MYCB2_HUMAN
ID MYCB2_HUMAN Reviewed; 4678 AA.
AC O75592; A6NJC6; Q5JSX8; Q5VZN6; Q6PIB6; Q9UQ11; Q9Y6E4;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2018, sequence version 4.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=E3 ubiquitin-protein ligase MYCBP2 {ECO:0000305};
DE EC=2.3.2.33 {ECO:0000269|PubMed:29643511};
DE AltName: Full=Myc-binding protein 2 {ECO:0000305};
DE AltName: Full=Protein associated with Myc {ECO:0000303|PubMed:9689053};
GN Name=MYCBP2 {ECO:0000312|HGNC:HGNC:23386};
GN Synonyms=KIAA0916 {ECO:0000303|PubMed:12168954},
GN PAM {ECO:0000303|PubMed:9689053};
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 [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH MYC,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9689053; DOI=10.1073/pnas.95.16.9172;
RA Guo Q., Xie J., Dang C.V., Liu E.T., Bishop J.M.;
RT "Identification of a large Myc-binding protein that contains RCC1-like
RT repeats.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9172-9177(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 2).
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3469-4678 (ISOFORM 1).
RC TISSUE=Brain {ECO:0000269|PubMed:10048485};
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3827-4678 (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:AAH37971.1};
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4405-4678.
RC TISSUE=Umbilical cord blood {ECO:0000269|PubMed:11042152};
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [8]
RP INTERACTION WITH TSC2.
RX PubMed=14559897; DOI=10.1074/jbc.m310208200;
RA Murthy V., Han S., Beauchamp R.L., Smith N., Haddad L.A., Ito N.,
RA Ramesh V.;
RT "Pam and its ortholog highwire interact with and may negatively regulate
RT the TSC1.TSC2 complex.";
RL J. Biol. Chem. 279:1351-1358(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3090, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP FUNCTION, AND AUTOUBIQUITINATION.
RX PubMed=18308511; DOI=10.1016/j.cellsig.2008.01.020;
RA Han S., Witt R.M., Santos T.M., Polizzano C., Sabatini B.L., Ramesh V.;
RT "Pam (Protein associated with Myc) functions as an E3 ubiquitin ligase and
RT regulates TSC/mTOR signaling.";
RL Cell. Signal. 20:1084-1091(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3505, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178; SER-181; SER-183;
RP THR-2683; SER-2789; SER-3478 AND SER-3505, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH FBXO45.
RX PubMed=19398581; DOI=10.1128/mcb.00364-09;
RA Saiga T., Fukuda T., Matsumoto M., Tada H., Okano H.J., Okano H.,
RA Nakayama K.I.;
RT "Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal
RT development.";
RL Mol. Cell. Biol. 29:3529-3543(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3505, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2683; SER-2920 AND SER-3505,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP FUNCTION.
RX PubMed=20534529; DOI=10.1073/pnas.1000438107;
RA Yin L., Joshi S., Wu N., Tong X., Lazar M.A.;
RT "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the
RT circadian heme receptor Rev-erb alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11614-11619(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2683 AND SER-3505, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP INTERACTION WITH RAE1.
RX PubMed=22357847; DOI=10.1523/jneurosci.2901-11.2012;
RA Grill B., Chen L., Tulgren E.D., Baker S.T., Bienvenut W., Anderson M.,
RA Quadroni M., Jin Y., Garner C.C.;
RT "RAE-1, a novel PHR binding protein, is required for axon termination and
RT synapse formation in Caenorhabditis elegans.";
RL J. Neurosci. 32:2628-2636(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-1624; THR-2683;
RP SER-2769; SER-2787; SER-2789; SER-2833; SER-2839; SER-2871; SER-2985;
RP SER-3505; SER-3931 AND SER-3932, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3478, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP FUNCTION, INTERACTION WITH RAN AND RANGAP1, AND SUBCELLULAR LOCATION.
RX PubMed=26304119; DOI=10.1074/jbc.m115.646901;
RA Doerr A., Pierre S., Zhang D.D., Henke M., Holland S., Scholich K.;
RT "MYCBP2 is a guanosine exchange factor for Ran protein and determines its
RT localization in neurons of dorsal root ganglia.";
RL J. Biol. Chem. 290:25620-25635(2015).
RN [25]
RP INTERACTION WITH ATP13A2.
RX PubMed=27278822; DOI=10.1038/ncomms11803;
RA Bento C.F., Ashkenazi A., Jimenez-Sanchez M., Rubinsztein D.C.;
RT "The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate
RT autophagy via a common pathway.";
RL Nat. Commun. 7:11803-11803(2016).
RN [26]
RP INTERACTION WITH USP11.
RX PubMed=29293652; DOI=10.1371/journal.pone.0190513;
RA Stockum A., Snijders A.P., Maertens G.N.;
RT "USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle
RT formation.";
RL PLoS ONE 13:e0190513-e0190513(2018).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 4416-4678 IN COMPLEX WITH ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITES, ZINC-BINDING, AND MUTAGENESIS
RP OF CYS-4558; GLU-4572; CYS-4610; PHE-4611; PHE-4616; HIS-4621 AND PHE-4624.
RX PubMed=29643511; DOI=10.1038/s41586-018-0026-1;
RA Pao K.C., Wood N.T., Knebel A., Rafie K., Stanley M., Mabbitt P.D.,
RA Sundaramoorthy R., Hofmann K., van Aalten D.M.F., Virdee S.;
RT "Activity-based E3 ligase profiling uncovers an E3 ligase with
RT esterification activity.";
RL Nature 556:381-385(2018).
CC -!- FUNCTION: Atypical E3 ubiquitin-protein ligase which specifically
CC mediates ubiquitination of threonine and serine residues on target
CC proteins, instead of ubiquitinating lysine residues (PubMed:29643511).
CC Shows esterification activity towards both threonine and serine, with a
CC preference for threonine, and acts via two essential catalytic cysteine
CC residues that relay ubiquitin to its substrate via thioester
CC intermediates (PubMed:29643511). Interacts with the E2 enzymes UBE2D1,
CC UBE2D3, UBE2E1 and UBE2L3 (PubMed:18308511, PubMed:29643511). Plays a
CC key role in neural development, probably by mediating ubiquitination of
CC threonine residues on target proteins (Probable). Involved in different
CC processes such as regulation of neurite outgrowth, synaptic growth,
CC synaptogenesis and axon degeneration (By similarity). Required for the
CC formation of major central nervous system axon tracts (By similarity).
CC Required for proper axon growth by regulating axon navigation and axon
CC branching: acts by regulating the subcellular location and stability of
CC MAP3K12/DLK (By similarity). Required for proper localization of
CC retinogeniculate projections but not for eye-specific segregation (By
CC similarity). Regulates axon guidance in the olfactory system (By
CC similarity). Involved in Wallerian axon degeneration, an evolutionarily
CC conserved process that drives the loss of damaged axons: acts by
CC promoting destabilization of NMNAT2, probably via ubiquitination of
CC NMNAT2 (By similarity). Catalyzes ubiquitination of threonine and/or
CC serine residues on NMNAT2, consequences of threonine and/or serine
CC ubiquitination are however unknown (PubMed:29643511). Regulates the
CC internalization of TRPV1 in peripheral sensory neurons (By similarity).
CC Mediates ubiquitination and subsequent proteasomal degradation of
CC TSC2/tuberin (PubMed:18308511, PubMed:27278822). Independently of the
CC E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange
CC factor (GEF) for RAN in neurons of dorsal root ganglia
CC (PubMed:26304119). May function as a facilitator or regulator of
CC transcriptional activation by MYC (PubMed:9689053). Acts in concert
CC with HUWE1 to regulate the circadian clock gene expression by promoting
CC the lithium-induced ubiquination and degradation of NR1D1
CC (PubMed:20534529). {ECO:0000250|UniProtKB:Q7TPH6,
CC ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:20534529,
CC ECO:0000269|PubMed:26304119, ECO:0000269|PubMed:27278822,
CC ECO:0000269|PubMed:29643511, ECO:0000269|PubMed:9689053}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine.;
CC EC=2.3.2.33; Evidence={ECO:0000269|PubMed:29643511};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:29643511}.
CC -!- SUBUNIT: Interacts with MYC (PubMed:9689053). Interacts with TSC2
CC (tuberin) when TSC2 is in complex with TSC1 (hamartin)
CC (PubMed:14559897). Interacts with FBXO45 (PubMed:19398581). Interacts
CC with RAE1 (PubMed:22357847). Interacts with CPNE1 (via VWFA domain) and
CC CPNE4 (via VWFA domain) (By similarity). Interacts with (sumoylated)
CC RANGAP1; interaction with sumoylated RANGAP1 inhibits E3 ubiquitin-
CC protein ligase activity and promotes MYCBP2 translocation to the
CC nucleus (PubMed:26304119). Interacts with RAN
CC (PubMed:26304119).Interacts with ATP13A2; the interaction inhibits the
CC ubiquitination of TSC2 by MYCBP2 (PubMed:27278822). Interacts with
CC USP11 (PubMed:29293652). {ECO:0000250|UniProtKB:Q7TPH6,
CC ECO:0000269|PubMed:14559897, ECO:0000269|PubMed:19398581,
CC ECO:0000269|PubMed:22357847, ECO:0000269|PubMed:26304119,
CC ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29293652,
CC ECO:0000269|PubMed:9689053}.
CC -!- INTERACTION:
CC O75592; P63104: YWHAZ; NbExp=2; IntAct=EBI-1043774, EBI-347088;
CC O75592; Q3SWS8: Rae1; Xeno; NbExp=2; IntAct=EBI-1043774, EBI-6920222;
CC O75592; PRO_0000045603 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-1043774, EBI-6927928;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26304119,
CC ECO:0000269|PubMed:9689053}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q7TPH6}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q7TPH6}. Note=Localizes to axon shafts and
CC associates with microtubule cytoskeleton (By similarity). Translocates
CC to the nucleus following interaction with sumoylated RANGAP1
CC (PubMed:26304119). {ECO:0000250|UniProtKB:Q7TPH6,
CC ECO:0000269|PubMed:26304119}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:9689053};
CC IsoId=O75592-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=O75592-2; Sequence=VSP_014183;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, expression is
CC exceptionally abundant in brain and thymus. Colocalizes with TSC1 and
CC TSC2 along the neurites and in the growth cones. Highly expressed in
CC peripheral and central neurons. Colocalized with TSC1 in one of the
CC filopodial extensions at the tip of a growth cone.
CC {ECO:0000269|PubMed:9689053}.
CC -!- DOMAIN: The PHR domains are compact beta-sandwich folds composed of 11
CC antiparallel strands and decorated with conserved apical loops. They
CC are likely to play a structural role and mediate interactions with
CC substrates or partners (By similarity). {ECO:0000250|UniProtKB:Q7TPH6}.
CC -!- DOMAIN: The tandem cysteine domain region confers threonine specificity
CC and contains the two essential catalytic cysteine residues that relay
CC ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
CC {ECO:0000269|PubMed:29643511}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:18308511}.
CC -!- SIMILARITY: Belongs to the RING-Cys relay (RCR) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD39842.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH37971.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAI39758.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF075587; AAC39928.1; -; mRNA.
DR EMBL; AL159154; CAH73736.1; -; Genomic_DNA.
DR EMBL; AL159158; CAH73736.1; JOINED; Genomic_DNA.
DR EMBL; AL359257; CAH73736.1; JOINED; Genomic_DNA.
DR EMBL; AC001226; CAH73736.1; JOINED; Genomic_DNA.
DR EMBL; AL159158; CAI16842.1; -; Genomic_DNA.
DR EMBL; AL159154; CAI16842.1; JOINED; Genomic_DNA.
DR EMBL; AL359257; CAI16842.1; JOINED; Genomic_DNA.
DR EMBL; AC001226; CAI16842.1; JOINED; Genomic_DNA.
DR EMBL; AL359257; CAI39759.1; -; Genomic_DNA.
DR EMBL; AL159158; CAI39759.1; JOINED; Genomic_DNA.
DR EMBL; AL159154; CAI39759.1; JOINED; Genomic_DNA.
DR EMBL; AC001226; CAI39759.1; JOINED; Genomic_DNA.
DR EMBL; AL359257; CAI39758.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC001226; CAI39758.1; JOINED; Genomic_DNA.
DR EMBL; CH471093; EAW80565.1; -; Genomic_DNA.
DR EMBL; AB020723; BAA74939.1; -; mRNA.
DR EMBL; BC037971; AAH37971.1; ALT_INIT; mRNA.
DR EMBL; AF083244; AAD39842.1; ALT_FRAME; mRNA.
DR RefSeq; NP_055872.4; NM_015057.4. [O75592-1]
DR PDB; 5O6C; X-ray; 1.75 A; A=4416-4678.
DR PDB; 6T7F; X-ray; 2.58 A; A=4423-4678.
DR PDBsum; 5O6C; -.
DR PDBsum; 6T7F; -.
DR SMR; O75592; -.
DR BioGRID; 116709; 205.
DR DIP; DIP-28142N; -.
DR IntAct; O75592; 115.
DR MINT; O75592; -.
DR STRING; 9606.ENSP00000444596; -.
DR GlyGen; O75592; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75592; -.
DR MetOSite; O75592; -.
DR PhosphoSitePlus; O75592; -.
DR SwissPalm; O75592; -.
DR BioMuta; MYCBP2; -.
DR EPD; O75592; -.
DR jPOST; O75592; -.
DR MassIVE; O75592; -.
DR MaxQB; O75592; -.
DR PaxDb; O75592; -.
DR PeptideAtlas; O75592; -.
DR PRIDE; O75592; -.
DR ProteomicsDB; 50101; -. [O75592-1]
DR ProteomicsDB; 50102; -. [O75592-2]
DR Antibodypedia; 24520; 54 antibodies from 12 providers.
DR DNASU; 23077; -.
DR Ensembl; ENST00000544440.7; ENSP00000444596.2; ENSG00000005810.19. [O75592-1]
DR GeneID; 23077; -.
DR KEGG; hsa:23077; -.
DR MANE-Select; ENST00000544440.7; ENSP00000444596.2; NM_015057.5; NP_055872.4.
DR UCSC; uc058xok.1; human. [O75592-1]
DR CTD; 23077; -.
DR DisGeNET; 23077; -.
DR GeneCards; MYCBP2; -.
DR HGNC; HGNC:23386; MYCBP2.
DR HPA; ENSG00000005810; Low tissue specificity.
DR MIM; 610392; gene.
DR neXtProt; NX_O75592; -.
DR OpenTargets; ENSG00000005810; -.
DR PharmGKB; PA134871126; -.
DR VEuPathDB; HostDB:ENSG00000005810; -.
DR eggNOG; KOG1428; Eukaryota.
DR GeneTree; ENSGT00940000155756; -.
DR HOGENOM; CLU_000063_0_0_1; -.
DR InParanoid; O75592; -.
DR OMA; NKLCILD; -.
DR OrthoDB; 215263at2759; -.
DR PhylomeDB; O75592; -.
DR TreeFam; TF313151; -.
DR BRENDA; 2.3.2.33; 2681.
DR PathwayCommons; O75592; -.
DR SignaLink; O75592; -.
DR SIGNOR; O75592; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23077; 8 hits in 282 CRISPR screens.
DR ChiTaRS; MYCBP2; human.
DR GeneWiki; MYCBP2; -.
DR GenomeRNAi; 23077; -.
DR Pharos; O75592; Tbio.
DR PRO; PR:O75592; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; O75592; protein.
DR Bgee; ENSG00000005810; Expressed in Brodmann (1909) area 23 and 207 other tissues.
DR ExpressionAtlas; O75592; baseline and differential.
DR Genevisible; O75592; HS.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0021785; P:branchiomotor neuron axon guidance; IEA:Ensembl.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0050905; P:neuromuscular process; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:1902667; P:regulation of axon guidance; ISS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IBA:GO_Central.
DR Gene3D; 2.130.10.30; -; 2.
DR Gene3D; 2.60.120.820; -; 2.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR004939; APC_su10/DOC_dom.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR012983; PHR.
DR InterPro; IPR038648; PHR_sf.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR003646; SH3-like_bac-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF03256; ANAPC10; 1.
DR Pfam; PF08005; PHR; 2.
DR Pfam; PF00415; RCC1; 1.
DR Pfam; PF08239; SH3_3; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM01337; APC10; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS51284; DOC; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS00626; RCC1_2; 2.
DR PROSITE; PS50012; RCC1_3; 3.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms; Cell projection;
KW Cytoplasm; Cytoskeleton; Disulfide bond;
KW Guanine-nucleotide releasing factor; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..4678
FT /note="E3 ubiquitin-protein ligase MYCBP2"
FT /id="PRO_0000055963"
FT REPEAT 600..655
FT /note="RCC1 1"
FT /evidence="ECO:0000255"
FT REPEAT 699..755
FT /note="RCC1 2"
FT /evidence="ECO:0000255"
FT REPEAT 907..957
FT /note="RCC1 3"
FT /evidence="ECO:0000255"
FT REPEAT 958..1008
FT /note="RCC1 4"
FT /evidence="ECO:0000255"
FT REPEAT 1010..1066
FT /note="RCC1 5"
FT /evidence="ECO:0000255"
FT REPEAT 2341..2443
FT /note="Filamin"
FT /evidence="ECO:0000255"
FT DOMAIN 3719..3897
FT /note="DOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00614"
FT ZN_FING 4428..4479
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 87..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 898..928
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1235..1386
FT /note="PHR domain 1"
FT /evidence="ECO:0000250"
FT REGION 1726..1884
FT /note="PHR domain 2"
FT /evidence="ECO:0000250"
FT REGION 1993..2012
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2022..2550
FT /note="RAE1 binding"
FT /evidence="ECO:0000269|PubMed:22357847"
FT REGION 2321..2340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2709..2931
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2943..2963
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2979..3020
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3066..3086
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3605..3631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3915..3934
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4539..4676
FT /note="Tandem cysteine domain"
FT /evidence="ECO:0000305|PubMed:29643511"
FT COMPBIAS 102..121
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..628
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 908..924
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2714..2735
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2736..2757
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2783..2815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2823..2856
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2860..2890
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2901..2923
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3919..3933
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 4558
FT /evidence="ECO:0000269|PubMed:29643511"
FT ACT_SITE 4610
FT /evidence="ECO:0000269|PubMed:29643511"
FT BINDING 4428
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4431
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4446
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4448
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4475
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4478
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4544
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4547
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4575
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4578
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4587
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4590
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4599
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4602
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4603
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4617
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4620
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4638
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4652
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4658
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4669
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT BINDING 4672
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:29643511,
FT ECO:0007744|PDB:5O6C"
FT SITE 4611
FT /note="Important for catalysis"
FT /evidence="ECO:0000269|PubMed:29643511"
FT SITE 4616
FT /note="Important for catalysis"
FT /evidence="ECO:0000269|PubMed:29643511"
FT SITE 4624
FT /note="Important for catalysis"
FT /evidence="ECO:0000269|PubMed:29643511"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1624
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2683
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2769
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2787
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2789
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2833
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2869
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPH6"
FT MOD_RES 2871
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2920
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2985
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3090
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 3478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 3505
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3921
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPH6"
FT MOD_RES 3931
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3932
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 1748..1863
FT /evidence="ECO:0000250|UniProtKB:Q7TPH6"
FT VAR_SEQ 3939..3941
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_014183"
FT VARIANT 1919
FT /note="A -> S (in dbSNP:rs35887505)"
FT /id="VAR_052086"
FT VARIANT 2626
FT /note="V -> M (in dbSNP:rs9574002)"
FT /id="VAR_030070"
FT MUTAGEN 4558
FT /note="C->S: Abolished E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4572
FT /note="E->A,Q: Does not affect E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4610
FT /note="C->A: Increased thiol-sensitive adduct formation."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4610
FT /note="C->S: Retains activity while also forming a discrete
FT monoubiquitin adduct that is resistant to thiolysis but is
FT reversible after base treatment."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4611
FT /note="F->A: Reduced E3 ubiquitin-protein ligase activity
FT in threonine discharge assay."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4616
FT /note="F->A: Reduced E3 ubiquitin-protein ligase activity
FT in threonine discharge assay."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4621
FT /note="H->N: Abolished E3 ubiquitin-protein ligase activity
FT in threonine discharge assay, associated with enhanced
FT thiol-sensitive ubiquitin adduct formation."
FT /evidence="ECO:0000269|PubMed:29643511"
FT MUTAGEN 4624
FT /note="F->A: Reduced E3 ubiquitin-protein ligase activity
FT in threonine discharge assay."
FT /evidence="ECO:0000269|PubMed:29643511"
FT CONFLICT 61
FT /note="R -> P (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="G -> V (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="G -> R (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="T -> I (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 903..904
FT /note="QL -> HV (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 1512..1513
FT /note="GV -> PL (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 2139
FT /note="K -> M (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 3201
FT /note="E -> GR (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT CONFLICT 3645
FT /note="A -> R (in Ref. 1; AAC39928)"
FT /evidence="ECO:0000305"
FT TURN 4429..4431
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4432..4435
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4436..4438
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4441..4443
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4449..4451
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4452..4461
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4464..4467
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4471..4473
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4476..4478
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4485..4487
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4488..4511
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4518..4521
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4526..4529
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4531..4538
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4539..4543
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4545..4547
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4550..4555
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4559..4562
FT /evidence="ECO:0007829|PDB:6T7F"
FT HELIX 4570..4572
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4577..4579
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4588..4590
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4592..4594
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4595..4598
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4602..4605
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4608..4610
FT /evidence="ECO:0007829|PDB:5O6C"
FT TURN 4611..4613
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4614..4616
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4618..4622
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4624..4629
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4632..4634
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4638..4641
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4642..4644
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4648..4650
FT /evidence="ECO:0007829|PDB:5O6C"
FT STRAND 4666..4669
FT /evidence="ECO:0007829|PDB:5O6C"
FT HELIX 4672..4674
FT /evidence="ECO:0007829|PDB:5O6C"
SQ SEQUENCE 4678 AA; 513636 MW; F76B95A12613E74B CRC64;
MMMCAATASP AAASSGLGGD GFYPAATFSS SPAPGALFMP VPDGSVAAAG LGLGLPAADS
RGHYQLLLSG RALADRYRRI YTAALNDRDQ GGGSAGHPAS RNKKILNKKK LKRKQKSKSK
VKTRSKSENL ENTVIIPDIK LHSNPSAFNI YCNVRHCVLE WQKKEISLAA ASKNSVQSGE
SDSDEEEESK EPPIKLPKII EVGLCEVFEL IKETRFSHPS LCLRSLQALL NVLQGQQPEG
LQSEPPEVLE SLFQLLLEIT VRSTGMNDST GQSLTALSCA CLFSLVASWG ETGRTLQAIS
AILTNNGSHA CQTIQVPTIL NSLQRSVQAV LVGKIQIQDW FSNGIKKAAL MHKWPLKEIS
VDEDDQCLLQ NDGFFLYLLC KDGLYKIGSG YSGTVRGHIY NSTSRIRNRK EKKSWLGYAQ
GYLLYRDVNN HSMTAIRISP ETLEQDGTVM LPDCHTEGQN ILFTDGEYIN QIAASRDDGF
VVRIFATSTE PVLQQELQLK LARKCLHACG ISLFDLEKDL HIISTGFDEE SAILGAGREF
ALMKTANGKI YYTGKYQSLG IKQGGPSAGK WVELPITKSP KIVHFSVGHD GSHALLVAED
GSIFFTGSAS KGEDGESTKS RRQSKPYKPK KIIKMEGKIV VYTACNNGSS SVISKDGELY
MFGKDAIYSD SSSLVTDLKG HFVTQVAMGK AHTCVLMKNG EVWTFGVNNK GQCGRDTGAM
NQGGKGFGVE NMATAMDEDL EEELDEKDEK SMMCPPGMHK WKLEQCMVCT VCGDCTGYGA
SCVSSGRPDR VPGGICGCGS GESGCAVCGC CKACARELDG QEARQRGILD AVKEMIPLDL
LLAVPVPGVN IEEHLQLRQE EKRQRVIRRH RLEEGRGPLV FAGPIFMNHR EQALARLRSH
PAQLKHKRDK HKDGSGERGE KDASKITTYP PGSVRFDCEL RAVQVSCGFH HSVVLMENGD
VYTFGYGQHG QLGHGDVNSR GCPTLVQALP GPSTQVTAGS NHTAVLLMDG QVFTFGSFSK
GQLGRPILDV PYWNAKPAPM PNIGSKYGRK ATWIGASGDQ TFLRIDEALI NSHVLATSEI
FASKHIIGLV PASISEPPPF KCLLINKVDG SCKTFNDSEQ EDLQGFGVCL DPVYDVIWRF
RPNTRELWCY NAVVADARLP SAADMQSRCS ILSPELALPT GSRALTTRSH AALHILGCLD
TLAAMQDLKM GVASTEEETQ AVMKVYSKED YSVVNRFESH GGGWGYSAHS VEAIRFSADT
DILLGGLGLF GGRGEYTAKI KLFELGPDGG DHETDGDLLA ETDVLAYDCA AREKYAMMFD
EPVLLQAGWW YVAWARVSGP SSDCGSHGQA SITTDDGVVF QFKSSKKSNN GTDVNAGQIP
QLLYRLPTSD GSASKGKQQT SEPVHILKRS FARTVSVECF ESLLSILHWS WTTLVLGVEE
LRGLKGFQFT ATLLDLERLR FVGTCCLRLL RVYTCEIYPV SATGKAVVEE TSKLAECIGK
TRTLLRKILS EGVDHCMVKL DNDPQGYLSQ PLSLLEAVLQ ECHNTFTACF HSFYPTPALQ
WACLCDLLNC LDQDIQEANF KTSSSRLLAA VMSALCHTSV KLTSIFPIAY DGEVLLRSIV
KQVSTENDST LVHRFPLLVA HMEKLSQSEE NISGMTSFRE VLEKMLVIVV LPVRNSLRRE
NELFSSHLVS NTCGLLASIV SELTASALGS EVDGLNSLHS VKASANRFTK TSQGRSWNTG
NGSPDAICFS VDKPGIVVVG FSVYGGGGIH EYELEVLVDD SEHAGDSTHS HRWTSLELVK
GTYTTDDSPS DIAEIRLDKV VPLKENVKYA VRLRNYGSRT ANGDGGMTTV QCPDGVTFTF
STCSLSSNGT NQTRGQIPQI LYYRSEFDGD LQSQLLSKAN EEDKNCSRAL SVVSTVVRAS
KDLLHRALAV DADDIPELLS SSSLFSMLLP LIIAYIGPVA AAIPKVAVEV FGLVQQLLPS
VAILNQKYAP PAFNPNQSTD STTGNQPEQG LSACTTSSHY AVIESEHPYK PACVMHYKVT
FPECVRWMTI EFDPQCGTAQ SEDVLRLLIP VRTVQNSGYG PKLTSVHENL NSWIELKKFS
GSSGWPTMVL VLPGNEALFS LETASDYVKD DKASFYGFKC FAIGYEFSPG PDEGVIQLEK
ELANLGGVCA AALMKKDLAL PIGNELEEDL EILEEAALQV CKTHSGILGK GLALSHSPTI
LEALEGNLPL QIQSNEQSFL DDFIACVPGS SGGRLARWLQ PDSYADPQKT SLILNKDDIR
CGWPTTITVQ TKDQYGDVVH VPNMKVEVKA VPVSQKKMSL QQDQAKKPQR IPGSPAVTAA
SSNTDMTYGG LASPKLDVSY EPMIVKEARY IAITMMKVYE NYSFEELRFA SPTPKRPSEN
MLIRVNNDGT YCANWTPGAI GLYTLHVTID GIEIDAGLEV KVKDPPKGMI PPGTQLVKPK
SEPQPNKVRK FVAKDSAGLR IRSHPSLQSE QIGIVKVNGT ITFIDEIHND DGVWLRLNDE
TIKKYVPNMN GYTEAWCLSF NQHLGKSLLV PVDESKTNTD DFFKDINSCC PQEATMQEQD
MPFLRGGPGM YKVVKTGPSG HNIRSCPNLR GIPIGMLVLG NKVKAVGEVT NSEGTWVQLD
QNSMVEFCES DEGEAWSLAR DRGGNQYLRH EDEQALLDQN SQTPPPSPFS VQAFNKGASC
SAQGFDYGLG NSKGDRGNIS TSSKPASTSG KSELSSKHSR SLKPDGRMSR TTADQKKPRG
TESLSASESL ILKSDAAKLR SDSHSRSLSP NHNTLQTLKS DGRMPSSSRA ESPGPGSRLS
SPKPKTLPAN RSSPSGASSP RSSSPHDKNL PQKSTAPVKT KLDPPRERSK SDSYTLDPDT
LRKKKMPLTE PLRGRSTSPK PKSVPKDSTD SPGSENRAPS PHVVQENLHS EVVEVCTSST
LKTNSLTDST CDDSSEFKSV DEGSNKVHFS IGKAPLKDEQ EMRASPKISR KCANRHTRPK
KEKSSFLFKG DGSKPLEPAK QAMSPSVAEC ARAVFASFLW HEGIVHDAMA CSSFLKFHPE
LSKEHAPIRS SLNSQQPTEE KETKLKNRHS LEISSALNMF NIAPHGPDIS KMGSINKNKV
LSMLKEPPLH EKCEDGKTET TFEMSMHNTM KSKSPLPLTL QHLVAFWEDI SLATIKAASQ
NMIFPSPGSC AVLKKKECEK ENKKSKKEKK KKEKAEVRPR GNLFGEMAQL AVGGPEKDTI
CELCGESHPY PVTYHMRQAH PGCGRYAGGQ GYNSIGHFCG GWAGNCGDGG IGGSTWYLVC
DRCREKYLRE KQAAAREKVK QSRRKPMQVK TPRALPTMEA HQVIKANALF LLSLSSAAEP
SILCYHPAKP FQSQLPSVKE GISEDLPVKM PCLYLQTLAR HHHENFVGYQ DDNLFQDEMR
YLRSTSVPAP YISVTPDASP NVFEEPESNM KSMPPSLETS PITDTDLAKR TVFQRSYSVV
ASEYDKQHSI LPARVKAIPR RRVNSGDTEV GSSLLRHPSP ELSRLISAHS SLSKGERNFQ
WPVLAFVIQH HDLEGLEIAM KQALRKSACR VFAMEAFNWL LCNVIQTTSL HDILWHFVAS
LTPAPVEPEE EEDEENKTSK ENSEQEKDTR VCEHPLSDIV IAGEAAHPLP HTFHRLLQTI
SDLMMSLPSG SSLQQMALRC WSLKFKQSDH QFLHQSNVFH HINNILSKSD DGDSEESFSI
SIQSGFEAMS QELCIVMCLK DLTSIVDIKT SSRPAMIGSL TDGSTETFWE SGDEDKNKTK
NITINCVKGI NARYVSVHVD NSRDLGNKVT SMTFLTGKAV EDLCRIKQVD LDSRHIGWVT
SELPGGDNHI IKIELKGPEN TLRVRQVKVL GWKDGESTKI AGQISASVAQ QRNCEAETLR
VFRLITSQVF GKLISGDAEP TPEQEEKALL SSPEGEEKVY NATSDADLKE HMVGIIFSRS
KLTNLQKQVC AHIVQAIRME ATRVREEWEH AISSKENANS QPNDEDASSD AYCFELLSMV
LALSGSNVGR QYLAQQLTLL QDLFSLLHTA SPRVQRQVTS LLRRVLPEVT PSRLASIIGV
KSLPPADISD IIHSTEKGDW NKLGILDMFL GCIAKALTVQ LKAKGTTITG TAGTTVGKGV
TTVTLPMIFN SSYLRRGESH WWMKGSTPTQ ISEIIIKLIK DMAAGHLSEA WSRVTKNAIA
ETIIALTKME EEFRSPVRCI ATTRLWLALA SLCVLDQDHV DRLSSGRWMG KDGQQKQMPM
CDNHDDGETA AIILCNVCGN LCTDCDRFLH LHRRTKTHQR QVFKEEEEAI KVDLHEGCGR
TKLFWLMALA DSKTMKAMVE FREHTGKPTT SSSEACRFCG SRSGTELSAV GSVCSDADCQ
EYAKIACSKT HPCGHPCGGV KNEEHCLPCL HGCDKSATSL KQDADDMCMI CFTEALSAAP
AIQLDCSHIF HLQCCRRVLE NRWLGPRITF GFISCPICKN KINHIVLKDL LDPIKELYED
VRRKALMRLE YEGLHKSEAI TTPGVRFYND PAGYAMNRYA YYVCYKCRKA YFGGEARCDA
EAGRGDDYDP RELICGACSD VSRAQMCPKH GTDFLEYKCR YCCSVAVFFC FGTTHFCNAC
HDDFQRMTSI PKEELPHCPA GPKGKQLEGT ECPLHVVHPP TGEEFALGCG VCRNAHTF
