MKRN_CAEEL
ID MKRN_CAEEL Reviewed; 413 AA.
AC Q9N373; H2L0R6;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=E3 ubiquitin-protein ligase makorin {ECO:0000303|PubMed:26811380};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9UHC7};
DE AltName: Full=Leptoderan male tail protein 2 {ECO:0000312|WormBase:Y55F3AM.6a};
DE AltName: Full=RING-type E3 ubiquitin transferase makorin {ECO:0000305};
GN Name=lep-2 {ECO:0000303|PubMed:26811380, ECO:0000312|WormBase:Y55F3AM.6a};
GN ORFNames=Y55F3AM.6 {ECO:0000312|WormBase:Y55F3AM.6a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF CYS-22 AND HIS-26.
RX PubMed=26811380; DOI=10.1242/dev.132738;
RA Herrera R.A., Kiontke K., Fitch D.H.;
RT "Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-
RT to-adult transition in Caenorhabditis elegans.";
RL Development 143:799-809(2016).
RN [3] {ECO:0000305}
RP FUNCTION, AND IDENTIFICATION IN COMPLEX WITH LIN-28.
RX PubMed=30956008; DOI=10.1016/j.devcel.2019.03.003;
RA Kiontke K.C., Herrera R.A., Vuong E., Luo J., Schwarz E.M., Fitch D.H.A.,
RA Portman D.S.;
RT "The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by
RT Destabilizing LIN-28.";
RL Dev. Cell 49:542-555(2019).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=31264582; DOI=10.7554/elife.43660;
RA Lawson H., Vuong E., Miller R.M., Kiontke K., Fitch D.H., Portman D.S.;
RT "The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual
RT maturation of the C. elegans nervous system.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: E3 ubiquitin ligase which catalyzes the covalent attachment
CC of ubiquitin moieties onto substrate proteins (By similarity). Promotes
CC the larval to adult transition by binding to the long non-coding RNA
CC lep-5 to target the heterochronic protein lin-28 for degradation by the
CC proteasome (PubMed:26811380, PubMed:30956008). This association and
CC degradation of lin-28 also controls the timing of the sexual
CC differentiation of individual neurons in males including the AIM, AWA,
CC ADF, ASJ and CEM neurons (PubMed:31264582). Plays a role in governing
CC the developmental timing of male tail tip morphogenesis
CC (PubMed:26811380). Plays a role in two aspects of male mating behavior:
CC response to hermaphrodite contact and vulva location (PubMed:26811380,
CC PubMed:31264582). May play a role in the detection of preferred food
CC sources (PubMed:31264582). {ECO:0000250|UniProtKB:Q9UHC7,
CC ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:30956008,
CC ECO:0000269|PubMed:31264582}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9UHC7};
CC -!- PATHWAY: Protein modification; protein ubiquitination. {ECO:0000305}.
CC -!- SUBUNIT: Component of a complex at least containing lep-2, lin-28 and
CC the long non-coding RNA lep-5, which mediates the degradation of lin-
CC 28. {ECO:0000269|PubMed:30956008}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26811380}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:Y55F3AM.6a};
CC IsoId=Q9N373-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y55F3AM.6b};
CC IsoId=Q9N373-2; Sequence=VSP_060559, VSP_060560;
CC -!- TISSUE SPECIFICITY: Expressed in seam, tail tip, and other hypodermal
CC cells, head and tail neurons, the pharynx, intestine and the developing
CC hermaphrodite somatic gonad (PubMed:26811380, PubMed:31264582). Not
CC expressed in body wall muscle cells (PubMed:26811380).
CC {ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:31264582}.
CC -!- DEVELOPMENTAL STAGE: Expressed from embryogenesis to adulthood
CC (PubMed:26811380). Expressed in head neurons in L3 and L4 larvae
CC (PubMed:31264582). {ECO:0000269|PubMed:26811380,
CC ECO:0000269|PubMed:31264582}.
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; BX284604; CCD74063.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD74064.1; -; Genomic_DNA.
DR RefSeq; NP_001023510.1; NM_001028339.3. [Q9N373-1]
DR RefSeq; NP_001023511.1; NM_001028340.3. [Q9N373-2]
DR AlphaFoldDB; Q9N373; -.
DR ComplexPortal; CPX-5081; lep-2-lep-5-lin-28 ubiquitin ligase complex.
DR IntAct; Q9N373; 3.
DR STRING; 6239.Y55F3AM.6a; -.
DR EPD; Q9N373; -.
DR PaxDb; Q9N373; -.
DR PeptideAtlas; Q9N373; -.
DR EnsemblMetazoa; Y55F3AM.6a.1; Y55F3AM.6a.1; WBGene00002278. [Q9N373-1]
DR EnsemblMetazoa; Y55F3AM.6b.1; Y55F3AM.6b.1; WBGene00002278. [Q9N373-2]
DR GeneID; 176918; -.
DR KEGG; cel:CELE_Y55F3AM.6; -.
DR UCSC; Y55F3AM.6a; c. elegans. [Q9N373-1]
DR CTD; 176918; -.
DR WormBase; Y55F3AM.6a; CE25488; WBGene00002278; lep-2. [Q9N373-1]
DR WormBase; Y55F3AM.6b; CE33891; WBGene00002278; lep-2. [Q9N373-2]
DR eggNOG; KOG1039; Eukaryota.
DR GeneTree; ENSGT00950000183077; -.
DR HOGENOM; CLU_040815_4_2_1; -.
DR InParanoid; Q9N373; -.
DR OMA; YESPCAW; -.
DR OrthoDB; 1388677at2759; -.
DR PhylomeDB; Q9N373; -.
DR Reactome; R-CEL-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-CEL-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q9N373; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002278; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IC:ComplexPortal.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0002119; P:nematode larval development; IC:ComplexPortal.
DR GO; GO:0042551; P:neuron maturation; IC:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IC:ComplexPortal.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045072; MKRN-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR11224; PTHR11224; 1.
DR Pfam; PF00642; zf-CCCH; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 4.
DR SUPFAM; SSF90229; SSF90229; 1.
DR PROSITE; PS50103; ZF_C3H1; 4.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Differentiation; Metal-binding;
KW Reference proteome; Repeat; RNA-binding; Sexual differentiation;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..413
FT /note="E3 ubiquitin-protein ligase makorin"
FT /id="PRO_0000449486"
FT ZN_FING 2..29
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 30..57
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 138..167
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 213..267
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 296..327
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 61..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 335..343
FT /note="EAPSSRRRP -> TTSSKLTRN (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060559"
FT VAR_SEQ 344..413
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060560"
FT MUTAGEN 22
FT /note="C->Y: In sy68; impaired male mating behavior. Some
FT hermaphrodites and males fail to exit the molting cycle and
FT undergo an additional molt. Such males do not fully shed
FT the molted cuticle and die by rupturing through the cloaca.
FT Surviving males have no spicules or fan and the rays appear
FT as finger-like processes. Disrupts tail tip morphogenesis
FT resulting in retention of the pointed larval tail tip in
FT adult males (also known as the Lep phenotype)."
FT /evidence="ECO:0000269|PubMed:26811380"
FT MUTAGEN 26
FT /note="H->N: In bx147; impaired male mating behavior. Some
FT hermaphrodites and males fail to exit the molting cycle and
FT undergo an additional molt. Such males do not fully shed
FT the molted cuticle and die by rupturing through the cloaca.
FT Surviving males have no spicules or fan and the rays appear
FT as finger-like processes. Disrupts tail tip morphogenesis
FT resulting in retention of the pointed larval tail tip in
FT adult males (also known as the Lep phenotype)."
FT /evidence="ECO:0000269|PubMed:26811380"
SQ SEQUENCE 413 AA; 48090 MW; 2A1BF797193A7356 CRC64;
MPRHETDCRY FANGYCSKGN TCTFTHDVAT RNENICHFNL VGKCSYGRAC RFLHTRPRND
ELPSCSTPQT SQNQQNLQNS GQRVRPKQLP ELKFNAQAAE FVPRWKMPQR GPVTSYAGAA
ASADHGESSS SFQSSHEQAQ LMMCPYHQKS GDCNRQDMDC PFAHGNYCDM CQQWSLHPYN
AELRKKHENE CVANHTTEME RAFLLQKTEQ KTCGICMENI FEKNLRFGIL NGCQHCFCLD
CIRQWRSKDQ ENVELATKTV RSCPECRQHS DYVIPSLFWV ESGQEKDLLI EMYKENTKRK
ICKYYSNERS RGACPFGNKC FYKHQLPDGS IDPGEAPSSR RRPRLVDFLF DDNSDSDEET
FRRFQEEHEE EQEELLRFVA ETLPEADEES ELFRQITEVL RHYQISGHRR GFQ
