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Q9Y3D8 (KAD6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylate kinase isoenzyme 6

Short name=AK6
EC=2.7.4.3
Alternative name(s):
Adrenal gland protein AD-004
Coilin-interacting nuclear ATPase protein
Short name=hCINAP
Dual activity adenylate kinase/ATPase
Short name=AK/ATPase
Gene names
Name:AK6
Synonyms:CINAP
ORF Names:AD-004, CGI-137
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length172 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. AMP and dAMP are the preferred substrates, but CMP and dCMP are also good substrates. IMP is phosphorylated to a much lesser extent. All nucleoside triphosphates ATP, GTP, UTP, CTP, dATP, dCTP, dGTP, and TTP are accepted as phosphate donors. CTP is the best phosphate donor, followed by UTP, ATP, GTP and dCTP. May have a role in nuclear energy homeostasis. Has also ATPase activity. May be involved in regulation of Cajal body (CB) formation. Ref.9

Catalytic activity

ATP + AMP = 2 ADP. Ref.9

Subunit structure

Monomer and homodimer By similarity. Interacts with COIL (via C-terminus). Ref.1 Ref.7

Subcellular location

Nucleusnucleoplasm. NucleusCajal body. Note: Displays widespread diffuse nucleoplasmic distribution but not detected in nucleoli. Detected in Cajal bodies but not in all cells. Ref.1 Ref.9

Tissue specificity

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, chorionic villi and the central nervous system. Ref.1

Sequence similarities

Belongs to the adenylate kinase family. AK6 subfamily.

Caution

AK6 and TAF9 were initially considered as products of the same gene since they share two exons. However, they are translated from different initiation codons and reading frames and encode unrelated proteins. This arrangement is conserved in some mammalian species.

Biophysicochemical properties

Kinetic parameters:

kcat is 6.3 sec(-1) for adenylate kinase activity. kcat is 4.8 sec(-1) for ATPase activity.

KM=192 µM for AMP Ref.1 Ref.9 Ref.10

KM=45 µM for ATP (for adenylate kinase activity)

KM=332 µM for ATP (for ATPase activity)

Vmax=1.27 µmol/min/mg enzyme for ATPase activity

Vmax=982 nmol/min/mg enzyme for the forward adenylate kinase reaction

Vmax=955 nmol/min/mg enzyme for the reverse adenylate kinase reaction

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnucleotide phosphorylation

Inferred from direct assay Ref.9. Source: GOC

   Cellular_componentCajal body

Inferred from direct assay Ref.1. Source: UniProtKB

nucleoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATPase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

adenylate kinase activity

Inferred from direct assay Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

COILP384325EBI-2896123,EBI-945751

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y3D8-1)

Also known as: AK6;

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: Q9Y3D8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2-9: LLPNILLT → CHRKP
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 172172Adenylate kinase isoenzyme 6 HAMAP-Rule MF_03173
PRO_0000153896

Regions

Nucleotide binding13 – 186ATP HAMAP-Rule MF_03173
Nucleotide binding148 – 1492ATP HAMAP-Rule MF_03173
Region33 – 5624NMPbind HAMAP-Rule MF_03173
Region108 – 11811LID HAMAP-Rule MF_03173

Sites

Binding site391AMP Probable
Binding site791ATP
Binding site1051ATP
Binding site1091ATP

Natural variations

Alternative sequence2 – 98LLPNILLT → CHRKP in isoform 2.
VSP_039714

Experimental info

Mutagenesis791H → G: Induces homodimerization. Reduces adenylate kinase activity by 72% and ATPase activity by 76%. Significantly changes Cajal body organization in the nucleus, resulting in enhanced apoptosis and reduced proliferation. Ref.10

Secondary structure

............................... 172
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (AK6) [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 33F62318FB434301

FASTA17220,061
        10         20         30         40         50         60 
MLLPNILLTG TPGVGKTTLG KELASKSGLK YINVGDLARE EQLYDGYDEE YDCPILDEDR 

        70         80         90        100        110        120 
VVDELDNQMR EGGVIVDYHG CDFFPERWFH IVFVLRTDTN VLYERLETRG YNEKKLTDNI 

       130        140        150        160        170 
QCEIFQVLYE EATASYKEEI VHQLPSNKPE ELENNVDQIL KWIEQWIKDH NS 

« Hide

Isoform 2 [UniParc].

Checksum: 3F341AE6C5898C66
Show »

FASTA16919,805

References

« Hide 'large scale' references
[1]"Characterization of hCINAP, a novel coilin-interacting protein encoded by a transcript from the transcription factor TAFIID32 locus."
Santama N., Ogg S.C., Malekkou A., Zographos S.E., Weis K., Lamond A.I.
J. Biol. Chem. 280:36429-36441(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH COIL, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
Tissue: Cervix carcinoma and Placenta.
[2]"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics."
Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.
Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Adrenal gland.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [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] (ISOFORM 1).
Tissue: Lymph.
[7]"Protein preparation, crystallization and preliminary X-ray analysis of human adrenal gland protein AD-004."
Ren H., Liang Y., Li R., Ding H., Qiu S., Lu S., An J., Li L., Luo M., Zheng X., Su X.D.
Acta Crystallogr. D 60:1292-1294(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[8]"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].
[9]"The crystal structure of human adenylate kinase 6: an adenylate kinase localized to the cell nucleus."
Ren H., Wang L., Bennett M., Liang Y., Zheng X., Lu F., Li L., Nan J., Luo M., Eriksson S., Zhang C., Su X.-D.
Proc. Natl. Acad. Sci. U.S.A. 102:303-308(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[10]"hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: structural and functional studies."
Drakou C.E., Malekkou A., Hayes J.M., Lederer C.W., Leonidas D.D., Oikonomakos N.G., Lamond A.I., Santama N., Zographos S.E.
Proteins 80:206-220(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) IN COMPLEX WITH ADP AND DADP, MUTAGENESIS OF HIS-79, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ878880 mRNA. Translation: CAI48030.1.
AJ878881 mRNA. Translation: CAI48031.1.
AF151895 mRNA. Translation: AAD34132.1.
AF110777 mRNA. Translation: AAF14860.1.
AC145132 Genomic DNA. No translation available.
CH471137 Genomic DNA. Translation: EAW51290.1.
CH471137 Genomic DNA. Translation: EAW51291.1.
CH471137 Genomic DNA. Translation: EAW51292.1.
CH471137 Genomic DNA. Translation: EAW51297.1.
BC007349 mRNA. Translation: AAH07349.1.
BC007426 mRNA. Translation: AAH07426.1.
CCDSCCDS4001.1. [Q9Y3D8-1]
CCDS43324.1. [Q9Y3D8-2]
RefSeqNP_001015891.1. NM_001015891.1. [Q9Y3D8-2]
NP_057367.1. NM_016283.4. [Q9Y3D8-1]
UniGeneHs.653163.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RKBX-ray2.00A1-172[»]
3IIJX-ray1.76A1-172[»]
3IIKX-ray1.95A1-172[»]
3IILX-ray2.00A1-172[»]
3IIMX-ray2.00A1-172[»]
ProteinModelPortalQ9Y3D8.
SMRQ9Y3D8. Positions 1-172.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112743. 70 interactions.
IntActQ9Y3D8. 4 interactions.
MINTMINT-1389230.
STRING9606.ENSP00000370201.

Polymorphism databases

DMDM6831735.

Proteomic databases

MaxQBQ9Y3D8.
PaxDbQ9Y3D8.
PeptideAtlasQ9Y3D8.
PRIDEQ9Y3D8.

Protocols and materials databases

DNASU6880.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID102157402.
KEGGhsa:102157402.
UCSCuc003jwa.3. human. [Q9Y3D8-1]
uc003jwb.3. human. [Q9Y3D8-2]

Organism-specific databases

CTD102157402.
GeneCardsGC05M068646.
GC05M068647.
HGNCHGNC:49151. AK6.
HPACAB005361.
neXtProtNX_Q9Y3D8.
PharmGKBPA36317.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1936.
HOGENOMHOG000224472.
HOVERGENHBG052207.
InParanoidQ9Y3D8.
OMADNVQCEI.

Gene expression databases

ArrayExpressQ9Y3D8.
BgeeQ9Y3D8.
GenevestigatorQ9Y3D8.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
HAMAPMF_00039. Adenylate_kinase_AK6.
InterProIPR020618. Adenyl_kinase_AK6.
IPR027417. P-loop_NTPase.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSTAF9. human.
EvolutionaryTraceQ9Y3D8.
GenomeRNAi102157402.
NextBio26873.

Entry information

Entry nameKAD6_HUMAN
AccessionPrimary (citable) accession number: Q9Y3D8
Secondary accession number(s): A8MSZ6, Q5F2S9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 128 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

Uncharacterized protein families (UPF)

List of uncharacterized protein family (UPF) entries

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM