Q13126 (MTAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
S-methyl-5'-thioadenosine phosphorylase
EC=2.4.2.28

Alternative name(s):
5'-methylthioadenosine phosphorylase
Short name=MTA phosphorylase
Short name=MTAP
Short name=MTAPase

Gene names

Name:	MTAP
Synonyms:	MSAP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	283 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	Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates. Ref.7
Catalytic activity	S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate.
Enzyme regulation	Inhibited by 5'-methylthiotubercin and 5'-chloroformycin.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; S-methyl-5-thio-alpha-D-ribose 1-phosphate from S-methyl-5'-thioadenosine (phosphorylase route): step 1/1.
Subunit structure	Homotrimer. Ref.7 Ref.8
Subcellular location	Cytoplasm. Nucleus By similarity.
Tissue specificity	Ubiquitously expressed.
Sequence similarities	Belongs to the PNP/MTAP phosphorylase family. MTAP subfamily.
Biophysicochemical properties	Kinetic parameters: KM=5 µM for S-methyl-5'-thioadenosine Ref.7 Ref.8 KM=580 µM for phosphate KM=23 µM for adenine KM=8 µM for S-methyl-5-thio-alpha-D-ribose 1-phosphate pH dependence: Optimum pH is 7.2-7.6.

Ontologies

Keywords
Biological process	Purine salvage
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-methionine salvage from methylthioadenosine Traceable author statement. Source: Reactome nucleoside metabolic process Inferred from electronic annotation. Source: InterPro polyamine metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	S-methyl-5-thioadenosine phosphorylase activity Traceable author statement. Source: Reactome phosphorylase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 283

282

S-methyl-5'-thioadenosine phosphorylase

PRO_0000184545

Regions

Region

60 – 61

2

Phosphate binding

Region

93 – 94

2

Phosphate binding

Region

220 – 222

3

Substrate binding

Sites

Binding site

18

1

Phosphate

Binding site

196

1

Substrate; via amide nitrogen

Binding site

197

1

Phosphate

Site

178

1

Important for substrate specificity

Site

233

1

Important for substrate specificity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.10

Modified residue

183

1

Phosphoserine Ref.9

Modified residue

188

1

Phosphothreonine Ref.9

Natural variations

Natural variant

56

1

V → I. Ref.1 Ref.3 Ref.6
Corresponds to variant rs7023954 [ dbSNP | Ensembl ].

VAR_031470

Experimental info

Sequence conflict

218

1

A → G in AAG38871. Ref.2

Sequence conflict

218

1

A → G in AAR24607. Ref.2

Secondary structure

1

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283

Helix Strand Turn

Details...

Beta strand

11 – 16

6

Helix

23 – 25

3

Beta strand

26 – 32

7

Beta strand

45 – 50

6

Beta strand

53 – 59

7

Turn

60 – 65

6

Helix

69 – 71

3

Helix

74 – 83

10

Beta strand

87 – 97

11

Beta strand

112 – 116

5

Beta strand

126 – 128

3

Beta strand

134 – 136

3

Beta strand

140 – 142

3

Helix

146 – 158

13

Beta strand

163 – 165

3

Beta strand

168 – 172

5

Helix

180 – 188

9

Beta strand

193 – 197

5

Helix

198 – 207

10

Beta strand

211 – 220

10

Helix

233 – 258

26

Helix

264 – 275

12

Sequences

	Sequence		Length	Mass (Da)
	Q13126 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 3B34C565EB5B99DA	FASTA	283	31,236
	10 20 30 40 50 60 MASGTTTTAV KIGIIGGTGL DDPEILEGRT EKYVDTPFGK PSDALILGKI KNVDCVLLAR 70 80 90 100 110 120 HGRQHTIMPS KVNYQANIWA LKEEGCTHVI VTTACGSLRE EIQPGDIVII DQFIDRTTMR 130 140 150 160 170 180 PQSFYDGSHS CARGVCHIPM AEPFCPKTRE VLIETAKKLG LRCHSKGTMV TIEGPRFSSR 190 200 210 220 230 240 AESFMFRTWG ADVINMTTVP EVVLAKEAGI CYASIAMATD YDCWKEHEEA VSVDRVLKTL 250 260 270 280 KENANKAKSL LLTTIPQIGS TEWSETLHNL KNMAQFSVLL PRH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21." Olopade O.I., Pomykala H.M., Hagos F., Sveen L.W., Espinosa R. III, Dreyling M.H., Gursky S., Stadler W.M., le Beau M.M., Bohlander S.K. Proc. Natl. Acad. Sci. U.S.A. 92:6489-6493(1995) [PubMed: 7604019] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-56. Tissue: Epidermis.
[2]	"Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers." Nobori T., Takabayashi K., Tran P., Orvis L., Batova A., Yu A.L., Carson D.A. Proc. Natl. Acad. Sci. U.S.A. 93:6203-6208(1996) [PubMed: 8650244] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Placenta.
[3]	"Identification of human methylthioadenosine phosphorylase (MTAP) mRNA mutation in colon cancer cell line COLO 205." Li Q., Cao W.-X., Zhang Y., Shi M.-M., Liu B.-Y., Zhu Z.-G., Lin Y.-Z. Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-56. Tissue: Colon.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-56. Tissue: Brain.
[7]	"Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta." Della Ragione F., Carteni-Farina M., Gragnaniello V., Schettino M.I., Zappia V. J. Biol. Chem. 261:12324-12329(1986) [PubMed: 3091600] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
[8]	"Purification and characterization of recombinant human 5'-methylthioadenosine phosphorylase: definite identification of coding cDNA." Ragione F.D., Takabayashi K., Mastropietro S., Mercurio C., Oliva A., Russo G.L., Pietra V.D., Borriello A., Nobori T., Carson D.A., Zappia V. Biochem. Biophys. Res. Commun. 223:514-519(1996) [PubMed: 8687427] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND THR-188, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7-A resolution provides insights into substrate binding and catalysis." Appleby T.C., Erion M.D., Ealick S.E. Structure 7:629-641(1999) [PubMed: 10404592] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH MTA.
[13]	"Structural comparison of MTA phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design." Lee J.E., Settembre E.C., Cornell K.A., Riscoe M.K., Sufrin J.R., Ealick S.E., Howell P.L. Biochemistry 43:5159-5169(2004) [PubMed: 15122881] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS.
[14]	"Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A." Singh V., Shi W., Evans G.B., Tyler P.C., Furneaux R.H., Almo S.C., Schramm V.L. Biochemistry 43:9-18(2004) [PubMed: 14705926] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
[15]	"The impact of human leukocyte antigen (HLA) micropolymorphism on ligand specificity within the HLA-B*41 allotypic family." Bade-Doeding C., Theodossis A., Gras S., Kjer-Nielsen L., Eiz-Vesper B., Seltsam A., Huyton T., Rossjohn J., McCluskey J., Blasczyk R. Haematologica 96:110-118(2011) [PubMed: 20934997] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 227-237.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U22233 mRNA. Translation: AAA81646.1.
L40432 mRNA. Translation: AAG38871.1.
L42634 , L42627, L42628, L42629, L42630, L42631, L42632, L42633 Genomic DNA. Translation: AAR24607.2.
AY712791 mRNA. Translation: AAU04442.1.
AL359922 Genomic DNA. Translation: CAI16481.1.
CH471071 Genomic DNA. Translation: EAW58606.1.
BC026106 mRNA. Translation: AAH26106.1.

IPI

IPI00011876.

PIR

I38969.

RefSeq

NP_002442.2. NM_002451.3.

UniGene

Hs.193268.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CB0	X-ray	1.70	A	1-283	[»]
1CG6	X-ray	1.70	A	1-283	[»]
1K27	X-ray	1.95	A	1-283	[»]
1SD1	X-ray	2.03	A	1-283	[»]
1SD2	X-ray	2.10	A	1-283	[»]
3LN5	X-ray	1.90	C	227-237	[»]
3OZC	X-ray	1.93	A	1-283	[»]
3OZD	X-ray	2.10	A/B	1-283	[»]
3OZE	X-ray	2.00	A/B/C/D/E/F	1-283	[»]

ProteinModelPortal

Q13126.

SMR

Q13126. Positions 9-281.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13126. 6 interactions.

MINT

MINT-268764.

STRING

Q13126.

PTM databases

PhosphoSite

Q13126.

Polymorphism databases

DMDM

143811423.

2D gel databases

REPRODUCTION-2DPAGE

Q13126.

UCD-2DPAGE

Q13126.

Proteomic databases

PRIDE

Q13126.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380172; ENSP00000369519; ENSG00000099810.

GeneID

4507.

KEGG

hsa:4507.

UCSC

uc003zph.1. human.

Organism-specific databases

CTD

4507.

GeneCards

GC09P021792.

H-InvDB

HIX0007954.
HIX0025895.

HGNC

HGNC:7413. MTAP.

MIM

156540. gene.

neXtProt

NX_Q13126.

PharmGKB

PA31220.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG002487.

InParanoid

Q13126.

OrthoDB

EOG4B8JDJ.

PhylomeDB

Q13126.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-1322.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q13126.

Bgee

Q13126.

CleanEx

HS_MTAP.

Genevestigator

Q13126.

GermOnline

ENSG00000099810. Homo sapiens.

Family and domain databases

InterPro

IPR010044. MeThioAdo_phosphorylase.
IPR000845. Nucleoside_phosphorylase_d.
IPR001369. Purine_phosphorylase-2.
IPR018099. Purine_phosphorylase-2_CS.
[Graphical view]

KO

K00772.

PANTHER

PTHR11904. Mtap_PNP. 1 hit.

Pfam

PF01048. PNP_UDP_1. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01694. MTAP. 1 hit.

PROSITE

PS01240. PNP_MTAP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13126.

DrugBank

DB00173. Adenine.

NextBio

17416.

SOURCE

Search...

Entry information

Entry name

MTAP_HUMAN

Accession

Primary (citable) accession number: Q13126
Secondary accession number(s): Q5T3P3, Q9H010

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 3, 2007
Last modified:	January 25, 2012
This is version 125 of the entry and version 2 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.