MPND_HUMAN
ID MPND_HUMAN Reviewed; 471 AA.
AC Q8N594; Q96SJ0; Q9Y2P1; Q9Y2P2;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=MPN domain-containing protein {ECO:0000305};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q5VVJ2};
GN Name=MPND {ECO:0000303|PubMed:30982744, ECO:0000312|HGNC:HGNC:25934};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178 AND SER-181, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-8, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION, DOMAIN, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=30982744; DOI=10.1016/j.molcel.2019.03.018;
RA Kweon S.M., Chen Y., Moon E., Kvederaviciute K., Klimasauskas S.,
RA Feldman D.E.;
RT "An adversarial DNA N6-methyladenine-sensor network preserves Polycomb
RT silencing.";
RL Mol. Cell 74:1138-1147(2019).
CC -!- FUNCTION: Probable protease (By similarity). Acts as a sensor of N(6)-
CC methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA,
CC leading to its degradation (PubMed:30982744).
CC {ECO:0000250|UniProtKB:Q5VVJ2, ECO:0000269|PubMed:30982744}.
CC -!- INTERACTION:
CC Q8N594; P05067: APP; NbExp=3; IntAct=EBI-2512452, EBI-77613;
CC Q8N594; P54253: ATXN1; NbExp=6; IntAct=EBI-2512452, EBI-930964;
CC Q8N594; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-2512452, EBI-25840379;
CC Q8N594; G5E9A7: DMWD; NbExp=3; IntAct=EBI-2512452, EBI-10976677;
CC Q8N594; P28358: HOXD10; NbExp=3; IntAct=EBI-2512452, EBI-12690664;
CC Q8N594; P04792: HSPB1; NbExp=3; IntAct=EBI-2512452, EBI-352682;
CC Q8N594; O43464: HTRA2; NbExp=3; IntAct=EBI-2512452, EBI-517086;
CC Q8N594; P42858: HTT; NbExp=3; IntAct=EBI-2512452, EBI-466029;
CC Q8N594; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2512452, EBI-1055254;
CC Q8N594; O60333-2: KIF1B; NbExp=3; IntAct=EBI-2512452, EBI-10975473;
CC Q8N594; P35240-4: NF2; NbExp=3; IntAct=EBI-2512452, EBI-1014514;
CC Q8N594; P29474: NOS3; NbExp=3; IntAct=EBI-2512452, EBI-1391623;
CC Q8N594; O60260-5: PRKN; NbExp=3; IntAct=EBI-2512452, EBI-21251460;
CC Q8N594; P60891: PRPS1; NbExp=3; IntAct=EBI-2512452, EBI-749195;
CC Q8N594; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-2512452, EBI-396669;
CC Q8N594; P37840: SNCA; NbExp=3; IntAct=EBI-2512452, EBI-985879;
CC Q8N594; P00441: SOD1; NbExp=3; IntAct=EBI-2512452, EBI-990792;
CC Q8N594; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2512452, EBI-5235340;
CC Q8N594; Q13148: TARDBP; NbExp=6; IntAct=EBI-2512452, EBI-372899;
CC Q8N594; O76024: WFS1; NbExp=3; IntAct=EBI-2512452, EBI-720609;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N594-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N594-2; Sequence=VSP_023400, VSP_023401;
CC -!- DOMAIN: The RAMA domain recognizes and binds N(6)-methyladenosine
CC methylation on DNA (m6A). {ECO:0000305|PubMed:30982744}.
CC -!- PTM: Degraded following binding to N(6)-methyladenosine methylated DNA
CC (m6A). {ECO:0000269|PubMed:30982744}.
CC -!- SIMILARITY: Belongs to the peptidase M67 family. {ECO:0000305}.
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; AK027887; BAB55432.1; -; mRNA.
DR EMBL; AC007292; AAD24592.1; -; Genomic_DNA.
DR EMBL; AC007292; AAD24593.1; -; Genomic_DNA.
DR EMBL; AC104521; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032652; AAH32652.1; -; mRNA.
DR CCDS; CCDS42470.1; -. [Q8N594-1]
DR CCDS; CCDS54200.1; -. [Q8N594-2]
DR RefSeq; NP_001153318.1; NM_001159846.2. [Q8N594-2]
DR RefSeq; NP_116257.2; NM_032868.5. [Q8N594-1]
DR AlphaFoldDB; Q8N594; -.
DR BioGRID; 124386; 10.
DR IntAct; Q8N594; 22.
DR MINT; Q8N594; -.
DR STRING; 9606.ENSP00000471735; -.
DR iPTMnet; Q8N594; -.
DR PhosphoSitePlus; Q8N594; -.
DR BioMuta; MPND; -.
DR DMDM; 74728961; -.
DR EPD; Q8N594; -.
DR jPOST; Q8N594; -.
DR MassIVE; Q8N594; -.
DR MaxQB; Q8N594; -.
DR PaxDb; Q8N594; -.
DR PeptideAtlas; Q8N594; -.
DR PRIDE; Q8N594; -.
DR ProteomicsDB; 72023; -. [Q8N594-1]
DR ProteomicsDB; 72024; -. [Q8N594-2]
DR Antibodypedia; 23593; 146 antibodies from 20 providers.
DR DNASU; 84954; -.
DR Ensembl; ENST00000262966.12; ENSP00000262966.7; ENSG00000008382.16. [Q8N594-1]
DR Ensembl; ENST00000359935.8; ENSP00000353015.3; ENSG00000008382.16. [Q8N594-2]
DR GeneID; 84954; -.
DR KEGG; hsa:84954; -.
DR UCSC; uc002mae.3; human. [Q8N594-1]
DR CTD; 84954; -.
DR DisGeNET; 84954; -.
DR GeneCards; MPND; -.
DR HGNC; HGNC:25934; MPND.
DR HPA; ENSG00000008382; Low tissue specificity.
DR neXtProt; NX_Q8N594; -.
DR OpenTargets; ENSG00000008382; -.
DR PharmGKB; PA162396091; -.
DR VEuPathDB; HostDB:ENSG00000008382; -.
DR eggNOG; KOG1555; Eukaryota.
DR GeneTree; ENSGT00940000160191; -.
DR InParanoid; Q8N594; -.
DR PhylomeDB; Q8N594; -.
DR TreeFam; TF324811; -.
DR PathwayCommons; Q8N594; -.
DR SignaLink; Q8N594; -.
DR BioGRID-ORCS; 84954; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; MPND; human.
DR GenomeRNAi; 84954; -.
DR Pharos; Q8N594; Tbio.
DR PRO; PR:Q8N594; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N594; protein.
DR Bgee; ENSG00000008382; Expressed in mucosa of transverse colon and 125 other tissues.
DR ExpressionAtlas; Q8N594; baseline and differential.
DR Genevisible; Q8N594; HS.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140492; F:metal-dependent deubiquitinase activity; IEA:InterPro.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR000555; JAMM/MPN+_dom.
DR InterPro; IPR037518; MPN.
DR InterPro; IPR040843; RAMA.
DR Pfam; PF01398; JAB; 1.
DR Pfam; PF18755; RAMA; 1.
DR PROSITE; PS50249; MPN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Hydrolase; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CHAIN 2..471
FT /note="MPN domain-containing protein"
FT /id="PRO_0000278804"
FT DOMAIN 71..166
FT /note="RAMA"
FT /evidence="ECO:0000255"
FT DOMAIN 272..407
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 170..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 349..362
FT /note="JAMM motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT COMPBIAS 15..29
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 179..199
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..215
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 351
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT VAR_SEQ 283..332
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023400"
FT VAR_SEQ 412
FT /note="E -> EQRPSDYGIPMDVEMAYVQDSFLTNDILHEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023401"
FT CONFLICT 193
FT /note="E -> K (in Ref. 1; BAB55432)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 471 AA; 50662 MW; 9D05932C816F828D CRC64;
MAAPEPLSPA GGAGEEAPEE DEDEAEAEDP ERPNAGAGGG RSGGGGSSVS GGGGGGGAGA
GGCGGPGGAL TRRAVTLRVL LKDALLEPGA GVLSIYYLGK KFLGDLQPDG RIMWQETGQT
FNSPSAWATH CKKLVNPAKK SGCGWASVKY KGQKLDKYKA TWLRLHQLHT PATAADESPA
SEGEEEELLM EEEEEDVLAG VSAEDKSRRP LGKSPSEPAH PEATTPGKRV DSKIRVPVRY
CMLGSRDLAR NPHTLVEVTS FAAINKFQPF NVAVSSNVLF LLDFHSHLTR SEVVGYLGGR
WDVNSQMLTV LRAFPCRSRL GDAETAAAIE EEIYQSLFLR GLSLVGWYHS HPHSPALPSL
QDIDAQMDYQ LRLQGSSNGF QPCLALLCSP YYSGNPGPES KISPFWVMPP PEMLLVEFYK
GSPDLVRLQE PWSQEHTYLD KLKISLASRT PKDQSLCHVL EQVCGVLKQG S
