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Reviewed, UniProtKB/Swiss-Prot Q86X55 (CARM1_HUMAN)

Last modified November 25, 2008. Version 48. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Histone-arginine methyltransferase CARM1
    EC=2.1.1.125
    EC=2.1.1.-
Alternative name(s):
    Protein arginine N-methyltransferase 4
    Coactivator-associated arginine methyltransferase 1
Gene names
Name: CARM1
Synonyms: PRMT4
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length585 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' and activates transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.

Catalytic activity

S-adenosyl-L-methionine + histone-arginine = S-adenosyl-L-homocysteine + histone-N(omega)-methyl-arginine.

Subunit structure

Homodimer Probable. Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1. Part of a complex consisting of CARM1, EP300/P300 and NCOA2/GRIP1. Interacts with FLII, TP53, myogenic factor MEF2, EP300/P300, CREBBP and CTNNB1. Interacts with SNRPC By similarity. Interacts with NR1H4. Interacts with RELA. Interacts with HTLV-1 Tax-1.

Subcellular location

Nucleus. Cytoplasm.

Tissue specificity

Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia.

Miscellaneous

Methylation of H3-R17 by CARM1 is stimulated by preacetylation of H3-K18/H3-K23 by EP300 and blocked by citrullination of H3-R17 by PADI4 By similarity.

Sequence similarities

Belongs to the protein arginine N-methyltransferase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q86X55-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q86X55-2)

The sequence of this isoform differs from the canonical sequence as follows:
     369-412: RIEIPFKFHM...WLSTAPTEPL → SACLASPAAT...SGLTLLSSAP
     413-585: Missing.
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 585585Histone-arginine methyltransferase CARM1
PRO_0000212338

Regions

Region499 – 58587Transactivation domain By similarity

Sites

Binding site1591S-adenosyl-L-methionine By similarity
Binding site1681S-adenosyl-L-methionine By similarity
Binding site1921S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site2141S-adenosyl-L-methionine By similarity
Binding site2431S-adenosyl-L-methionine By similarity

Natural variations

Alternative sequence369 – 41244RIEIP…PTEPL → SACLASPAATALCLPGKSHS NSTCCIQGWSTAWLSGLTLL SSAP in isoform 2.
VSP_012506
Alternative sequence413 – 585173Missing in isoform 2.
VSP_012507

Experimental info

Sequence conflict1861K → Q in BU176535. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 4, 2005. Version 2.
Checksum: 15C6720FBEB864FE

FASTA58563,460
        10         20         30         40         50         60 
MAAAAAAVGP GAGGAGSAVP GGAGPCATVS VFPGARLLTI GDANGEIQRH AEQQALRLEV 

        70         80         90        100        110        120 
RAGPDSAGIA LYSHEDVCVF KCSVSRETEC SRVGKQSFII TLGCNSVLIQ FATPNDFCSF 

       130        140        150        160        170        180 
YNILKTCRGH TLERSVFSER TEESSAVQYF QFYGYLSQQQ NMMQDYVRTG TYQRAILQNH 

       190        200        210        220        230        240 
TDFKDKIVLD VGCGSGILSF FAAQAGARKI YAVEASTMAQ HAEVLVKSNN LTDRIVVIPG 

       250        260        270        280        290        300 
KVEEVSLPEQ VDIIISEPMG YMLFNERMLE SYLHAKKYLK PSGNMFPTIG DVHLAPFTDE 

       310        320        330        340        350        360 
QLYMEQFTKA NFWYQPSFHG VDLSALRGAA VDEYFRQPVV DTFDIRILMA KSVKYTVNFL 

       370        380        390        400        410        420 
EAKEGDLHRI EIPFKFHMLH SGLVHGLAFW FDVAFIGSIM TVWLSTAPTE PLTHWYQVRC 

       430        440        450        460        470        480 
LFQSPLFAKA GDTLSGTCLL IANKRQSYDI SIVAQVDQTG SKSSNLLDLK NPFFRYTGTT 

       490        500        510        520        530        540 
PSPPPGSHYT SPSENMWNTG STYNLSSGMA VAGMPTAYDL SSVIASGSSV GHNNLIPLGS 

       550        560        570        580 
SGAQGSGGGS TSAHYAVNSQ FTMGGPAISM ASPMSIPTNT MHYGS 

« Hide

Isoform 2 [UniParc].

Checksum: 372F014D93E0E97B
Show »

41244,803

References

« Hide 'large scale' references
[1]The MGC Project Team
Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-203 (ISOFORMS 1/2).
Tissue: Retinoblastoma.
[2]The German cDNA consortium
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 43-585 (ISOFORM 2).
Tissue: Amygdala.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 194-585 (ISOFORM 1).
Tissue: Skin.
[4]"Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase."
Li H., Park S., Kilburn B., Jelinek M.A., Henschen-Edman A., Aswad D.W., Stallcup M.R., Laird-Offringa I.A.
J. Biol. Chem. 277:44623-44630(2002) [PubMed: 12237300] [Abstract]
Cited for: METHYLATION OF ELAVL1.
[5]"Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status."
Hong H., Kao C., Jeng M.-H., Eble J.N., Koch M.O., Gardner T.A., Zhang S., Li L., Pan C.-X., Hu Z., MacLennan G.T., Cheng L.
Cancer 101:83-89(2004) [PubMed: 15221992] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[6]"Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1."
Ananthanarayanan M., Li S., Balasubramaniyan N., Suchy F.J., Walsh M.J.
J. Biol. Chem. 279:54348-54357(2004) [PubMed: 15471871] [Abstract]
Cited for: INTERACTION WITH NR1H4.
[7]"Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination."
Lee Y.-H., Coonrod S.A., Kraus W.L., Jelinek M.A., Stallcup M.R.
Proc. Natl. Acad. Sci. U.S.A. 102:3611-3616(2005) [PubMed: 15731352] [Abstract]
Cited for: METHYLATION OF EP300.
[8]"Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17."
Miao F., Li S., Chavez V., Lanting L., Natarajan R.
Mol. Endocrinol. 20:1562-1573(2006) [PubMed: 16497732] [Abstract]
Cited for: METHYLATION OF HISTONE H3, INTERACTION WITH RELA, FUNCTION.
[9]"Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax."
Jeong S.J., Lu H., Cho W.K., Park H.U., Pise-Masison C., Brady J.N.
J. Virol. 80:10036-10044(2006) [PubMed: 17005681] [Abstract]
Cited for: INTERACTION WITH HTLV-1 TAX-1.
+Additional computationally mapped references.

Cross-references

Sequence databases

BU176535 mRNA. No translation available.
AL833242 mRNA. No translation available.
BC046240 mRNA. Translation: AAH46240.1.
UniGeneHs.371416

3D structure databases

HSSPHSSP built from PDB template 1OR8 based on UniProtKB Q63009.
ModBaseSearch...

PTM databases

PhosphoSiteQ86X55.

Genome annotation databases

EnsemblENSG00000142453. Homo sapiens. [Contig view]

Organism-specific databases

H-InvDBHIX0014757.
HGNCHGNC:23393. CARM1.
MIM603934. gene.
PharmGKBPA134959553.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENQ86X55.

Gene expression databases

CleanExHS_CARM1.
GermOnlineENSG00000142453. Homo sapiens.

Family and domain databases

InterProIPR013216. Methyltransf_11.
[Graphical view]
PfamPF08241. Methyltransf_11. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

Entry information

Entry nameCARM1_HUMAN
AccessionPrimary (citable) accession number: Q86X55
Entry history
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 4, 2005
Last modified: November 25, 2008
This is version 48 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents