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Protein

Histone-arginine methyltransferase CARM1

Gene

CARM1

Organism
Homo sapiens (Human)
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 activate 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.2 Publications

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.1 Publication

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 sitei159S-adenosyl-L-methionine1
Binding sitei168S-adenosyl-L-methionine1
Binding sitei192S-adenosyl-L-methionine; via carbonyl oxygen1
Binding sitei214S-adenosyl-L-methionine1
Binding sitei243S-adenosyl-L-methionine1
Binding sitei271S-adenosyl-L-methionine1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciZFISH:HS13925-MONOMER.
BRENDAi2.1.1.125. 2681.
ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
R-HSA-3214858. RMTs methylate histone arginines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).
R-HSA-400253. Circadian Clock.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
SIGNORiQ86X55.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-arginine methyltransferase CARM1 (EC:2.1.1.3191 Publication)
Alternative name(s):
Coactivator-associated arginine methyltransferase 1
Protein arginine N-methyltransferase 4
Gene namesi
Name:CARM1
Synonyms:PRMT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:23393. 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.

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi10498.
OpenTargetsiENSG00000142453.
PharmGKBiPA134959553.

Chemistry databases

ChEMBLiCHEMBL5406.
GuidetoPHARMACOLOGYi1255.

Polymorphism and mutation databases

BioMutaiCARM1.
DMDMi308153622.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002123382 – 608Histone-arginine methyltransferase CARM1Add BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei216Phosphoserine1 Publication1
Modified residuei550Dimethylated arginineBy similarity1

Post-translational modificationi

Auto-methylated on Arg-550. 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-216 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity (By similarity). Phosphorylation at Ser-216 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-216 may promote location in the cytosol.By similarity1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ86X55.
PaxDbiQ86X55.
PeptideAtlasiQ86X55.
PRIDEiQ86X55.

PTM databases

iPTMnetiQ86X55.
PhosphoSitePlusiQ86X55.

Expressioni

Tissue specificityi

Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia.1 Publication

Gene expression databases

BgeeiENSG00000142453.
CleanExiHS_CARM1.
ExpressionAtlasiQ86X55. baseline and differential.
GenevisibleiQ86X55. HS.

Organism-specific databases

HPAiCAB032961.
HPA043561.
HPA048073.

Interactioni

Subunit structurei

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, TRIM24, CREBBP and CTNNB1. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3. Interacts with SNRPC (By similarity). Interacts with NR1H4. Interacts with RELA. Interacts with HTLV-1 Tax-1.By similarityCurated4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CEBPBP176762EBI-2339854,EBI-969696
CEBPBQ058263EBI-2339854,EBI-7774198From a different organism.
DNAJA3Q96EY12EBI-2339854,EBI-356767
NCOA3Q9Y6Q912EBI-2339854,EBI-81196
NUDT21O438092EBI-2339854,EBI-355720
QKIQ96PU82EBI-2339854,EBI-945792
SMARCC1Q929224EBI-2339854,EBI-355653

GO - Molecular functioni

  • beta-catenin binding Source: AgBase
  • lysine-acetylated histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115760. 112 interactors.
DIPiDIP-44071N.
IntActiQ86X55. 29 interactors.
MINTiMINT-3379851.
STRINGi9606.ENSP00000325690.

Chemistry databases

BindingDBiQ86X55.

Structurei

Secondary structure

1608
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi136 – 140Combined sources5
Helixi143 – 153Combined sources11
Helixi156 – 164Combined sources9
Helixi166 – 178Combined sources13
Helixi180 – 182Combined sources3
Turni183 – 185Combined sources3
Beta strandi187 – 192Combined sources6
Helixi197 – 204Combined sources8
Beta strandi208 – 214Combined sources7
Helixi218 – 228Combined sources11
Turni232 – 234Combined sources3
Beta strandi235 – 240Combined sources6
Turni242 – 244Combined sources3
Beta strandi251 – 256Combined sources6
Turni264 – 266Combined sources3
Helixi268 – 274Combined sources7
Helixi275 – 278Combined sources4
Beta strandi279 – 287Combined sources9
Beta strandi289 – 297Combined sources9
Helixi300 – 310Combined sources11
Helixi311 – 314Combined sources4
Helixi324 – 326Combined sources3
Helixi327 – 335Combined sources9
Beta strandi339 – 341Combined sources3
Helixi345 – 347Combined sources3
Beta strandi353 – 358Combined sources6
Turni359 – 361Combined sources3
Helixi364 – 367Combined sources4
Beta strandi368 – 377Combined sources10
Beta strandi382 – 396Combined sources15
Beta strandi401 – 405Combined sources5
Beta strandi417 – 428Combined sources12
Beta strandi433 – 442Combined sources10
Beta strandi446 – 456Combined sources11
Turni457 – 459Combined sources3
Beta strandi462 – 468Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y1WX-ray2.10A/B/C/D135-482[»]
2Y1XX-ray2.40A/B/C/D135-482[»]
4IKPX-ray2.00A/B/C/D140-480[»]
5DWQX-ray2.36A/B/C/D134-479[»]
5DX0X-ray2.05A/B/C/D134-479[»]
5DX1X-ray1.93A/B/C/D134-479[»]
5DX8X-ray1.94A/B/C/D134-479[»]
5DXAX-ray2.07A/B/C/D134-479[»]
5DXJX-ray1.95A/B/C/D134-479[»]
ProteinModelPortaliQ86X55.
SMRiQ86X55.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini146 – 453SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST308

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni499 – 608Transactivation domainBy similarityAdd BLAST110

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.
InParanoidiQ86X55.
KOiK05931.
OMAiCNSVLLQ.
OrthoDBiEOG091G04X2.
PhylomeDBiQ86X55.
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 (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 3 (identifier: Q86X55-3) [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
MAAAAAAVGP GAGGAGSAVP GGAGPCATVS VFPGARLLTI GDANGEIQRH
60 70 80 90 100
AEQQALRLEV RAGPDSAGIA LYSHEDVCVF KCSVSRETEC SRVGKQSFII
110 120 130 140 150
TLGCNSVLIQ FATPNDFCSF YNILKTCRGH TLERSVFSER TEESSAVQYF
160 170 180 190 200
QFYGYLSQQQ NMMQDYVRTG TYQRAILQNH TDFKDKIVLD VGCGSGILSF
210 220 230 240 250
FAAQAGARKI YAVEASTMAQ HAEVLVKSNN LTDRIVVIPG KVEEVSLPEQ
260 270 280 290 300
VDIIISEPMG YMLFNERMLE SYLHAKKYLK PSGNMFPTIG DVHLAPFTDE
310 320 330 340 350
QLYMEQFTKA NFWYQPSFHG VDLSALRGAA VDEYFRQPVV DTFDIRILMA
360 370 380 390 400
KSVKYTVNFL EAKEGDLHRI EIPFKFHMLH SGLVHGLAFW FDVAFIGSIM
410 420 430 440 450
TVWLSTAPTE PLTHWYQVRC LFQSPLFAKA GDTLSGTCLL IANKRQSYDI
460 470 480 490 500
SIVAQVDQTG SKSSNLLDLK NPFFRYTGTT PSPPPGSHYT SPSENMWNTG
510 520 530 540 550
STYNLSSGMA VAGMPTAYDL SSVIASGSSV GHNNLIPLAN TGIVNHTHSR
560 570 580 590 600
MGSIMSTGIV QGSSGAQGSG GGSTSAHYAV NSQFTMGGPA ISMASPMSIP

TNTMHYGS
Length:608
Mass (Da):65,854
Last modified:October 5, 2010 - v3
Checksum:i094AC60D4A70B263
GO
Isoform 1 (identifier: Q86X55-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     539-561: Missing.

Show »
Length:585
Mass (Da):63,460
Checksum:i15C6720FBEB864FE
GO
Isoform 2 (identifier: Q86X55-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     369-384: RIEIPFKFHMLHSGLV → SACLASPAATALCLPG
     385-608: Missing.

Note: No experimental confirmation available.
Show »
Length:384
Mass (Da):41,885
Checksum:i722E8576DD6353D6
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012506369 – 384RIEIP…HSGLV → SACLASPAATALCLPG in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_012507385 – 608Missing in isoform 2. 1 PublicationAdd BLAST224
Alternative sequenceiVSP_039876539 – 561Missing in isoform 1. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC007565 Genomic DNA. No translation available.
AC011442 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84156.1.
BC046240 mRNA. Translation: AAH46240.1.
BC172490 mRNA. No translation available.
AL833242 mRNA. No translation available.
CCDSiCCDS12250.1. [Q86X55-3]
RefSeqiNP_954592.1. NM_199141.1. [Q86X55-3]
XP_005259765.1. XM_005259708.4. [Q86X55-1]
UniGeneiHs.323213.

Genome annotation databases

EnsembliENST00000327064; ENSP00000325690; ENSG00000142453. [Q86X55-3]
ENST00000344150; ENSP00000340934; ENSG00000142453. [Q86X55-1]
GeneIDi10498.
KEGGihsa:10498.
UCSCiuc002mpz.4. human. [Q86X55-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC007565 Genomic DNA. No translation available.
AC011442 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84156.1.
BC046240 mRNA. Translation: AAH46240.1.
BC172490 mRNA. No translation available.
AL833242 mRNA. No translation available.
CCDSiCCDS12250.1. [Q86X55-3]
RefSeqiNP_954592.1. NM_199141.1. [Q86X55-3]
XP_005259765.1. XM_005259708.4. [Q86X55-1]
UniGeneiHs.323213.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y1WX-ray2.10A/B/C/D135-482[»]
2Y1XX-ray2.40A/B/C/D135-482[»]
4IKPX-ray2.00A/B/C/D140-480[»]
5DWQX-ray2.36A/B/C/D134-479[»]
5DX0X-ray2.05A/B/C/D134-479[»]
5DX1X-ray1.93A/B/C/D134-479[»]
5DX8X-ray1.94A/B/C/D134-479[»]
5DXAX-ray2.07A/B/C/D134-479[»]
5DXJX-ray1.95A/B/C/D134-479[»]
ProteinModelPortaliQ86X55.
SMRiQ86X55.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115760. 112 interactors.
DIPiDIP-44071N.
IntActiQ86X55. 29 interactors.
MINTiMINT-3379851.
STRINGi9606.ENSP00000325690.

Chemistry databases

BindingDBiQ86X55.
ChEMBLiCHEMBL5406.
GuidetoPHARMACOLOGYi1255.

PTM databases

iPTMnetiQ86X55.
PhosphoSitePlusiQ86X55.

Polymorphism and mutation databases

BioMutaiCARM1.
DMDMi308153622.

Proteomic databases

EPDiQ86X55.
PaxDbiQ86X55.
PeptideAtlasiQ86X55.
PRIDEiQ86X55.

Protocols and materials databases

DNASUi10498.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327064; ENSP00000325690; ENSG00000142453. [Q86X55-3]
ENST00000344150; ENSP00000340934; ENSG00000142453. [Q86X55-1]
GeneIDi10498.
KEGGihsa:10498.
UCSCiuc002mpz.4. human. [Q86X55-3]

Organism-specific databases

CTDi10498.
DisGeNETi10498.
GeneCardsiCARM1.
H-InvDBHIX0014757.
HGNCiHGNC:23393. CARM1.
HPAiCAB032961.
HPA043561.
HPA048073.
MIMi603934. gene.
neXtProtiNX_Q86X55.
OpenTargetsiENSG00000142453.
PharmGKBiPA134959553.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1500. Eukaryota.
ENOG410XPDD. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198522.
HOVERGENiHBG050797.
InParanoidiQ86X55.
KOiK05931.
OMAiCNSVLLQ.
OrthoDBiEOG091G04X2.
PhylomeDBiQ86X55.
TreeFamiTF323332.

Enzyme and pathway databases

BioCyciZFISH:HS13925-MONOMER.
BRENDAi2.1.1.125. 2681.
ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
R-HSA-3214858. RMTs methylate histone arginines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-400206. Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).
R-HSA-400253. Circadian Clock.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
SIGNORiQ86X55.

Miscellaneous databases

ChiTaRSiCARM1. human.
GenomeRNAii10498.
PROiQ86X55.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142453.
CleanExiHS_CARM1.
ExpressionAtlasiQ86X55. baseline and differential.
GenevisibleiQ86X55. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q86X55
Secondary accession number(s): A6NN38
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: October 5, 2010
Last modified: November 30, 2016
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.