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Protein

Histone-arginine methyltransferase CARM1

Gene

Carm1

Organism
Mus musculus (Mouse)
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.17 Publications

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.5 Publications

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 PADI4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei160S-adenosyl-L-methionine1
Binding sitei169S-adenosyl-L-methionine1
Binding sitei193S-adenosyl-L-methionine; via carbonyl oxygen1
Binding sitei215S-adenosyl-L-methionine1
Binding sitei244S-adenosyl-L-methionine1
Binding sitei272S-adenosyl-L-methionine1

GO - Molecular functioni

  • histone-arginine N-methyltransferase activity Source: MGI
  • histone methyltransferase activity Source: UniProtKB
  • histone methyltransferase activity (H3-R17 specific) Source: UniProtKB
  • ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB
  • protein-arginine N-methyltransferase activity Source: UniProtKB
  • protein-arginine omega-N asymmetric methyltransferase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein methyltransferase activity Source: MGI
  • RNA polymerase II transcription coactivator activity Source: MGI
  • transcription coactivator activity Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • aging Source: Ensembl
  • endochondral bone morphogenesis Source: MGI
  • histone arginine methylation Source: UniProtKB
  • histone H3-R17 methylation Source: UniProtKB
  • histone H3-R2 methylation Source: MGI
  • histone methylation Source: MGI
  • intracellular estrogen receptor signaling pathway Source: MGI
  • intracellular steroid hormone receptor signaling pathway Source: HGNC
  • negative regulation of dendrite development Source: Ensembl
  • negative regulation of protein binding Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein localization to chromatin Source: MGI
  • protein methylation Source: MGI
  • regulation of growth plate cartilage chondrocyte proliferation Source: MGI
  • regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
  • regulation of mRNA binding Source: Ensembl
  • regulation of transcription, DNA-templated Source: MGI
  • response to cAMP Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-arginine methyltransferase CARM1 (EC:2.1.1.3195 Publications)
Alternative name(s):
Coactivator-associated arginine methyltransferase 1
Protein arginine N-methyltransferase 4
Gene namesi
Name:Carm1
Synonyms:Prmt4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1913208. Carm1.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Mainly nuclear during the G1, S and G2 phases of the cell cycle. Cytoplasmic during mitosis, after breakup of the nuclear membrane (By similarity).By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Neonatal lethality. The lungs of neonates do not inflate and they do not breathe. The same neonate lethality is observed with mutants that produce CARM1 protein without enzyme activity. Embryos are distinctly smaller at 18.5 dpc. They show reduced lipid accumulation in brown adipose tissue and reduced amounts of brown adipose tissue. Thymocyte differentiation is blocked at an early stage. Mutants display complete loss of protein methylation of the CARM1 substrates PABPC1 and EP300/P300.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi154Y → A, F or R: Loss of S-adenosyl-L-methionine binding. Loss of protein methyltransferase activity. 1 Publication1
Mutagenesisi169R → A: Loss of protein methyltransferase activity. 1 Publication1
Mutagenesisi173Y → A: Reduces protein methyltransferase activity. 1 Publication1
Mutagenesisi189 – 191VLD → AAA: Abolishes histone methyltransferase activity and coactivator activity. 2 Publications3
Mutagenesisi217S → A: Loss of S-adenosyl-L-methionine binding. Loss of protein methyltransferase activity. Localized in the nucleus. 1 Publication1
Mutagenesisi217S → C or T: Loss of S-adenosyl-L-methionine binding. Loss of protein methyltransferase activity. 1 Publication1
Mutagenesisi217S → E: Loss of S-adenosyl-L-methionine binding. Loss of protein methyltransferase activity. Localized in the cytosol. 1 Publication1
Mutagenesisi229S → E: Abolishes dimerization. 1 Publication1
Mutagenesisi267E → Q: Abolishes histone methyltransferase activity and reduces coactivator activity. 2 Publications1
Mutagenesisi551R → K: Abolishes dimethylation. Impairs transcription coactivator activity and regulation of alternative splicing. No effect on methyltransferase activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5538.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002123391 – 608Histone-arginine methyltransferase CARM1Add BLAST608

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei217PhosphoserineBy similarity1
Modified residuei551Dimethylated arginine1 Publication1

Post-translational modificationi

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 (By similarity). Phosphorylation at Ser-217 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity. Phosphorylation at Ser-217 may promote cytosolic location.By similarity1 Publication
Auto-methylated on Arg-551. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing.11 Publications

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ9WVG6.
PRIDEiQ9WVG6.

PTM databases

iPTMnetiQ9WVG6.
PhosphoSitePlusiQ9WVG6.

Expressioni

Tissue specificityi

Ubiquitously expressed. Within the brain, present in proliferating cells from lateral ventricular zone and dentate gyrus (at protein level).2 Publications

Developmental stagei

At E9, expression is prominent in the neural tube and somites.1 Publication

Gene expression databases

BgeeiENSMUSG00000032185.
ExpressionAtlasiQ9WVG6. baseline and differential.
GenevisibleiQ9WVG6. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with NR1H4. Interacts with SNRPC (By similarity). 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. Interacts with RELA. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3.By similarity12 Publications

GO - Molecular functioni

  • lysine-acetylated histone binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi208501. 7 interactors.
DIPiDIP-44593N.
IntActiQ9WVG6. 4 interactors.
MINTiMINT-6166798.
STRINGi10090.ENSMUSP00000034703.

Chemistry databases

BindingDBiQ9WVG6.

Structurei

Secondary structure

1608
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi148 – 153Combined sources6
Helixi157 – 164Combined sources8
Helixi167 – 179Combined sources13
Helixi180 – 183Combined sources4
Turni184 – 186Combined sources3
Beta strandi188 – 193Combined sources6
Helixi198 – 206Combined sources9
Beta strandi209 – 215Combined sources7
Helixi219 – 229Combined sources11
Turni233 – 235Combined sources3
Beta strandi236 – 241Combined sources6
Turni243 – 245Combined sources3
Beta strandi252 – 256Combined sources5
Helixi266 – 268Combined sources3
Helixi269 – 275Combined sources7
Helixi276 – 279Combined sources4
Beta strandi280 – 288Combined sources9
Beta strandi290 – 298Combined sources9
Helixi301 – 311Combined sources11
Helixi312 – 315Combined sources4
Beta strandi319 – 321Combined sources3
Helixi325 – 327Combined sources3
Helixi328 – 336Combined sources9
Beta strandi340 – 342Combined sources3
Helixi346 – 348Combined sources3
Beta strandi354 – 359Combined sources6
Turni360 – 362Combined sources3
Helixi365 – 369Combined sources5
Beta strandi370 – 378Combined sources9
Beta strandi383 – 395Combined sources13
Beta strandi404 – 406Combined sources3
Beta strandi418 – 429Combined sources12
Beta strandi434 – 442Combined sources9
Turni445 – 447Combined sources3
Beta strandi450 – 457Combined sources8
Turni458 – 461Combined sources4
Beta strandi462 – 469Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V74X-ray2.70B/D/F/H147-490[»]
2V7EX-ray2.70A/B147-490[»]
ProteinModelPortaliQ9WVG6.
SMRiQ9WVG6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9WVG6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini147 – 454SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST308

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni500 – 608Transactivation domainAdd BLAST109

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

eggNOGiKOG1500. Eukaryota.
ENOG410XPDD. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198522.
HOVERGENiHBG050797.
InParanoidiQ9WVG6.
KOiK05931.
PhylomeDBiQ9WVG6.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9WVG6-1) [UniParc]FASTAAdd to basket

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 VQGSSGAQGG GGSSSAHYAV NNQFTMGGPA ISMASPMSIP

TNTMHYGS
Length:608
Mass (Da):65,854
Last modified:September 13, 2004 - v2
Checksum:iC621F2AA9FBA2DA3
GO
Isoform 2 (identifier: Q9WVG6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     540-562: Missing.

Note: No experimental confirmation available.
Show »
Length:585
Mass (Da):63,460
Checksum:iC419059E314B2D51
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti400I → L in BAE34644 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012508540 – 562Missing in isoform 2. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF117887 mRNA. Translation: AAD41265.2.
BC003964 mRNA. Translation: AAH03964.1.
BC008263 mRNA. Translation: AAH08263.1.
BC036974 mRNA. Translation: AAH36974.1.
AK158757 mRNA. Translation: BAE34644.1.
CCDSiCCDS22906.1. [Q9WVG6-1]
CCDS52736.1. [Q9WVG6-2]
RefSeqiNP_067506.2. NM_021531.6. [Q9WVG6-1]
NP_694781.1. NM_153141.1. [Q9WVG6-2]
UniGeneiMm.178115.

Genome annotation databases

EnsembliENSMUST00000034703; ENSMUSP00000034703; ENSMUSG00000032185. [Q9WVG6-1]
ENSMUST00000115395; ENSMUSP00000111053; ENSMUSG00000032185. [Q9WVG6-2]
GeneIDi59035.
KEGGimmu:59035.
UCSCiuc009olu.2. mouse. [Q9WVG6-1]
uc009olw.2. mouse. [Q9WVG6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF117887 mRNA. Translation: AAD41265.2.
BC003964 mRNA. Translation: AAH03964.1.
BC008263 mRNA. Translation: AAH08263.1.
BC036974 mRNA. Translation: AAH36974.1.
AK158757 mRNA. Translation: BAE34644.1.
CCDSiCCDS22906.1. [Q9WVG6-1]
CCDS52736.1. [Q9WVG6-2]
RefSeqiNP_067506.2. NM_021531.6. [Q9WVG6-1]
NP_694781.1. NM_153141.1. [Q9WVG6-2]
UniGeneiMm.178115.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V74X-ray2.70B/D/F/H147-490[»]
2V7EX-ray2.70A/B147-490[»]
ProteinModelPortaliQ9WVG6.
SMRiQ9WVG6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208501. 7 interactors.
DIPiDIP-44593N.
IntActiQ9WVG6. 4 interactors.
MINTiMINT-6166798.
STRINGi10090.ENSMUSP00000034703.

Chemistry databases

BindingDBiQ9WVG6.
ChEMBLiCHEMBL5538.

PTM databases

iPTMnetiQ9WVG6.
PhosphoSitePlusiQ9WVG6.

Proteomic databases

PaxDbiQ9WVG6.
PRIDEiQ9WVG6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034703; ENSMUSP00000034703; ENSMUSG00000032185. [Q9WVG6-1]
ENSMUST00000115395; ENSMUSP00000111053; ENSMUSG00000032185. [Q9WVG6-2]
GeneIDi59035.
KEGGimmu:59035.
UCSCiuc009olu.2. mouse. [Q9WVG6-1]
uc009olw.2. mouse. [Q9WVG6-2]

Organism-specific databases

CTDi10498.
MGIiMGI:1913208. Carm1.

Phylogenomic databases

eggNOGiKOG1500. Eukaryota.
ENOG410XPDD. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198522.
HOVERGENiHBG050797.
InParanoidiQ9WVG6.
KOiK05931.
PhylomeDBiQ9WVG6.
TreeFamiTF323332.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiCarm1. mouse.
EvolutionaryTraceiQ9WVG6.
PROiQ9WVG6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032185.
ExpressionAtlasiQ9WVG6. baseline and differential.
GenevisibleiQ9WVG6. MM.

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...

Entry informationi

Entry nameiCARM1_MOUSE
AccessioniPrimary (citable) accession number: Q9WVG6
Secondary accession number(s): Q3TYB9
, Q8K1Y5, Q91W24, Q99KX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: September 13, 2004
Last modified: November 30, 2016
This is version 136 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.