Q9Y3D8 (KAD6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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:	TAF9
Synonyms:	AK6, CINAP
ORF Names:	AD-004, CGI-137

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	172 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Catalytic activity	ATP + AMP = 2 ADP.
Subunit structure	Monomer and homodimer By similarity. Interacts with COIL (via C-terminus).
Subcellular location	Nucleus › nucleoplasm. Nucleus › Cajal 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
Sequence similarities	Belongs to the adenylate kinase family. AK6 subfamily.
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 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 component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	Cajal body Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate kinase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COIL	P38432	5	EBI-2896123,EBI-945751

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms 1/3 and isoform 2 are produced by the same gene but are translated from different initiation codons and use different reading frames so they display no identity in their protein sequences. This arrangement is conserved in mammals but these proteins are produced by separate genes in non-mammalian species.

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: Q16594-1)

Also known as: TAF9;

The sequence of this isoform can be found in the external entry Q16594.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Isoform 3 (identifier: Q9Y3D8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2-9: LLPNILLT → CHRKP

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 172

172

Adenylate kinase isoenzyme 6

PRO_0000153896

Regions

Nucleotide binding

13 – 18

6

ATP

Nucleotide binding

148 – 149

2

ATP

Region

33 – 56

24

NMPbind

Region

108 – 118

11

LID

Sites

Binding site

39

1

AMP Probable

Binding site

79

1

ATP

Binding site

105

1

ATP

Binding site

109

1

ATP

Natural variations

Alternative sequence

2 – 9

8

LLPNILLT → CHRKP in isoform 3.

VSP_039714

Experimental info

Mutagenesis

79

1

H → 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.

Secondary structure

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172

Helix Strand Turn

Details...

Beta strand

6 – 9

4

Helix

16 – 27

12

Beta strand

30 – 33

4

Helix

34 – 41

8

Beta strand

44 – 48

5

Turn

49 – 52

4

Beta strand

53 – 56

4

Helix

58 – 71

14

Beta strand

74 – 77

4

Helix

86 – 88

3

Beta strand

90 – 96

7

Helix

99 – 108

10

Helix

113 – 124

12

Helix

127 – 135

9

Helix

138 – 140

3

Beta strand

141 – 145

5

Helix

149 – 169

21

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (AK6) [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 33F62318FB434301	FASTA	172	20,061
	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
	Isoform 2 (TAF9) [UniParc]. See Q16594.		–	–
	Isoform 3 [UniParc]. Checksum: 3F341AE6C5898C66	FASTA	169	19,805
	10 20 30 40 50 60 MCHRKPGTPG VGKTTLGKEL ASKSGLKYIN VGDLAREEQL YDGYDEEYDC PILDEDRVVD 70 80 90 100 110 120 ELDNQMREGG VIVDYHGCDF FPERWFHIVF VLRTDTNVLY ERLETRGYNE KKLTDNIQCE 130 140 150 160 IFQVLYEEAT ASYKEEIVHQ LPSNKPEELE NNVDQILKWI EQWIKDHNS

References

	« Hide 'large scale' referencesShow '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], BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH COIL, SUBCELLULAR LOCATION, 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].
[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. , 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]. 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. , 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. , 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: 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.

IPI

IPI00032879.
IPI00556532.

RefSeq

NP_001015891.1. NM_001015891.1.
NP_057367.1. NM_016283.4.

UniGene

Hs.653163.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RKB	X-ray	2.00	A	1-172	[»]
3IIJ	X-ray	1.76	A	1-172	[»]
3IIK	X-ray	1.95	A	1-172	[»]
3IIL	X-ray	2.00	A	1-172	[»]
3IIM	X-ray	2.00	A	1-172	[»]

ProteinModelPortal

Q9Y3D8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y3D8. 3 interactions.

MINT

MINT-1389230.

STRING

9606.ENSP00000370201.

Polymorphism databases

DMDM

6831735.

Proteomic databases

PaxDb

Q9Y3D8.

PeptideAtlas

Q9Y3D8.

PRIDE

Q9Y3D8.

Protocols and materials databases

DNASU

6880.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380818; ENSP00000370197; ENSG00000085231.
ENST00000380822; ENSP00000370201; ENSG00000085231.
ENST00000575603; ENSP00000459871; ENSG00000263302.
ENST00000576354; ENSP00000461237; ENSG00000263302.

GeneID

6880.

KEGG

hsa:6880.

UCSC

uc003jwa.3. human.
uc003jwb.3. human.

Organism-specific databases

CTD

6880.

GeneCards

GC05M068646.

HGNC

HGNC:11542. TAF9.

HPA

CAB005361.

neXtProt

NX_Q9Y3D8.

PharmGKB

PA36317.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1936.

HOGENOM

HOG000224472.

HOVERGEN

HBG052207.

InParanoid

Q9Y3D8.

KO

K14535.

OMA

DNVQCEI.

OrthoDB

EOG4X3H2N.

Gene expression databases

ArrayExpress

Q9Y3D8.

Bgee

Q9Y3D8.

Genevestigator

Q9Y3D8.

GermOnline

ENSG00000185057. Homo sapiens.

Family and domain databases

HAMAP

MF_00039. Adenylate_kinase_AK6.

ProtoNet

Search...

Other

ChiTaRS

TAF9. human.

EvolutionaryTrace

Q9Y3D8.

GenomeRNAi

6880.

NextBio

26873.

Entry information

Entry name

KAD6_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 116 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.