MAML2_HUMAN
ID MAML2_HUMAN Reviewed; 1156 AA.
AC Q8IZL2; A7MD26; Q6AI23; Q6Y3A3; Q8IUL3; Q96JK6;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Mastermind-like protein 2;
DE Short=Mam-2;
GN Name=MAML2; Synonyms=KIAA1819;
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 [MRNA], FUNCTION, AND CHROMOSOMAL TRANSLOCATION WITH
RP MECT1.
RX PubMed=12539049; DOI=10.1038/ng1083;
RA Tonon G., Modi S., Wu L., Kubo A., Coxon A.B., Komiya T., O'Neil K.,
RA Stover K., El-Naggar A., Griffin J.D., Kirsch I.R., Kaye F.J.;
RT "t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a
RT novel fusion product that disrupts a Notch signaling pathway.";
RL Nat. Genet. 33:208-213(2003).
RN [2]
RP ERRATUM OF PUBMED:12539049.
RA Tonon G., Modi S., Wu L., Kubo A., Coxon A.B., Komiya T., O'Neil K.,
RA Stover K., El-Naggar A., Griffin J.D., Kirsch I.R., Kaye F.J.;
RL Nat. Genet. 33:408-408(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-1156, TISSUE SPECIFICITY, AND CHROMOSOMAL
RP TRANSLOCATION WITH CRTC1/MECT1.
RC TISSUE=Carcinoma;
RX PubMed=14720503; DOI=10.1016/j.yexcr.2003.09.007;
RA Enlund F., Behboudi A., Andren Y., Oberg C., Lendahl U., Mark J.,
RA Stenman G.;
RT "Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene
RT fusion in mucoepidermoid carcinomas and benign Warthin's tumors.";
RL Exp. Cell Res. 292:21-28(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 818-1156.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH NOTCH1.
RX PubMed=12386158; DOI=10.1074/jbc.m209529200;
RA Lin S.-E., Oyama T., Nagase T., Harigaya K., Kitagawa M.;
RT "Identification of new human mastermind proteins defines a family that
RT consists of positive regulators for Notch signaling.";
RL J. Biol. Chem. 277:50612-50620(2002).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NOTCH1; NOTCH2; NOTCH3
RP AND NOTCH4.
RX PubMed=12370315; DOI=10.1128/mcb.22.21.7688-7700.2002;
RA Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D.;
RT "Identification of a family of mastermind-like transcriptional coactivators
RT for mammalian notch receptors.";
RL Mol. Cell. Biol. 22:7688-7700(2002).
RN [10]
RP CHROMOSOMAL TRANSLOCATION WITH CRTC1.
RX PubMed=15729701; DOI=10.1002/gcc.20168;
RA Behboudi A., Winnes M., Gorunova L., van den Oord J.J., Mertens F.,
RA Enlund F., Stenman G.;
RT "Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)-
RT associated TORC1-MAML2 gene fusion.";
RL Genes Chromosomes Cancer 43:202-205(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-175, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
CC -!- FUNCTION: Acts as a transcriptional coactivator for NOTCH proteins. Has
CC been shown to amplify NOTCH-induced transcription of HES1. Potentiates
CC activation by NOTCH3 and NOTCH4 more efficiently than MAML1 or MAML3.
CC {ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:12386158,
CC ECO:0000269|PubMed:12539049}.
CC -!- SUBUNIT: Interacts through its N-terminal region with the ankyrin
CC repeat region of the Notch proteins NOTCH1, NOTCH2, NOTCH3 and NOTCH4.
CC Forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa.
CC {ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:12386158}.
CC -!- INTERACTION:
CC Q8IZL2; PRO_0000007676 [P46531]: NOTCH1; NbExp=2; IntAct=EBI-2864946, EBI-9692333;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:12370315}.
CC Note=Nuclear, in a punctate manner.
CC -!- TISSUE SPECIFICITY: Widely expressed with high levels detected in
CC placenta, salivary gland and skeletal muscle.
CC {ECO:0000269|PubMed:14720503}.
CC -!- DOMAIN: The C-terminal domain is required for transcriptional
CC activation.
CC -!- DISEASE: Note=A chromosomal aberration involving MAML2 is found in
CC mucoepidermoid carcinomas, benign Warthin tumors and clear cell
CC hidradenomas. Translocation t(11;19)(q21;p13) with CRTC1. The fusion
CC protein consists of the N-terminus of CRTC1 joined to the C-terminus of
CC MAML2. The reciprocal fusion protein consisting of the N-terminus of
CC MAML2 joined to the C-terminus of CRTC1 has been detected in a small
CC number of mucoepidermoid carcinomas. {ECO:0000269|PubMed:15729701}.
CC -!- SIMILARITY: Belongs to the mastermind family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK93833.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAP12462.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB47448.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAML2ID472.html";
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DR EMBL; AY040322; AAK93831.1; -; mRNA.
DR EMBL; AY040324; AAK93833.1; ALT_INIT; mRNA.
DR EMBL; AB058722; BAB47448.1; ALT_INIT; mRNA.
DR EMBL; AP000779; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC152449; AAI52450.1; -; mRNA.
DR EMBL; AY186997; AAP12462.1; ALT_INIT; mRNA.
DR EMBL; AY186998; AAP12463.1; ALT_TERM; mRNA.
DR EMBL; CR627398; CAH10491.1; -; mRNA.
DR CCDS; CCDS44714.1; -.
DR RefSeq; NP_115803.1; NM_032427.3.
DR AlphaFoldDB; Q8IZL2; -.
DR SMR; Q8IZL2; -.
DR BioGRID; 124080; 27.
DR IntAct; Q8IZL2; 6.
DR STRING; 9606.ENSP00000434552; -.
DR iPTMnet; Q8IZL2; -.
DR PhosphoSitePlus; Q8IZL2; -.
DR BioMuta; MAML2; -.
DR DMDM; 296435513; -.
DR EPD; Q8IZL2; -.
DR MassIVE; Q8IZL2; -.
DR MaxQB; Q8IZL2; -.
DR PaxDb; Q8IZL2; -.
DR PeptideAtlas; Q8IZL2; -.
DR PRIDE; Q8IZL2; -.
DR ProteomicsDB; 71366; -.
DR Antibodypedia; 31687; 267 antibodies from 26 providers.
DR DNASU; 84441; -.
DR Ensembl; ENST00000524717.6; ENSP00000434552.1; ENSG00000184384.14.
DR GeneID; 84441; -.
DR KEGG; hsa:84441; -.
DR MANE-Select; ENST00000524717.6; ENSP00000434552.1; NM_032427.4; NP_115803.1.
DR UCSC; uc001pfw.3; human.
DR CTD; 84441; -.
DR DisGeNET; 84441; -.
DR GeneCards; MAML2; -.
DR HGNC; HGNC:16259; MAML2.
DR HPA; ENSG00000184384; Low tissue specificity.
DR MIM; 607537; gene.
DR neXtProt; NX_Q8IZL2; -.
DR OpenTargets; ENSG00000184384; -.
DR PharmGKB; PA134946327; -.
DR VEuPathDB; HostDB:ENSG00000184384; -.
DR eggNOG; ENOG502QVWD; Eukaryota.
DR GeneTree; ENSGT00950000183201; -.
DR HOGENOM; CLU_012528_0_0_1; -.
DR InParanoid; Q8IZL2; -.
DR OMA; QMMDPEL; -.
DR OrthoDB; 296895at2759; -.
DR PhylomeDB; Q8IZL2; -.
DR TreeFam; TF332922; -.
DR PathwayCommons; Q8IZL2; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2197563; NOTCH2 intracellular domain regulates transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR SignaLink; Q8IZL2; -.
DR SIGNOR; Q8IZL2; -.
DR BioGRID-ORCS; 84441; 21 hits in 1081 CRISPR screens.
DR ChiTaRS; MAML2; human.
DR GeneWiki; MAML2; -.
DR GenomeRNAi; 84441; -.
DR Pharos; Q8IZL2; Tbio.
DR PRO; PR:Q8IZL2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IZL2; protein.
DR Bgee; ENSG00000184384; Expressed in mucosa of paranasal sinus and 181 other tissues.
DR ExpressionAtlas; Q8IZL2; baseline and differential.
DR Genevisible; Q8IZL2; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; IBA:GO_Central.
DR Gene3D; 6.10.250.970; -; 1.
DR InterPro; IPR046369; MAML1-3.
DR InterPro; IPR046370; MAML_N_sf.
DR InterPro; IPR019082; Mastermind-like_N.
DR PANTHER; PTHR15692; PTHR15692; 2.
DR Pfam; PF09596; MamL-1; 1.
DR SMART; SM01275; MamL-1; 1.
PE 1: Evidence at protein level;
KW Activator; Chromosomal rearrangement; Notch signaling pathway; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..1156
FT /note="Mastermind-like protein 2"
FT /id="PRO_0000129495"
FT REGION 81..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 658..680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 705..743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..129
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 481..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 557..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 171..172
FT /note="Breakpoint for translocation to form the CRTC1-MAML2
FT and MAML2-CRTC1 fusion proteins"
FT /evidence="ECO:0000269|PubMed:15729701"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 896
FT /note="P -> T (in dbSNP:rs7123133)"
FT /id="VAR_063127"
FT CONFLICT 619..621
FT /note="Missing (in Ref. 1; AAK93831/AAK93833, 3; BAB47448,
FT 5; AAI52450 and 6; AAP12462)"
FT /evidence="ECO:0000305"
FT CONFLICT 836
FT /note="V -> I (in Ref. 6; CAH10491)"
FT /evidence="ECO:0000305"
FT CONFLICT 863
FT /note="A -> T (in Ref. 6; CAH10491)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1156 AA; 125197 MW; E0DBDB669BDE6DA1 CRC64;
MGDTAPPQAP AGGLGGASGA GLLGGGSVTP RVHSAIVERL RARIAVCRQH HLSCEGRYER
GRAESSDRER ESTLQLLSLV QHGQGARKAG KHTKATATAA TTTAPPPPPA APPAASQAAA
TAAPPPPPDY HHHHQQHLLN SSNNGGSGGI NGEQQPPAST PGDQRNSALI ALQGSLKRKQ
VVNLSPANSK RPNGFVDNSF LDIKRIRVGE NLSAGQGGLQ INNGQSQIMS GTLPMSQAPL
RKTNTLPSHT HSPGNGLFNM GLKEVKKEPG ETLSCSKHMD GQMTQENIFP NRYGDDPGEQ
LMDPELQELF NELTNISVPP MSDLELENMI NATIKQDDPF NIDLGQQSQR STPRPSLPME
KIVIKSEYSP GLTQGPSGSP QLRPPSAGPA FSMANSALST SSPIPSVPQS QAQPQTGSGA
SRALPSWQEV SHAQQLKQIA ANRQQHARMQ QHQQQHQPTN WSALPSSAGP SPGPFGQEKI
PSPSFGQQTF SPQSSPMPGV AGGSGQSKVM ANYMYKAGPS AQGGHLDVLM QQKPQDLSRS
FINNPHPAME PRQGNTKPLF HFNSDQANQQ MPSVLPSQNK PSLLHYTQQQ QQQQQQQQQQ
QQQQQQQQQQ QQQQQQQQQQ QSSISAQQQQ QQQSSISAQQ QQQQQQQQQQ QQQQQQQQQQ
QQQQQPSSQP AQSLPSQPLL RSPLPLQQKL LLQQMQNQPI AGMGYQVSQQ QRQDQHSVVG
QNTGPSPSPN PCSNPNTGSG YMNSQQSLLN QQLMGKKQTL QRQIMEQKQQ LLLQQQMLAD
AEKIAPQDQI NRHLSRPPPD YKDQRRNVGN MQPTAQYSGG SSTISLNSNQ ALANPVSTHT
ILTPNSSLLS TSHGTRMPSL STAVQNMGMY GNLPCNQPNT YSVTSGMNQL TQQRNPKQLL
ANQNNPMMPR PPTLGPSNNN NVATFGAGSV GNSQQLRPNL THSMASMPPQ RTSNVMITSN
TTAPNWASQE GTSKQQEALT SAGVRFPTGT PAAYTPNQSL QQAVGSQQFS QRAVAPPNQL
TPAVQMRPMN QMSQTLNGQT MGPLRGLNLR PNQLSTQILP NLNQSGTGLN QSRTGINQPP
SLTPSNFPSP NQSSRAFQGT DHSSDLAFDF LSQQNDNMGP ALNSDADFID SLLKTEPGND
DWMKDINLDE ILGNNS
