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Protein

Histone-arginine methyltransferase CARM1

Gene

Carm1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, 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' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to 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. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. 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.1 Publication
Isoform 3 specifically affects pre-mRNA splicing. This activity is independent from methyltransferase activity.1 Publication

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.By similarity

Enzyme regulationi

Methylation of H3R17 (H3R17me) by CARM1 is stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23' (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17' (H3R17ci) by PADI4.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei160 – 1601S-adenosyl-L-methionine
Binding sitei169 – 1691S-adenosyl-L-methionine
Binding sitei193 – 1931S-adenosyl-L-methionine; via carbonyl oxygen
Binding sitei215 – 2151S-adenosyl-L-methionine
Binding sitei244 – 2441S-adenosyl-L-methionine
Binding sitei272 – 2721S-adenosyl-L-methionine

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

mRNA processing, mRNA splicing, Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

BRENDAi2.1.1.125. 5301.
ReactomeiR-RNO-3214858. RMTs methylate histone arginines.
R-RNO-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-arginine methyltransferase CARM1 (EC:2.1.1.319By similarity)
Alternative name(s):
Coactivator-associated arginine methyltransferase 1
Protein arginine N-methyltransferase 4
Gene namesi
Name:Carm1
Synonyms:Prmt4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi1305879. Carm1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB
  • nucleoplasm Source: Ensembl
  • nucleus Source: RGD
  • RNA polymerase II transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 651651Histone-arginine methyltransferase CARM1PRO_0000249250Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei217 – 2171PhosphoserineBy similarity
Modified residuei551 – 5511Dimethylated arginineBy similarity

Post-translational modificationi

Auto-methylated on Arg-551. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing (By similarity).By similarity
Phosphorylation at Ser-217 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity. Phosphorylation at Ser-217 is strongly increased during mitosis, and decreases rapidly to a very low, basal level after entry into the G1 phase of the cell cycle. Phosphorylation at Ser-217 may promote location in the cytosol (By similarity).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PRIDEiQ4AE70.

Expressioni

Tissue specificityi

Isoform 1 is expressed at low levels in brain, liver and testis. Isoform 2 is highly expressed in brain, liver, skeletal muscle and testis. Isoform 3 is highly expressed in spleen, liver and kidney. Isoform 4 is expressed in spleen, liver and kidney.1 Publication

Developmental stagei

Isoforms 2 and 3 are expressed in fetal brain.1 Publication

Gene expression databases

GenevisibleiQ4AE70. RN.

Interactioni

Subunit structurei

Homodimer (Probable). Interacts with NR1H4. 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, TRIM24, CREBBP and CTNNB1. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3. Interacts with RELA (By similarity). Interacts with SNRPC.By similarityCurated2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ4AE70. 1 interaction.

Structurei

Secondary structure

1
651
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi31 – 4212Combined sources
Beta strandi49 – 6315Combined sources
Beta strandi65 – 739Combined sources
Beta strandi79 – 868Combined sources
Beta strandi89 – 946Combined sources
Turni95 – 973Combined sources
Beta strandi98 – 1036Combined sources
Beta strandi106 – 1116Combined sources
Helixi115 – 12814Combined sources
Helixi143 – 15412Combined sources
Helixi157 – 1659Combined sources
Helixi167 – 17913Combined sources
Helixi180 – 1834Combined sources
Turni184 – 1863Combined sources
Beta strandi188 – 1936Combined sources
Beta strandi195 – 1973Combined sources
Helixi198 – 2058Combined sources
Beta strandi209 – 2157Combined sources
Helixi219 – 22911Combined sources
Turni233 – 2353Combined sources
Beta strandi236 – 2416Combined sources
Turni243 – 2453Combined sources
Beta strandi252 – 2576Combined sources
Helixi261 – 2644Combined sources
Turni265 – 2673Combined sources
Helixi269 – 2757Combined sources
Helixi276 – 2794Combined sources
Beta strandi280 – 2889Combined sources
Beta strandi290 – 2989Combined sources
Helixi301 – 31111Combined sources
Helixi312 – 3143Combined sources
Helixi325 – 3273Combined sources
Helixi328 – 3369Combined sources
Beta strandi340 – 3423Combined sources
Helixi346 – 3483Combined sources
Beta strandi354 – 3596Combined sources
Turni360 – 3623Combined sources
Helixi365 – 3684Combined sources
Beta strandi369 – 37810Combined sources
Beta strandi383 – 39715Combined sources
Beta strandi402 – 4065Combined sources
Beta strandi410 – 4123Combined sources
Beta strandi418 – 42912Combined sources
Beta strandi434 – 44411Combined sources
Turni445 – 4473Combined sources
Beta strandi448 – 45710Combined sources
Turni458 – 4603Combined sources
Beta strandi463 – 4697Combined sources
Beta strandi474 – 4774Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2OQBX-ray1.69A/B28-140[»]
3B3FX-ray2.20A/B/C/D140-480[»]
3B3GX-ray2.40A/B140-480[»]
3B3JX-ray2.55A28-507[»]
ProteinModelPortaliQ4AE70.
SMRiQ4AE70. Positions 28-131, 142-478.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ4AE70.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini147 – 454308SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni500 – 651152Transactivation domainBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.PROSITE-ProRule annotation
Contains 1 SAM-dependent MTase PRMT-type domain.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198522.
HOVERGENiHBG050797.
InParanoidiQ4AE70.
KOiK05931.
OMAiCNSVLLQ.
OrthoDBiEOG72NRPM.
PhylomeDBiQ4AE70.
TreeFamiTF323332.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR020989. Histone-Arg_MeTrfase_N.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR11006. PTHR11006. 1 hit.
PfamiPF11531. CARM1. 1 hit.
PF05185. PRMT5. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Named isoforms=2.

Isoform 1 (identifier: Q4AE70-1) [UniParc]FASTAAdd to basket

Also known as: CARM1-v2

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.

« Hide

        10         20         30         40         50
MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR
60 70 80 90 100
HAEQQALRLE VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI
110 120 130 140 150
ITLGCNSVLI QFATPHDFCS FYNILKTCRG HTLERSVFSE RTEESSAVQY
160 170 180 190 200
FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN HTDFKDKIVL DVGCGSGILS
210 220 230 240 250
FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP GKVEEVSLPE
260 270 280 290 300
QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD
310 320 330 340 350
EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM
360 370 380 390 400
AKSVKYTVNF LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI
410 420 430 440 450
MTVWLSTAPT EPLTHWYQVR CLFQSPLFAK AGDTLSGTCL LIANKRQSYD
460 470 480 490 500
ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT TPSPPPGSHY TSPSENMWNT
510 520 530 540 550
GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLA NTGIVNHTHS
560 570 580 590 600
RMGSIMSTGI VQGNRVAGPW AGDLPPGLRT RSSYQWGPGR LRGHAGSSVP
610 620 630 640 650
MTCPTGSSGA QGGGGSSSAH YAVNNQFTMG GPAISMASPM SIPTNTMHYG

S
Length:651
Mass (Da):70,341
Last modified:September 13, 2005 - v1
Checksum:i2C71ED2D8E1BE12F
GO
Isoform 2 (identifier: Q4AE70-2) [UniParc]FASTAAdd to basket

Also known as: CARM1-v1

The sequence of this isoform differs from the canonical sequence as follows:
     564-606: Missing.

Show »
Length:608
Mass (Da):65,854
Checksum:iC621F2AA9FBA2DA3
GO
Isoform 3 (identifier: Q4AE70-3) [UniParc]FASTAAdd to basket

Also known as: CARM1-v3

The sequence of this isoform differs from the canonical sequence as follows:
     540-643: ANTGIVNHTH...ISMASPMSIP → GECPLGSMACQGRTGICQWPAKPVLGSLPPLSLS
     644-651: Missing.

Show »
Length:573
Mass (Da):62,453
Checksum:i19E82DC42316B317
GO
Isoform 4 (identifier: Q4AE70-4) [UniParc]FASTAAdd to basket

Also known as: CARM1-v4

The sequence of this isoform differs from the canonical sequence as follows:
     540-605: Missing.

Show »
Length:585
Mass (Da):63,460
Checksum:iC419059E314B2D51
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei540 – 643104ANTGI…PMSIP → GECPLGSMACQGRTGICQWP AKPVLGSLPPLSLS in isoform 3. 1 PublicationVSP_020382Add
BLAST
Alternative sequencei540 – 60566Missing in isoform 4. 1 PublicationVSP_020383Add
BLAST
Alternative sequencei564 – 60643Missing in isoform 2. 1 PublicationVSP_020384Add
BLAST
Alternative sequencei644 – 6518Missing in isoform 3. 1 PublicationVSP_020385

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB201114 mRNA. Translation: BAE16333.1.
AB201115 mRNA. Translation: BAE16334.1.
AB201116 mRNA. Translation: BAE16335.1.
AB201117 mRNA. Translation: BAE16336.1.
RefSeqiNP_001025212.1. NM_001030041.3. [Q4AE70-2]
NP_001029260.1. NM_001034088.2. [Q4AE70-4]
UniGeneiRn.94869.

Genome annotation databases

EnsembliENSRNOT00000041577; ENSRNOP00000049428; ENSRNOG00000031129. [Q4AE70-4]
ENSRNOT00000048245; ENSRNOP00000042739; ENSRNOG00000031129. [Q4AE70-2]
GeneIDi363026.
KEGGirno:363026.
UCSCiRGD:1305879. rat. [Q4AE70-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB201114 mRNA. Translation: BAE16333.1.
AB201115 mRNA. Translation: BAE16334.1.
AB201116 mRNA. Translation: BAE16335.1.
AB201117 mRNA. Translation: BAE16336.1.
RefSeqiNP_001025212.1. NM_001030041.3. [Q4AE70-2]
NP_001029260.1. NM_001034088.2. [Q4AE70-4]
UniGeneiRn.94869.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2OQBX-ray1.69A/B28-140[»]
3B3FX-ray2.20A/B/C/D140-480[»]
3B3GX-ray2.40A/B140-480[»]
3B3JX-ray2.55A28-507[»]
ProteinModelPortaliQ4AE70.
SMRiQ4AE70. Positions 28-131, 142-478.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4AE70. 1 interaction.

Proteomic databases

PRIDEiQ4AE70.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000041577; ENSRNOP00000049428; ENSRNOG00000031129. [Q4AE70-4]
ENSRNOT00000048245; ENSRNOP00000042739; ENSRNOG00000031129. [Q4AE70-2]
GeneIDi363026.
KEGGirno:363026.
UCSCiRGD:1305879. rat. [Q4AE70-1]

Organism-specific databases

CTDi10498.
RGDi1305879. Carm1.

Phylogenomic databases

GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198522.
HOVERGENiHBG050797.
InParanoidiQ4AE70.
KOiK05931.
OMAiCNSVLLQ.
OrthoDBiEOG72NRPM.
PhylomeDBiQ4AE70.
TreeFamiTF323332.

Enzyme and pathway databases

BRENDAi2.1.1.125. 5301.
ReactomeiR-RNO-3214858. RMTs methylate histone arginines.
R-RNO-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).

Miscellaneous databases

EvolutionaryTraceiQ4AE70.
NextBioi682177.
PROiQ4AE70.

Gene expression databases

GenevisibleiQ4AE70. RN.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR020989. Histone-Arg_MeTrfase_N.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR11006. PTHR11006. 1 hit.
PfamiPF11531. CARM1. 1 hit.
PF05185. PRMT5. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA splicing in an isoform-specific manner."
    Ohkura N., Takahashi M., Yaguchi H., Nagamura Y., Tsukada T.
    J. Biol. Chem. 280:28927-28935(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION OF ISOFORM 3, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH SNRPC.
    Tissue: Fetal brain.
  2. Cited for: METHYLATION OF ELAV4, SUBCELLULAR LOCATION.
  3. "Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains."
    Troffer-Charlier N., Cura V., Hassenboehler P., Moras D., Cavarelli J.
    EMBO J. 26:4391-4401(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 28-507 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiCARM1_RAT
AccessioniPrimary (citable) accession number: Q4AE70
Secondary accession number(s): Q4AE68, Q4AE69, Q4AE71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 13, 2005
Last modified: May 11, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.