MKRN2_XENLA
ID MKRN2_XENLA Reviewed; 409 AA.
AC B0F0H3;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 2.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=E3 ubiquitin-protein ligase makorin-2;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9ERV1};
DE AltName: Full=RING-type E3 ubiquitin transferase makorin-2 {ECO:0000305};
GN Name=mkrn2 {ECO:0000312|EMBL:ABR68861.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Oocyte {ECO:0000269|PubMed:18198183};
RX PubMed=18198183; DOI=10.1074/jbc.m704768200;
RA Yang P.-H., Cheung W.K.C., Peng Y., He M.-L., Wu G.-Q., Xie D.,
RA Jiang B.-H., Huang Q.-H., Chen Z., Lin M.C.M., Kung H.-F.;
RT "Makorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol
RT 3-kinase/Akt (PI3K/Akt) signal.";
RL J. Biol. Chem. 283:8486-8495(2008).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of
CC ubiquitin moieties onto substrate proteins (By similarity). Inhibits
CC neurogenesis and axis formation during embryonic development by
CC modulating the phosphatidylinositol 3-kinase (PI3K) pathway
CC (PubMed:18198183). Acts downstream of PI3K and akt1 to up-regulate
CC gsk3b mRNA expression (PubMed:18198183). {ECO:0000250|UniProtKB:Q9ERV1,
CC ECO:0000269|PubMed:18198183}.
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:Q9ERV1};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9ERV1}. Nucleus
CC {ECO:0000250|UniProtKB:Q9ERV1}.
CC -!- TISSUE SPECIFICITY: In adult males, highly expressed in testis, small
CC intestine, large intestine, stomach, heart, liver, kidney, lung and
CC muscle. Consistent with its role as a neurogenic inhibitor, expression
CC is much lower in the brain, and also in skin.
CC {ECO:0000269|PubMed:18198183}.
CC -!- CAUTION: Although the makorin-type Cys-His region lacks the final His
CC residue, the following Asp residue may be able to coordinate Zn(2+).
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABR68861.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; EF626804; ABR68861.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001116070.1; NM_001122598.1.
DR AlphaFoldDB; B0F0H3; -.
DR PRIDE; B0F0H3; -.
DR GeneID; 100141485; -.
DR CTD; 23609; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030274; F:LIM domain binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0009798; P:axis specification; IMP:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR026293; Makorin_2.
DR InterPro; IPR045072; MKRN-like.
DR InterPro; IPR041367; Znf-CCCH_4.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
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 PANTHER; PTHR11224:SF17; PTHR11224:SF17; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR Pfam; PF00642; zf-CCCH; 1.
DR Pfam; PF18044; zf-CCCH_4; 2.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 4.
DR SUPFAM; SSF90229; SSF90229; 2.
DR PROSITE; PS50103; ZF_C3H1; 4.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Developmental protein; Differentiation; Metal-binding;
KW Neurogenesis; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..409
FT /note="E3 ubiquitin-protein ligase makorin-2"
FT /id="PRO_0000361049"
FT ZN_FING 2..29
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 31..58
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 157..184
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 230..284
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 313..342
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 185..214
FT /note="Makorin-type Cys-His"
FT /evidence="ECO:0000255"
SQ SEQUENCE 409 AA; 45999 MW; BAB1C98AFB8928DE CRC64;
MSPKQVTCRY FLHGVCREGS RCLFSHDLAT SKPSTVCRFF LRGQCAYGTR CRYDHVKPCN
GTVFIPPQEM SPVLSPPPLF PAQEAAVPPT IPAPQRREKK TLVLRDRDLC GASVDPALQP
GCITESQGSE GEAKPHSYLE AICTGLDESQ DPASYPGAPQ QLCPFAQAGE CHCGDSCPYL
HGDACEICGL QVLHPHDQEQ RRDHEKLCME NFELDMERAF AVQASEGRVC SICMERVYEK
QSPAQRRFRI LSDCNHTYCL TCIRQWRCAR QFDNPVIKSC PECRVISEFV IPSAYWVEDQ
SKKDELIEAF KQGMGKKLCK YFDQGRGTCP FGGKCLYLHS YPDGTRAQPE KPRKQLGSEG
SVRFLNSLRL WDFIEDREQR GVPNAEVGKL GELFMHLSGA DEELPAPFN
