NucEnvDB

NucEnvDB

A database of Nuclear Envelope Proteins and their Interactions

Ubiquitin carboxyl-terminal hydrolase CYLD - Mus musculus - NucEnvDB

Ubiquitin carboxyl-terminal hydrolase CYLD (Mus musculus)

FASTA TEXT XML

Subcellular Location Biology & Function Interactions Cross-References

General Information

Protein Information
Protein Name	Ubiquitin carboxyl-terminal hydrolase CYLD
Accession Code	Q80TQ2
Gene	Cyld
Organism	Mus musculus \| House mouse (Taxonomy: 10090)
Part of Reference Proteome?	Yes
Sequence (Length: 952)
MSSGLWSQEKVTSPYWEERIFYLLLQECSVTDKQTQKLLKVPKGSIGQYIQDRSVGHSRVPSTKGKKNQIGLKILEQPHAVLFVDEKDVVEINEKFTELLLAITNCEERLSLFRNRLRLSKGLQVDVGSP VKVQLRSGEEKFPGVVRFRGPLLAERTVSGIFFGVELLEEGRGQGFTDGVYQGKQLFQCDEDCGVFVALDKLELIEDDDNGLESDFAGPGDTMQVEPPPLEINSRVSLKVGESTESGTVIFCDVLPGKES LGYFVGVDMDNPIGNWDGRFDGVQLCSFASVESTILLHINDIIPDSVTQERRPPKLAFMSRGVGDKGSSSHNKPKVTGSTSDPGSRNRSELFYTLNGSSVDSQQSKSKNPWYIDEVAEDPAKSLTEMSSD FGHSSPPPQPPSMNSLSSENRFHSLPFSLTKMPNTNGSMAHSPLSLSVQSVMGELNSTPVQESPPLPISSGNAHGLEVGSLAEVKENPPFYGVIRWIGQPPGLSDVLAGLELEDECAGCTDGTFRGTRYF TCALKKALFVKLKSCRPDSRFASLQPVSNQIERCNSLAFGGYLSEVVEENTPPKMEKEGLEIMIGKKKGIQGHYNSCYLDSTLFCLFAFSSALDTVLLRPKEKNDIEYYSETQELLRTEIVNPLRIYGYV CATKIMKLRKILEKVEAASGFTSEEKDPEEFLNILFHDILRVEPLLKIRSAGQKVQDCNFYQIFMEKNEKVGVPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFKKIFPSLELNITDLLEDT PRQCRICGGLAMYECRECYDDPDISAGKIKQFCKTCSTQVHLHPRRLNHSYHPVSLPKDLPDWDWRHGCIPCQKMELFAVLCIETSHYVAFVKYGKDDSAWLFFDSMADRDGGQNGFNIPQVTPCPEVGE YLKMSLEDLHSLDSRRIQGCARRLLCDAYMCMYQSPTMSLYK

Subcellular Location

Description
Cytoplasm. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cell membrane {By SimilarityUniProtKB:Q9NQC7}; Peripheral membrane protein {By SimilarityUniProtKB:Q9NQC7}; Cytoplasmic side {By SimilarityUniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {By SimilarityUniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton, spindle {By SimilarityUniProtKB:Q9NQC7}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269\|PubMed:25134987}. Note=Detected at the microtubule cytoskeleton during interphase (By similarity). Detected at the midbody during telophase (By similarity). During metaphase, it remains localized to the centrosome but is also present along the spindle (By similarity). {By SimilarityUniProtKB:Q9NQC7, ECO:0000269\|PubMed:25134987}.
Position in the Nuclear Envelope
Location	Location ID	Description
Perinuclear Region	SL-0198	The perinuclear region is the cytoplasmic region just around the nucleus.
Membrane Topology
Topology	Source	Annotation Type
Peripheral	UniProt	By Similarity {ECO:0000250\|UniProtKB:Q9NQC7}
Assigned Ontology terms

Cellular Component	Centrosome (GO:0005813) Ciliary Basal Body (GO:0036064) Ciliary Tip (GO:0097542) Cytoplasmic Microtubule (GO:0005881) Cytosol (GO:0005829) Extrinsic Component Of Cytoplasmic Side Of Plasma Membrane (GO:0031234) Midbody (GO:0030496) Perinuclear Region Of Cytoplasm (GO:0048471) Spindle (GO:0005819)

Biology & Function

Description
Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis (PubMed:17548520, PubMed:28701375, PubMed:29291351, PubMed:32185393, PubMed:32424362). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:16713561). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF- kappa-B activation (PubMed:16713561). Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha- tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:16713561, PubMed:20194890, PubMed:19893491). Required for normal cell cycle progress and normal cytokinesis (PubMed:19893491). Inhibits nuclear translocation of NF- kappa-B (By similarity). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (By similarity). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (PubMed:16501569, PubMed:18643924). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (PubMed:18382763). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (PubMed:25134987). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:28701375). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (By similarity). Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (PubMed:28701375). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (PubMed:32424362). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:17548520, PubMed:29291351). {By SimilarityUniProtKB:Q9NQC7, Experimental EvidencePubMed:16501569, Experimental EvidencePubMed:16713561, Experimental EvidencePubMed:17548520, Experimental EvidencePubMed:18382763, Experimental EvidencePubMed:18643924, Experimental EvidencePubMed:19893491, Experimental EvidencePubMed:20194890, Experimental EvidencePubMed:25134987, Experimental EvidencePubMed:28701375, Experimental EvidencePubMed:29291351, Experimental EvidencePubMed:32185393, Experimental EvidencePubMed:32424362}.
Assigned Ontology terms

Biological Process	CD4-Positive Or CD8-Positive, Alpha-Beta T Cell Lineage Commitment (GO:0043369) Homeostasis Of Number Of Cells (GO:0048872) Innate Immune Response (GO:0045087) Necroptotic Process (GO:0070266) Negative Regulation Of Canonical Wnt Signaling Pathway (GO:0090090) Negative Regulation Of Inflammatory Response (GO:0050728) Negative Regulation Of Interleukin-18-Mediated Signaling Pathway (GO:2000493) Negative Regulation Of JNK Cascade (GO:0046329) Negative Regulation Of NF-KappaB Transcription Factor Activity (GO:0032088) Negative Regulation Of NIK/NF-KappaB Signaling (GO:1901223) Negative Regulation Of P38MAPK Cascade (GO:1903753) Positive Regulation Of Extrinsic Apoptotic Signaling Pathway (GO:2001238) Positive Regulation Of Protein Localization (GO:1903829) Positive Regulation Of T Cell Differentiation (GO:0045582) Positive Regulation Of T Cell Receptor Signaling Pathway (GO:0050862) Protein Deubiquitination (GO:0016579) Protein K63-Linked Deubiquitination (GO:0070536) Protein Linear Deubiquitination (GO:1990108) Regulation Of B Cell Differentiation (GO:0045577) Regulation Of Cilium Assembly (GO:1902017) Regulation Of Inflammatory Response (GO:0050727) Regulation Of Intrinsic Apoptotic Signaling Pathway (GO:2001242) Regulation Of Microtubule Cytoskeleton Organization (GO:0070507) Regulation Of Mitotic Cell Cycle (GO:0007346) Regulation Of Necroptotic Process (GO:0060544) Regulation Of Protein Binding (GO:0043393) Regulation Of T Cell Receptor Signaling Pathway (GO:0050856) Regulation Of Tumor Necrosis Factor-Mediated Signaling Pathway (GO:0010803) Ripoptosome Assembly Involved In Necroptotic Process (GO:1901026) Ubiquitin-Dependent Protein Catabolic Process (GO:0006511) Wnt Signaling Pathway (GO:0016055)
Molecular Function	Cysteine-Type Deubiquitinase Activity (GO:0004843) K48-Linked Deubiquitinase Activity (GO:1990380) K63-Linked Deubiquitinase Activity (GO:0061578) Proline-Rich Region Binding (GO:0070064) Protein Kinase Binding (GO:0019901) Zinc Ion Binding (GO:0008270)

Protein-Protein Interactions

Interactions with Nuclear Envelope proteins (1 interactors)

Partner (NucEnvDB)		IntAct	Confidence score
Q9Z2F6	B-cell lymphoma 3 protein homolog	EBI-943890	0.67
Interactions with other proteins (7 interactors)

Partner (UniProt)		IntAct	Confidence score
P68369	Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 1) (Alpha-tubulin isotype M-alpha-1) (Tubulin alpha-1 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain]	EBI-7572707	0.56
Q9Z2V5	Histone deacetylase 6 (HD6) (EC 3.5.1.98) (Histone deacetylase mHDA2) (Tubulin-lysine deacetylase HDAC6) (EC 3.5.1.-)	EBI-7572735	0.50
Q8C863	E3 ubiquitin-protein ligase Itchy (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase Itchy homolog)	EBI-5326509	0.40
P01375	Tumor necrosis factor (Cachectin) (TNF-alpha) (Tumor necrosis factor ligand superfamily member 2) (TNF-a) [Cleaved into: Tumor necrosis factor, membrane form (N-terminal fragment) (NTF); Intracellular domain 1 (ICD1); Intracellular domain 2 (ICD2); C-domain 1; C-domain 2; Tumor necrosis factor, soluble form]	EBI-16186378	0.35
Q9D415	Disks large-associated protein 1 (DAP-1) (Guanylate kinase-associated protein) (PSD-95/SAP90-binding protein 1) (SAP90/PSD-95-associated protein 1) (SAPAP1)	EBI-16725590	0.35
Q4ACU6	SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) (SPANK-2)	EBI-16726570	0.35
Q9QWI6	SRC kinase signaling inhibitor 1 (SNAP-25-interacting protein) (SNIP) (p130Cas-associated protein) (p140Cap)	EBI-27100778	0.35

Cross-References

Database	Links
UNIPROT	Q80TQ2 Q80VB3 Q8BXZ3 Q8BYL9 Q8CGB0
Pfam	PF01302 PF00443
PROSITE	PS00845 PS50245 PS00972 PS50235

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