Q5TCY1 (TTBK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tau-tubulin kinase 1
EC=2.7.11.1

Alternative name(s):
Brain-derived tau kinase

Gene names

Name:	TTBK1
Synonyms:	BDTK, KIAA1855

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	1321 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. Ref.1
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Divalent cations. Magnesium or, to a lesser extent, manganese, but not calcium or zinc. Ref.1
Subcellular location	Cytoplasm Ref.1.
Tissue specificity	Expressed in the brain, particularly in cortical and hippocampal neurons. Weakly expressed in spinal cord and testis. No expression in adipose tissue, bladder, cervix, colon, esophagus, heart, kidney, liver, lung, ovary, placenta, prostate, skeletal muscle, small intestine, spleen, testis, thymus, thyroid or trachea. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Caution	It is uncertain whether Met-1 or Met-14 is the initiator.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cell junction Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity 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: Q5TCY1-1)

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: Q5TCY1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     592-672: TVRPRGRSMQ...VFSVAPPFEV → FPLTPALGTP...RFPHSAQPLG
     673-1321: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1321	1321	Tau-tubulin kinase 1		PRO_0000234341
Regions
	Domain	34 – 297	264	Protein kinase
	Nucleotide binding	40 – 48	9	ATP By similarity
	Coiled coil	685 – 781	97	Potential
	Compositional bias	733 – 771	39	Glu-rich
	Compositional bias	772 – 777	6	Poly-Ala
	Compositional bias	1110 – 1114	5	Poly-Ser
	Compositional bias	1197 – 1289	93	Pro-rich
Sites
	Active site	154	1	Proton acceptor By similarity
	Binding site	63	1	ATP By similarity
Natural variations
	Alternative sequence	1 – 51	51	Missing in isoform 2.		VSP_026497
	Alternative sequence	592 – 672	81	TVRPR…PPFEV → FPLTPALGTPPSTERVGPHR PTETVGGGQTLGALPPAVQP PATTGVLRVLLLHAGDGALP SPRRRRLLGLLRFPHSAQPL G in isoform 2.		VSP_026498
	Alternative sequence	673 – 1321	649	Missing in isoform 2.		VSP_026499
	Natural variant	613	1	P → L. Ref.6 Corresponds to variant rs34993661 [ dbSNP | Ensembl ].		VAR_041252
	Natural variant	623	1	G → A. Ref.6 Corresponds to variant rs3800294 [ dbSNP | Ensembl ].		VAR_041253
	Natural variant	649	1	P → R. Ref.6 Corresponds to variant rs35175743 [ dbSNP | Ensembl ].		VAR_041254
	Natural variant	741	1	D → E. Ref.6 Corresponds to variant rs56377340 [ dbSNP | Ensembl ].		VAR_041255
	Natural variant	744	1	E → D. Ref.6 Corresponds to variant rs3800295 [ dbSNP | Ensembl ].		VAR_041256
	Natural variant	806	1	S → F in a lung large cell carcinoma sample; somatic mutation. Ref.6		VAR_041257
	Natural variant	855	1	P → S in a metastatic melanoma sample; somatic mutation. Ref.6		VAR_041258
	Natural variant	1145	1	K → R. Ref.6 Corresponds to variant rs3800297 [ dbSNP | Ensembl ].		VAR_041259
	Natural variant	1184	1	L → S. Ref.6 Corresponds to variant rs3800298 [ dbSNP | Ensembl ].		VAR_041260
Experimental info
	Sequence conflict	37	1	L → V in BAE78660. Ref.1
	Sequence conflict	402	1	E → G in BAD18405. Ref.2
	Sequence conflict	1190	1	S → SS in AAH36764. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: 844FAA1EB7A45DE2	FASTA	1,321	142,737
	10 20 30 40 50 60 MQCLAAALKD ETNMSGGGEQ ADILPANYVV KDRWKVLKKI GGGGFGEIYE AMDLLTRENV 70 80 90 100 110 120 ALKVESAQQP KQVLKMEVAV LKKLQGKDHV CRFIGCGRNE KFNYVVMQLQ GRNLADLRRS 130 140 150 160 170 180 QPRGTFTLST TLRLGKQILE SIEAIHSVGF LHRDIKPSNF AMGRLPSTYR KCYMLDFGLA 190 200 210 220 230 240 RQYTNTTGDV RPPRNVAGFR GTVRYASVNA HKNREMGRHD DLWSLFYMLV EFAVGQLPWR 250 260 270 280 290 300 KIKDKEQVGM IKEKYEHRML LKHMPSEFHL FLDHIASLDY FTKPDYQLIM SVFENSMKER 310 320 330 340 350 360 GIAENEAFDW EKAGTDALLS TSTSTPPQQN TRQTAAMFGV VNVTPVPGDL LRENTEDVLQ 370 380 390 400 410 420 GEHLSDQENA PPILPGRPSE GLGPSPHLVP HPGGPEAEVW EETDVNRNKL RINIGKSPCV 430 440 450 460 470 480 EEEQSRGMGV PSSPVRAPPD SPTTPVRSLR YRRVNSPESE RLSTADGRVE LPERRSRMDL 490 500 510 520 530 540 PGSPSRQACS SQPAQMLSVD TGHADRQASG RMDVSASVEQ EALSNAFRSV PLAEEEDFDS 550 560 570 580 590 600 KEWVIIDKET ELKDFPPGAE PSTSGTTDEE PEELRPLPEE GEERRRLGAE PTVRPRGRSM 610 620 630 640 650 660 QALAEEDLQH LPPQPLPPQL SQGDGRSETS QPPTPGSPSH SPLHSGPRPR RRESDPTGPQ 670 680 690 700 710 720 RQVFSVAPPF EVNGLPRAVP LSLPYQDFKR DLSDYRERAR LLNRVRRVGF SHMLLTTPQV 730 740 750 760 770 780 PLAPVQPQAN GKEEEEEEEE DEEEEEEDEE EEEEEEEEEE EEEEEEEEEE EAAAAVALGE 790 800 810 820 830 840 VLGPRSGSSS EGSERSTDRS QEGAPSTLLA DDQKESRGRA SMADGDLEPE EGSKTLVLVS 850 860 870 880 890 900 PGDMKKSPVT AELAPDPDLG TLAALTPQHE RPQPTGSQLD VSEPGTLSSV LKSEPKPPGP 910 920 930 940 950 960 GAGLGAGTVT TGVGGVAVTS SPFTKVERTF VHIAEKTHLN VMSSGGQALR SEEFSAGGEL 970 980 990 1000 1010 1020 GLELASDGGA VEEGARAPLE NGLALSGLNG AEIEGSALSG APRETPSEMA TNSLPNGPAL 1030 1040 1050 1060 1070 1080 ADGPAPVSPL EPSPEKVATI SPRRHAMPGS RPRSRIPVLL SEEDTGSEPS GSLSAKERWS 1090 1100 1110 1120 1130 1140 KRARPQQDLA RLVMEKRQGR LLLRLASGAS SSSSEEQRRA SETLSGTGSE EDTPASEPAA 1150 1160 1170 1180 1190 1200 ALPRKSGRAA ATRSRIPRPI GLRMPMPVAA QQPASRSHGA APALDTAITS RLQLQTPPGS 1210 1220 1230 1240 1250 1260 ATAADLRPKQ PPGRGLGPGR AQAGARPPAP RSPRLPASTS AARNASASPR SQSLSRRESP 1270 1280 1290 1300 1310 1320 SPSHQARPGV PPPRGVPPAR AQPDGTPSPG GSKKGPRGKL QAQRATTKGR AGGAEGRAGA R
	Isoform 2 [UniParc]. Checksum: 4A99A34F76D7DD59	FASTA	621	69,084
	10 20 30 40 50 60 MDLLTRENVA LKVESAQQPK QVLKMEVAVL KKLQGKDHVC RFIGCGRNEK FNYVVMQLQG 70 80 90 100 110 120 RNLADLRRSQ PRGTFTLSTT LRLGKQILES IEAIHSVGFL HRDIKPSNFA MGRLPSTYRK 130 140 150 160 170 180 CYMLDFGLAR QYTNTTGDVR PPRNVAGFRG TVRYASVNAH KNREMGRHDD LWSLFYMLVE 190 200 210 220 230 240 FAVGQLPWRK IKDKEQVGMI KEKYEHRMLL KHMPSEFHLF LDHIASLDYF TKPDYQLIMS 250 260 270 280 290 300 VFENSMKERG IAENEAFDWE KAGTDALLST STSTPPQQNT RQTAAMFGVV NVTPVPGDLL 310 320 330 340 350 360 RENTEDVLQG EHLSDQENAP PILPGRPSEG LGPSPHLVPH PGGPEAEVWE ETDVNRNKLR 370 380 390 400 410 420 INIGKSPCVE EEQSRGMGVP SSPVRAPPDS PTTPVRSLRY RRVNSPESER LSTADGRVEL 430 440 450 460 470 480 PERRSRMDLP GSPSRQACSS QPAQMLSVDT GHADRQASGR MDVSASVEQE ALSNAFRSVP 490 500 510 520 530 540 LAEEEDFDSK EWVIIDKETE LKDFPPGAEP STSGTTDEEP EELRPLPEEG EERRRLGAEP 550 560 570 580 590 600 FPLTPALGTP PSTERVGPHR PTETVGGGQT LGALPPAVQP PATTGVLRVL LLHAGDGALP 610 620 SPRRRRLLGL LRFPHSAQPL G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation." Sato S., Cerny R.L., Buescher J.L., Ikezu T. J. Neurochem. 98:1573-1584(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"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] (ISOFORM 2). Tissue: Testis.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O. DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 52-1321 (ISOFORM 1). Tissue: Brain.
[5]	"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] OF 979-1321 (ISOFORM 1). Tissue: Brain.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-613; ALA-623; ARG-649; GLU-741; ASP-744; PHE-806; SER-855; ARG-1145 AND SER-1184.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB218664 mRNA. Translation: BAE78660.1. AK131217 mRNA. Translation: BAD18405.1. AL133375 Genomic DNA. Translation: CAI20206.2. AL133375 Genomic DNA. Translation: CAM28234.1. AB058758 mRNA. Translation: BAB47484.1. BC036764 mRNA. Translation: AAH36764.1.
IPI	IPI00064158. IPI00793581.
RefSeq	NP_115927.1. NM_032538.1.
UniGene	Hs.485436.
3D structure databases
ProteinModelPortal	Q5TCY1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000259750.
PTM databases
PhosphoSite	Q5TCY1.
Polymorphism databases
DMDM	97203020.
Proteomic databases
PaxDb	Q5TCY1.
PRIDE	Q5TCY1.
Protocols and materials databases
DNASU	84630.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259750; ENSP00000259750; ENSG00000146216. ENST00000304139; ENSP00000307357; ENSG00000146216.
GeneID	84630.
KEGG	hsa:84630.
UCSC	uc003ouq.1. human.
Organism-specific databases
CTD	84630.
GeneCards	GC06P043259.
H-InvDB	HIX0005900.
HGNC	HGNC:19140. TTBK1.
HPA	HPA031736.
neXtProt	NX_Q5TCY1.
PharmGKB	PA134866142.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000154701.
HOVERGEN	HBG094095.
InParanoid	Q5TCY1.
KO	K08815.
OMA	RGKLQTQ.
OrthoDB	EOG4BVRSW.
Gene expression databases
ArrayExpress	Q5TCY1.
Bgee	Q5TCY1.
CleanEx	HS_TTBK1.
Genevestigator	Q5TCY1.
GermOnline	ENSG00000146216. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1926492.
GenomeRNAi	84630.
NextBio	74547.

Entry information

Entry name

TTBK1_HUMAN

Accession

Primary (citable) accession number: Q5TCY1
Secondary accession number(s): A2A2U5 , Q2L6C6, Q6ZNH0, Q8N444, Q96JH2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	May 16, 2006
Last modified:	May 1, 2013
This is version 79 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.