MKRN2_MOUSE
ID MKRN2_MOUSE Reviewed; 416 AA.
AC Q9ERV1; Q6GTY9; Q9D0L9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 ubiquitin-protein ligase makorin-2 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:28378844};
DE AltName: Full=RING-type E3 ubiquitin transferase makorin-2 {ECO:0000305};
GN Name=Mkrn2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11597136; DOI=10.1006/geno.2001.6627;
RA Gray T.A., Azama K., Whitmore K., Min A., Abe S., Nicholls R.D.;
RT "Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-
RT finger protein, antisense to the raf1 proto-oncogene.";
RL Genomics 77:119-126(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28008940; DOI=10.1038/srep39318;
RA Qian X., Wang L., Zheng B., Shi Z.M., Ge X., Jiang C.F., Qian Y.C.,
RA Li D.M., Li W., Liu X., Yin Y., Zheng J.T., Shen H., Wang M., Guo X.J.,
RA He J., Lin M., Liu L.Z., Sha J.H., Jiang B.H.;
RT "Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and
RT impairs male fertility.";
RL Sci. Rep. 6:39318-39318(2016).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PDLIM2 AND RELA, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28378844; DOI=10.1038/srep46097;
RA Shin C., Ito Y., Ichikawa S., Tokunaga M., Sakata-Sogawa K., Tanaka T.;
RT "MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-kappaB and
RT negatively regulates inflammatory responses.";
RL Sci. Rep. 7:46097-46097(2017).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of
CC ubiquitin moieties onto substrate proteins (PubMed:28378844). Promotes
CC the polyubiquitination and proteasome-dependent degradation of
CC RELA/p65, thereby suppressing RELA-mediated NF-kappa-B transactivation
CC and negatively regulating inflammatory responses (PubMed:28378844).
CC Plays a role in the regulation of spermiation and in male fertility
CC (PubMed:28008940). {ECO:0000269|PubMed:28008940,
CC ECO:0000269|PubMed:28378844}.
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:0000269|PubMed:28378844};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with PDLIM2 (via LIM zinc-binding domain)
CC (PubMed:28378844). Interacts with RELA (PubMed:28378844).
CC {ECO:0000269|PubMed:28378844}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28378844}. Nucleus
CC {ECO:0000269|PubMed:28378844}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the testis, and lower
CC expression in the brain, thymus, heart, lung, liver, spleen, kidney,
CC ovary, uterus, and seminal vesicle (at protein level)
CC (PubMed:28008940). Expressed in primary immune cells, such as CD4-
CC positive and CD8-positive T cells, CD19-positive B cells and CD11c-
CC positive dendritic cells, and in embryonic fibroblasts (at protein
CC level) (PubMed:28378844). {ECO:0000269|PubMed:28008940,
CC ECO:0000269|PubMed:28378844}.
CC -!- DISRUPTION PHENOTYPE: Male and female knockout mice are viable with a
CC lighter birthweight than wild-type animals (PubMed:28008940). Causes
CC infertility in male mice, whereas female mice are fertile, but display
CC reduced fecundity (PubMed:28008940). Leads to abnormal sperms
CC characterized by low number, poor motility, and aberrant morphology
CC (PubMed:28008940). Sperms have deformed heads with abnormal or missing
CC acrosomes, disorganized axonemal structure, and disorganized flagellar
CC structure (PubMed:28008940). Complete loss of the axoneme doublets in
CC one side of the fibrous sheath and disordered assembly of axoneme
CC doublets (PubMed:28008940). Causes failure of sperm release
CC (spermiation failure) and misarrangement of ectoplasmic specialization
CC in testes, thus impairing spermiogenesis and spermiation
CC (PubMed:28008940). Disrupted arrangement of ectoplasmic specialization,
CC the adhesion junction found in Sertoli cells at sites of attachment to
CC elongated spermatids or neighboring Sertoli cells in the testes, and
CC decreased expression of Espn (PubMed:28008940). The outer dense fiber,
CC which is an important component of flagellae, is absent or improperly
CC arranged in epididymal sperms (PubMed:28008940). Decreased expression
CC levels of Odf2 in spermatogenesis (PubMed:28008940).
CC {ECO:0000269|PubMed:28008940}.
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DR EMBL; AF277171; AAG27596.1; -; mRNA.
DR EMBL; AK011295; BAB27523.1; -; mRNA.
DR EMBL; AK077926; BAC37068.1; -; mRNA.
DR EMBL; CH466523; EDK99532.1; -; Genomic_DNA.
DR EMBL; BC025547; AAH25547.1; -; mRNA.
DR CCDS; CCDS39600.1; -.
DR RefSeq; NP_075779.2; NM_023290.2.
DR AlphaFoldDB; Q9ERV1; -.
DR BioGRID; 211885; 4.
DR STRING; 10090.ENSMUSP00000000449; -.
DR iPTMnet; Q9ERV1; -.
DR PhosphoSitePlus; Q9ERV1; -.
DR EPD; Q9ERV1; -.
DR jPOST; Q9ERV1; -.
DR MaxQB; Q9ERV1; -.
DR PaxDb; Q9ERV1; -.
DR PeptideAtlas; Q9ERV1; -.
DR PRIDE; Q9ERV1; -.
DR ProteomicsDB; 252574; -.
DR Antibodypedia; 26240; 307 antibodies from 28 providers.
DR DNASU; 67027; -.
DR Ensembl; ENSMUST00000000449; ENSMUSP00000000449; ENSMUSG00000000439.
DR GeneID; 67027; -.
DR KEGG; mmu:67027; -.
DR UCSC; uc009diw.1; mouse.
DR CTD; 23609; -.
DR MGI; MGI:1914277; Mkrn2.
DR VEuPathDB; HostDB:ENSMUSG00000000439; -.
DR eggNOG; KOG1039; Eukaryota.
DR GeneTree; ENSGT00950000183077; -.
DR HOGENOM; CLU_040815_0_1_1; -.
DR InParanoid; Q9ERV1; -.
DR OMA; RYDHIRL; -.
DR OrthoDB; 1388677at2759; -.
DR PhylomeDB; Q9ERV1; -.
DR TreeFam; TF315108; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67027; 9 hits in 59 CRISPR screens.
DR ChiTaRS; Mkrn2; mouse.
DR PRO; PR:Q9ERV1; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9ERV1; protein.
DR Bgee; ENSMUSG00000000439; Expressed in temporalis muscle and 252 other tissues.
DR Genevisible; Q9ERV1; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030274; F:LIM domain binding; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IMP:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; ISS: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; 2.
DR Pfam; PF18044; zf-CCCH_4; 1.
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 1: Evidence at protein level;
KW Cytoplasm; Differentiation; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Spermatogenesis; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..416
FT /note="E3 ubiquitin-protein ligase makorin-2"
FT /id="PRO_0000055956"
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 165..192
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 238..292
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 321..350
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 61..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..222
FT /note="Makorin-type Cys-His"
FT COMPBIAS 80..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H000"
FT CONFLICT 181
FT /note="F -> L (in Ref. 1; AAG27596)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 46597 MW; E29055040BC3090C CRC64;
MSTKQVTCRY FMHGVCREGS QCLFSHDLAN SKPSTICKYY QKGYCAYGAR CRYDHTKPPA
AAGGAVGPAP NPSPSSGLHS PHPSPDIATS VMRTHSNEPG KREKKTLVLR DRNLTGLAED
KTPPSKVNNP GGCSDPQTSP EMKPHSYLDA IRTGLDDLEA SSSYSNEPQL CPYAAAGECR
FGDACVYLHG DMCEICRLQV LHPFDPEQRK AHEKMCMSTF EHEMEKAFAF QASQDKVCSI
CMEVILEKAS ASERRFGILS NCSHTYCLSC IRQWRCAKQF ENPIIKSCPE CRVISEFVIP
SVYWVEDQNK KNELIEAFKQ GMGKKACKYF EQGKGTCPFG SKCLYRHAYP DGRLAEPEKP
RKQLSSEGTV RFFNSVRLWD FIENRETRQV PSTDDVDVTE LGDLFMHLSG VESSEP
