Full text data of MKRN1
MKRN1
(RNF61)
[Confidence: low (only semi-automatic identification from reviews)]
E3 ubiquitin-protein ligase makorin-1; 6.3.2.- (RING finger protein 61)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
E3 ubiquitin-protein ligase makorin-1; 6.3.2.- (RING finger protein 61)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UHC7
ID MKRN1_HUMAN Reviewed; 482 AA.
AC Q9UHC7; A4D1T7; B3KXB4; Q256Y7; Q59G11; Q6GSF1; Q9H0G0; Q9UEZ7;
read moreAC Q9UHW2;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=E3 ubiquitin-protein ligase makorin-1;
DE EC=6.3.2.-;
DE AltName: Full=RING finger protein 61;
GN Name=MKRN1; Synonyms=RNF61;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT LEU-243,
RP AND TISSUE 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
RT featuring RING and C(3)H zinc-finger motifs with abundant expression
RT in developing brain and nervous system.";
RL Genomics 66:76-86(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Miroci H., Mohr E.;
RT "Role of trans-acting factors in the subcellular transport of
RT vasopressin mRNA.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-243.
RC TISSUE=Brain, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-243.
RC TISSUE=Brain, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-452 (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP MUTAGENESIS OF HIS-307, UBIQUITINATION, AND INTERACTION WITH TERT.
RX PubMed=15805468; DOI=10.1101/gad.1289405;
RA Kim J.H., Park S.-M., Kang M.R., Oh S.-Y., Lee T.H., Muller M.T.,
RA Chung I.K.;
RT "Ubiquitin ligase MKRN1 modulates telomere length homeostasis through
RT a proteolysis of hTERT.";
RL Genes Dev. 19:776-781(2005).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
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
RT effects on RNA polymerase II-dependent transcription.";
RL Endocrine 29:363-373(2006).
RN [13]
RP INDUCTION.
RX PubMed=19604354; DOI=10.1186/1471-2407-9-232;
RA Shimada H., Shiratori T., Yasuraoka M., Kagaya A., Kuboshima M.,
RA Nomura F., Takiguchi M., Ochiai T., Matsubara H., Hiwasa T.;
RT "Identification of Makorin 1 as a novel SEREX antigen of esophageal
RT squamous cell carcinoma.";
RL BMC Cancer 9:232-232(2009).
RN [14]
RP FUNCTION, AND INTERACTION WITH TP53 AND CDKN1A.
RX PubMed=19536131; DOI=10.1038/emboj.2009.164;
RA Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C.,
RA Lane D.P., Song J.;
RT "Differential regulation of p53 and p21 by MKRN1 E3 ligase controls
RT cell cycle arrest and apoptosis.";
RL EMBO J. 28:2100-2113(2009).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment
CC of ubiquitin moieties onto substrate proteins. These substrates
CC include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by
CC suppressing p53/TP53 under normal conditions, but stimulates
CC apoptosis by repressing CDKN1A under stress conditions. Acts as a
CC negative regulator of telomerase. Has negative and positive
CC effects on RNA polymerase II-dependent transcription.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with p53/TP53 and CDKN1A. Interacts with TERT,
CC modulating telomere length homeostasis.
CC -!- INTERACTION:
CC P38936:CDKN1A; NbExp=5; IntAct=EBI-373524, EBI-375077;
CC P04637:TP53; NbExp=8; IntAct=EBI-373524, EBI-366083;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UHC7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UHC7-2; Sequence=VSP_040361;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UHC7-3; Sequence=VSP_040363, VSP_040364;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9UHC7-4; Sequence=VSP_040362;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: Frequently induced in esophageal squamous cell
CC carcinoma (SCC) tissues.
CC -!- PTM: Auto-ubiquitinated; which leads to proteasomal degradation.
CC -!- SIMILARITY: Contains 4 C3H1-type zinc fingers.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
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DR EMBL; AF192784; AAF17487.1; -; mRNA.
DR EMBL; AF192793; AAF18979.1; -; Genomic_DNA.
DR EMBL; AF192789; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192790; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192791; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192792; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AM236048; CAJ84705.1; -; mRNA.
DR EMBL; AF117233; AAF17214.1; -; mRNA.
DR EMBL; AL136812; CAB66746.1; -; mRNA.
DR EMBL; AK127030; BAG54426.1; -; mRNA.
DR EMBL; AK315552; BAG37929.1; -; mRNA.
DR EMBL; AC069335; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236950; EAL24026.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83949.1; -; Genomic_DNA.
DR EMBL; BC025955; AAH25955.1; -; mRNA.
DR EMBL; BC037400; AAH37400.1; -; mRNA.
DR EMBL; BC064838; AAH64838.1; -; mRNA.
DR EMBL; AB209298; BAD92535.1; -; mRNA.
DR RefSeq; NP_001138597.1; NM_001145125.1.
DR RefSeq; NP_038474.2; NM_013446.3.
DR UniGene; Hs.744883; -.
DR ProteinModelPortal; Q9UHC7; -.
DR SMR; Q9UHC7; 276-364.
DR IntAct; Q9UHC7; 12.
DR MINT; MINT-1365598; -.
DR STRING; 9606.ENSP00000255977; -.
DR PhosphoSite; Q9UHC7; -.
DR DMDM; 67477468; -.
DR PaxDb; Q9UHC7; -.
DR PRIDE; Q9UHC7; -.
DR DNASU; 23608; -.
DR Ensembl; ENST00000255977; ENSP00000255977; ENSG00000133606.
DR Ensembl; ENST00000443720; ENSP00000416369; ENSG00000133606.
DR Ensembl; ENST00000474576; ENSP00000417863; ENSG00000133606.
DR GeneID; 23608; -.
DR KEGG; hsa:23608; -.
DR UCSC; uc003vvs.2; human.
DR CTD; 23608; -.
DR GeneCards; GC07M140152; -.
DR HGNC; HGNC:7112; MKRN1.
DR HPA; HPA000567; -.
DR MIM; 607754; gene.
DR neXtProt; NX_Q9UHC7; -.
DR PharmGKB; PA30831; -.
DR eggNOG; COG5084; -.
DR HOVERGEN; HBG066965; -.
DR InParanoid; Q9UHC7; -.
DR KO; K15687; -.
DR OMA; YQRGCCA; -.
DR OrthoDB; EOG79W95Q; -.
DR PhylomeDB; Q9UHC7; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 23608; -.
DR NextBio; 46308; -.
DR PRO; PR:Q9UHC7; -.
DR ArrayExpress; Q9UHC7; -.
DR Bgee; Q9UHC7; -.
DR CleanEx; HS_MKRN1; -.
DR Genevestigator; Q9UHC7; -.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 4.10.1000.10; -; 3.
DR InterPro; IPR026290; Makorin-related.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR000571; Znf_CCCH.
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; PF00097; zf-C3HC4; 1.
DR Pfam; PF00642; zf-CCCH; 3.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 4.
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; Complete proteome; Ligase; Metal-binding;
KW Polymorphism; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 482 E3 ubiquitin-protein ligase makorin-1.
FT /FTId=PRO_0000055952.
FT ZN_FING 55 82 C3H1-type 1.
FT ZN_FING 84 111 C3H1-type 2.
FT ZN_FING 208 235 C3H1-type 3.
FT ZN_FING 281 335 RING-type.
FT ZN_FING 364 393 C3H1-type 4.
FT REGION 236 263 Makorin-type Cys-His.
FT VAR_SEQ 1 64 Missing (in isoform 2).
FT /FTId=VSP_040361.
FT VAR_SEQ 330 482 Missing (in isoform 4).
FT /FTId=VSP_040362.
FT VAR_SEQ 366 412 SNKACRYFDEGRGSCPFGGNCFYKHAYPDGRREEPQRQKVG
FT TSSRYR -> RYEHCSLFSSEEPNRAWVHFEKNGAALYTPT
FT SFLPFFDFPGQFILSP (in isoform 3).
FT /FTId=VSP_040363.
FT VAR_SEQ 413 482 Missing (in isoform 3).
FT /FTId=VSP_040364.
FT VARIANT 243 243 V -> L (in dbSNP:rs2272095).
FT /FTId=VAR_012161.
FT VARIANT 439 439 V -> A (in dbSNP:rs1062786).
FT /FTId=VAR_057214.
FT MUTAGEN 307 307 H->E: Loss of E3 ligase activity, but no
FT effect on transcription regulation.
FT CONFLICT 149 149 A -> R (in Ref. 3; AAF17214).
FT CONFLICT 197 197 K -> E (in Ref. 5; BAG54426).
FT CONFLICT 274 275 QR -> S (in Ref. 3; AAF17214).
FT CONFLICT 395 396 GR -> AG (in Ref. 1; AAF17487).
SQ SEQUENCE 482 AA; 53349 MW; AE8FAF010A5CDFC0 CRC64;
MAEAATPGTT ATTSGAGAAA ATAAAASPTP IPTVTAPSLG AGGGGGGSDG SGGGWTKQVT
CRYFMHGVCK EGDNCRYSHD LSDSPYSVVC KYFQRGYCIY GDRCRYEHSK PLKQEEATAT
ELTTKSSLAA SSSLSSIVGP LVEMNTGEAE SRNSNFATVG AGSEDWVNAI EFVPGQPYCG
RTAPSCTEAP LQGSVTKEES EKEQTAVETK KQLCPYAAVG ECRYGENCVY LHGDSCDMCG
LQVLHPMDAA QRSQHIKSCI EAHEKDMELS FAVQRSKDMV CGICMEVVYE KANPSERRFG
ILSNCNHTYC LKCIRKWRSA KQFESKIIKS CPECRITSNF VIPSEYWVEE KEEKQKLILK
YKEAMSNKAC RYFDEGRGSC PFGGNCFYKH AYPDGRREEP QRQKVGTSSR YRAQRRNHFW
ELIEERENSN PFDNDEEEVV TFELGEMLLM LLAAGGDDEL TDSEDEWDLF HDELEDFYDL
DL
//
ID MKRN1_HUMAN Reviewed; 482 AA.
AC Q9UHC7; A4D1T7; B3KXB4; Q256Y7; Q59G11; Q6GSF1; Q9H0G0; Q9UEZ7;
read moreAC Q9UHW2;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=E3 ubiquitin-protein ligase makorin-1;
DE EC=6.3.2.-;
DE AltName: Full=RING finger protein 61;
GN Name=MKRN1; Synonyms=RNF61;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT LEU-243,
RP AND TISSUE 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
RT featuring RING and C(3)H zinc-finger motifs with abundant expression
RT in developing brain and nervous system.";
RL Genomics 66:76-86(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Miroci H., Mohr E.;
RT "Role of trans-acting factors in the subcellular transport of
RT vasopressin mRNA.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-243.
RC TISSUE=Brain, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-243.
RC TISSUE=Brain, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-452 (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP MUTAGENESIS OF HIS-307, UBIQUITINATION, AND INTERACTION WITH TERT.
RX PubMed=15805468; DOI=10.1101/gad.1289405;
RA Kim J.H., Park S.-M., Kang M.R., Oh S.-Y., Lee T.H., Muller M.T.,
RA Chung I.K.;
RT "Ubiquitin ligase MKRN1 modulates telomere length homeostasis through
RT a proteolysis of hTERT.";
RL Genes Dev. 19:776-781(2005).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
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
RT effects on RNA polymerase II-dependent transcription.";
RL Endocrine 29:363-373(2006).
RN [13]
RP INDUCTION.
RX PubMed=19604354; DOI=10.1186/1471-2407-9-232;
RA Shimada H., Shiratori T., Yasuraoka M., Kagaya A., Kuboshima M.,
RA Nomura F., Takiguchi M., Ochiai T., Matsubara H., Hiwasa T.;
RT "Identification of Makorin 1 as a novel SEREX antigen of esophageal
RT squamous cell carcinoma.";
RL BMC Cancer 9:232-232(2009).
RN [14]
RP FUNCTION, AND INTERACTION WITH TP53 AND CDKN1A.
RX PubMed=19536131; DOI=10.1038/emboj.2009.164;
RA Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C.,
RA Lane D.P., Song J.;
RT "Differential regulation of p53 and p21 by MKRN1 E3 ligase controls
RT cell cycle arrest and apoptosis.";
RL EMBO J. 28:2100-2113(2009).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment
CC of ubiquitin moieties onto substrate proteins. These substrates
CC include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by
CC suppressing p53/TP53 under normal conditions, but stimulates
CC apoptosis by repressing CDKN1A under stress conditions. Acts as a
CC negative regulator of telomerase. Has negative and positive
CC effects on RNA polymerase II-dependent transcription.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with p53/TP53 and CDKN1A. Interacts with TERT,
CC modulating telomere length homeostasis.
CC -!- INTERACTION:
CC P38936:CDKN1A; NbExp=5; IntAct=EBI-373524, EBI-375077;
CC P04637:TP53; NbExp=8; IntAct=EBI-373524, EBI-366083;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UHC7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UHC7-2; Sequence=VSP_040361;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UHC7-3; Sequence=VSP_040363, VSP_040364;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9UHC7-4; Sequence=VSP_040362;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: Frequently induced in esophageal squamous cell
CC carcinoma (SCC) tissues.
CC -!- PTM: Auto-ubiquitinated; which leads to proteasomal degradation.
CC -!- SIMILARITY: Contains 4 C3H1-type zinc fingers.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC -----------------------------------------------------------------------
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DR EMBL; AF192784; AAF17487.1; -; mRNA.
DR EMBL; AF192793; AAF18979.1; -; Genomic_DNA.
DR EMBL; AF192789; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192790; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192791; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AF192792; AAF18979.1; JOINED; Genomic_DNA.
DR EMBL; AM236048; CAJ84705.1; -; mRNA.
DR EMBL; AF117233; AAF17214.1; -; mRNA.
DR EMBL; AL136812; CAB66746.1; -; mRNA.
DR EMBL; AK127030; BAG54426.1; -; mRNA.
DR EMBL; AK315552; BAG37929.1; -; mRNA.
DR EMBL; AC069335; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236950; EAL24026.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83949.1; -; Genomic_DNA.
DR EMBL; BC025955; AAH25955.1; -; mRNA.
DR EMBL; BC037400; AAH37400.1; -; mRNA.
DR EMBL; BC064838; AAH64838.1; -; mRNA.
DR EMBL; AB209298; BAD92535.1; -; mRNA.
DR RefSeq; NP_001138597.1; NM_001145125.1.
DR RefSeq; NP_038474.2; NM_013446.3.
DR UniGene; Hs.744883; -.
DR ProteinModelPortal; Q9UHC7; -.
DR SMR; Q9UHC7; 276-364.
DR IntAct; Q9UHC7; 12.
DR MINT; MINT-1365598; -.
DR STRING; 9606.ENSP00000255977; -.
DR PhosphoSite; Q9UHC7; -.
DR DMDM; 67477468; -.
DR PaxDb; Q9UHC7; -.
DR PRIDE; Q9UHC7; -.
DR DNASU; 23608; -.
DR Ensembl; ENST00000255977; ENSP00000255977; ENSG00000133606.
DR Ensembl; ENST00000443720; ENSP00000416369; ENSG00000133606.
DR Ensembl; ENST00000474576; ENSP00000417863; ENSG00000133606.
DR GeneID; 23608; -.
DR KEGG; hsa:23608; -.
DR UCSC; uc003vvs.2; human.
DR CTD; 23608; -.
DR GeneCards; GC07M140152; -.
DR HGNC; HGNC:7112; MKRN1.
DR HPA; HPA000567; -.
DR MIM; 607754; gene.
DR neXtProt; NX_Q9UHC7; -.
DR PharmGKB; PA30831; -.
DR eggNOG; COG5084; -.
DR HOVERGEN; HBG066965; -.
DR InParanoid; Q9UHC7; -.
DR KO; K15687; -.
DR OMA; YQRGCCA; -.
DR OrthoDB; EOG79W95Q; -.
DR PhylomeDB; Q9UHC7; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 23608; -.
DR NextBio; 46308; -.
DR PRO; PR:Q9UHC7; -.
DR ArrayExpress; Q9UHC7; -.
DR Bgee; Q9UHC7; -.
DR CleanEx; HS_MKRN1; -.
DR Genevestigator; Q9UHC7; -.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 4.10.1000.10; -; 3.
DR InterPro; IPR026290; Makorin-related.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR000571; Znf_CCCH.
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; PF00097; zf-C3HC4; 1.
DR Pfam; PF00642; zf-CCCH; 3.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 4.
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; Complete proteome; Ligase; Metal-binding;
KW Polymorphism; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 482 E3 ubiquitin-protein ligase makorin-1.
FT /FTId=PRO_0000055952.
FT ZN_FING 55 82 C3H1-type 1.
FT ZN_FING 84 111 C3H1-type 2.
FT ZN_FING 208 235 C3H1-type 3.
FT ZN_FING 281 335 RING-type.
FT ZN_FING 364 393 C3H1-type 4.
FT REGION 236 263 Makorin-type Cys-His.
FT VAR_SEQ 1 64 Missing (in isoform 2).
FT /FTId=VSP_040361.
FT VAR_SEQ 330 482 Missing (in isoform 4).
FT /FTId=VSP_040362.
FT VAR_SEQ 366 412 SNKACRYFDEGRGSCPFGGNCFYKHAYPDGRREEPQRQKVG
FT TSSRYR -> RYEHCSLFSSEEPNRAWVHFEKNGAALYTPT
FT SFLPFFDFPGQFILSP (in isoform 3).
FT /FTId=VSP_040363.
FT VAR_SEQ 413 482 Missing (in isoform 3).
FT /FTId=VSP_040364.
FT VARIANT 243 243 V -> L (in dbSNP:rs2272095).
FT /FTId=VAR_012161.
FT VARIANT 439 439 V -> A (in dbSNP:rs1062786).
FT /FTId=VAR_057214.
FT MUTAGEN 307 307 H->E: Loss of E3 ligase activity, but no
FT effect on transcription regulation.
FT CONFLICT 149 149 A -> R (in Ref. 3; AAF17214).
FT CONFLICT 197 197 K -> E (in Ref. 5; BAG54426).
FT CONFLICT 274 275 QR -> S (in Ref. 3; AAF17214).
FT CONFLICT 395 396 GR -> AG (in Ref. 1; AAF17487).
SQ SEQUENCE 482 AA; 53349 MW; AE8FAF010A5CDFC0 CRC64;
MAEAATPGTT ATTSGAGAAA ATAAAASPTP IPTVTAPSLG AGGGGGGSDG SGGGWTKQVT
CRYFMHGVCK EGDNCRYSHD LSDSPYSVVC KYFQRGYCIY GDRCRYEHSK PLKQEEATAT
ELTTKSSLAA SSSLSSIVGP LVEMNTGEAE SRNSNFATVG AGSEDWVNAI EFVPGQPYCG
RTAPSCTEAP LQGSVTKEES EKEQTAVETK KQLCPYAAVG ECRYGENCVY LHGDSCDMCG
LQVLHPMDAA QRSQHIKSCI EAHEKDMELS FAVQRSKDMV CGICMEVVYE KANPSERRFG
ILSNCNHTYC LKCIRKWRSA KQFESKIIKS CPECRITSNF VIPSEYWVEE KEEKQKLILK
YKEAMSNKAC RYFDEGRGSC PFGGNCFYKH AYPDGRREEP QRQKVGTSSR YRAQRRNHFW
ELIEERENSN PFDNDEEEVV TFELGEMLLM LLAAGGDDEL TDSEDEWDLF HDELEDFYDL
DL
//
MIM
607754
*RECORD*
*FIELD* NO
607754
*FIELD* TI
*607754 MAKORIN 1; MKRN1
*FIELD* TX
DESCRIPTION
The Makorin ring finger protein-1 gene (MKRN1) is a highly transcribed,
read moreintron-containing source for a family of intronless mammalian genes
encoding a novel class of zinc finger proteins. Phylogenetic analyses
indicate that the MKRN1 gene is the ancestral founder of this gene
family (Gray et al., 2000).
CLONING
Gray et al. (2000) cloned MKRN1 orthologs from human, mouse, wallaby,
chicken, fruit fly, and nematode, underscoring the age and conservation
of this gene. The human MKRN1 cDNA contains a contiguous sequence of
3,026 basepairs including an open reading frame (ORF) from nucleotide
121 to 1567 that encodes a putative protein of 482 amino acids. Mouse
and Drosophila Mkrn1 proteins share 92% and 27% with the human protein,
respectively, with Drosophila Mkrn1 reaching 63% identity over 123 amino
acids spanning from upstream of the RING finger through the C-terminal
C3H zinc finger. Northern blot analysis of human tissues detected a
single prominent 3.2-kb transcript, suggesting that the MKRN1 gene is
highly and uniformly expressed in all tissues, including different
regions of the brain. High levels were observed in murine embryonic
nervous system and adult testis.
GENE FUNCTION
Using a yeast 2-hybrid system, Kim et al. (2005) found that MKRN1
interacts with a C-terminal domain of TERT (187270), the catalytic
subunit of the telomerase ribonucleoprotein. They demonstrated that
MKRN1 functions as an E3 ubiquitin ligase, promoting TERT ubiquitination
and proteasomal degradation. Mutation of his307 of MKRN1 or deletion of
its C-terminal RING finger domain inactivated the enzyme. Overexpression
of MKRN1 in telomerase-positive human cells decreased telomerase
activity and reduced telomere length. Kim et al. (2005) concluded that
MKRN1 plays a negative role in telomere homeostasis.
GENE FAMILY
The MKRN gene family encodes putative ribonuclear proteins with a
distinctive array of zinc finger motifs, including 2 to 4 C3H zinc
fingers, an unusual cys/his arrangement that may represent a novel zinc
finger structure, and a highly conserved RING zinc finger. Gray et al.
(2000) provided a summary of 9 MKRN family loci distributed throughout
the human genome.
GENE STRUCTURE
The MKRN1 gene consists of 8 exons and spans approximately 28 kb (Gray
et al., 2000).
MAPPING
By FISH and interspecific backcross analysis, respectively, Gray et al.
(2000) determined that the human and mouse MKRN1 loci map to a conserved
syntenic group proximal to the T-cell receptor-beta cluster (TCRB; see
186930) in chromosome 7q34-q35 in human and chromosome 6A in mouse.
ANIMAL MODEL
Hirotsune et al. (2003) reported that transgenic disruption of a
putative pseudogene, Mkrn1-p1, resulted in destabilization of Mkrn1 mRNA
in trans and generated a phenotype with polycystic kidneys and bone
deformity. Gray et al. (2006) were unable to replicate the findings of
Hirotsune et al. (2003). They showed that 5-prime Mkrn1-p1 is fully
methylated on both alleles, indicative of silenced chromatin, and that
Mkrn1-p1 is not transcribed and therefore cannot stabilize Mkrn1
transcripts in trans. They determined that the putative Mkrn1-p1
reported by Hirotsune et al. (2003) is actually a short splice variant
of the Mkrn1 gene. Mice in which Mkrn1 had been directly disrupted
showed none of the phenotypes attributed by Hirotsune et al. (2003) to a
partial reduction of an Mkrn1 isoform. In addition, Gray et al. (2006)
found that Mkrn1-p1 appeared specific to mouse; it was not found in any
other species, including rat.
*FIELD* RF
1. Gray, T. A.; Hernandez, L.; Carey, A. H.; Schaldach, M. A.; Smithwick,
M. J.; Rus, K.; Graves, J. A. M.; Stewart, C. L.; Nicholls, R. D.
: The ancient source of a distinct gene family encoding proteins featuring
RING and C(3)H zinc-finger motifs with abundant expression in developing
brain and nervous system. Genomics 66: 76-86, 2000.
2. Gray, T. A.; Wilson, A.; Fortin, P. J.; Nicholls, R. D.: The putatively
functional Mkrn1-p1 pseudogene is neither expressed nor imprinted,
nor does it regulate its source gene in trans. Proc. Nat. Acad. Sci. 103:
12039-12044, 2006.
3. Hirotsune, S.; Yoshida, N.; Chen, A.; Garrett, L.; Sugiyama, F.;
Takahashi, S.; Yagami, K.; Wynshaw-Boris, A.; Yoshiki, A.: An expressed
pseudogene regulates the messenger-RNA stability of its homologous
coding gene. Nature 423: 91-96, 2003. Note: Addendum: Nature 426:
100 only, 2003.
4. Kim, J. H.; Park, S.-M.; Kang, M. R.; Oh, S.-Y.; Lee, T. H.; Muller,
M. T.; Chung, I. K.: Ubiquitin ligase MKRN1 modulates telomere length
homeostasis through a proteolysis of hTERT. Gene Dev. 19: 776-781,
2005.
*FIELD* CN
Patricia A. Hartz - updated: 9/15/2006
Patricia A. Hartz - updated: 5/5/2005
*FIELD* CD
Ada Hamosh: 5/6/2003
*FIELD* ED
mgross: 10/07/2013
wwang: 9/28/2006
wwang: 9/22/2006
terry: 9/15/2006
mgross: 5/12/2005
terry: 5/5/2005
tkritzer: 4/22/2005
alopez: 12/16/2003
alopez: 12/1/2003
alopez: 5/6/2003
*RECORD*
*FIELD* NO
607754
*FIELD* TI
*607754 MAKORIN 1; MKRN1
*FIELD* TX
DESCRIPTION
The Makorin ring finger protein-1 gene (MKRN1) is a highly transcribed,
read moreintron-containing source for a family of intronless mammalian genes
encoding a novel class of zinc finger proteins. Phylogenetic analyses
indicate that the MKRN1 gene is the ancestral founder of this gene
family (Gray et al., 2000).
CLONING
Gray et al. (2000) cloned MKRN1 orthologs from human, mouse, wallaby,
chicken, fruit fly, and nematode, underscoring the age and conservation
of this gene. The human MKRN1 cDNA contains a contiguous sequence of
3,026 basepairs including an open reading frame (ORF) from nucleotide
121 to 1567 that encodes a putative protein of 482 amino acids. Mouse
and Drosophila Mkrn1 proteins share 92% and 27% with the human protein,
respectively, with Drosophila Mkrn1 reaching 63% identity over 123 amino
acids spanning from upstream of the RING finger through the C-terminal
C3H zinc finger. Northern blot analysis of human tissues detected a
single prominent 3.2-kb transcript, suggesting that the MKRN1 gene is
highly and uniformly expressed in all tissues, including different
regions of the brain. High levels were observed in murine embryonic
nervous system and adult testis.
GENE FUNCTION
Using a yeast 2-hybrid system, Kim et al. (2005) found that MKRN1
interacts with a C-terminal domain of TERT (187270), the catalytic
subunit of the telomerase ribonucleoprotein. They demonstrated that
MKRN1 functions as an E3 ubiquitin ligase, promoting TERT ubiquitination
and proteasomal degradation. Mutation of his307 of MKRN1 or deletion of
its C-terminal RING finger domain inactivated the enzyme. Overexpression
of MKRN1 in telomerase-positive human cells decreased telomerase
activity and reduced telomere length. Kim et al. (2005) concluded that
MKRN1 plays a negative role in telomere homeostasis.
GENE FAMILY
The MKRN gene family encodes putative ribonuclear proteins with a
distinctive array of zinc finger motifs, including 2 to 4 C3H zinc
fingers, an unusual cys/his arrangement that may represent a novel zinc
finger structure, and a highly conserved RING zinc finger. Gray et al.
(2000) provided a summary of 9 MKRN family loci distributed throughout
the human genome.
GENE STRUCTURE
The MKRN1 gene consists of 8 exons and spans approximately 28 kb (Gray
et al., 2000).
MAPPING
By FISH and interspecific backcross analysis, respectively, Gray et al.
(2000) determined that the human and mouse MKRN1 loci map to a conserved
syntenic group proximal to the T-cell receptor-beta cluster (TCRB; see
186930) in chromosome 7q34-q35 in human and chromosome 6A in mouse.
ANIMAL MODEL
Hirotsune et al. (2003) reported that transgenic disruption of a
putative pseudogene, Mkrn1-p1, resulted in destabilization of Mkrn1 mRNA
in trans and generated a phenotype with polycystic kidneys and bone
deformity. Gray et al. (2006) were unable to replicate the findings of
Hirotsune et al. (2003). They showed that 5-prime Mkrn1-p1 is fully
methylated on both alleles, indicative of silenced chromatin, and that
Mkrn1-p1 is not transcribed and therefore cannot stabilize Mkrn1
transcripts in trans. They determined that the putative Mkrn1-p1
reported by Hirotsune et al. (2003) is actually a short splice variant
of the Mkrn1 gene. Mice in which Mkrn1 had been directly disrupted
showed none of the phenotypes attributed by Hirotsune et al. (2003) to a
partial reduction of an Mkrn1 isoform. In addition, Gray et al. (2006)
found that Mkrn1-p1 appeared specific to mouse; it was not found in any
other species, including rat.
*FIELD* RF
1. Gray, T. A.; Hernandez, L.; Carey, A. H.; Schaldach, M. A.; Smithwick,
M. J.; Rus, K.; Graves, J. A. M.; Stewart, C. L.; Nicholls, R. D.
: The ancient source of a distinct gene family encoding proteins featuring
RING and C(3)H zinc-finger motifs with abundant expression in developing
brain and nervous system. Genomics 66: 76-86, 2000.
2. Gray, T. A.; Wilson, A.; Fortin, P. J.; Nicholls, R. D.: The putatively
functional Mkrn1-p1 pseudogene is neither expressed nor imprinted,
nor does it regulate its source gene in trans. Proc. Nat. Acad. Sci. 103:
12039-12044, 2006.
3. Hirotsune, S.; Yoshida, N.; Chen, A.; Garrett, L.; Sugiyama, F.;
Takahashi, S.; Yagami, K.; Wynshaw-Boris, A.; Yoshiki, A.: An expressed
pseudogene regulates the messenger-RNA stability of its homologous
coding gene. Nature 423: 91-96, 2003. Note: Addendum: Nature 426:
100 only, 2003.
4. Kim, J. H.; Park, S.-M.; Kang, M. R.; Oh, S.-Y.; Lee, T. H.; Muller,
M. T.; Chung, I. K.: Ubiquitin ligase MKRN1 modulates telomere length
homeostasis through a proteolysis of hTERT. Gene Dev. 19: 776-781,
2005.
*FIELD* CN
Patricia A. Hartz - updated: 9/15/2006
Patricia A. Hartz - updated: 5/5/2005
*FIELD* CD
Ada Hamosh: 5/6/2003
*FIELD* ED
mgross: 10/07/2013
wwang: 9/28/2006
wwang: 9/22/2006
terry: 9/15/2006
mgross: 5/12/2005
terry: 5/5/2005
tkritzer: 4/22/2005
alopez: 12/16/2003
alopez: 12/1/2003
alopez: 5/6/2003