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Q9BSI4 (TINF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
TERF1-interacting nuclear factor 2
Alternative name(s):
TRF1-interacting nuclear protein 2
Gene names
Name:TINF2
Synonyms:TIN2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.9 Ref.10 Ref.13

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.5 Ref.6 Ref.7 Ref.8

Subcellular location

Nucleus. Chromosometelomere. Note: Associated with telomeres. Ref.12 Ref.13

Isoform 1: Nucleus matrix Ref.12 Ref.13.

Tissue specificity

Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Domain

The TBM domain mediates interaction with TERF1. Ref.17

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.18

Dyskeratosis congenita, autosomal dominant, 5 (DKCA5) [MIM:268130]: A disease characterized by bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, oral leukoplakia, bilateral exudative retinopathy, cerebellar hypoplasia, and growth retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18

Ontologies

Keywords
   Cellular componentChromosome
Nucleus
Telomere
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Dyskeratosis congenita
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative 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

Inferred from mutant phenotype PubMed 15133513. 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.10. Source: BHF-UCL

telomere maintenance

Traceable author statement. Source: Reactome

telomere maintenance via telomere lengthening

Inferred from mutant phenotype PubMed 18669893. Source: BHF-UCL

   Cellular_componentchromosome, telomeric region

Inferred from direct assay Ref.1Ref.5PubMed 15380063. Source: BHF-UCL

nuclear matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear telomere cap complex

Inferred from direct assay Ref.10. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

perinucleolar chromocenter

Inferred from direct assay PubMed 15741234. Source: BHF-UCL

   Molecular_functionprotein binding

Inferred from physical interaction Ref.8. Source: IntAct

telomeric DNA binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

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)

Also known as: TIN2S;

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.16
Chain2 – 451450TERF1-interacting nuclear factor 2
PRO_0000072541

Regions

Motif256 – 27823TBM
Motif262 – 2687Nuclear localization signal Potential

Amino acid modifications

Modified residue21N-acetylalanine Ref.16
Modified residue2951Phosphoserine Ref.11

Natural variations

Alternative sequence134 – 1374ELEQ → VRLV in isoform 3.
VSP_003987
Alternative sequence138 – 451314Missing in isoform 3.
VSP_003988
Alternative sequence355 – 45197Missing in isoform 2.
VSP_003989
Natural variant431A → T.
Corresponds to variant rs35653076 [ dbSNP | Ensembl ].
VAR_051423
Natural variant2371G → D.
Corresponds to variant rs17102313 [ dbSNP | Ensembl ].
VAR_051424
Natural variant2411P → S.
Corresponds to variant rs17102311 [ dbSNP | Ensembl ].
VAR_051425
Natural variant2801K → E in DKCA3. Ref.18
VAR_043914
Natural variant2821R → H in DKCA3 and DKCA5. Ref.18
VAR_043915
Natural variant2821R → S in DKCA3. Ref.18
VAR_043916

Experimental info

Mutagenesis2581F → A: Abolishes interaction with TERF1. Ref.17
Mutagenesis2621P → A: Does not effect interaction with TERF1. Ref.17
Sequence conflict441V → I in BAB14440. Ref.2
Sequence conflict671Missing in BAB14440. Ref.2
Sequence conflict3021K → N in AAF18439. Ref.1
Sequence conflict323 – 33210ASTGKSKSPC → PSNGKYKGPY in AAF18439. Ref.1

Secondary structure

... 451
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TIN2L) [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: E5A7FD11CE523979

FASTA45150,023
        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 

« Hide

Isoform 2 (TIN2S) [UniParc].

Checksum: 903B69D7B6A15C01
Show »

FASTA35439,444
Isoform 3 [UniParc].

Checksum: 3BA7286B15EAC870
Show »

FASTA13715,434

References

« Hide '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. expand/collapse author list , 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]"A novel form of telomere-associated TIN2 localizes to the nuclear matrix."
Kaminker P.G., Kim S.-H., Desprez P.Y., Campisi J.
Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 163-451 (ISOFORM 1).
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"The long and short of it: a new isoform of TIN2 in the nuclear matrix."
Smith S.
Cell Cycle 8:797-798(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION.
[13]"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).
[14]"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.
[15]"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].
[16]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[17]"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.
[18]"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 DKCA5 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.
EU851975 mRNA. Translation: ACF17559.1.
CCDSCCDS41936.1. [Q9BSI4-1]
CCDS41937.1. [Q9BSI4-2]
RefSeqNP_001092744.1. NM_001099274.1. [Q9BSI4-1]
NP_036593.2. NM_012461.2. [Q9BSI4-2]
UniGeneHs.496191.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BQOX-ray2.00B257-276[»]
3BU8X-ray2.15C/D258-275[»]
ProteinModelPortalQ9BSI4.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117660. 93 interactions.
DIPDIP-29413N.
IntActQ9BSI4. 10 interactions.
MINTMINT-221357.
STRING9606.ENSP00000267415.

PTM databases

PhosphoSiteQ9BSI4.

Polymorphism databases

DMDM21542262.

Proteomic databases

MaxQBQ9BSI4.
PaxDbQ9BSI4.
PRIDEQ9BSI4.

Protocols and materials databases

DNASU26277.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000267415; ENSP00000267415; ENSG00000092330. [Q9BSI4-1]
ENST00000399423; ENSP00000382350; ENSG00000092330. [Q9BSI4-2]
GeneID26277.
KEGGhsa:26277.
UCSCuc001woa.4. human. [Q9BSI4-1]

Organism-specific databases

CTD26277.
GeneCardsGC14M024708.
GeneReviewsTINF2.
HGNCHGNC:11824. TINF2.
HPAHPA059061.
MIM268130. phenotype.
604319. gene.
613990. phenotype.
neXtProtNX_Q9BSI4.
Orphanet1775. Dyskeratosis congenita.
3322. Hoyeraal-Hreidarsson syndrome.
3088. Retinopathy - anemia- central nervous system anomalies.
PharmGKBPA36530.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43106.
HOGENOMHOG000247003.
HOVERGENHBG057120.
InParanoidQ9BSI4.
KOK11112.
OMAGRPWAQV.
PhylomeDBQ9BSI4.
TreeFamTF334731.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressQ9BSI4.
BgeeQ9BSI4.
CleanExHS_TINF2.
GenevestigatorQ9BSI4.

Family and domain databases

InterProIPR029400. TINF2_N.
[Graphical view]
PfamPF14973. TINF2_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9BSI4.
GeneWikiTINF2.
GenomeRNAi26277.
NextBio35470863.
PROQ9BSI4.
SOURCESearch...

Entry information

Entry nameTINF2_HUMAN
AccessionPrimary (citable) accession number: Q9BSI4
Secondary accession number(s): B3W5Q7, Q9H904, Q9UHC2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM