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P27144 (KAD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylate kinase 4, mitochondrial

Short name=AK 4
EC=2.7.4.10
EC=2.7.4.6
Alternative name(s):
Adenylate kinase 3-like
GTP:AMP phosphotransferase AK4
Gene names
Name:AK4
Synonyms:AK3, AK3L1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length223 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Also displays broad nucleoside diphosphate kinase activity. Ref.8 Ref.10 Ref.12

Catalytic activity

NTP + AMP = NDP + ADP. Ref.8 Ref.10

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate. Ref.8 Ref.10

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 223223Adenylate kinase 4, mitochondrial HAMAP-Rule MF_03170
PRO_0000158926

Regions

Nucleotide binding15 – 206NTP HAMAP-Rule MF_03170
Nucleotide binding62 – 643AMP HAMAP-Rule MF_03170
Nucleotide binding89 – 924AMP HAMAP-Rule MF_03170
Nucleotide binding135 – 1362NTP By similarity
Region35 – 6430NMPbind HAMAP-Rule MF_03170
Region125 – 16238LID HAMAP-Rule MF_03170

Sites

Binding site361AMP
Binding site411AMP By similarity
Binding site961AMP By similarity
Binding site1261NTP
Binding site1701AMP
Binding site1991NTP; via carbonyl oxygen

Amino acid modifications

Modified residue601N6-succinyllysine By similarity
Modified residue1751N6-acetyllysine By similarity
Modified residue1791N6-acetyllysine; alternate By similarity
Modified residue1791N6-succinyllysine; alternate By similarity
Modified residue1861N6-acetyllysine; alternate By similarity
Modified residue1861N6-succinyllysine; alternate By similarity

Experimental info

Mutagenesis41K → G: Abolishes mitochondrial import; when associated with G-7. Ref.8
Mutagenesis71R → G: Abolishes mitochondrial import; when associated with G-4. Ref.8
Sequence conflict221C → S in AAH40224. Ref.6
Sequence conflict221C → S in AAI46654. Ref.6
Sequence conflict231Q → R in AAH66944. Ref.6

Secondary structure

........................................ 223
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P27144 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 653341A8EB3BC723

FASTA22325,268
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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]"The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase."
Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.
Int. J. Biochem. Cell Biol. 45:925-931(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[11]"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.
[12]"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.
PIRKIHUA3. A42820.
RefSeqNP_001005353.1. NM_001005353.2.
NP_037542.1. NM_013410.3.
NP_982289.1. NM_203464.2.
XP_003119578.1. XM_003119530.3.
UniGeneHs.10862.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AR7X-ray2.15A/B1-223[»]
2BBWX-ray2.05A/B1-223[»]
3NDPX-ray2.30A/B1-223[»]
ProteinModelPortalP27144.
SMRP27144. Positions 4-223.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106708. 5 interactions.
IntActP27144. 3 interactions.

Chemistry

BindingDBP27144.
ChEMBLCHEMBL4926.

PTM databases

PhosphoSiteP27144.

Polymorphism databases

DMDM125157.

2D gel databases

UCD-2DPAGEP27144.

Proteomic databases

PaxDbP27144.
PRIDEP27144.

Protocols and materials databases

DNASU205.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327299; ENSP00000322175; ENSG00000162433.
ENST00000395334; ENSP00000378743; ENSG00000162433.
ENST00000545314; ENSP00000445912; ENSG00000162433.
GeneID100507855.
205.
KEGGhsa:100507855.
hsa:205.
UCSCuc001dby.3. human.

Organism-specific databases

CTD205.
GeneCardsGC01P065614.
HGNCHGNC:363. AK4.
HPAHPA042753.
HPA049461.
MIM103030. gene.
neXtProtNX_P27144.
PharmGKBPA165750325.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0563.
HOGENOMHOG000238772.
HOVERGENHBG000458.
InParanoidP27144.
KOK00939.
OMAGDVAKQY.
PhylomeDBP27144.
TreeFamTF312916.

Gene expression databases

ArrayExpressP27144.
BgeeP27144.
CleanExHS_AK3.
HS_AK3L1.
GenevestigatorP27144.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
HAMAPMF_00235. Adenylate_kinase_Adk.
MF_03169. Adenylate_kinase_AK3.
MF_03170. Adenylate_kinase_AK4.
InterProIPR006259. Adenyl_kin_sub.
IPR000850. Adenylat/UMP-CMP_kin.
IPR007862. Adenylate_kinase_lid-dom.
IPR028586. AK3/Ak4_mitochondrial.
IPR028585. AK4_mitochondrial.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR23359. PTHR23359. 1 hit.
PfamPF05191. ADK_lid. 1 hit.
[Graphical view]
PRINTSPR00094. ADENYLTKNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
SSF57774. SSF57774. 1 hit.
TIGRFAMsTIGR01351. adk. 1 hit.
PROSITEPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP27144.
GeneWikiAK3L1.
NextBio818.
PROP27144.
SOURCESearch...

Entry information

Entry nameKAD4_HUMAN
AccessionPrimary (citable) accession number: P27144
Secondary accession number(s): B2R927 expand/collapse secondary AC list , D3DQ62, Q6IBH4, Q6NXQ5, Q8IUU9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM