:0000250|UniProtKB:Q9NQC7}.
CC -!- PTM: Ubiquitinated. Polyubiquitinated in hepatocytes treated with
CC palmitic acid. Ubiquitination is mediated by E3 ligase TRIM47 and leads
CC to proteasomal degradation. {ECO:0000269|PubMed:29291351}.
CC -!- DISRUPTION PHENOTYPE: No obvious phenotype, but mice are highly
CC susceptible to carcinogens and are prone to chemically induced skin
CC tumors (PubMed:16501569, PubMed:16713561, PubMed:17548520,
CC PubMed:18382763, PubMed:18643924). The number of natural killer T-cells
CC is much reduced (PubMed:16501569, PubMed:16713561, PubMed:17548520,
CC PubMed:18382763, PubMed:18643924). Animals are highly susceptible to
CC bacteria-induced pneumonia, due to an over active innate immune
CC response (PubMed:16501569, PubMed:16713561, PubMed:17548520,
CC PubMed:18382763, PubMed:18643924). Mice are more susceptible to
CC C.rodentium infection, leading to severe inflammation in the intestine
CC (PubMed:32424362). Animals spontaneously develop colonic inflammation,
CC due to constitutive expression of several pro-inflammatory genes in the
CC colon (PubMed:16501569, PubMed:16713561, PubMed:17548520,
CC PubMed:18382763, PubMed:18643924). Animals exhibit abnormal osteoclast
CC differentiation, leading to osteoporosis (PubMed:16501569,
CC PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924).
CC Hepatocyte-specific knockout mice do not exhibit any liver-related
CC pathological phenotype under unstressed conditions (PubMed:29291351).
CC In response to a 24-week high fat dier, they exhibit higher body and
CC liver weight as well as reduced glucose tolerance and insulin
CC resistance compared to controls (PubMed:29291351). They also show a
CC considerable inflammatory response, including elevation of cytokine and
CC chemokine concentrations in serum and mRNA expression in liver
CC (PubMed:29291351). {ECO:0000269|PubMed:16501569,
CC ECO:0000269|PubMed:16713561, ECO:0000269|PubMed:17548520,
CC ECO:0000269|PubMed:18382763, ECO:0000269|PubMed:18643924,
CC ECO:0000269|PubMed:29291351, ECO:0000269|PubMed:32424362}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65671.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK122389; BAC65671.1; ALT_INIT; mRNA.
DR EMBL; AK039054; BAC30222.1; -; mRNA.
DR EMBL; AK042764; BAC31357.1; -; mRNA.
DR EMBL; BC042438; AAH42438.1; -; mRNA.
DR EMBL; BC049879; AAH49879.1; -; mRNA.
DR CCDS; CCDS22513.1; -. [Q80TQ2-1]
DR CCDS; CCDS52633.1; -. [Q80TQ2-2]
DR RefSeq; NP_001121642.1; NM_001128170.2. [Q80TQ2-2]
DR RefSeq; NP_001121643.1; NM_001128171.2. [Q80TQ2-1]
DR RefSeq; NP_775545.1; NM_173369.3. [Q80TQ2-1]
DR RefSeq; XP_006531477.1; XM_006531414.1. [Q80TQ2-2]
DR RefSeq; XP_006531478.1; XM_006531415.1. [Q80TQ2-2]
DR RefSeq; XP_006531479.1; XM_006531416.3. [Q80TQ2-2]
DR RefSeq; XP_006531480.1; XM_006531417.2. [Q80TQ2-2]
DR RefSeq; XP_006531481.1; XM_006531418.2. [Q80TQ2-2]
DR RefSeq; XP_011246825.1; XM_011248523.2. [Q80TQ2-2]
DR RefSeq; XP_011246826.1; XM_011248524.1. [Q80TQ2-2]
DR RefSeq; XP_011246827.1; XM_011248525.2. [Q80TQ2-2]
DR RefSeq; XP_017168478.1; XM_017312989.1. [Q80TQ2-2]
DR AlphaFoldDB; Q80TQ2; -.
DR SMR; Q80TQ2; -.
DR BioGRID; 216612; 25.
DR DIP; DIP-35656N; -.
DR IntAct; Q80TQ2; 8.
DR MINT; Q80TQ2; -.
DR STRING; 10090.ENSMUSP00000039834; -.
DR MEROPS; C67.001; -.
DR iPTMnet; Q80TQ2; -.
DR PhosphoSitePlus; Q80TQ2; -.
DR SwissPalm; Q80TQ2; -.
DR EPD; Q80TQ2; -.
DR MaxQB; Q80TQ2; -.
DR PaxDb; Q80TQ2; -.
DR PeptideAtlas; Q80TQ2; -.
DR PRIDE; Q80TQ2; -.
DR ProteomicsDB; 279252; -. [Q80TQ2-1]
DR ProteomicsDB; 279253; -. [Q80TQ2-2]
DR ProteomicsDB; 279254; -. [Q80TQ2-3]
DR Antibodypedia; 3193; 325 antibodies from 39 providers.
DR DNASU; 74256; -.
DR Ensembl; ENSMUST00000098519; ENSMUSP00000096119; ENSMUSG00000036712. [Q80TQ2-2]
DR Ensembl; ENSMUST00000109626; ENSMUSP00000105254; ENSMUSG00000036712. [Q80TQ2-1]
DR Ensembl; ENSMUST00000209532; ENSMUSP00000147654; ENSMUSG00000036712. [Q80TQ2-2]
DR Ensembl; ENSMUST00000209559; ENSMUSP00000147426; ENSMUSG00000036712. [Q80TQ2-1]
DR Ensembl; ENSMUST00000211554; ENSMUSP00000148037; ENSMUSG00000036712. [Q80TQ2-1]
DR GeneID; 74256; -.
DR KEGG; mmu:74256; -.
DR UCSC; uc009mrt.3; mouse. [Q80TQ2-1]
DR UCSC; uc033jgq.1; mouse. [Q80TQ2-3]
DR UCSC; uc033jgr.1; mouse. [Q80TQ2-2]
DR CTD; 1540; -.
DR MGI; MGI:1921506; Cyld.
DR VEuPathDB; HostDB:ENSMUSG00000036712; -.
DR eggNOG; KOG3556; Eukaryota.
DR GeneTree; ENSGT00390000018123; -.
DR HOGENOM; CLU_003910_0_0_1; -.
DR InParanoid; Q80TQ2; -.
DR OMA; WYIDEAA; -.
DR OrthoDB; 119442at2759; -.
DR PhylomeDB; Q80TQ2; -.
DR BRENDA; 3.4.19.12; 3474.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-936440; Negative regulators of DDX58/IFIH1 signaling.
DR BioGRID-ORCS; 74256; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Cyld; mouse.
DR PRO; PR:Q80TQ2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q80TQ2; protein.
DR Bgee; ENSMUSG00000036712; Expressed in caudate-putamen and 232 other tissues.
DR ExpressionAtlas; Q80TQ2; baseline and differential.
DR Genevisible; Q80TQ2; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; IDA:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:MGI.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0070064; F:proline-rich region binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0043369; P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; IMP:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0070266; P:necroptotic process; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:2000493; P:negative regulation of interleukin-18-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1903829; P:positive regulation of protein localization; IDA:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:1990108; P:protein linear deubiquitination; IDA:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; IMP:MGI.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0060544; P:regulation of necroptotic process; IDA:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IDA:MGI.
DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:1901026; P:ripoptosome assembly involved in necroptotic process; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.30.30.190; -; 3.
DR InterPro; IPR036859; CAP-Gly_dom_sf.
DR InterPro; IPR000938; CAP-Gly_domain.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF01302; CAP_GLY; 2.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM01052; CAP_GLY; 3.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF74924; SSF74924; 3.
DR PROSITE; PS00845; CAP_GLY_1; 1.
DR PROSITE; PS50245; CAP_GLY_2; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Hydrolase; Immunity; Innate immunity; Membrane;
KW Metal-binding; Microtubule; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc.
FT CHAIN 1..952
FT /note="Ubiquitin carboxyl-terminal hydrolase CYLD"
FT /id="PRO_0000080699"
FT DOMAIN 153..198
FT /note="CAP-Gly 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT DOMAIN 253..286
FT /note="CAP-Gly 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT DOMAIN 488..531
FT /note="CAP-Gly 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT DOMAIN 588..946
FT /note="USP"
FT REGION 106..589
FT /note="Interaction with TRIP"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT REGION 311..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..465
FT /note="Interaction with TRAF2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT REGION 466..680
FT /note="Interaction with IKBKG/NEMO"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT REGION 777..829
FT /note="B-box"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT COMPBIAS 325..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 597
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000305|PubMed:32424362"
FT ACT_SITE 867
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092"
FT BINDING 784
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 787
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 795
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 798
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 813
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 816
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 821
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT BINDING 829
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQC7"
FT VAR_SEQ 304
FT /note="P -> PALS (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011278"
FT VAR_SEQ 305..318
FT /note="DSVTQERRPPKLAF -> GTSKNILDQQLKGK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011279"
FT VAR_SEQ 319..952
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011280"
FT MUTAGEN 597
FT /note="C->A: Loss of deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:32424362"
FT MUTAGEN 677
FT /note="D->G: Decreased inhibition of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:32185393"
FT MUTAGEN 715
FT /note="M->V: Increased inhibition of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:32185393"
FT CONFLICT 403
FT /note="M -> V (in Ref. 2; BAC30222)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 952 AA; 106586 MW; 0AC0C7D4FF215A9C CRC64;
MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRV
PSTKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERL SLFRNRLRLS
KGLQVDVGSP VKVQLRSGEE KFPGVVRFRG PLLAERTVSG IFFGVELLEE GRGQGFTDGV
YQGKQLFQCD EDCGVFVALD KLELIEDDDN GLESDFAGPG DTMQVEPPPL EINSRVSLKV
GESTESGTVI FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN
DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE LFYTLNGSSV
DSQQSKSKNP WYIDEVAEDP AKSLTEMSSD FGHSSPPPQP PSMNSLSSEN RFHSLPFSLT
KMPNTNGSMA HSPLSLSVQS VMGELNSTPV QESPPLPISS GNAHGLEVGS LAEVKENPPF
YGVIRWIGQP PGLSDVLAGL ELEDECAGCT DGTFRGTRYF TCALKKALFV KLKSCRPDSR
FASLQPVSNQ IERCNSLAFG GYLSEVVEEN TPPKMEKEGL EIMIGKKKGI QGHYNSCYLD
STLFCLFAFS SALDTVLLRP KEKNDIEYYS ETQELLRTEI VNPLRIYGYV CATKIMKLRK
ILEKVEAASG FTSEEKDPEE FLNILFHDIL RVEPLLKIRS AGQKVQDCNF YQIFMEKNEK
VGVPTIQQLL EWSFINSNLK FAEAPSCLII QMPRFGKDFK LFKKIFPSLE LNITDLLEDT
PRQCRICGGL AMYECRECYD DPDISAGKIK QFCKTCSTQV HLHPRRLNHS YHPVSLPKDL
PDWDWRHGCI PCQKMELFAV LCIETSHYVA FVKYGKDDSA WLFFDSMADR DGGQNGFNIP
QVTPCPEVGE YLKMSLEDLH SLDSRRIQGC ARRLLCDAYM CMYQSPTMSL YK
