P27144 (KAD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GTP:AMP phosphotransferase AK4, mitochondrial
EC=2.7.4.10

Alternative name(s):
Adenylate kinase 3-like
Adenylate kinase isoenzyme 4
Short name=AK 4

Gene names

Name:	AK4
Synonyms:	AK3, AK3L1

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

General annotation (Comments)

Function	Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Ref.8 Ref.11
Catalytic activity	NTP + AMP = NDP + ADP. Ref.8
Subunit structure	Monomer.
Subcellular location	Mitochondrion matrix Ref.7 Ref.8.
Tissue specificity	Highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain. Ref.7
Domain	Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis. HAMAP-Rule MF_03170
Sequence similarities	Belongs to the adenylate kinase family. AK3 subfamily.
Biophysicochemical properties	Kinetic parameters: KM=5.3 µM for AMP with ATP as phosphate donor Ref.8 KM=1.4 µM for AMP with GTP as phosphate donor KM=507 µM for dAMP with ATP as phosphate donor Vmax=90 pmol/min/µg enzyme with AMP as substrate and ATP as phosphate donor Vmax=80 pmol/min/µg enzyme with AMP as substrate and GTP as phosphate donor Vmax=88 pmol/min/µg enzyme with dAMP as substrate and ATP as phosphate donor

Ontologies

Keywords
Cellular component	Mitochondrion
Ligand	ATP-binding GTP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	AMP metabolic process Inferred from direct assay Ref.8. Source: BHF-UCL ATP metabolic process Inferred from direct assay Ref.8. Source: BHF-UCL GTP metabolic process Inferred from direct assay Ref.8. Source: BHF-UCL brain development Inferred from electronic annotation. Source: Compara carbon tetrachloride metabolic process Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara tetracycline metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial matrix Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate kinase activity Inferred from direct assay Ref.8. Source: BHF-UCL nucleoside triphosphate adenylate kinase activity Inferred from direct assay Ref.8. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 223

223

GTP:AMP phosphotransferase AK4, mitochondrial HAMAP-Rule MF_03170

PRO_0000158926

Regions

Nucleotide binding

15 – 20

6

NTP HAMAP-Rule MF_03170

Nucleotide binding

62 – 64

3

AMP HAMAP-Rule MF_03170

Nucleotide binding

89 – 92

4

AMP HAMAP-Rule MF_03170

Nucleotide binding

135 – 136

2

NTP By similarity

Region

35 – 64

30

NMPbind HAMAP-Rule MF_03170

Region

125 – 162

38

LID HAMAP-Rule MF_03170

Sites

Binding site

36

1

AMP

Binding site

41

1

AMP By similarity

Binding site

96

1

AMP By similarity

Binding site

126

1

NTP

Binding site

170

1

AMP

Binding site

199

1

NTP; via carbonyl oxygen

Experimental info

Mutagenesis

4

1

K → G: Abolishes mitochondrial import; when associated with G-7. Ref.8

Mutagenesis

7

1

R → G: Abolishes mitochondrial import; when associated with G-4. Ref.8

Sequence conflict

22

1

C → S in AAH40224. Ref.6

Sequence conflict

22

1

C → S in AAI46654. Ref.6

Sequence conflict

23

1

Q → R in AAH66944. Ref.6

Secondary structure

1

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223

Helix Strand Turn

Details...

Beta strand

7 – 11

5

Helix

18 – 29

12

Beta strand

32 – 34

3

Helix

36 – 45

10

Helix

49 – 59

11

Helix

66 – 78

13

Turn

79 – 82

4

Beta strand

85 – 89

5

Helix

94 – 101

8

Beta strand

108 – 113

6

Helix

116 – 124

9

Beta strand

126 – 129

4

Turn

130 – 133

4

Beta strand

134 – 137

4

Turn

138 – 140

3

Turn

150 – 152

3

Helix

160 – 162

3

Helix

164 – 187

24

Beta strand

191 – 195

5

Helix

199 – 211

13

Helix

217 – 219

3

Helix

220 – 222

3

Sequences

	Sequence		Length	Mass (Da)
	P27144 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 653341A8EB3BC723	FASTA	223	25,268
	10 20 30 40 50 60 MASKLLRAVI LGPPGSGKGT VCQRIAQNFG LQHLSSGHFL RENIKASTEV GEMAKQYIEK 70 80 90 100 110 120 SLLVPDHVIT RLMMSELENR RGQHWLLDGF PRTLGQAEAL DKICEVDLVI SLNIPFETLK 130 140 150 160 170 180 DRLSRRWIHP PSGRVYNLDF NPPHVHGIDD VTGEPLVQQE DDKPEAVAAR LRQYKDVAKP 190 200 210 220 VIELYKSRGV LHQFSGTETN KIWPYVYTLF SNKITPIQSK EAY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene." Xu G., O'Connell P., Stevens J., White R. Genomics 13:537-542(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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]. Tissue: Testis.
[4]	"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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Colon and Lung.
[7]	"Structure and expression of human mitochondrial adenylate kinase targeted to the mitochondrial matrix." Noma T., Fujisawa K., Yamashiro Y., Shinohara M., Nakazawa A., Gondo T., Ishihara T., Yoshinobu K. Biochem. J. 358:225-232(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]	"Evidence of an intact N-terminal translocation sequence of human mitochondrial adenylate kinase 4." Panayiotou C., Solaroli N., Johansson M., Karlsson A. Int. J. Biochem. Cell Biol. 42:62-69(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-4 AND ARG-7.
[9]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Crystal structure of human adenylate kinase 4 (AK4) in complex with diguanosine pentaphosphate." Structural genomics consortium (SGC) Submitted (DEC-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) IN COMPLEX WITH DIGUANOSINE PENTAPHOSPHATE.
[11]	"Crystal structure of human adenylate kinase 4 (L171P) suggests the role of hinge region in protein domain motion." Liu R., Xu H., Wei Z., Wang Y., Lin Y., Gong W. Biochem. Biophys. Res. Commun. 379:92-97(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X60673 mRNA. Translation: CAA43088.1.
CR456830 mRNA. Translation: CAG33111.1.
AK313611 mRNA. Translation: BAG36374.1.
AL356212, AC099680 Genomic DNA. Translation: CAI22412.1.
CH471059 Genomic DNA. Translation: EAX06538.1.
CH471059 Genomic DNA. Translation: EAX06540.1.
CH471059 Genomic DNA. Translation: EAX06544.1.
BC016180 mRNA. Translation: AAH16180.1.
BC040224 mRNA. Translation: AAH40224.1.
BC066944 mRNA. Translation: AAH66944.1.
BC136886 mRNA. Translation: AAI36887.1.
BC136887 mRNA. Translation: AAI36888.1.
BC148270 mRNA. Translation: AAI48271.1.
BC146653 mRNA. Translation: AAI46654.1.

IPI

IPI00016568.

PIR

KIHUA3. A42820.

RefSeq

NP_001005353.1. NM_001005353.2.
NP_037542.1. NM_013410.3.
NP_982289.1. NM_203464.2.
XP_003119578.1. XM_003119530.1.

UniGene

Hs.10862.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AR7	X-ray	2.15	A/B	1-223	[»]
2BBW	X-ray	2.05	A/B	1-223	[»]
3NDP	X-ray	2.30	A/B	1-223	[»]

ProteinModelPortal

P27144.

ModBase

Search...

Protein-protein interaction databases

IntAct

P27144. 2 interactions.

PTM databases

PhosphoSite

P27144.

Polymorphism databases

DMDM

125157.

2D gel databases

UCD-2DPAGE

P27144.

Proteomic databases

PaxDb

P27144.

PRIDE

P27144.

Protocols and materials databases

DNASU

205.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327299; ENSP00000322175; ENSG00000162433.
ENST00000395334; ENSP00000378743; ENSG00000162433.
ENST00000545314; ENSP00000445912; ENSG00000162433.

GeneID

100507855.
205.

KEGG

hsa:100507855.
hsa:205.

UCSC

uc001dby.3. human.

Organism-specific databases

CTD

205.

GeneCards

GC01P065614.

HGNC

HGNC:363. AK4.

HPA

HPA042753.
HPA049461.

MIM

103030. gene.

neXtProt

NX_P27144.

PharmGKB

PA165750325.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0563.

HOGENOM

HOG000238772.

HOVERGEN

HBG000458.

InParanoid

P27144.

KO

K00939.

OMA

VMMVKDR.

OrthoDB

EOG4XPQGR.

PhylomeDB

P27144.

Gene expression databases

ArrayExpress

P27144.

Bgee

P27144.

CleanEx

HS_AK3.
HS_AK3L1.

Genevestigator

P27144.

GermOnline

ENSG00000162433. Homo sapiens.

Family and domain databases

HAMAP

MF_00235. Adenylate_kinase_Adk.
MF_03169. Adenylate_kinase_AK3.
MF_03170. Adenylate_kinase_AK4.

InterPro

IPR006259. Adenyl_kin_sub.
IPR000850. Adenylate_kin.
IPR007862. Adenylate_kinase_lid-dom.
[Graphical view]

PANTHER

PTHR23359. PTHR23359. 1 hit.

Pfam

PF00406. ADK. 1 hit.
PF05191. ADK_lid. 1 hit.
[Graphical view]

PRINTS

PR00094. ADENYLTKNASE.

SUPFAM

SSF57774. Adenylate_kinase_Znf_lid. 1 hit.

TIGRFAMs

TIGR01351. adk. 1 hit.

PROSITE

PS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P27144.

ChEMBL

CHEMBL4926.

EvolutionaryTrace

P27144.

NextBio

818.

SOURCE

Search...

Entry information

Entry name

KAD4_HUMAN

Accession

Primary (citable) accession number: P27144
Secondary accession number(s): B2R927 , D3DQ62, Q6IBH4, Q6NXQ5, Q8IUU9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 1, 2013
This is version 134 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.