MINY2_HUMAN
ID MINY2_HUMAN Reviewed; 621 AA.
AC Q8NBR6; B2RTT8; Q9ULQ6;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase MINDY-2 {ECO:0000303|PubMed:27292798};
DE EC=3.4.19.12 {ECO:0000269|PubMed:27292798};
DE AltName: Full=Deubiquitinating enzyme MINDY-2 {ECO:0000303|PubMed:27292798};
DE AltName: Full=Protein FAM63B;
GN Name=MINDY2 {ECO:0000312|HGNC:HGNC:26954}; Synonyms=FAM63B, KIAA1164;
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-605 (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-621 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND GENE FAMILY.
RX PubMed=27292798; DOI=10.1016/j.molcel.2016.05.009;
RA Abdul Rehman S.A., Kristariyanto Y.A., Choi S.Y., Nkosi P.J., Weidlich S.,
RA Labib K., Hofmann K., Kulathu Y.;
RT "MINDY-1 is a member of an evolutionarily conserved and structurally
RT distinct new family of deubiquitinating enzymes.";
RL Mol. Cell 63:146-155(2016).
RN [8]
RP BINDING TO POLYUBIQUITIN CHAINS, AND MUTAGENESIS OF ALA-519 AND ALA-546.
RX PubMed=28082312; DOI=10.15252/embr.201643205;
RA Kristariyanto Y.A., Abdul Rehman S.A., Weidlich S., Knebel A., Kulathu Y.;
RT "A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin
RT chains.";
RL EMBO Rep. 18:392-402(2017).
CC -!- FUNCTION: Hydrolase that can remove 'Lys-48'-linked conjugated
CC ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin
CC chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-
CC 29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a
CC regulatory role at the level of protein turnover (PubMed:27292798).
CC {ECO:0000269|PubMed:27292798, ECO:0000269|PubMed:28082312}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:27292798};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NBR6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NBR6-2; Sequence=VSP_034719;
CC -!- SIMILARITY: Belongs to the MINDY deubiquitinase family. FAM63
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW77545.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CH471082; EAW77545.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471082; EAW77546.1; -; Genomic_DNA.
DR EMBL; BC140811; AAI40812.1; -; mRNA.
DR EMBL; BC144616; AAI44617.1; -; mRNA.
DR EMBL; AK075319; BAC11545.1; -; mRNA.
DR EMBL; AB032990; BAA86478.1; -; mRNA.
DR CCDS; CCDS42046.1; -. [Q8NBR6-1]
DR CCDS; CCDS45268.1; -. [Q8NBR6-2]
DR RefSeq; NP_001035540.1; NM_001040450.2. [Q8NBR6-1]
DR RefSeq; NP_001035543.1; NM_001040453.2. [Q8NBR6-2]
DR PDB; 6Z49; X-ray; 2.00 A; A/B/C/D=241-504.
DR PDB; 6Z7V; X-ray; 2.65 A; A/B=241-504.
DR PDB; 7NPI; X-ray; 2.81 A; A/G/M/S/Y/e/k=241-504.
DR PDBsum; 6Z49; -.
DR PDBsum; 6Z7V; -.
DR PDBsum; 7NPI; -.
DR AlphaFoldDB; Q8NBR6; -.
DR SASBDB; Q8NBR6; -.
DR SMR; Q8NBR6; -.
DR BioGRID; 120085; 31.
DR IntAct; Q8NBR6; 17.
DR MINT; Q8NBR6; -.
DR STRING; 9606.ENSP00000452885; -.
DR iPTMnet; Q8NBR6; -.
DR PhosphoSitePlus; Q8NBR6; -.
DR BioMuta; MINDY2; -.
DR DMDM; 205831477; -.
DR EPD; Q8NBR6; -.
DR jPOST; Q8NBR6; -.
DR MassIVE; Q8NBR6; -.
DR MaxQB; Q8NBR6; -.
DR PaxDb; Q8NBR6; -.
DR PeptideAtlas; Q8NBR6; -.
DR PRIDE; Q8NBR6; -.
DR ProteomicsDB; 72812; -. [Q8NBR6-1]
DR ProteomicsDB; 72813; -. [Q8NBR6-2]
DR Antibodypedia; 63975; 60 antibodies from 12 providers.
DR DNASU; 54629; -.
DR Ensembl; ENST00000450403.3; ENSP00000393231.2; ENSG00000128923.11. [Q8NBR6-2]
DR Ensembl; ENST00000559228.6; ENSP00000452885.1; ENSG00000128923.11. [Q8NBR6-1]
DR GeneID; 54629; -.
DR KEGG; hsa:54629; -.
DR MANE-Select; ENST00000559228.6; ENSP00000452885.1; NM_001040450.3; NP_001035540.1.
DR UCSC; uc002afi.4; human. [Q8NBR6-1]
DR CTD; 54629; -.
DR DisGeNET; 54629; -.
DR GeneCards; MINDY2; -.
DR HGNC; HGNC:26954; MINDY2.
DR HPA; ENSG00000128923; Low tissue specificity.
DR MIM; 618408; gene.
DR neXtProt; NX_Q8NBR6; -.
DR OpenTargets; ENSG00000128923; -.
DR PharmGKB; PA142671873; -.
DR VEuPathDB; HostDB:ENSG00000128923; -.
DR eggNOG; KOG2427; Eukaryota.
DR GeneTree; ENSGT00390000016607; -.
DR HOGENOM; CLU_022566_3_1_1; -.
DR InParanoid; Q8NBR6; -.
DR OMA; THLCPDN; -.
DR OrthoDB; 1601180at2759; -.
DR PhylomeDB; Q8NBR6; -.
DR TreeFam; TF314589; -.
DR PathwayCommons; Q8NBR6; -.
DR SignaLink; Q8NBR6; -.
DR BioGRID-ORCS; 54629; 106 hits in 1116 CRISPR screens.
DR ChiTaRS; MINDY2; human.
DR GenomeRNAi; 54629; -.
DR Pharos; Q8NBR6; Tbio.
DR PRO; PR:Q8NBR6; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8NBR6; protein.
DR Bgee; ENSG00000128923; Expressed in trigeminal ganglion and 204 other tissues.
DR ExpressionAtlas; Q8NBR6; baseline and differential.
DR Genevisible; Q8NBR6; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0016807; F:cysteine-type carboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR GO; GO:0071795; F:K11-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0071796; F:K6-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IBA:GO_Central.
DR InterPro; IPR007518; MINDY.
DR InterPro; IPR033979; MINDY_domain.
DR PANTHER; PTHR18063; PTHR18063; 1.
DR Pfam; PF04424; MINDY_DUB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..621
FT /note="Ubiquitin carboxyl-terminal hydrolase MINDY-2"
FT /id="PRO_0000344042"
FT REGION 1..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..559
FT /note="Ubiquitin-binding domain (UBD)"
FT /evidence="ECO:0000305|PubMed:27292798"
FT REGION 556..621
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..594
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 595..621
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 266
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8N5J2"
FT ACT_SITE 448
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8N5J2"
FT SITE 542
FT /note="Ubiquitin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8N5J2"
FT SITE 545..546
FT /note="Ubiquitin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8N5J2"
FT SITE 549
FT /note="Ubiquitin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8N5J2"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 580
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10574461,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_034719"
FT MUTAGEN 519
FT /note="A->G: Strongly decreased binding to 'Lys-48' or
FT 'Lys-63'-tetraubiquitin chains."
FT /evidence="ECO:0000269|PubMed:28082312"
FT MUTAGEN 546
FT /note="A->G: No effect on binding to 'Lys-48'- or 'Lys-63'-
FT tetraubiquitin chains."
FT /evidence="ECO:0000269|PubMed:28082312"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:6Z7V"
FT HELIX 267..277
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 292..305
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 318..330
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:6Z7V"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:6Z7V"
FT HELIX 376..382
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 387..398
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 403..418
FT /evidence="ECO:0007829|PDB:6Z49"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 425..434
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 448..455
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 458..462
FT /evidence="ECO:0007829|PDB:6Z49"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:6Z49"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:6Z49"
SQ SEQUENCE 621 AA; 67106 MW; ED97D0BBCA6DC421 CRC64;
MESSPESLQP LEHGVAAGPA SGTGSSQEGL QETRLAAGDG PGVWAAETSG GNGLGAAAAR
RSLPDSASPA GSPEVPGPCS SSAGLDLKDS GLESPAAAEA PLRGQYKVTA SPETAVAGVG
HELGTAGDAG ARPDLAGTCQ AELTAAGSEE PSSAGGLSSS CSDPSPPGES PSLDSLESFS
NLHSFPSSCE FNSEEGAENR VPEEEEGAAV LPGAVPLCKE EEGEETAQVL AASKERFPGQ
SVYHIKWIQW KEENTPIITQ NENGPCPLLA ILNVLLLAWK VKLPPMMEII TAEQLMEYLG
DYMLDAKPKE ISEIQRLNYE QNMSDAMAIL HKLQTGLDVN VRFTGVRVFE YTPECIVFDL
LDIPLYHGWL VDPQIDDIVK AVGNCSYNQL VEKIISCKQS DNSELVSEGF VAEQFLNNTA
TQLTYHGLCE LTSTVQEGEL CVFFRNNHFS TMTKYKGQLY LLVTDQGFLT EEKVVWESLH
NVDGDGNFCD SEFHLRPPSD PETVYKGQQD QIDQDYLMAL SLQQEQQSQE INWEQIPEGI
SDLELAKKLQ EEEDRRASQY YQEQEQAAAA AAAASTQAQQ GQPAQASPSS GRQSGNSERK
RKEPREKDKE KEKEKNSCVI L
