The following text describes a protein:
Function:
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (By similarity). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (By similarity). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration. Required for the formation of major central nervous system axon tracts. Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK. Required for proper localization of retinogeniculate projections but not for eye-specific segregation. Regulates axon guidance in the olfactory system. Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2. Catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, consequences of threonine and/or serine ubiquitination are however unknown (By similarity). Regulates the internalization of TRPV1 in peripheral sensory neurons. May mediate ubiquitination and subsequent proteasomal degradation of TSC2/tuberin (By similarity). Independently of the E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia. May function as a facilitator or regulator of transcriptional activation by MYC (By similarity). Acts in concert with HUWE1 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1.
Subcellular Localization:
Nucleus. Cell projection, axon. Cytoplasm, cytoskeleton. Note=Localizes to axon shafts and associates with microtubule cytoskeleton. Translocates to the nucleus following interaction with sumoylated RANGAP1.
Domain:
The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners; The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
Sequence:
MMMCAATASPAAASSGPGGDGFFAAATISSSPAPGALFMPVPDGSVAAAGLGLGLPTTDSRGHYQLLLSGRALADRYRRIYTTALSDRDQAGSSTGHPASRNKKILNKKKLKRKQKSKSKVKTRSKSENVENTVIIPDIKLHSNPSAFNIYCNVRHCVLEWQKKETSLAAASKNSVQSGESDSDEEEESREPPIKLPKIIEVGLCEVFELIKETRFSHPSLCLRSLQALLNVLQGQQPEGLQSEPPEVLESLFQLLLEITVRSTGMNDSTGQSLTALSCACLFSLVASWGETGRTLQAISAILTNNGSHACQTIQVPTILNSLQRSVQAVLVGKIQVQDWFSNGIKKAALMHKWPLKEVSVDEDDQCLLQNDGFFLYLLCKDGLYKIGSGYSGTVRGHIYNSTSRIRNRKEKKSWLGYAQGYLLYRDLNNHSMTAIRISPETLEQDGTVLLPDCHTEGQNILFTDGEYINQIAASRDDGFVVRIFATSTEPVLQQELQLKLARKCLHACGISLFDLEKDLHIISTGFDEESAILGAGREFALMKTANGKIYYTGKYQSLGIKQGGPSAGKWVELPITKSPKIVHFSVGHDGSHALLVAEDGSVFFTGSASKGEDGESTKSRRQSKPYKPKKIIKMEGKIVVYTACNNGSSSVISKDGELYMFGKDAIYSDSSSLVSDLKGHFVTQVAMGKAHTCVLMKNGEVWTFGVNNKGQCGRDTGAMNQGGKGFGVENMATAMDEDLEEELDEKDEKSMMCPPGMHKWKLEQCMVCTVCGDCTGYGASCVSSGRPDRVPGGICGCGSGESGCAVCGCCKACARELDGQEARQRGILDAVKEMIPLDLLLAVPVPGVNIEEHLQLRQEEKRQRVIRRHRLEDGRGPLVFAGPIFMNHREQALARLRSHPAQLKHKRDKHKDGSGDRGEKDASKITTYPPGSVRFDCELRAVQVSCGFHHSVVLMENGDVYTFGYGQHGQLGHGDVNSRGCPTLVQALPGPSTQVTAGSNHTAVLLMDGQVFTFGSFSKGQLGRPILDIPYWNAKPAPMPNIGSKYGRKATWIGASGDQTFLRIDEALINSHVLATSEIFASKHIIGLVPASISEPPPFKCLLINKVDGSCKTFNDSEQEDLQGFGVCLDPVYDVLWRFRPSTRELWCYNAVVADARLPSATDMQSRCSILSPELALPTGSRALTTRSHAALHILGCLDTLAAMQDLKMGIASTEEETQAVMKVYSKEDYSVVNRFESHGGGWGYSAHSVEAIRFSADTDILLGGLGLFGGRGEYTAKIKLFELGPDGGDHETDGDLLAETDVLAYDCAAREKYAMMFDEPVLLQAGWWYVAWARVSGPSSDCGSHGQASITTDDGVIFQFKSSKKSNNGTDVNAGQIPQLLYRLPTSDGSTSKGKQQTSEPVHILKRSFARTVSVECFESLLSILHWSWTTLVLGVEELRGLKGFQFTATLLDLERLRFVGTCCLRLLRVYTCEIYPVSATGKAVVEETSKLAECIGKTRTLLRKILSEGVDHCMVKLDNDPQGYLSQPLRLLEAVLQECHNTFTACFHSFYPTPALQWACLCDLLNCLDQEANFKTSSSRLLAAVMSALCHTSVKLTSLFPIAYDGEVLLRSIVKQVSTENDSTLVHRFPLLVGHMEKLSQSEENISGMTSFREVLEKMLVIVVLPVRNSLRRESELFSSHLVSNTCGLLASIVSELTASALGSEVDGLNSLHSVKASANRFTKTSQGRSWNTGNGSPDAICFAVDKPGIVVVGFAVYGGGGIHEYELEVLVDDSEHAGDSTHSHRWTSLELVKGTYTTDDSPSDIAEIRLDKVVPLKENVKYAVRLRNYGSRTANGDGGMTTVQCPDGVTFTFSTCSLSSNGTNQTRGQIPQILYYRSEFDGDLQSQLLSKANEEDKNCSRALSVVSTVVRAAKDLLHRALAVDADDIPELLSSSSLFSMLLPLIIAYIGPVAAAIPKVAVEVFGLVQQLLPSVAILNQKYAPPAFNPNQSTDSTTGNQPEQGLSACTTSNHYAVIESEHPYKPACVMHYKVTFPECVRWMTIEFDPQCGTAQSEDVIRLLIPVRTIQNSGYGAKLTSVHENLNSWVELKKYSGSSGWPTMVLVLPGNEALFSLETASDYVKDDKASFYGFKCFAIGYEFSPGPDEGVIQLEKELANLGGVCAAALMKKDLALPVGNELEEDLEILEEAALQVCKTHSGILGKGLALSHSPTILEALEGNLPLQIQSNEQSFLDDFIACVPGSSGGRLARWLQPDSYADPQKTSLILNKDDIRCGWPTTITVQTKDQYGDVVHVPNMKVEVKAVPVSQKKTSLQQDQGKKCQRIPGSPSAAASSADMTFGGLASPKLDVSYEPMIVKEARYIAITMMKVYENYSFEELRFASPTPKRPSENMLIRVNNDGTYCANWTPGAIGLYTVHVTIDGIEIDAGLEVKVKDPPKGMIPPGTQLVKPKADPQPNKIRKFVAKDSAGLRIRSHPSLQSEQIGIVRVNGTITFIDEIHNDDGVWLRLNEETIKKYVPNMNGYTEAWCLSFNQHLGKSLLVPVDNIFNASQGVRDLDVFSWTSKAFFPQEPKTNTDDFFKDMNSCGPQEATMQERDHPFLRGGPGMYKVVKTGPSGHNIRSCPNLRGIPIGMLVLGNKVKAVGEVTNSEGAWVQLDKNSMVEFCESDEGEAWSLARDRGGNQYLRHEDEQVLLDQNSQPPPPSPFSVQAFNKGASCSAQGFDYGLGNNKGDQLSAILNSIQSRPNLPAPSIFDQAAKPPSSLVHSPFVFGQPLSFQQRQLQSDRGTISTSSRPVSTSGKSELPSKHSRSVKPDGHVSRTPADQKKPRGTEGLSASESLMLKSDAAKLRSDSHSRSLSPNHNTLQTLKSDGRTSSGFRAESPGPGSRSSSPKPKPLPTPRSSPSGASSPRSSSPQDKNLPQKSTAPAKTKLDPPRERSKSDSYTLDPDTLRKKKMPLTEPLRGRSTSPKPKPVPKDPKDSPGSENRAPSPHVVQENLHSEVVEVCTSSTLKTNGVTDSTCDDSGDLKSVDEGSNKVHFSIGKAPLKDEQEMRASPKISRKCANRHTRPKKEKSNFLFKGDGTKSLEPAKQAMSPSVAECARAVFASFLWHEGIVHDAMACSSFLKFNPDLSKEHAPIRSSLNSQPPTEEKEIKLKNRHSLEISSALNMFNIAPHGPDISKMGSINKNKVLSMLKEPPLHEKCEDGKSEATFEMSMHHTMKSKSPLPLTLQHLVAFWEDISLATIKAASQNMIFPSPGSCAVLKKKECEKENKKTKKEKKKKEKTEIRPRGNLFGEMAQLAVGGPEKDTICELCGESHPYPVTYHMRQAHPGCGRYAGGQGYNSIGHFCGGWAGNCGDGGMGGSTWYLVCDRCREKYLREKQAAAREKVKQSRRKPMQVKTPRALPTMEAHQVIKANALFLLSLSSAAEPSILCYHPAKPFQSQLPIVKEGVSEDLPVKMPCLYLQTLARHHHENFVGYQDDNLFQDEMRYLRSTSVPAPYISVTPDASPNVFEEPESNMKSMPPSLETSPITDTDLAKRTVFQRSYSVVASEYDKQHSILPARVKAIPRRRVNSGDTVGSSLLRHPSPELSRLISAHSSLSKGERNFQWPVLAFVIQHHDLEGLEIAMKQALRKSACRVFAMEAFNWLLCNVIQTTSLHDILWHFVAALTPSPVEAEEDEDEDNKSNKENAEQEKDTRVCEHPLSDIVIAGEAAHPLPHTFHRLLQTISDLMMSLPSGSSLQQMALRCWSLKFKQSDHQFLHQSNVFHHINNILSKSDDGDSEESFSISVQSGFEAMSQELCIVMCLKDLTSIVDIKTSSRPAMIGSLTDGSTETFWESGDEDKNKTKNITINCVKGINARYVSVHVDNSRDLGNKVTSMTFLTGKAVEELCRIKQVDLDSRHIGWVTSELPGGDNQIIKIELKGPENTLRVRQVKVLGWKDGESTKIAGQISASVAQQRSCEAETLRVFRLITSQVFGKLISGDAEPTPEQEEKALLSSPEGEEKVYNATSDADLKEHMVGIIFSRSKLTNLQKQVCAHIVQAIRMEATRVREEWEHAISSKENANSQPSDEDASSDAYCFELLSMVLALSGSNVGRQYLAQQLTLLQDLFSLLHTASPRVQRQVTSLLRRVLPEVTPNRLASIIGVKSLPPADISDIIHSTEKGDWNKLGILDMFLGCIAKALTVQLKAKGTTITGTAGTTVGKGVTTVTLPMIFNSSYLRRGESHWWMKGSTPTQISEIIIRLIKDMAAGHLSEAWSRVTKNAIAETIIALTKMEEEFRSPVRCIATTRLWLALASLCVLDQDHVDRLSSGRWMGKDGQQKQMPMCDNHDDGETAAIILCNICGNLCTDCDRFLHLHRRTKTHQRQVFKEEEEAIKVDLHEGCGRTKLFWLMALADSKTMKAMVEFREHTGKPTTSSSEACRFCGSRSGTELSAVGSVCSDADCQEYAKIACSKTHPCGHPCGGVRNEEHCLPCLHGCDKSATTLKQDADDMCMICFTEALSAAPAIQLDCSHVFHLQCCRRVLENRWLGPRITFGFISCPICKNKINHIVLKDLLDPIKELYEDVRRKALMRLEYEGLHKSEAITTPGVRFYNDAAGYAMNRYAYYVCYKCRKAYFGGEARCDAEAGQGDDYDPRELICGACSDVSRAQMCPKHGTDFLEYKCRYCCSVAVFFCFGTTHFCNACHDDFQRMTSIPKEELPHCPAGPKGKQLEGTECPLHVVHPPTGEEFALGCGVCRNAHTF