P23109 (AMPD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
AMP deaminase 1
EC=3.5.4.6

Alternative name(s):
AMP deaminase isoform M
Myoadenylate deaminase

Gene names

Name:

AMPD1

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	780 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	AMP deaminase plays a critical role in energy metabolism.
Catalytic activity	AMP + H2O = IMP + NH3.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Pathway	Purine metabolism; IMP biosynthesis via salvage pathway; IMP from AMP: step 1/1.
Subunit structure	Homotetramer.
Tissue specificity	Three isoforms are present in mammals: AMP deaminase 1 is the predominant form in skeletal muscle; AMP deaminase 2 predominates in smooth muscle, non-muscle tissue, embryonic muscle and undifferentiated myoblasts; AMP deaminase 3 is found in erythrocytes.
Involvement in disease	Adenosine monophosphate deaminase deficiency muscle type (AMPDDM) [MIM:102770]: A metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the adenosine and AMP deaminases family.
Caution	It is uncertain whether Met-1 or Met-34 is the initiator.
Sequence caution	The sequence AAA57281.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAG24258.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAF84038.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAG36918.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAI18828.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Nucleotide metabolism
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	IMP salvage Inferred from electronic annotation. Source: UniProtKB-UniPathway purine nucleobase metabolic process Traceable author statement. Source: Reactome purine-containing compound salvage Traceable author statement. Source: Reactome response to organic substance Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	AMP deaminase activity Traceable author statement PubMed 644316. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P23109-1)

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: P23109-2)

The sequence of this isoform differs from the canonical sequence as follows:
     41-45: AEEKQ → E

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 780	780	AMP deaminase 1		PRO_0000194403
Regions
	Region	407 – 412	6	Substrate binding By similarity
	Region	683 – 686	4	Substrate binding By similarity
Sites
	Active site	627	1	Proton acceptor By similarity
	Metal binding	336	1	Zinc; catalytic By similarity
	Metal binding	338	1	Zinc; catalytic By similarity
	Metal binding	605	1	Zinc; catalytic By similarity
	Metal binding	682	1	Zinc; catalytic By similarity
	Binding site	338	1	Substrate By similarity
	Binding site	608	1	Substrate By similarity
Natural variations
	Alternative sequence	41 – 45	5	AEEKQ → E in isoform 2.		VSP_042638
	Natural variant	55	1	E → K. Corresponds to variant rs2273268 [ dbSNP | Ensembl ].		VAR_048860
	Natural variant	81	1	P → L Polymorphism; activity comparable to wild-type. Ref.6		VAR_013270
	Natural variant	421	1	R → W in AMPDDM; loss of activity. Ref.7 Corresponds to variant rs35859650 [ dbSNP | Ensembl ].		VAR_013271
	Natural variant	458	1	R → H in AMPDDM; loss of activity. Ref.7		VAR_013272
	Natural variant	666	1	P → H in a colorectal cancer sample; somatic mutation. Ref.8		VAR_035801
Experimental info
	Sequence conflict	234	1	P → S in BAF84038. Ref.5
	Sequence conflict	306	1	V → A in BAF84038. Ref.5
	Sequence conflict	467	1	D → G in BAG36918. Ref.5
	Sequence conflict	475	1	W → R in BAF84038. Ref.5
	Sequence conflict	659	1	F → S in BAF84038. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 18, 2012. Version 2. Checksum: 2449E96D00312629	FASTA	780	90,219
	10 20 30 40 50 60 MNVRIFYSVS QSPHSLLSLL FYCAILESRI SATMPLFKLP AEEKQIDDAM RNFAEKVFAS 70 80 90 100 110 120 EVKDEGGRQE ISPFDVDEIC PISHHEMQAH IFHLETLSTS TEARRKKRFQ GRKTVNLSIP 130 140 150 160 170 180 LSETSSTKLS HIDEYISSSP TYQTVPDFQR VQITGDYASG VTVEDFEIVC KGLYRALCIR 190 200 210 220 230 240 EKYMQKSFQR FPKTPSKYLR NIDGEAWVAN ESFYPVFTPP VKKGEDPFRT DNLPENLGYH 250 260 270 280 290 300 LKMKDGVVYV YPNEAAVSKD EPKPLPYPNL DTFLDDMNFL LALIAQGPVK TYTHRRLKFL 310 320 330 340 350 360 SSKFQVHQML NEMDELKELK NNPHRDFYNC RKVDTHIHAA ACMNQKHLLR FIKKSYQIDA 370 380 390 400 410 420 DRVVYSTKEK NLTLKELFAK LKMHPYDLTV DSLDVHAGRQ TFQRFDKFND KYNPVGASEL 430 440 450 460 470 480 RDLYLKTDNY INGEYFATII KEVGADLVEA KYQHAEPRLS IYGRSPDEWS KLSSWFVCNR 490 500 510 520 530 540 IHCPNMTWMI QVPRIYDVFR SKNFLPHFGK MLENIFMPVF EATINPQADP ELSVFLKHIT 550 560 570 580 590 600 GFDSVDDESK HSGHMFSSKS PKPQEWTLEK NPSYTYYAYY MYANIMVLNS LRKERGMNTF 610 620 630 640 650 660 LFRPHCGEAG ALTHLMTAFM IADDISHGLN LKKSPVLQYL FFLAQIPIAM SPLSNNSLFL 670 680 690 700 710 720 EYAKNPFLDF LQKGLMISLS TDDPMQFHFT KEPLMEEYAI AAQVFKLSTC DMCEVARNSV 730 740 750 760 770 780 LQCGISHEEK VKFLGDNYLE EGPAGNDIRR TNVAQIRMAY RYETWCYELN LIAEGLKSTE
	Isoform 2 [UniParc]. Checksum: B831F57E1D7AA491	FASTA	776	89,763
	10 20 30 40 50 60 MNVRIFYSVS QSPHSLLSLL FYCAILESRI SATMPLFKLP EIDDAMRNFA EKVFASEVKD 70 80 90 100 110 120 EGGRQEISPF DVDEICPISH HEMQAHIFHL ETLSTSTEAR RKKRFQGRKT VNLSIPLSET 130 140 150 160 170 180 SSTKLSHIDE YISSSPTYQT VPDFQRVQIT GDYASGVTVE DFEIVCKGLY RALCIREKYM 190 200 210 220 230 240 QKSFQRFPKT PSKYLRNIDG EAWVANESFY PVFTPPVKKG EDPFRTDNLP ENLGYHLKMK 250 260 270 280 290 300 DGVVYVYPNE AAVSKDEPKP LPYPNLDTFL DDMNFLLALI AQGPVKTYTH RRLKFLSSKF 310 320 330 340 350 360 QVHQMLNEMD ELKELKNNPH RDFYNCRKVD THIHAAACMN QKHLLRFIKK SYQIDADRVV 370 380 390 400 410 420 YSTKEKNLTL KELFAKLKMH PYDLTVDSLD VHAGRQTFQR FDKFNDKYNP VGASELRDLY 430 440 450 460 470 480 LKTDNYINGE YFATIIKEVG ADLVEAKYQH AEPRLSIYGR SPDEWSKLSS WFVCNRIHCP 490 500 510 520 530 540 NMTWMIQVPR IYDVFRSKNF LPHFGKMLEN IFMPVFEATI NPQADPELSV FLKHITGFDS 550 560 570 580 590 600 VDDESKHSGH MFSSKSPKPQ EWTLEKNPSY TYYAYYMYAN IMVLNSLRKE RGMNTFLFRP 610 620 630 640 650 660 HCGEAGALTH LMTAFMIADD ISHGLNLKKS PVLQYLFFLA QIPIAMSPLS NNSLFLEYAK 670 680 690 700 710 720 NPFLDFLQKG LMISLSTDDP MQFHFTKEPL MEEYAIAAQV FKLSTCDMCE VARNSVLQCG 730 740 750 760 770 ISHEEKVKFL GDNYLEEGPA GNDIRRTNVA QIRMAYRYET WCYELNLIAE GLKSTE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the human and rat myoadenylate deaminase genes." Sabina R.L., Morisaki T., Clarke P., Eddy R., Shows T.B., Morton C.C., Holmes E.W. J. Biol. Chem. 265:9423-9433(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Molecular analysis of the myoadenylate deaminase deficiencies." Sabina R.L., Fishbein W.N., Pezeshkpour G., Clarke P.R., Holmes E.W. Neurology 42:170-179(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-780 (ISOFORM 1).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-780 (ISOFORM 1). Tissue: Pericardium and Tongue.
[6]	"Molecular basis of AMP deaminase deficiency in skeletal muscle." Morisaki T., Gross M., Morisaki H., Pongratz D., Zoellner N., Holmes E.W. Proc. Natl. Acad. Sci. U.S.A. 89:6457-6461(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-81.
[7]	"First missense mutations (R388W and R425H) of AMPD1 accompanied with myopathy found in a Japanese patient." Morisaki H., Higuchi I., Abe M., Osame M., Morisaki T. Hum. Mutat. 16:467-472(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AMPDDM TRP-421 AND HIS-458.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-666.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M37931 , M37920, M37921, M37922, M37923, M37924, M37927, M37928, M37929, M37930 Genomic DNA. Translation: AAG24258.1. Different initiation. AL096773 Genomic DNA. Translation: CAI18828.1. Different initiation. AL096773 Genomic DNA. Translation: CAI18830.1. CH471122 Genomic DNA. Translation: EAW56607.1. M60092 mRNA. Translation: AAA57281.1. Different initiation. AK314252 mRNA. Translation: BAG36918.1. Different initiation. AK291349 mRNA. Translation: BAF84038.1. Different initiation.
IPI	IPI00185631. IPI00980902.
PIR	I39444.
RefSeq	NP_000027.2. NM_000036.2. NP_001166097.1. NM_001172626.1.
UniGene	Hs.89570.
3D structure databases
ProteinModelPortal	P23109.
SMR	P23109. Positions 225-775.
ModBase	Search...
Protein-protein interaction databases
IntAct	P23109. 5 interactions.
STRING	9606.ENSP00000316520.
PTM databases
PhosphoSite	P23109.
Polymorphism databases
DMDM	113697.
Proteomic databases
PaxDb	P23109.
PRIDE	P23109.
Protocols and materials databases
DNASU	270.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000353928; ENSP00000316520; ENSG00000116748. ENST00000369538; ENSP00000358551; ENSG00000116748. ENST00000520113; ENSP00000430075; ENSG00000116748.
GeneID	270.
KEGG	hsa:270.
UCSC	uc001efe.2. human. uc001eff.2. human.
Organism-specific databases
CTD	270.
GeneCards	GC01M115215.
H-InvDB	HIX0199913.
HGNC	HGNC:468. AMPD1.
HPA	HPA026478. HPA028080.
MIM	102770. gene+phenotype.
neXtProt	NX_P23109.
Orphanet	45. Adenosine monophosphate deaminase deficiency.
PharmGKB	PA24776.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1816.
HOGENOM	HOG000092200.
HOVERGEN	HBG050494.
KO	K01490.
OMA	NMTWMIQ.
OrthoDB	EOG402WRH.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	P23109.
UniPathway	UPA00591; UER00663.
Gene expression databases
ArrayExpress	P23109.
Bgee	P23109.
CleanEx	HS_AMPD1.
Genevestigator	P23109.
GermOnline	ENSG00000116748. Homo sapiens.
Family and domain databases
InterPro	IPR006650. A/AMP_deam_AS. IPR001365. A/AMP_deaminase_dom. IPR006329. AMP_deaminase. [Graphical view]
PANTHER	PTHR11359. PTHR11359. 1 hit.
Pfam	PF00962. A_deaminase. 1 hit. [Graphical view]
PIRSF	PIRSF001251. AMP_deaminase_met. 1 hit.
TIGRFAMs	TIGR01429. AMP_deaminase. 1 hit.
PROSITE	PS00485. A_DEAMINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P23109.
ChEMBL	CHEMBL2869.
ChiTaRS	AMPD1. human.
DrugBank	DB00131. Adenosine monophosphate.
GenomeRNAi	270.
NextBio	1061.
SOURCE	Search...

Entry information

Entry name

AMPD1_HUMAN

Accession

Primary (citable) accession number: P23109
Secondary accession number(s): A8K5N4 , B2RAM1, F2Z3B3, Q5TF00, Q5TF02

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	April 18, 2012
Last modified:	May 29, 2013
This is version 122 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.