Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)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

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)DescriptionActionsGraphical viewLength
ChainiPRO_00002492501 – 651Histone-arginine methyltransferase CARM1Add BLAST651

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei217PhosphoserineBy similarity1
Modified residuei551Dimethylated arginineBy similarity1

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.

PTM databases

PhosphoSitePlusiQ4AE70.

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

BgeeiENSRNOG00000031129.
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 interactor.

Structurei

Secondary structure

1651
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 42Combined sources12
Beta strandi49 – 63Combined sources15
Beta strandi65 – 73Combined sources9
Beta strandi79 – 86Combined sources8
Beta strandi89 – 94Combined sources6
Turni95 – 97Combined sources3
Beta strandi98 – 103Combined sources6
Beta strandi106 – 111Combined sources6
Helixi115 – 128Combined sources14
Helixi143 – 154Combined sources12
Helixi157 – 165Combined sources9
Helixi167 – 179Combined sources13
Helixi180 – 183Combined sources4
Turni184 – 186Combined sources3
Beta strandi188 – 193Combined sources6
Beta strandi195 – 197Combined sources3
Helixi198 – 205Combined sources8
Beta strandi209 – 215Combined sources7
Helixi219 – 229Combined sources11
Turni233 – 235Combined sources3
Beta strandi236 – 241Combined sources6
Turni243 – 245Combined sources3
Beta strandi252 – 257Combined sources6
Helixi261 – 264Combined sources4
Turni265 – 267Combined sources3
Helixi269 – 275Combined sources7
Helixi276 – 279Combined sources4
Beta strandi280 – 288Combined sources9
Beta strandi290 – 298Combined sources9
Helixi301 – 311Combined sources11
Helixi312 – 314Combined sources3
Helixi325 – 327Combined sources3
Helixi328 – 336Combined sources9
Beta strandi340 – 342Combined sources3
Helixi346 – 348Combined sources3
Beta strandi354 – 359Combined sources6
Turni360 – 362Combined sources3
Helixi365 – 368Combined sources4
Beta strandi369 – 378Combined sources10
Beta strandi383 – 397Combined sources15
Beta strandi402 – 406Combined sources5
Beta strandi410 – 412Combined sources3
Beta strandi418 – 429Combined sources12
Beta strandi434 – 444Combined sources11
Turni445 – 447Combined sources3
Beta strandi448 – 457Combined sources10
Turni458 – 460Combined sources3
Beta strandi463 – 469Combined sources7
Beta strandi474 – 477Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ4AE70.

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 – 651Transactivation domainBy similarityAdd BLAST152

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.
OrthoDBiEOG091G04X2.
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_020382540 – 643ANTGI…PMSIP → GECPLGSMACQGRTGICQWP AKPVLGSLPPLSLS in isoform 3. 1 PublicationAdd BLAST104
Alternative sequenceiVSP_020383540 – 605Missing in isoform 4. 1 PublicationAdd BLAST66
Alternative sequenceiVSP_020384564 – 606Missing in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_020385644 – 651Missing in isoform 3. 1 Publication8

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4AE70. 1 interactor.

PTM databases

PhosphoSitePlusiQ4AE70.

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.
OrthoDBiEOG091G04X2.
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.
PROiQ4AE70.

Gene expression databases

BgeeiENSRNOG00000031129.
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...

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: November 2, 2016
This is version 109 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.