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Description:
Methyl-CpG-binding domain protein 4 (EC 3.2.2.-) (Methyl-CpG-bindingprotein MBD4) (Methyl-CpG-binding endonuclease 1) (Mismatch-specificDNA N-glycosylase).
Molecular weight: 66051
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) base-excision repair( GO:0006284 )
Important dates:
19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
01-MAY-1999, sequence version 1.
07-MAR-2006, entry version 35.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein MBD4_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AF072250 | AAC68879.1 | - |
| EMBL | AF120999 | AAD50374.1 | - |
| EMBL | AF120997 | AAD50374.1 | JOINED |
| EMBL | AF120998 | AAD50374.1 | JOINED |
| EMBL | AF114784 | AAD22195.1 | - |
| EMBL | AF532602 | AAP97338.1 | - |
| EMBL | CR450305 | CAG29301.1 | - |
| EMBL | AF494057 | AAM00008.1 | - |
| EMBL | BC011752 | AAH11752.1 | - |
| HSSP | Q9Z2D7 | 1NGN | |
| SMR | O95243 | 437-580.1 | |
| IntAct | O95243 | -.1 | |
| Ensembl | ENSG00000129071 | Homo sapiens.1 | |
| H-InvDB | HIX0003669 | -.1 | |
| HGNC | HGNC:6919 | MBD4.1 | |
| MIM | 603574 | gene. | |
| Reactome | O95243 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0004520 | F:endodeoxyribonuclease activity | TAS. |
| GO | GO:0005515 | F:protein binding | IPI. |
| GO | GO:0003696 | F:satellite DNA binding | TAS. |
| GO | GO:0006281 | P:DNA repair | TAS. |
| InterPro | IPR003265 | Endo_3c. | |
| InterPro | IPR001739 | Methyl_CpG_bd. | |
| Pfam | PF00730 | HhH-GPD | 1. |
| Pfam | PF01429 | MBD | 1. |
| SMART | SM00391 | MBD | 1. |
| PROSITE | PS50982 | MBD | 1. |
Keywords:
Alternative splicing; DNA damage; DNA repair; DNA-binding; Hydrolase; Nuclear protein; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX MEDLINE=98449942; PubMed=9774669;
RA Hendrich B., Bird A.;
RT "Identification and characterization of a family of mammalian methyl-
RT CpG binding proteins.";
RL Mol. Cell. Biol. 18:6538-6547(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX MEDLINE=99373255; PubMed=10441743; DOI=10.1007/s003359901112;
RA Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A.;
RT "Genomic structure and chromosomal mapping of the murine and human
RT mbd1, mbd2, mbd3, and mbd4 genes.";
RL Mamm. Genome 10:906-912(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, AND INTERACTION WITH MLH1.
RC TISSUE=Fetal brain;
RX MEDLINE=99199294; PubMed=10097147; DOI=10.1073/pnas.96.7.3969;
RA Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T.,
RA Matsumoto Y., Golemis E.A., Genuardi M., Neri G.;
RT "MED1, a novel human methyl-CpG-binding endonuclease, interacts with
RT DNA mismatch repair protein MLH1.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Lung;
RA Guo J.H., Chen L., Yu L.;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-273; PRO-342;
RP LYS-346 AND HIS-568.
RA Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P.,
RA Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [8]
RP FUNCTION.
RX MEDLINE=20490664; PubMed=10930409; DOI=10.1074/jbc.M004535200;
RA Petronzelli F., Riccio A., Markham G.D., Seeholzer S.H., Stoerker J.,
RA Genuardi M., Yeung A.T., Matsumoto Y., Bellacosa A.;
RT "Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a
RT mismatch-specific DNA N-glycosylase.";
RL J. Biol. Chem. 275:32422-32429(2000).
RN [9]
RP INTERACTION WITH FADD.
RX MEDLINE=22608636; PubMed=12702765; DOI=10.1073/pnas.0431215100;
RA Screaton R.A., Kiessling S., Sansom O.J., Millar C.B., Maddison K.,
RA Bird A., Clarke A.R., Frisch S.M.;
RT "Fas-associated death domain protein interacts with methyl-CpG binding
RT domain protein 4: a potential link between genome surveillance and
RT apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5211-5216(2003).
Feature:
CHAIN 1 580 Methyl-CpG-binding domain protein 4.
/FTId=PRO_0000096264.
DOMAIN 76 148 MBD.
DOMAIN 461 524 HhH-GPD.
ACT_SITE 560 560 By similarity.
VARSPLIC 395 400 Missing (in isoform 2).
/FTId=VSP_010816.
VARSPLIC 539 540 KY -> AP (in isoform 3).
/FTId=VSP_010817.
VARSPLIC 541 580 Missing (in isoform 3).
/FTId=VSP_010818.
VARIANT 273 273 A -> S (in dbSNP:10342).
/FTId=VAR_019357.
VARIANT 273 273 A -> T (in dbSNP:10342).
/FTId=VAR_019514.
VARIANT 342 342 S -> P (in dbSNP:2307289).
/FTId=VAR_019358.
VARIANT 346 346 E -> K (in dbSNP:140693).
/FTId=VAR_019359.
VARIANT 358 358 I -> T (in dbSNP:2307298).
/FTId=VAR_019515.
VARIANT 568 568 D -> H (in dbSNP:2307293).
/FTId=VAR_019360.
Comments:
-!- FUNCTION: Mismatch-specific DNA N-glycosylase involved in DNA
repair. Has thymine glycosylase activity and is specific for G:T
mismatches within methylated and unmethylated CpG sites. Can also
remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase
activity. Was first identified as methyl-CpG-binding protein.
-!- SUBUNIT: Interacts with MLH1.
-!- INTERACTION:
P67870:CSNK2B; NbExp=1; IntAct=EBI-348011, EBI-348169;
Q13158:FADD; NbExp=5; IntAct=EBI-348011, EBI-494804;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=O95243-1; Sequence=Displayed;
Name=2;
IsoId=O95243-2; Sequence=VSP_010816;
Note=No experimental confirmation available;
Name=3;
IsoId=O95243-3; Sequence=VSP_010817, VSP_010818;
Note=No experimental confirmation available;
-!- SIMILARITY: Contains 1 MBD (methyl-CpG-binding) domain.
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Sequence length: 580
MGTTGLESLS LGDRGAAPTV TSSERLVPDP PNDLRKEDVA MELERVGEDE EQMMIKRSSE
CNPLLQEPIA SAQFGATAGT ECRKSVPCGW ERVVKQRLFG KTAGRFDVYF ISPQGLKFRS
KSSLANYLHK NGETSLKPED FDFTVLSKRG IKSRYKDCSM AALTSHLQNQ SNNSNWNLRT
RSKCKKDVFM PPSSSSELQE SRGLSNFTST HLLLKEDEGV DDVNFRKVRK PKGKVTILKG
IPIKKTKKGC RKSCSGFVQS DSKRESVCNK ADAESEPVAQ KSQLDRTVCI SDAGACGETL
SVTSEENSLV KKKERSLSSG SNFCSEQKTS GIINKFCSAK DSEHNEKYED TFLESEEIGT
KVEVVERKEH LHTDILKRGS EMDNNCSPTR KDFTGEKIFQ EDTIPRTQIE RRKTSLYFSS
KYNKEALSPP RRKAFKKWTP PRSPFNLVQE TLFHDPWKLL IATIFLNRTS GKMAIPVLWK
FLEKYPSAEV ARTADWRDVS ELLKPLGLYD LRAKTIVKFS DEYLTKQWKY PIELHGIGKY
GNDSYRIFCV NEWKQVHPED HKLNKYHDWL WENHEKLSLS