Q9BSI4 (TINF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TERF1-interacting nuclear factor 2

Alternative name(s):
TRF1-interacting nuclear protein 2

Gene names

Name:	TINF2
Synonyms:	TIN2

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

General annotation (Comments)

Function	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix. Ref.8 Ref.9 Ref.11
Subunit structure	Monomer. Found in a complex with POT1; TERF1 and TNKS1. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with TERF1, TERF2 and ACD. Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Nucleus. Chromosome › telomere. Note: Associated with telomeres. Ref.11 Isoform 1: Nucleus matrix Ref.11.
Tissue specificity	Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Domain	The TBM domain mediates interaction with TERF1. Ref.14
Involvement in disease	Dyskeratosis congenita, autosomal dominant, 3 (DKCA3) [MIM:613990]: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Retinopathy exudative with bone marrow failure (ERBMF) [MIM:268130]: A disease characterized by bilateral exudative retinopathy, bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, cerebellar hypoplasia, and growth retardation. ERBMF appears to be part of the dyskeratosis congenita disease spectrum. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Ontologies

Keywords
Cellular component	Chromosome Nucleus Telomere
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dyskeratosis congenita
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 15741234. Source: BHF-UCL negative regulation of protein ADP-ribosylation Inferred from genetic interaction PubMed 15133513. Source: BHF-UCL negative regulation of telomere maintenance via telomerase Inferred from genetic interaction Ref.1. Source: BHF-UCL positive regulation of telomere maintenance Inferred from mutant phenotype PubMed 18443218. Source: BHF-UCL protein localization to chromosome, telomeric region Inferred from mutant phenotype PubMed 18443218. Source: BHF-UCL telomere assembly Inferred from mutant phenotype Ref.9. Source: BHF-UCL telomere maintenance via telomere lengthening Inferred from mutant phenotype PubMed 18669893. Source: BHF-UCL
Cellular_component	nuclear matrix Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear telomere cap complex Inferred from direct assay Ref.9. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome perinucleolar chromocenter Inferred from direct assay PubMed 15741234. Source: BHF-UCL
Molecular_function	telomeric DNA binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACD	Q96AP0	5	EBI-717418,EBI-717666
TERF1	P54274	2	EBI-717418,EBI-710997
TERF2	Q15554	4	EBI-717418,EBI-706637
TERF2IP	Q9NYB0	3	EBI-717418,EBI-750109

Alternative products

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

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9BSI4-1)

Also known as: TIN2L;

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: Q9BSI4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     355-451: Missing.

Isoform 3 (identifier: Q9BSI4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     134-137: ELEQ → VRLV
     138-451: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 451

451

TERF1-interacting nuclear factor 2

PRO_0000072541

Regions

Motif

256 – 278

23

TBM

Motif

262 – 268

7

Nuclear localization signal Potential

Amino acid modifications

Modified residue

295

1

Phosphoserine Ref.10

Natural variations

Alternative sequence

134 – 137

4

ELEQ → VRLV in isoform 3.

VSP_003987

Alternative sequence

138 – 451

314

Missing in isoform 3.

VSP_003988

Alternative sequence

355 – 451

97

Missing in isoform 2.

VSP_003989

Natural variant

43

1

A → T.
Corresponds to variant rs35653076 [ dbSNP | Ensembl ].

VAR_051423

Natural variant

237

1

G → D.
Corresponds to variant rs17102313 [ dbSNP | Ensembl ].

VAR_051424

Natural variant

241

1

P → S.
Corresponds to variant rs17102311 [ dbSNP | Ensembl ].

VAR_051425

Natural variant

280

1

K → E in DKCA3. Ref.15

VAR_043914

Natural variant

282

1

R → H in DKCA3 and ERBMF. Ref.15

VAR_043915

Natural variant

282

1

R → S in DKCA3. Ref.15

VAR_043916

Experimental info

Mutagenesis

258

1

F → A: Abolishes interaction with TERF1. Ref.14

Mutagenesis

262

1

P → A: Does not effect interaction with TERF1. Ref.14

Sequence conflict

44

1

V → I in BAB14440. Ref.2

Sequence conflict

67

1

Missing in BAB14440. Ref.2

Sequence conflict

302

1

K → N in AAF18439. Ref.1

Sequence conflict

323 – 332

10

ASTGKSKSPC → PSNGKYKGPY in AAF18439. Ref.1

Secondary structure

1

.

.

.

451

Helix Strand Turn

Details...

Beta strand

263 – 265

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TIN2L) [UniParc]. Last modified June 1, 2001. Version 1. Checksum: E5A7FD11CE523979	FASTA	451	50,023
	10 20 30 40 50 60 MATPLVAGPA ALRFAAAASW QVVRGRCVEH FPRVLEFLRS LRAVAPGLVR YRHHERLCMG 70 80 90 100 110 120 LKAKVVVELI LQGRPWAQVL KALNHHFPES GPIVRDPKAT KQDLRKILEA QETFYQQVKQ 130 140 150 160 170 180 LSEAPVDLAS KLQELEQEYG EPFLAAMEKL LFEYLCQLEK ALPTPQAQQL QDVLSWMQPG 190 200 210 220 230 240 VSITSSLAWR QYGVDMGWLL PECSVTDSVN LAEPMEQNPP QQQRLALHNP LPKAKPGTHL 250 260 270 280 290 300 PQGPSSRTHP EPLAGRHFNL APLGRRRVQS QWASTRGGHK ERPTVMLFPF RNLGSPTQVI 310 320 330 340 350 360 SKPESKEEHA IYTADLAMGT RAASTGKSKS PCQTLGGRAL KENPVDLPAT EQKENCLDCY 370 380 390 400 410 420 MDPLRLSLLP PRARKPVCPP SLCSSVITIG DLVLDSDEEE NGQGEGKESL ENYQKTKFDT 430 440 450 LIPTLCEYLP PSGHGAIPVS SCDCRDSSRP L
	Isoform 2 [UniParc]. Checksum: 903B69D7B6A15C01	FASTA	354	39,444
	10 20 30 40 50 60 MATPLVAGPA ALRFAAAASW QVVRGRCVEH FPRVLEFLRS LRAVAPGLVR YRHHERLCMG 70 80 90 100 110 120 LKAKVVVELI LQGRPWAQVL KALNHHFPES GPIVRDPKAT KQDLRKILEA QETFYQQVKQ 130 140 150 160 170 180 LSEAPVDLAS KLQELEQEYG EPFLAAMEKL LFEYLCQLEK ALPTPQAQQL QDVLSWMQPG 190 200 210 220 230 240 VSITSSLAWR QYGVDMGWLL PECSVTDSVN LAEPMEQNPP QQQRLALHNP LPKAKPGTHL 250 260 270 280 290 300 PQGPSSRTHP EPLAGRHFNL APLGRRRVQS QWASTRGGHK ERPTVMLFPF RNLGSPTQVI 310 320 330 340 350 SKPESKEEHA IYTADLAMGT RAASTGKSKS PCQTLGGRAL KENPVDLPAT EQKE
	Isoform 3 [UniParc]. Checksum: 3BA7286B15EAC870	FASTA	137	15,434
	10 20 30 40 50 60 MATPLVAGPA ALRFAAAASW QVVRGRCVEH FPRVLEFLRS LRAVAPGLVR YRHHERLCMG 70 80 90 100 110 120 LKAKVVVELI LQGRPWAQVL KALNHHFPES GPIVRDPKAT KQDLRKILEA QETFYQQVKQ 130 LSEAPVDLAS KLQVRLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TIN2, a new regulator of telomere length in human cells." Kim S.-H., Kaminker P., Campisi J. Nat. Genet. 23:405-412(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Fibroblast.
[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 3). Tissue: Teratocarcinoma.
[3]	"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: Placenta and Uterus.
[4]	"POT1 as a terminal transducer of TRF1 telomere length control." Loayza D., De Lange T. Nature 423:1013-1018(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH POT1; TERF1 AND TNKS1.
[5]	"POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex." Ye J.Z.-S., Hockemeyer D., Krutchinsky A.N., Loayza D., Hooper S.M., Chait B.T., de Lange T. Genes Dev. 18:1649-1654(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACD.
[6]	"TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres." Ye J.Z.-S., Donigian J.R., van Overbeek M., Loayza D., Luo Y., Krutchinsky A.N., Chait B.T., de Lange T. J. Biol. Chem. 279:47264-47271(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[7]	"Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins." Liu D., O'Connor M.S., Qin J., Songyang Z. J. Biol. Chem. 279:51338-51342(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[8]	"Shelterin: the protein complex that shapes and safeguards human telomeres." de Lange T. Genes Dev. 19:2100-2110(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE SHELTERIN COMPLEX.
[9]	"A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly." O'Connor M.S., Safari A., Xin H., Liu D., Songyang Z. Proc. Natl. Acad. Sci. U.S.A. 103:11874-11879(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SHELTERIN COMPLEX ASSEMBLY.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A novel form of the telomere-associated protein TIN2 localizes to the nuclear matrix." Kaminker P.G., Kim S.H., Desprez P.Y., Campisi J. Cell Cycle 8:931-939(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1).
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins." Chen Y., Yang Y., van Overbeek M., Donigian J.R., Baciu P., de Lange T., Lei M. Science 319:1092-1096(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 258-275 IN COMPLEX WITH TERF1 OR TERF2, DOMAIN TBM, MUTAGENESIS OF PHE-258 AND PRO-262.
[15]	"TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita." Savage S.A., Giri N., Baerlocher G.M., Orr N., Lansdorp P.M., Alter B.P. Am. J. Hum. Genet. 82:501-509(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DKCA3 GLU-280; HIS-282 AND SER-282, VARIANT ERBMF HIS-282.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF195512 mRNA. Translation: AAF18439.1.
AK023166 mRNA. Translation: BAB14440.1.
BC005030 mRNA. Translation: AAH05030.1.
BC019343 mRNA. Translation: AAH19343.1.

IPI

IPI00074109.
IPI00218680.
IPI00218681.

RefSeq

NP_001092744.1. NM_001099274.1.
NP_036593.2. NM_012461.2.

UniGene

Hs.496191.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BQO	X-ray	2.00	B	257-276	[»]
3BU8	X-ray	2.15	C/D	258-275	[»]

ProteinModelPortal

Q9BSI4.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29413N.

IntAct

Q9BSI4. 8 interactions.

MINT

MINT-221357.

STRING

9606.ENSP00000267415.

PTM databases

PhosphoSite

Q9BSI4.

Polymorphism databases

DMDM

21542262.

Proteomic databases

PaxDb

Q9BSI4.

PRIDE

Q9BSI4.

Protocols and materials databases

DNASU

26277.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267415; ENSP00000267415; ENSG00000092330.
ENST00000399423; ENSP00000382350; ENSG00000092330.

GeneID

26277.

KEGG

hsa:26277.

UCSC

uc001woa.4. human.
uc001woc.4. human.

Organism-specific databases

CTD

26277.

GeneCards

GC14M024708.

HGNC

HGNC:11824. TINF2.

MIM

268130. phenotype.
604319. gene.
613990. phenotype.

neXtProt

NX_Q9BSI4.

Orphanet

1775. Dyskeratosis congenita.
3088. Retinopathy - anemia- central nervous system anomalies.

PharmGKB

PA36530.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43106.

HOGENOM

HOG000247003.

HOVERGEN

HBG057120.

InParanoid

Q9BSI4.

KO

K11112.

OMA

YGVDMGW.

OrthoDB

EOG4R503S.

PhylomeDB

Q9BSI4.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Reactome

REACT_111183. Meiosis.
REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpress

Q9BSI4.

Bgee

Q9BSI4.

CleanEx

HS_TINF2.

Genevestigator

Q9BSI4.

GermOnline

ENSG00000092330. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other

EvolutionaryTrace

Q9BSI4.

GenomeRNAi

26277.

NextBio

48587.

SOURCE

Search...

Entry information

Entry name

TINF2_HUMAN

Accession

Primary (citable) accession number: Q9BSI4
Secondary accession number(s): Q9H904, Q9UHC2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 110 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.