Q4AE70 (CARM1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-arginine methyltransferase CARM1
EC=2.1.1.-
EC=2.1.1.125

Alternative name(s):
Coactivator-associated arginine methyltransferase 1
Protein arginine N-methyltransferase 4

Gene names

Name:	Carm1
Synonyms:	Prmt4

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	651 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, 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. Ref.1 Isoform 3 specifically affects pre-mRNA splicing. This activity is independent from methyltransferase activity. Ref.1
Catalytic activity	S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone].
Enzyme regulation	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.
Subunit structure	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. Ref.1 Ref.3
Subcellular location	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. Ref.2
Tissue specificity	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. Ref.1
Developmental stage	Isoforms 2 and 3 are expressed in fetal brain. Ref.1
Post-translational modification	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. Ref.2 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.
Sequence similarities	Belongs to the protein arginine N-methyltransferase family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Transferase
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Inferred from electronic annotation. Source: InterPro positive regulation of cell proliferation Inferred from mutant phenotype Ref.2. Source: RGD positive regulation of fat cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of intracellular estrogen receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to cAMP Inferred from direct assay. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: RGD
Molecular function	histone acetyl-lysine binding Inferred from sequence or structural similarity. Source: UniProtKB histone methyltransferase activity (H3-R17 specific) Inferred from sequence or structural similarity. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB protein-arginine omega-N asymmetric methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Named isoforms=2.

Isoform 1 (identifier: Q4AE70-1)

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.

Isoform 2 (identifier: Q4AE70-2)

Also known as: CARM1-v1;

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

Isoform 3 (identifier: Q4AE70-3)

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.

Isoform 4 (identifier: Q4AE70-4)

Also known as: CARM1-v4;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 651

650

Histone-arginine methyltransferase CARM1

PRO_0000249250

Regions

Region

500 – 651

152

Transactivation domain By similarity

Sites

Binding site

160

1

S-adenosyl-L-methionine

Binding site

169

1

S-adenosyl-L-methionine

Binding site

193

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

215

1

S-adenosyl-L-methionine

Binding site

244

1

S-adenosyl-L-methionine

Binding site

272

1

S-adenosyl-L-methionine

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

217

1

Phosphoserine By similarity

Modified residue

551

1

Dimethylated arginine By similarity

Natural variations

Alternative sequence

540 – 643

104

ANTGI…PMSIP → GECPLGSMACQGRTGICQWP AKPVLGSLPPLSLS in isoform 3.

VSP_020382

Alternative sequence

540 – 605

66

Missing in isoform 4.

VSP_020383

Alternative sequence

564 – 606

43

Missing in isoform 2.

VSP_020384

Alternative sequence

644 – 651

8

Missing in isoform 3.

VSP_020385

Secondary structure

1

.

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651

Helix Strand Turn

Details...

Beta strand

31 – 33

3

Beta strand

37 – 41

5

Beta strand

52 – 54

3

Beta strand

58 – 61

4

Beta strand

70 – 73

4

Beta strand

79 – 86

8

Beta strand

89 – 94

6

Beta strand

98 – 102

5

Beta strand

107 – 111

5

Helix

115 – 128

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CARM1-v2) [UniParc]. Last modified September 13, 2005. Version 1. Checksum: 2C71ED2D8E1BE12F	FASTA	651	70,341
	10 20 30 40 50 60 MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR HAEQQALRLE 70 80 90 100 110 120 VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI ITLGCNSVLI QFATPHDFCS 130 140 150 160 170 180 FYNILKTCRG HTLERSVFSE RTEESSAVQY FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN 190 200 210 220 230 240 HTDFKDKIVL DVGCGSGILS FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP 250 260 270 280 290 300 GKVEEVSLPE QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD 310 320 330 340 350 360 EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM AKSVKYTVNF 370 380 390 400 410 420 LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI MTVWLSTAPT EPLTHWYQVR 430 440 450 460 470 480 CLFQSPLFAK AGDTLSGTCL LIANKRQSYD ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT 490 500 510 520 530 540 TPSPPPGSHY TSPSENMWNT GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLA 550 560 570 580 590 600 NTGIVNHTHS RMGSIMSTGI VQGNRVAGPW AGDLPPGLRT RSSYQWGPGR LRGHAGSSVP 610 620 630 640 650 MTCPTGSSGA QGGGGSSSAH YAVNNQFTMG GPAISMASPM SIPTNTMHYG S
	Isoform 2 (CARM1-v1) [UniParc]. Checksum: C621F2AA9FBA2DA3	FASTA	608	65,854
	10 20 30 40 50 60 MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR HAEQQALRLE 70 80 90 100 110 120 VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI ITLGCNSVLI QFATPHDFCS 130 140 150 160 170 180 FYNILKTCRG HTLERSVFSE RTEESSAVQY FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN 190 200 210 220 230 240 HTDFKDKIVL DVGCGSGILS FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP 250 260 270 280 290 300 GKVEEVSLPE QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD 310 320 330 340 350 360 EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM AKSVKYTVNF 370 380 390 400 410 420 LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI MTVWLSTAPT EPLTHWYQVR 430 440 450 460 470 480 CLFQSPLFAK AGDTLSGTCL LIANKRQSYD ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT 490 500 510 520 530 540 TPSPPPGSHY TSPSENMWNT GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLA 550 560 570 580 590 600 NTGIVNHTHS RMGSIMSTGI VQGSSGAQGG GGSSSAHYAV NNQFTMGGPA ISMASPMSIP TNTMHYGS
	Isoform 3 (CARM1-v3) [UniParc]. Checksum: 19E82DC42316B317	FASTA	573	62,453
	10 20 30 40 50 60 MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR HAEQQALRLE 70 80 90 100 110 120 VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI ITLGCNSVLI QFATPHDFCS 130 140 150 160 170 180 FYNILKTCRG HTLERSVFSE RTEESSAVQY FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN 190 200 210 220 230 240 HTDFKDKIVL DVGCGSGILS FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP 250 260 270 280 290 300 GKVEEVSLPE QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD 310 320 330 340 350 360 EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM AKSVKYTVNF 370 380 390 400 410 420 LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI MTVWLSTAPT EPLTHWYQVR 430 440 450 460 470 480 CLFQSPLFAK AGDTLSGTCL LIANKRQSYD ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT 490 500 510 520 530 540 TPSPPPGSHY TSPSENMWNT GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLG 550 560 570 ECPLGSMACQ GRTGICQWPA KPVLGSLPPL SLS
	Isoform 4 (CARM1-v4) [UniParc]. Checksum: C419059E314B2D51	FASTA	585	63,460
	10 20 30 40 50 60 MAAAAATAVG PGAGSAGVAG PGGAGPCATV SVFPGARLLT IGDANGEIQR HAEQQALRLE 70 80 90 100 110 120 VRAGPDAAGI ALYSHEDVCV FKCSVSRETE CSRVGRQSFI ITLGCNSVLI QFATPHDFCS 130 140 150 160 170 180 FYNILKTCRG HTLERSVFSE RTEESSAVQY FQFYGYLSQQ QNMMQDYVRT GTYQRAILQN 190 200 210 220 230 240 HTDFKDKIVL DVGCGSGILS FFAAQAGARK IYAVEASTMA QHAEVLVKSN NLTDRIVVIP 250 260 270 280 290 300 GKVEEVSLPE QVDIIISEPM GYMLFNERML ESYLHAKKYL KPSGNMFPTI GDVHLAPFTD 310 320 330 340 350 360 EQLYMEQFTK ANFWYQPSFH GVDLSALRGA AVDEYFRQPV VDTFDIRILM AKSVKYTVNF 370 380 390 400 410 420 LEAKEGDLHR IEIPFKFHML HSGLVHGLAF WFDVAFIGSI MTVWLSTAPT EPLTHWYQVR 430 440 450 460 470 480 CLFQSPLFAK AGDTLSGTCL LIANKRQSYD ISIVAQVDQT GSKSSNLLDL KNPFFRYTGT 490 500 510 520 530 540 TPSPPPGSHY TSPSENMWNT GSTYNLSSGV AVAGMPTAYD LSSVIAGGSS VGHNNLIPLG 550 560 570 580 SSGAQGGGGS SSAHYAVNNQ FTMGGPAISM ASPMSIPTNT MHYGS

References

[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: 15944154] [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]	"CARM1 regulates proliferation of PC12 cells by methylating HuD." Fujiwara T., Mori Y., Chu D.L., Koyama Y., Miyata S., Tanaka H., Yachi K., Kubo T., Yoshikawa H., Tohyama M. Mol. Cell. Biol. 26:2273-2285(2006) [PubMed: 16508003] [Abstract] 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: 17882262] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 28-507 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB201114 mRNA. Translation: BAE16333.1.
AB201115 mRNA. Translation: BAE16334.1.
AB201116 mRNA. Translation: BAE16335.1.
AB201117 mRNA. Translation: BAE16336.1.

IPI

IPI00366497.
IPI00568674.
IPI00650083.
IPI00655258.

RefSeq

NP_001025212.1. NM_001030041.3.
NP_001029260.1. NM_001034088.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OQB	X-ray	1.69	A/B	28-140	[»]
3B3F	X-ray	2.20	A/B/C/D	140-480	[»]
3B3G	X-ray	2.40	A/B	140-480	[»]
3B3J	X-ray	2.55	A	28-507	[»]

ProteinModelPortal

Q4AE70.

SMR

Q4AE70. Positions 28-131, 142-478.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q4AE70. 1 interaction.

STRING

Q4AE70.

Proteomic databases

PRIDE

Q4AE70.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000041577; ENSRNOP00000049428; ENSRNOG00000031129.
ENSRNOT00000048245; ENSRNOP00000042739; ENSRNOG00000031129.

GeneID

363026.

KEGG

rno:363026.

Organism-specific databases

CTD

10498.

RGD

1305879. Carm1.

Phylogenomic databases

eggNOG

roNOG12713.

GeneTree

ENSGT00550000074406.

HOVERGEN

HBG050797.

InParanoid

Q4AE70.

OMA

LTIGDAN.

OrthoDB

EOG4XKV6M.

PhylomeDB

Q4AE70.

Gene expression databases

ArrayExpress

Q4AE70.

Genevestigator

Q4AE70.

GermOnline

ENSRNOG00000031129. Rattus norvegicus.

Family and domain databases

InterPro

IPR020989. Histone-Arg_MeTrfase_N.
IPR007857. Skb1_MeTrfase.
[Graphical view]

KO

K05931.

Pfam

PF11531. CARM1. 1 hit.
PF05185. PRMT5. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

682177.

Entry information

Entry name

CARM1_RAT

Accession

Primary (citable) accession number: Q4AE70
Secondary accession number(s): Q4AE68, Q4AE69, Q4AE71

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	September 13, 2005
Last modified:	January 25, 2012
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program