MKRN1_MOUSE
ID MKRN1_MOUSE Reviewed; 481 AA.
AC Q9QXP6;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=E3 ubiquitin-protein ligase makorin-1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase makorin-1 {ECO:0000305};
GN Name=Mkrn1;
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] (ISOFORM 1), DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RX PubMed=10843807; DOI=10.1006/geno.2000.6199;
RA Gray T.A., Hernandez L., Carey A.H., Schaldach M.A., Smithwick M.J.,
RA Rus K., Marshall Graves J.A., Stewart C.L., Nicholls R.D.;
RT "The ancient source of a distinct gene family encoding proteins featuring
RT RING and C(3)H zinc-finger motifs with abundant expression in developing
RT brain and nervous system.";
RL Genomics 66:76-86(2000).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=12968785; DOI=10.1111/j.1749-0774.2003.tb00132.x;
RA Yoshida N., Yano Y., Yoshiki A., Ueno M., Deguchi N., Hirotsune S.;
RT "Identification of a new target molecule for a cascade therapy of
RT polycystic kidney.";
RL Hum. Cell 16:65-72(2003).
RN [3]
RP REGULATION BY A PSEUDOGENE, AND TISSUE SPECIFICITY.
RX PubMed=12721631; DOI=10.1038/nature01535;
RA Hirotsune S., Yoshida N., Chen A., Garrett L., Sugiyama F., Takahashi S.,
RA Yagami K., Wynshaw-Boris A., Yoshiki A.;
RT "An expressed pseudogene regulates the messenger-RNA stability of its
RT homologous coding gene.";
RL Nature 423:91-96(2003).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=12971993; DOI=10.1016/s1567-133x(03)00113-3;
RA Lee S., Walker C.L., Wevrick R.;
RT "Prader-Willi syndrome transcripts are expressed in phenotypically
RT significant regions of the developing mouse brain.";
RL Gene Expr. Patterns 3:599-609(2003).
RN [5]
RP ALTERNATIVE SPLICING (ISOFORM 2), AND DISRUPTION PHENOTYPE.
RX PubMed=16882727; DOI=10.1073/pnas.0602216103;
RA Gray T.A., Wilson A., Fortin P.J., Nicholls R.D.;
RT "The putatively functional Mkrn1-p1 pseudogene is neither expressed nor
RT imprinted, nor does it regulate its source gene in trans.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:12039-12044(2006).
RN [6]
RP FUNCTION.
RX PubMed=16785614; DOI=10.1385/endo:29:2:363;
RA Omwancha J., Zhou X.-F., Chen S.-Y., Baslan T., Fisher C.J., Zheng Z.,
RA Cai C., Shemshedini L.;
RT "Makorin RING finger protein 1 (MKRN1) has negative and positive effects on
RT RNA polymerase II-dependent transcription.";
RL Endocrine 29:363-373(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
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).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of
CC ubiquitin moieties onto substrate proteins. These substrates include
CC FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing
CC p53/TP53 under normal conditions, but stimulates apoptosis by
CC repressing CDKN1A under stress conditions. Acts as a negative regulator
CC of telomerase (By similarity). Has negative and positive effects on RNA
CC polymerase II-dependent transcription. {ECO:0000250,
CC ECO:0000269|PubMed:16785614}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with p53/TP53 and CDKN1A. Interacts with TERT,
CC modulating telomere length homeostasis (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QXP6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QXP6-2; Sequence=VSP_038081, VSP_038082;
CC -!- TISSUE SPECIFICITY: Highly expressed in embryo, in specific cell types
CC of the central nervous system, in brain with the strongest levels of
CC expression in the mantle layers and in testis. Moderate to low levels
CC in somatic tissues. {ECO:0000269|PubMed:10843807,
CC ECO:0000269|PubMed:12721631, ECO:0000269|PubMed:12971993}.
CC -!- DEVELOPMENTAL STAGE: Not detected until 11 dpc. Restricted to
CC developing central nervous system in 13 days embryos.
CC {ECO:0000269|PubMed:10843807}.
CC -!- PTM: Auto-ubiquitinated; which leads to proteasomal degradation.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: PubMed:12968785 describes 80 % of lethality
CC within 2 days of birth in heterozygotes and polycystic kidney and bone
CC deformity in survivors. However, PubMed:16882727 reports no apparent
CC developmental deficits with viable and fertile mice.
CC {ECO:0000269|PubMed:12968785, ECO:0000269|PubMed:16882727}.
CC -!- CAUTION: PubMed:12968785 shows that the expression of the transcribed
CC processed pseudogenes (TPP) Makorin1-p1 prevents the decay of
CC functional Mkrn1 mRNAs. In contrast, PubMed:16882727 shows that
CC Makorin1-p1 is not transcribed and that the putative transcripts
CC represent an alternative isoform of the Mkrn1 source gene.
CC {ECO:0000305}.
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DR EMBL; AF192785; AAF17488.1; -; mRNA.
DR CCDS; CCDS20022.1; -. [Q9QXP6-1]
DR AlphaFoldDB; Q9QXP6; -.
DR STRING; 10090.ENSMUSP00000031985; -.
DR iPTMnet; Q9QXP6; -.
DR PhosphoSitePlus; Q9QXP6; -.
DR EPD; Q9QXP6; -.
DR MaxQB; Q9QXP6; -.
DR PaxDb; Q9QXP6; -.
DR PRIDE; Q9QXP6; -.
DR ProteomicsDB; 252572; -. [Q9QXP6-1]
DR ProteomicsDB; 252573; -. [Q9QXP6-2]
DR Antibodypedia; 437; 362 antibodies from 30 providers.
DR Ensembl; ENSMUST00000114822; ENSMUSP00000110470; ENSMUSG00000029922. [Q9QXP6-2]
DR MGI; MGI:1859353; Mkrn1.
DR VEuPathDB; HostDB:ENSMUSG00000029922; -.
DR eggNOG; KOG1039; Eukaryota.
DR GeneTree; ENSGT00950000183077; -.
DR HOGENOM; CLU_128529_0_0_1; -.
DR InParanoid; Q9QXP6; -.
DR PhylomeDB; Q9QXP6; -.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR ChiTaRS; Mkrn1; mouse.
DR PRO; PR:Q9QXP6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9QXP6; protein.
DR Bgee; ENSMUSG00000029922; Expressed in blood and 267 other tissues.
DR ExpressionAtlas; Q9QXP6; baseline and differential.
DR Genevisible; Q9QXP6; MM.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045072; MKRN-like.
DR InterPro; IPR031644; MKRN1_C.
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 Pfam; PF15815; MKRN1_C; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR Pfam; PF18044; zf-CCCH_4; 3.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 4.
DR SUPFAM; SSF90229; SSF90229; 3.
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; Metal-binding; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..481
FT /note="E3 ubiquitin-protein ligase makorin-1"
FT /id="PRO_0000055954"
FT ZN_FING 55..82
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 84..111
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 208..235
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 281..335
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 364..393
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 236..263
FT /note="Makorin-type Cys-His"
FT VAR_SEQ 182..196
FT /note="TAPSCTEVPPQGSVT -> SKYCEDPVNCNQRAK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038081"
FT VAR_SEQ 197..481
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038082"
SQ SEQUENCE 481 AA; 53008 MW; B6E8DEE5E785CE4E CRC64;
MAEAAAPGTT ATTSGAGAAA AAVAAASLTS IPTVAAPSPG AGGGGGGSDG SGGGWTKQVT
CRYFMHGVCK EGDNCRYSHD LSDSPYGVVC KYFQRGYCVY GDRCRYEHSK PLKQEEVTAT
DLSAKPSLAA SSSLSSGVGS LAEMNSGEAE SRNPSFPTVG AGSEDWVNAI EFVPGQPYCG
RTAPSCTEVP PQGSVTKEES EKEPTTVETK KQLCPYAAVG ECRYGENCVY LHGDSCDMCG
LQVLHPVDAA QRSQHIKSCI EAHEKDMELS FAVQRTKDMV CGICMEVVYE KANPSERRFG
ILSNCNHTYC LKCIRKWRSA KQFESKIIKS CPECRITSNF VIPSEYWVEE KEEKQKLIQK
YKEAMSNKAC RYFDEGRGSC PFGGNCFYKH AYPDGRREEP QRQKVGTSSR YRAQRRSHFW
ELIEERENNP FDNDEEEVVT FELGEMLLML LAAGGDDELT DSEDEWDLFH DELEDFYDLD
L
