Reviewed, UniProtKB/Swiss-Prot Q6IQ55 (TTBK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Tau-tubulin kinase 2
    EC=2.7.11.1

Gene names

Name:	TTBK2
Synonyms:	KIAA0847

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1244 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Serine/threonine kinase which is able to phosphorylate tau on serines By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Involvement in disease	Defects in TTBK2 are the cause of spinocerebellar ataxia type 11 (SCA11) [MIM:604432]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar ataxia (ADCA). It is a relatively benign, late-onset, slowly progressive neurologic disorder. Ref.4
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Neurodegeneration Spinocerebellar ataxia
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6IQ55-1)

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: Q6IQ55-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVESAQQPKQVLKMEVAVLKKLQ → MES
     1233-1244: QGKSKPASKLSR → PREE

Notes: No experimental confirmation available.

Isoform 3 (identifier: Q6IQ55-3)

The sequence of this isoform differs from the canonical sequence as follows:
     470-478: CLEKMQKDT → WYKIVYFSF
     479-1244: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1244	1244	Tau-tubulin kinase 2		PRO_0000234342
Regions
	Domain	21 – 284	264	Protein kinase
	Nucleotide binding	27 – 35	9	ATP By similarity
	Compositional bias	307 – 314	8	Poly-Thr
	Compositional bias	1150 – 1203	54	Ser-rich
Sites
	Active site	141	1	Proton acceptor By similarity
	Binding site	50	1	ATP By similarity
Natural variations
	Alternative sequence	1 – 72	72	MSGGG…LKKLQ → MES in isoform 2.		VSP_018272
	Alternative sequence	470 – 478	9	CLEKMQKDT → WYKIVYFSF in isoform 3.		VSP_018273
	Alternative sequence	479 – 1244	766	Missing in isoform 3.		VSP_018274
	Alternative sequence	1233 – 1244	12	QGKSK…SKLSR → PREE in isoform 2.		VSP_018275
	Natural variant	8	1	L → P: dbSNP rs6493068.		VAR_041261
	Natural variant	120	1	R → Q: dbSNP rs35328266.		VAR_041262
	Natural variant	313	1	T → A Ref.5		VAR_041263
	Natural variant	440	1	V → M Ref.5		VAR_041264
	Natural variant	500	1	R → P Ref.5		VAR_041265
	Natural variant	635	1	D → G in a lung small cell carcinoma sample; somatic mutation. Ref.5		VAR_041266
	Natural variant	1062	1	T → I Ref.5		VAR_041267
	Natural variant	1084	1	T → M: dbSNP rs34348991.		VAR_041268
	Natural variant	1097	1	V → A Ref.5		VAR_041269
	Natural variant	1122	1	P → R Ref.5		VAR_041270
	Natural variant	1241	1	K → T: dbSNP rs36104367.		VAR_041271
Experimental info
	Sequence conflict	309	1	T → I in BAD18523. Ref.1
	Sequence conflict	456	1	T → A in BAD18523. Ref.1
	Sequence conflict	557	1	K → N in BAD18523. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: EAB8FC28370966DE	FASTA	1,244	137,412
	10 20 30 40 50 60 MSGGGEQLDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK VESAQQPKQV 70 80 90 100 110 120 LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN LADLRRSQSR GTFTISTTLR 130 140 150 160 170 180 LGRQILESIE SIHSVGFLHR DIKPSNFAMG RFPSTCRKCY MLDFGLARQF TNSCGDVRPP 190 200 210 220 230 240 RAVAGFRGTV RYASINAHRN REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE 250 260 270 280 290 300 RYDHRLMLKH LPPEFSIFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKT 310 320 330 340 350 360 GNDGSLTTTT TSTTPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE QLSDGENGIP 370 380 390 400 410 420 VGVSPDKLPG SLGHPRPQEK DVWEEMDANK NKIKLGICKA ATEEENSHGQ ANGLLNAPSL 430 440 450 460 470 480 GSPIRVRSEI TQPDRDIPLV RKLRSIHSFE LEKRLTLEPK PDTDKFLETC LEKMQKDTSA 490 500 510 520 530 540 GKESILPALL HKPCVPAVSR TDHIWHYDEE YLPDASKPAS ANTPEQADGG GSNGFIAVNL 550 560 570 580 590 600 SSCKQEIDSK EWVIVDKEQD LQDFRTNEAV GHKTTGSPSD EEPEVLQVLE ASPQDEKLQL 610 620 630 640 650 660 GPWAENDHLK KETSGVVLAL SAEGPPTAAS EQYTDRLELQ PGAASQFIAA TPTSLMEAQA 670 680 690 700 710 720 EGPLTAITIP RPSVASTQST SGSFHCGQQP EKKDLQPMEP TVELYSPREN FSGLVVTEGE 730 740 750 760 770 780 PPSGGSRTDL GLQIDHIGHD MLPNIRESNK SQDLGPKELP DHNRLVVREF ENLPGETEEK 790 800 810 820 830 840 SILLESDNED EKLSRGQHCI EISSLPGDLV IVEKDHSATT EPLDVTKTQT FSVVPNQDKN 850 860 870 880 890 900 NEIMKLLTVG TSEISSRDID PHVEGQIGQV AEMQKNKISK DDDIMSEDLP GHQGDLSTFL 910 920 930 940 950 960 HQEGKREKIT PRNGELFHCV SENEHGAPTR KDMVRSSFVT RHSRIPVLAQ EIDSTLESSS 970 980 990 1000 1010 1020 PVSAKEKLLQ KKAYQPDLVK LLVEKRQFKS FLGDLSSASD KLLEEKLATV PAPFCEEEVL 1030 1040 1050 1060 1070 1080 TPFSRLTVDS HLSRSAEDSF LSPIISQSRK SKIPRPVSWV NTDQVNSSTS SQFFPRPPPG 1090 1100 1110 1120 1130 1140 KPPTRPGVEA RLRRYKVLGS SNSDSDLFSR LAQILQNGSQ KPRSTTQCKS PGSPHNPKTP 1150 1160 1170 1180 1190 1200 PKSPVVPRRS PSASPRSSSL PRTSSSSPSR AGRPHHDQRS SSPHLGRSKS PPSHSGSSSS 1210 1220 1230 1240 RRSCQQEHCK PSKNGLKGSG SLHHHSASTK TPQGKSKPAS KLSR
	Isoform 2. Checksum: 5517B88C9E5E86E9		1,167	129,110
	10 20 30 40 50 60 MESGKDHVCR FIGCGRNDRF NYVVMQLQGR NLADLRRSQS RGTFTISTTL RLGRQILESI 70 80 90 100 110 120 ESIHSVGFLH RDIKPSNFAM GRFPSTCRKC YMLDFGLARQ FTNSCGDVRP PRAVAGFRGT 130 140 150 160 170 180 VRYASINAHR NREMGRHDDL WSLFYMLVEF VVGQLPWRKI KDKEQVGSIK ERYDHRLMLK 190 200 210 220 230 240 HLPPEFSIFL DHISSLDYFT KPDYQLLTSV FDNSIKTFGV IESDPFDWEK TGNDGSLTTT 250 260 270 280 290 300 TTSTTPQLHT RLTPAAIGIA NATPIPGDLL RENTDEVFPD EQLSDGENGI PVGVSPDKLP 310 320 330 340 350 360 GSLGHPRPQE KDVWEEMDAN KNKIKLGICK AATEEENSHG QANGLLNAPS LGSPIRVRSE 370 380 390 400 410 420 ITQPDRDIPL VRKLRSIHSF ELEKRLTLEP KPDTDKFLET CLEKMQKDTS AGKESILPAL 430 440 450 460 470 480 LHKPCVPAVS RTDHIWHYDE EYLPDASKPA SANTPEQADG GGSNGFIAVN LSSCKQEIDS 490 500 510 520 530 540 KEWVIVDKEQ DLQDFRTNEA VGHKTTGSPS DEEPEVLQVL EASPQDEKLQ LGPWAENDHL 550 560 570 580 590 600 KKETSGVVLA LSAEGPPTAA SEQYTDRLEL QPGAASQFIA ATPTSLMEAQ AEGPLTAITI 610 620 630 640 650 660 PRPSVASTQS TSGSFHCGQQ PEKKDLQPME PTVELYSPRE NFSGLVVTEG EPPSGGSRTD 670 680 690 700 710 720 LGLQIDHIGH DMLPNIRESN KSQDLGPKEL PDHNRLVVRE FENLPGETEE KSILLESDNE 730 740 750 760 770 780 DEKLSRGQHC IEISSLPGDL VIVEKDHSAT TEPLDVTKTQ TFSVVPNQDK NNEIMKLLTV 790 800 810 820 830 840 GTSEISSRDI DPHVEGQIGQ VAEMQKNKIS KDDDIMSEDL PGHQGDLSTF LHQEGKREKI 850 860 870 880 890 900 TPRNGELFHC VSENEHGAPT RKDMVRSSFV TRHSRIPVLA QEIDSTLESS SPVSAKEKLL 910 920 930 940 950 960 QKKAYQPDLV KLLVEKRQFK SFLGDLSSAS DKLLEEKLAT VPAPFCEEEV LTPFSRLTVD 970 980 990 1000 1010 1020 SHLSRSAEDS FLSPIISQSR KSKIPRPVSW VNTDQVNSST SSQFFPRPPP GKPPTRPGVE 1030 1040 1050 1060 1070 1080 ARLRRYKVLG SSNSDSDLFS RLAQILQNGS QKPRSTTQCK SPGSPHNPKT PPKSPVVPRR 1090 1100 1110 1120 1130 1140 SPSASPRSSS LPRTSSSSPS RAGRPHHDQR SSSPHLGRSK SPPSHSGSSS SRRSCQQEHC 1150 1160 KPSKNGLKGS GSLHHHSAST KTPPREE
	Isoform 3. Checksum: 2F3AF5039B6F021A		478	54,037
	10 20 30 40 50 60 MSGGGEQLDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK VESAQQPKQV 70 80 90 100 110 120 LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN LADLRRSQSR GTFTISTTLR 130 140 150 160 170 180 LGRQILESIE SIHSVGFLHR DIKPSNFAMG RFPSTCRKCY MLDFGLARQF TNSCGDVRPP 190 200 210 220 230 240 RAVAGFRGTV RYASINAHRN REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE 250 260 270 280 290 300 RYDHRLMLKH LPPEFSIFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKT 310 320 330 340 350 360 GNDGSLTTTT TSTTPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE QLSDGENGIP 370 380 390 400 410 420 VGVSPDKLPG SLGHPRPQEK DVWEEMDANK NKIKLGICKA ATEEENSHGQ ANGLLNAPSL 430 440 450 460 470 GSPIRVRSEI TQPDRDIPLV RKLRSIHSFE LEKRLTLEPK PDTDKFLETW YKIVYFSF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cerebellum.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT PRO-8. Tissue: Testis.
[3]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 600-1244 (ISOFORM 1). Tissue: Brain.
[4]	"Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11." Houlden H., Johnson J., Gardner-Thorpe C., Lashley T., Hernandez D., Worth P., Singleton A.B., Hilton D.A., Holton J., Revesz T., Davis M.B., Giunti P., Wood N.W. Nat. Genet. 39:1434-1436(2007) [PubMed: 18037885] [Abstract] Cited for: INVOLVEMENT IN SCA11.
[5]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-8; GLN-120; ALA-313; MET-440; PRO-500; GLY-635; ILE-1062; MET-1084; ALA-1097; ARG-1122 AND THR-1241.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK131372 mRNA. Translation: BAD18523.1. BC041876 mRNA. Translation: AAH41876.1. BC071556 mRNA. Translation: AAH71556.1. AB020654 mRNA. Translation: BAA74870.1.
RefSeq	NP_775771.3.
UniGene	Hs.659846 Hs.695195
3D structure databases
HSSP	HSSP built from PDB template 1CKI based on UniProtKB Q06486.
ModBase	Search...
Proteomic databases
PRIDE	Q6IQ55.
Genome annotation databases
Ensembl	ENSG00000128881. Homo sapiens. [Contig view]
GeneID	146057.
KEGG	hsa:146057.
Organism-specific databases
GeneCards	GC15M040825.
HGNC	HGNC:19141. TTBK2.
HPA	HPA018113.
MIM	604432. phenotype. 611695. gene.
Orphanet	98767. SCA11.
PharmGKB	PA134913925.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q6IQ55.
Gene expression databases
ArrayExpress	Q6IQ55.
CleanEx	HS_TTBK2.
GermOnline	ENSG00000128881. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	85251.
SOURCE	Search...

Entry information

Entry name

TTBK2_HUMAN

Accession

Primary (citable) accession number: Q6IQ55
Secondary accession number(s): O94932, Q6ZN52, Q8IVV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	October 17, 2006
Last modified:	December 16, 2008
This is version 54 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)