Reviewed, UniProtKB/Swiss-Prot O95271 (TNKS1_HUMAN)

Names and origin

Protein names

Recommended name:
    Tankyrase-1
      Short name=TANK1
    EC=2.4.2.30
Alternative name(s):
    Tankyrase I
    TNKS-1
    TRF1-interacting ankyrin-related ADP-ribose polymerase

Gene names

Name:	TNKS
Synonyms:	PARP5A, PARPL, TIN1, TINF1, TNKS1

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	1327 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. Has PARP activity and can modify TERF1, and thereby contribute to the regulation of telomere length. Ref.4 Ref.5
Catalytic activity	NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor.
Subunit structure	Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2.
Subcellular location	Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Nucleus › nuclear pore complex. Telomere Potential. Note: Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles. A minor proportion is also found at nuclear pore complexes and around the pericentriolar matrix of mitotic centromeres. During interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1.
Tissue specificity	Ubiquitous; highest levels in testis.
Post-translational modification	Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Ref.4 Ref.7 ADP-ribosylated (-auto).
Sequence similarities	Contains 15 ANK repeats. Contains 1 PARP catalytic domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport mRNA transport
Cellular component	Chromosomal protein Cytoplasm Golgi apparatus Membrane Nuclear pore complex Nucleus Telomere
Coding sequence diversity	Alternative splicing
Domain	ANK repeat Repeat
Ligand	NAD
Molecular function	Glycosyltransferase Transferase
PTM	ADP-ribosylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	intracellular protein transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle organization Traceable author statement. Source: UniProtKB negative regulation of DNA binding Ref.1 Inferred from direct assay. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay. Source: MGI peptidyl-threonine phosphorylation Inferred from direct assay. Source: MGI positive regulation of telomere maintenance via telomerase Ref.5 Inferred from direct assay. Source: UniProtKB protein amino acid auto-ADP-ribosylation Ref.1 Inferred from direct assay. Source: UniProtKB protein amino acid poly-ADP-ribosylation Ref.1 Inferred from direct assay. Source: UniProtKB protein localization to telomere Inferred from mutant phenotype. Source: UniProtKB spindle assembly Traceable author statement. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from direct assay. Source: UniProtKB nuclear chromosome, telomeric region Ref.5 Inferred from direct assay. Source: UniProtKB nuclear membrane Traceable author statement. Source: UniProtKB nuclear pore Traceable author statement. Source: UniProtKB pericentriolar material Traceable author statement. Source: UniProtKB
Molecular function	NAD+ ADP-ribosyltransferase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Ref.1 Ref.6 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FNBP1	Q96RU3	2	EBI-1105254,EBI-1111248

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95271-1)

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: O95271-2)

The sequence of this isoform differs from the canonical sequence as follows:
     641-643: EST → GHS
     644-1327: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1327	1327	Tankyrase-1		PRO_0000211333
Regions
	Repeat	215 – 247	33	ANK 1
	Repeat	248 – 280	33	ANK 2
	Repeat	281 – 313	33	ANK 3
	Repeat	368 – 400	33	ANK 4
	Repeat	401 – 433	33	ANK 5
	Repeat	434 – 466	33	ANK 6
	Repeat	521 – 556	36	ANK 7
	Repeat	557 – 589	33	ANK 8
	Repeat	590 – 622	33	ANK 9
	Repeat	683 – 715	33	ANK 10
	Repeat	716 – 748	33	ANK 11
	Repeat	749 – 781	33	ANK 12
	Repeat	836 – 868	33	ANK 13
	Repeat	869 – 901	33	ANK 14
	Repeat	902 – 934	33	ANK 15
	Domain	1030 – 1089	60	SAM
	Domain	1112 – 1317	206	PARP catalytic
	Compositional bias	9 – 14	6	Poly-His
	Compositional bias	27 – 34	8	Poly-Pro
	Compositional bias	128 – 134	7	Poly-Ser
	Compositional bias	137 – 145	9	Poly-Ser
Amino acid modifications
	Modified residue	365	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	641 – 643	3	EST → GHS in isoform 2.		VSP_004538
	Alternative sequence	644 – 1327	684	Missing in isoform 2.		VSP_004539
Experimental info
	Mutagenesis	1184	1	H → A: Loss of activity; when associated with A-1291. Ref.5
	Mutagenesis	1291	1	E → A: Loss of activity; when associated with A-1184. Ref.5
	Sequence conflict	802	1	R → K in AAC79841. Ref.1
	Sequence conflict	802	1	R → K in AAC79842. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 14, 2009. Version 2. Checksum: 44BDE985C715BEFF	FASTA	1,327	142,039
	10 20 30 40 50 60 MAASRRSQHH HHHHQQQLQP APGASAPPPP PPPPLSPGLA PGTTPASPTA SGLAPFASPR 70 80 90 100 110 120 HGLALPEGDG SRDPPDRPRS PDPVDGTSCC STTSTICTVA AAPVVPAVST SSAAGVAPNP 130 140 150 160 170 180 AGSGSNNSPS SSSSPTSSSS SSPSSPGSSL AESPEAAGVS STAPLGPGAA GPGTGVPAVS 190 200 210 220 230 240 GALRELLEAC RNGDVSRVKR LVDAANVNAK DMAGRKSSPL HFAAGFGRKD VVEHLLQMGA 250 260 270 280 290 300 NVHARDDGGL IPLHNACSFG HAEVVSLLLC QGADPNARDN WNYTPLHEAA IKGKIDVCIV 310 320 330 340 350 360 LLQHGADPNI RNTDGKSALD LADPSAKAVL TGEYKKDELL EAARSGNEEK LMALLTPLNV 370 380 390 400 410 420 NCHASDGRKS TPLHLAAGYN RVRIVQLLLQ HGADVHAKDK GGLVPLHNAC SYGHYEVTEL 430 440 450 460 470 480 LLKHGACVNA MDLWQFTPLH EAASKNRVEV CSLLLSHGAD PTLVNCHGKS AVDMAPTPEL 490 500 510 520 530 540 RERLTYEFKG HSLLQAAREA DLAKVKKTLA LEIINFKQPQ SHETALHCAV ASLHPKRKQV 550 560 570 580 590 600 TELLLRKGAN VNEKNKDFMT PLHVAAERAH NDVMEVLHKH GAKMNALDTL GQTALHRAAL 610 620 630 640 650 660 AGHLQTCRLL LSYGSDPSII SLQGFTAAQM GNEAVQQILS ESTPIRTSDV DYRLLEASKA 670 680 690 700 710 720 GDLETVKQLC SSQNVNCRDL EGRHSTPLHF AAGYNRVSVV EYLLHHGADV HAKDKGGLVP 730 740 750 760 770 780 LHNACSYGHY EVAELLVRHG ASVNVADLWK FTPLHEAAAK GKYEICKLLL KHGADPTKKN 790 800 810 820 830 840 RDGNTPLDLV KEGDTDIQDL LRGDAALLDA AKKGCLARVQ KLCTPENINC RDTQGRNSTP 850 860 870 880 890 900 LHLAAGYNNL EVAEYLLEHG ADVNAQDKGG LIPLHNAASY GHVDIAALLI KYNTCVNATD 910 920 930 940 950 960 KWAFTPLHEA AQKGRTQLCA LLLAHGADPT MKNQEGQTPL DLATADDIRA LLIDAMPPEA 970 980 990 1000 1010 1020 LPTCFKPQAT VVSASLISPA STPSCLSAAS SIDNLTGPLA ELAVGGASNA GDGAAGTERK 1030 1040 1050 1060 1070 1080 EGEVAGLDMN ISQFLKSLGL EHLRDIFETE QITLDVLADM GHEELKEIGI NAYGHRHKLI 1090 1100 1110 1120 1130 1140 KGVERLLGGQ QGTNPYLTFH CVNQGTILLD LAPEDKEYQS VEEEMQSTIR EHRDGGNAGG 1150 1160 1170 1180 1190 1200 IFNRYNVIRI QKVVNKKLRE RFCHRQKEVS EENHNHHNER MLFHGSPFIN AIIHKGFDER 1210 1220 1230 1240 1250 1260 HAYIGGMFGA GIYFAENSSK SNQYVYGIGG GTGCPTHKDR SCYICHRQML FCRVTLGKSF 1270 1280 1290 1300 1310 1320 LQFSTMKMAH APPGHHSVIG RPSVNGLAYA EYVIYRGEQA YPEYLITYQI MKPEAPSQTA TAAEQKT
	Isoform 2. Checksum: FA67DE30C2A2F3B8	FASTA	643	67,203
	10 20 30 40 50 60 MAASRRSQHH HHHHQQQLQP APGASAPPPP PPPPLSPGLA PGTTPASPTA SGLAPFASPR 70 80 90 100 110 120 HGLALPEGDG SRDPPDRPRS PDPVDGTSCC STTSTICTVA AAPVVPAVST SSAAGVAPNP 130 140 150 160 170 180 AGSGSNNSPS SSSSPTSSSS SSPSSPGSSL AESPEAAGVS STAPLGPGAA GPGTGVPAVS 190 200 210 220 230 240 GALRELLEAC RNGDVSRVKR LVDAANVNAK DMAGRKSSPL HFAAGFGRKD VVEHLLQMGA 250 260 270 280 290 300 NVHARDDGGL IPLHNACSFG HAEVVSLLLC QGADPNARDN WNYTPLHEAA IKGKIDVCIV 310 320 330 340 350 360 LLQHGADPNI RNTDGKSALD LADPSAKAVL TGEYKKDELL EAARSGNEEK LMALLTPLNV 370 380 390 400 410 420 NCHASDGRKS TPLHLAAGYN RVRIVQLLLQ HGADVHAKDK GGLVPLHNAC SYGHYEVTEL 430 440 450 460 470 480 LLKHGACVNA MDLWQFTPLH EAASKNRVEV CSLLLSHGAD PTLVNCHGKS AVDMAPTPEL 490 500 510 520 530 540 RERLTYEFKG HSLLQAAREA DLAKVKKTLA LEIINFKQPQ SHETALHCAV ASLHPKRKQV 550 560 570 580 590 600 TELLLRKGAN VNEKNKDFMT PLHVAAERAH NDVMEVLHKH GAKMNALDTL GQTALHRAAL 610 620 630 640 AGHLQTCRLL LSYGSDPSII SLQGFTAAQM GNEAVQQILS GHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tankyrase, a poly(ADP-ribose) polymerase at human telomeres." Smith S., Giriat I., Schmitt A., de Lange T. Science 282:1484-1487(1998) [PubMed: 9822378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Testis.
[2]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes." Smith S., de Lange T. J. Cell Sci. 112:3649-3656(1999) [PubMed: 10523501] [Abstract] Cited for: SUBCELLULAR LOCATION.
[4]	"Tankyrase is a Golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles." Chi N.-W., Lodish H.F. J. Biol. Chem. 275:38437-38444(2000) [PubMed: 10988299] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION.
[5]	"Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres." Cook B.D., Dynek J.N., Chang W., Shostak G., Smith S. Mol. Cell. Biol. 22:332-342(2002) [PubMed: 11739745] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-1184 AND GLU-1291.
[6]	"POT1 as a terminal transducer of TRF1 telomere length control." Loayza D., De Lange T. Nature 423:1013-1018(2003) [PubMed: 12768206] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH POT1; TERF1 AND TINF2.
[7]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF082556 mRNA. Translation: AAC79841.1.
AF082557 mRNA. Translation: AAC79842.1.
AF082558 mRNA. Translation: AAC79843.1.
AF082559 mRNA. Translation: AAC79844.1.
AC103834 Genomic DNA. No translation available.
AC103877 Genomic DNA. No translation available.
AC104052 Genomic DNA. No translation available.
AC021242 Genomic DNA. No translation available.

IPI

IPI00021493.
IPI00221159.

RefSeq

NP_003738.2.

UniGene

Hs.370267

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RF5	X-ray	2.30	A	1091-1325	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O95271. 3 interactions.

PTM databases

PhosphoSite

O95271.

Genome annotation databases

Ensembl

ENSG00000173273. Homo sapiens. [Contig view]

GeneID

8658.

KEGG

hsa:8658.

Organism-specific databases

GeneCards

GC08P009450.

H-InvDB

HIX0034248.

HGNC

HGNC:11941. TNKS.

MIM

603303. gene.

PharmGKB

PA36631.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O95271.

HOVERGEN

O95271.

OMA

O95271. IINFKQP.

Enzyme and pathway databases

BRENDA

2.4.2.30. 247.

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Gene expression databases

ArrayExpress

O95271.

Bgee

O95271.

CleanEx

HS_TNKS.

GermOnline

ENSG00000173273. Homo sapiens.

Family and domain databases

InterPro

IPR002110. ANK.
IPR012317. PARP_catalytic.
IPR001660. SAM.
IPR011510. SAM_2.
IPR013761. SAM_type.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 4 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.

Pfam

PF00023. Ank. 19 hits.
PF00644. PARP. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]

SMART

SM00248. ANK. 17 hits.
SM00454. SAM. 1 hit.
[Graphical view]

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 15 hits.
PS51059. PARP_CATALYTIC. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

32469.

SOURCE

Search...

Entry information

Entry name

TNKS1_HUMAN

Accession

Primary (citable) accession number: O95271
Secondary accession number(s): O95272

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	April 14, 2009
Last modified:	June 16, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)