P05102 (MTH1_HAEPH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Modification methylase HhaI
Short name=M.HhaI
EC=2.1.1.37

Alternative name(s):
Cytosine-specific methyltransferase HhaI

Gene names

Name:

hhaIM

Organism

Haemophilus parahaemolyticus

Taxonomic identifier

735 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Pasteurellales › Pasteurellaceae › Haemophilus

Protein attributes

Sequence length	327 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Subunit structure	Monomer.
Sequence similarities	Belongs to the C5-methyltransferase family.
Caution	Strain ATCC 10014 was originally thought to originate from H.haemolyticus.
Biophysicochemical properties	Kinetic parameters: KM=69 nM for DNA Ref.3 KM=15 nM for S-adenosyl-L-methionine (SAM) Vmax=87.0 nmol/min/mg enzyme

Ontologies

Keywords
Biological process	Restriction system
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	C-5 methylation of cytosine Inferred from electronic annotation. Source: GOC DNA restriction-modification system Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA (cytosine-5-)-methyltransferase activity Inferred from electronic annotation. Source: EC DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 327

327

Modification methylase HhaI

PRO_0000087882

Sites

Active site

81

1

Experimental info

Mutagenesis

237

1

Q → X: Decrease in enzyme activity due to 98%-99% loss of DNA-binding activity. No change in substrate specificity. Ref.3

Secondary structure

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327

Helix Strand Turn

Details...

Turn

8 – 11

4

Beta strand

13 – 17

5

Turn

20 – 22

3

Helix

23 – 30

8

Beta strand

34 – 39

6

Helix

43 – 53

11

Helix

61 – 63

3

Helix

66 – 68

3

Beta strand

73 – 78

6

Turn

82 – 84

3

Turn

86 – 89

4

Helix

92 – 94

3

Helix

96 – 98

3

Helix

100 – 111

12

Beta strand

114 – 121

8

Helix

122 – 125

4

Helix

127 – 130

4

Helix

131 – 142

12

Beta strand

148 – 153

6

Helix

154 – 157

4

Beta strand

164 – 172

9

Helix

173 – 175

3

Helix

192 – 194

3

Helix

199 – 201

3

Helix

203 – 205

3

Beta strand

213 – 216

4

Beta strand

228 – 232

5

Beta strand

240 – 243

4

Beta strand

244 – 246

3

Turn

258 – 262

5

Beta strand

264 – 267

4

Beta strand

270 – 273

4

Helix

276 – 282

7

Helix

295 – 304

10

Helix

308 – 323

16

Sequences

	Sequence		Length	Mass (Da)
	P05102 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: EF8A297E1DF819EB	FASTA	327	36,996
	10 20 30 40 50 60 MIEIKDKQLT GLRFIDLFAG LGGFRLALES CGAECVYSNE WDKYAQEVYE MNFGEKPEGD 70 80 90 100 110 120 ITQVNEKTIP DHDILCAGFP CQAFSISGKQ KGFEDSRGTL FFDIARIVRE KKPKVVFMEN 130 140 150 160 170 180 VKNFASHDNG NTLEVVKNTM NELDYSFHAK VLNALDYGIP QKRERIYMIC FRNDLNIQNF 190 200 210 220 230 240 QFPKPFELNT FVKDLLLPDS EVEHLVIDRK DLVMTNQEIE QTTPKTVRLG IVGKGGQGER 250 260 270 280 290 300 IYSTRGIAIT LSAYGGGIFA KTGGYLVNGK TRKLHPRECA RVMGYPDSYK VHPSTSQAYK 310 320 QFGNSVVINV LQYIAYNIGS SLNFKPY

References

[1]	"Cloning, sequencing, in vivo promoter mapping, and expression in Escherichia coli of the gene for the HhaI methyltransferase." Caserta M., Zacharias W., Nwankwo D.O., Wilson G.G., Wells R.D. J. Biol. Chem. 262:4770-4777(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 10014 / CCUG 3716 / NCTC 8479.
[2]	"The DNA binding affinity of HhaI methylase is increased by a single amino acid substitution in the catalytic center." Mi S., Roberts R.J. Nucleic Acids Res. 21:2459-2464(1993) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[3]	"Functional analysis of Gln-237 mutants of HhaI methyltransferase." Mi S., Alonso D., Roberts R.J. Nucleic Acids Res. 23:620-627(1995) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLN-237.
[4]	"Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine." Cheng X., Kumar S., Posfai J., Pflugrath J.W., Roberts R.J. Cell 74:299-307(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[5]	"HhaI methyltransferase flips its target base out of the DNA helix." Klimasauskas S., Kumar S., Roberts R.J., Cheng X. Cell 76:357-369(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[6]	"DNA containing 4'-thio-2'-deoxycytidine inhibits methylation by HhaI methyltransferase." Kumar S., Horton J.R., Jones G.D., Walker R.T., Roberts R.J., Cheng X. Nucleic Acids Res. 25:2773-2783(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
[7]	"Structures of HhaI methyltransferase complexed with substrates containing mismatches at the target base." O'Gara M., Horton J.R., Roberts R.J., Cheng X. Nat. Struct. Biol. 5:872-877(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS).
[8]	"Structure of a binary complex of HhaI methyltransferase with S-adenosyl-L-methionine formed in the presence of a short non-specific DNA oligonucleotide." O'Gara M., Zhang X., Roberts R.J., Cheng X. J. Mol. Biol. 287:201-209(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02677 Genomic DNA. Translation: AAA24989.1.

PIR

XYHIH1. A26260.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
10MH	X-ray	2.55	A	1-327	[»]
1FJX	X-ray	2.26	A	1-327	[»]
1HMY	X-ray	2.50	A	1-327	[»]
1M0E	X-ray	2.50	A	1-327	[»]
1MHT	X-ray	2.60	A	1-327	[»]
1SKM	X-ray	2.20	A	1-327	[»]
1SVU	X-ray	2.66	A/B	1-327	[»]
2C7O	X-ray	1.90	A	1-327	[»]
2C7P	X-ray	1.70	A	1-327	[»]
2C7Q	X-ray	1.85	A	1-327	[»]
2C7R	X-ray	1.90	A	1-327	[»]
2HMY	X-ray	2.61	B	1-327	[»]
2HR1	X-ray	1.96	A	1-327	[»]
2I9K	X-ray	2.65	A	1-327	[»]
2UYC	X-ray	2.00	A	1-327	[»]
2UYH	X-ray	2.63	A	1-327	[»]
2UZ4	X-ray	2.10	A	1-327	[»]
2Z6A	X-ray	2.88	A	1-327	[»]
2Z6Q	X-ray	2.79	A	1-327	[»]
2Z6U	X-ray	2.72	A	1-327	[»]
2ZCJ	X-ray	2.75	A	1-327	[»]
3EEO	X-ray	1.94	A	1-327	[»]
3MHT	X-ray	2.70	A	1-327	[»]
4MHT	X-ray	2.70	A	1-327	[»]
5MHT	X-ray	2.70	A	1-327	[»]
6MHT	X-ray	2.05	A	1-327	[»]
7MHT	X-ray	2.87	A	1-327	[»]
8MHT	X-ray	2.76	A	1-327	[»]
9MHT	X-ray	2.39	A	1-327	[»]

ProteinModelPortal

P05102.

SMR

P05102. Positions 1-327.

ModBase

Search...

Protein family/group databases

REBASE

3421. M.HhaI.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
[Graphical view]

PANTHER

PTHR10629. PTHR10629. 1 hit.

Pfam

PF00145. DNA_methylase. 1 hit.
[Graphical view]

PRINTS

PR00105. C5METTRFRASE.

TIGRFAMs

TIGR00675. dcm. 1 hit.

PROSITE

PS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05102.

Entry information

Entry name

MTH1_HAEPH

Accession

Primary (citable) accession number: P05102

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	April 3, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program