Q53H47 (SETMR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase SETMAR

Alternative name(s):
SET domain and mariner transposase fusion gene-containing protein
Short name=HsMar1
Short name=Metnase

Including the following 2 domains:

1. Histone-lysine N-methyltransferase
   EC=2.1.1.43
2. Mariner transposase Hsmar1
   EC=3.1.-.-

Gene names

Name:

SETMAR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	671 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3, 2 specific tags for epigenetic transcriptional activation. Specifically mediates dimethylation of H3 'Lys-36'. Has sequence-specific DNA-binding activity and recognizes the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element. Has DNA nicking activity. Has in vivo end joining activity and may mediate genomic integration of foreign DNA. Ref.1 Ref.5 Ref.7 Ref.8
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
Cofactor	Binds 1 magnesium ion per subunit.
Subcellular location	Nucleus Probable. Chromosome Probable.
Tissue specificity	Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle. Ref.1
Domain	The mariner transposase Hsmar1 region mediates DNA-binding. It has no transposase activity because the active site contains an Asn in position 610 instead of a Asp residue.
Miscellaneous	The mariner transposase region in only present in primates and appeared 40-58 million years ago, after the insertion of a transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously non-coding sequence and the creation of a new intron.
Sequence similarities	In the N-terminal section; belongs to the histone-lysine methyltransferase family. In the C-terminal section; belongs to the mariner transposase family. Contains 1 post-SET domain. Contains 1 pre-SET domain. Contains 1 SET domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosome Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Ligand	DNA-binding Magnesium Metal-binding
Molecular function	Chromatin regulator Endonuclease Hydrolase Methyltransferase Nuclease Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	DNA catabolic process, endonucleolytic Inferred from direct assay PubMed 20521842PubMed 21491884. Source: UniProtKB DNA double-strand break processing Inferred from direct assay PubMed 21491884. Source: UniProtKB DNA integration Inferred from electronic annotation. Source: InterPro negative regulation of cell cycle arrest Inferred from mutant phenotype PubMed 19390626. Source: UniProtKB negative regulation of chromosome organization Inferred from direct assay PubMed 20620605. Source: UniProtKB positive regulation of double-strand break repair via nonhomologous end joining Inferred from direct assay PubMed 20620605PubMed 21491884. Source: UniProtKB transposition, DNA-mediated Traceable author statement Ref.6. Source: UniProtKB
Cellular_component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred by curator PubMed 21491884. Source: UniProtKB
Molecular_function	endonuclease activity Inferred from direct assay PubMed 20620605PubMed 21491884. Source: UniProtKB histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC structure-specific DNA binding Inferred from direct assay PubMed 20521842. Source: UniProtKB transposase activity Traceable author statement PubMed 21491884Ref.6. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q53H47-1)

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: Q53H47-2)

The sequence of this isoform differs from the canonical sequence as follows:
     328-352: TMKMMLDKKQIRAIFLFEFKMGRKA → VSLFSDKQLAPPYSGRQWLASFTSA
     353-671: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 671

671

Histone-lysine N-methyltransferase SETMAR

PRO_0000259526

Regions

Domain

60 – 123

64

Pre-SET

Domain

125 – 254

130

SET

Domain

270 – 286

17

Post-SET

DNA binding

351 – 382

32

H-T-H motif By similarity

DNA binding

415 – 435

21

H-T-H motif Ref.5

Region

1 – 332

332

Histone-lysine N-methyltransferase

Region

333 – 671

339

Mariner transposase Hsmar1

Coiled coil

539 – 569

31

Potential

Sites

Metal binding

483

1

Magnesium

Metal binding

575

1

Magnesium

Amino acid modifications

Modified residue

495

1

Phosphoserine Ref.9 Ref.11 Ref.12

Natural variations

Alternative sequence

328 – 352

25

TMKMM…MGRKA → VSLFSDKQLAPPYSGRQWLA SFTSA in isoform 2.

VSP_021440

Alternative sequence

353 – 671

319

Missing in isoform 2.

VSP_021441

Experimental info

Mutagenesis

210

1

N → S: Reduces activity in double strand break repair. Ref.1

Mutagenesis

248

1

D → S: Reduces activity in double strand break repair. Ref.1

Mutagenesis

432

1

R → A: Abolishes TIR-specific DNA-binding. Ref.7

Mutagenesis

483

1

D → A: Abolishes DNA cleavage. Ref.7

Mutagenesis

490

1

D → S: Reduces activity in double strand break repair. Ref.1

Sequence conflict

330

1

K → E in AAC52010. Ref.6

Sequence conflict

426

1

N → D in AAC52010. Ref.6

Sequence conflict

452

1

T → S in AAC52010. Ref.6

Sequence conflict

471

1

H → N in AAC52010. Ref.6

Sequence conflict

495

1

S → P in AAC52010. Ref.6

Sequence conflict

501

1

Q → R in AAC52010. Ref.6

Sequence conflict

512

1

I → N in AAC52010. Ref.6

Sequence conflict

515

1

P → Q in AAC52010. Ref.6

Sequence conflict

522

1

I → V in AAC52010. Ref.6

Sequence conflict

549

1

E → Q in AAC52010. Ref.6

Sequence conflict

554 – 555

2

NQ → HR in AAC52010. Ref.6

Sequence conflict

562

1

L → P in AAC52010. Ref.6

Sequence conflict

607

1

L → S in AAC52010. Ref.6

Sequence conflict

610

1

N → D in AAC52010. Ref.6

Sequence conflict

613

1

V → F in AAC52010. Ref.6

Sequence conflict

618

1

N → D in AAC52010. Ref.6

Sequence conflict

643

1

Q → R in AAC52010. Ref.6

Sequence conflict

654

1

Q → K in AAC52010. Ref.6

Secondary structure

1

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671

Helix Strand Turn

Details...

Turn

17 – 20

4

Beta strand

22 – 24

3

Beta strand

27 – 30

4

Turn

71 – 73

3

Helix

75 – 77

3

Helix

120 – 122

3

Beta strand

128 – 132

5

Beta strand

134 – 144

11

Beta strand

151 – 154

4

Beta strand

157 – 160

4

Helix

162 – 169

8

Beta strand

181 – 185

5

Beta strand

193 – 203

11

Helix

205 – 208

4

Beta strand

216 – 228

13

Beta strand

230 – 237

8

Beta strand

244 – 247

4

Beta strand

257 – 266

10

Helix

453 – 472

20

Helix

476 – 478

3

Beta strand

479 – 490

12

Beta strand

517 – 525

9

Beta strand

528 – 534

7

Helix

543 – 560

18

Helix

561 – 563

3

Beta strand

571 – 573

3

Helix

578 – 581

4

Helix

585 – 592

8

Helix

604 – 606

3

Helix

608 – 611

4

Helix

613 – 621

9

Helix

629 – 641

13

Helix

647 – 653

7

Helix

655 – 664

10

Turn

665 – 667

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: A0349ADF2F12D920	FASTA	671	76,669
	10 20 30 40 50 60 MAEFKEKPEA PTEQLDVACG QENLPVGAWP PGAAPAPFQY TPDHVVGPGA DIDPTQITFP 70 80 90 100 110 120 GCICVKTPCL PGTCSCLRHG ENYDDNSCLR DIGSGGKYAE PVFECNVLCR CSDHCRNRVV 130 140 150 160 170 180 QKGLQFHFQV FKTHKKGWGL RTLEFIPKGR FVCEYAGEVL GFSEVQRRIH LQTKSDSNYI 190 200 210 220 230 240 IAIREHVYNG QVMETFVDPT YIGNIGRFLN HSCEPNLLMI PVRIDSMVPK LALFAAKDIV 250 260 270 280 290 300 PEEELSYDYS GRYLNLTVSE DKERLDHGKL RKPCYCGAKS CTAFLPFDSS LYCPVEKSNI 310 320 330 340 350 360 SCGNEKEPSM CGSAPSVFPS CKRLTLETMK MMLDKKQIRA IFLFEFKMGR KAAETTRNIN 370 380 390 400 410 420 NAFGPGTANE RTVQWWFKKF CKGDESLEDE ERSGRPSEVD NDQLRAIIEA DPLTTTREVA 430 440 450 460 470 480 EELNVNHSTV VRHLKQIGKV KKLDKWVPHE LTENQKNRRF EVSSSLILRN HNEPFLDRIV 490 500 510 520 530 540 TCDEKWILYD NRRRSAQWLD QEEAPKHFPK PILHPKKVMV TIWWSAAGLI HYSFLNPGET 550 560 570 580 590 600 ITSEKYAQEI DEMNQKLQRL QLALVNRKGP ILLHDNARPH VAQPTLQKLN ELGYEVLPHP 610 620 630 640 650 660 PYSPDLLPTN YHVFKHLNNF LQGKRFHNQQ DAENAFQEFV ESQSTDFYAT GINQLISRWQ 670 KCVDCNGSYF D
	Isoform 2 [UniParc]. Checksum: 053C81EE8219AE96	FASTA	352	39,146
	10 20 30 40 50 60 MAEFKEKPEA PTEQLDVACG QENLPVGAWP PGAAPAPFQY TPDHVVGPGA DIDPTQITFP 70 80 90 100 110 120 GCICVKTPCL PGTCSCLRHG ENYDDNSCLR DIGSGGKYAE PVFECNVLCR CSDHCRNRVV 130 140 150 160 170 180 QKGLQFHFQV FKTHKKGWGL RTLEFIPKGR FVCEYAGEVL GFSEVQRRIH LQTKSDSNYI 190 200 210 220 230 240 IAIREHVYNG QVMETFVDPT YIGNIGRFLN HSCEPNLLMI PVRIDSMVPK LALFAAKDIV 250 260 270 280 290 300 PEEELSYDYS GRYLNLTVSE DKERLDHGKL RKPCYCGAKS CTAFLPFDSS LYCPVEKSNI 310 320 330 340 350 SCGNEKEPSM CGSAPSVFPS CKRLTLEVSL FSDKQLAPPY SGRQWLASFT SA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair." Lee S.-H., Oshige M., Durant S.T., Rasila K.K., Williamson E.A., Ramsey H., Kwan L., Nickoloff J.A., Hromas R. Proc. Natl. Acad. Sci. U.S.A. 102:18075-18080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ASN-210; ASP-248 AND ASP-490.
[2]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Dermoid cancer.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Uterus.
[5]	"Birth of a chimeric primate gene by capture of the transposase gene from a mobile element." Cordaux R., Udit S., Batzer M.A., Feschotte C. Proc. Natl. Acad. Sci. U.S.A. 103:8101-8106(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 328-671, FUNCTION, DNA-BINDING.
[6]	"Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome." Robertson H.M., Zumpano K.L. Gene 205:203-217(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 329-671.
[7]	"Biochemical characterization of a SET and transposase fusion protein, Metnase: its DNA binding and DNA cleavage activity." Roman Y., Oshige M., Lee Y.J., Goodwin K., Georgiadis M.M., Hromas R.A., Lee S.H. Biochemistry 46:11369-11376(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA CLEAVAGE ACTIVITY, MUTAGENESIS OF ARG-432 AND ASP-483.
[8]	"The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends." Miskey C., Papp B., Mates L., Sinzelle L., Keller H., Izsvak Z., Ivics Z. Mol. Cell. Biol. 27:4589-4600(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, LACK OF TRANSPOSASE ACTIVITY.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, MASS SPECTROMETRY.
[13]	"The crystal structure of transposase domain of human histone-lysine N-methyltransferase SETMAR." Structural genomics consortium (SGC) Submitted (AUG-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 446-671 IN COMPLEX WITH MAGNESIUM IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY952295 mRNA. Translation: AAY29570.1.
AK222734 mRNA. Translation: BAD96454.1.
AC023483 Genomic DNA. No translation available.
AC034191 Genomic DNA. No translation available.
BC011635 mRNA. Translation: AAH11635.1.
DQ341316 Genomic DNA. Translation: ABC72087.1.
U52077 Genomic DNA. Translation: AAC52010.1.

IPI

IPI00171821.
IPI00879669.

RefSeq

NP_001230652.1. NM_001243723.1.
NP_006506.3. NM_006515.3.

UniGene

Hs.475300.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BO5	X-ray	1.59	A	2-290	[»]
3F2K	X-ray	1.85	A/B	446-671	[»]
3K9J	X-ray	1.90	A/B	433-671	[»]
3K9K	X-ray	2.55	A/B	433-671	[»]

ProteinModelPortal

Q53H47.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000373354.

PTM databases

PhosphoSite

Q53H47.

Polymorphism databases

DMDM

74740552.

Proteomic databases

PaxDb

Q53H47.

PRIDE

Q53H47.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358065; ENSP00000373354; ENSG00000170364.

GeneID

6419.

KEGG

hsa:6419.

UCSC

uc003bpw.4. human.
uc010hbx.3. human.

Organism-specific databases

CTD

6419.

GeneCards

GC03P004344.

HGNC

HGNC:10762. SETMAR.

MIM

609834. gene.

neXtProt

NX_Q53H47.

PharmGKB

PA35680.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2940.

HOGENOM

HOG000154295.

HOVERGEN

HBG093941.

InParanoid

Q53H47.

KO

K11433.

OrthoDB

EOG48D0TR.

PhylomeDB

Q53H47.

Gene expression databases

ArrayExpress

Q53H47.

Bgee

Q53H47.

CleanEx

HS_SETMAR.

Genevestigator

Q53H47.

GermOnline

ENSG00000170364. Homo sapiens.

Family and domain databases

InterPro

IPR003616. Post-SET_dom.
IPR007728. Pre-SET_dom.
IPR003606. Pre-SET_Zn-bd_sub.
IPR001214. SET_dom.
IPR001888. Transposase_1.
IPR002492. Transposase_Tc1-like.
[Graphical view]

Pfam

PF01498. HTH_Tnp_Tc3_2. 1 hit.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
PF01359. Transposase_1. 1 hit.
[Graphical view]

SMART

SM00508. PostSET. 1 hit.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]

PROSITE

PS50868. POST_SET. 1 hit.
PS50867. PRE_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q53H47.

GenomeRNAi

6419.

NextBio

24930.

SOURCE

Search...

Entry information

Entry name

SETMR_HUMAN

Accession

Primary (citable) accession number: Q53H47
Secondary accession number(s): Q13579, Q1G668, Q96F41

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	May 24, 2005
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.