Q96BK5 (PINX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PIN2/TERF1-interacting telomerase inhibitor 1

Alternative name(s):
Liver-related putative tumor suppressor
Pin2-interacting protein X1
Protein 67-11-3
TRF1-interacting protein 1

Gene names

Name:	PINX1
Synonyms:	LPTL, LPTS

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

General annotation (Comments)

Function	Microtubule-binding protein essential for faithful chromosome segregation. Mediates TRF1 and TERT accumulation in nucleolus and enhances TRF1 binding to telomeres. Inhibits telomerase activity. May inhibit cell proliferation and act as tumor suppressor. Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17
Subunit structure	Interacts with MCRS1, TERT, TERF1, NCL/nucleolin, and the telomerase RNA. Ref.10 Ref.11 Ref.13 Ref.14
Subcellular location	Nucleus. Nucleus › nucleolus. Chromosome › telomere. Chromosome › centromere › kinetochore. Note: Localizes in nucleoli, at telomere speckles and to the outer plate of kinetochores. Localization to the kinetochore is mediated by its central region and depends on NDC80 and CENPE. Ref.14 Ref.16 Ref.17
Tissue specificity	Ubiquitous; expressed at low levels. Not detectable in a number of hepatocarcinoma cell lines.
Domain	The TID (telomerase inhibiting domain) domain is sufficient to bind TERT and inhibit its activity. Ref.13 The TBM domain mediates interaction with TERF1. Ref.13
Sequence similarities	Belongs to the PINX1 family. Contains 1 G-patch domain.

Ontologies

Keywords
Cellular component	Centromere Chromosome Kinetochore Nucleus Telomere
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mitotic metaphase plate congression Inferred from mutant phenotype Ref.14. Source: UniProtKB negative regulation of cell proliferation Non-traceable author statement Ref.1. Source: UniProtKB
Cellular component	chromosome, telomeric region Inferred from electronic annotation. Source: UniProtKB-SubCell condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay. Source: HPA nuclear chromosome Inferred from direct assay Ref.14. Source: UniProtKB nucleolus Inferred from direct assay Ref.14. Source: UniProtKB spindle Inferred from direct assay Ref.14. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.11Ref.14. Source: UniProtKB telomerase inhibitor activity Traceable author statement Ref.11. Source: UniProtKB telomeric RNA binding Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AHCY	P23526	1	EBI-721782,EBI-1053240
CALM1	P62158	1	EBI-721782,EBI-397435
CAPRIN1	Q14444	1	EBI-721782,EBI-1047080
GTPBP4	Q9BZE4	1	EBI-721782,EBI-1056249
HRNR	Q86YZ3	1	EBI-721782,EBI-1047017
PABPC1	P11940	1	EBI-721782,EBI-81531
PABPC4	Q13310	1	EBI-721782,EBI-372844
PLEKHJ1	Q9NW61	1	EBI-721782,EBI-1057560
RPL23A	P62750	1	EBI-721782,EBI-353254
RPL31	P62899	1	EBI-721782,EBI-1053664
RPS10	P46783	1	EBI-721782,EBI-354442
RPS16	P62249	1	EBI-721782,EBI-352480
RPS19	P39019	1	EBI-721782,EBI-354451
RPS28	P62857	1	EBI-721782,EBI-353027
RPS3A	P61247	1	EBI-721782,EBI-352378
TXN	P10599	1	EBI-721782,EBI-594644

Alternative products

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

Isoform 1 (identifier: Q96BK5-1)

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: Q96BK5-2)

Also known as: PINY1;

The sequence of this isoform differs from the canonical sequence as follows:
     133-174: KDLSSRSKTD...PEENETTTTS → RCQSLHSRGE...EQAPGSSSRV
     175-328: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 328	328	PIN2/TERF1-interacting telomerase inhibitor 1		PRO_0000058443
Regions
	Domain	26 – 72	47	G-patch
	Region	254 – 328	75	Telomerase inhibitory domain (TID)
	Motif	287 – 297	11	TBM
Natural variations
	Alternative sequence	133 – 174	42	KDLSS…TTTTS → RCQSLHSRGERNHDNQRLHH PGVLCQADGSTEEQAPGSSS RV in isoform 2.		VSP_003945
	Alternative sequence	175 – 328	154	Missing in isoform 2.		VSP_003946
	Natural variant	206	1	Q → H. Corresponds to variant rs35530857 [ dbSNP | Ensembl ].		VAR_054024
	Natural variant	215	1	R → I. Ref.7 Corresponds to variant rs17855458 [ dbSNP | Ensembl ].		VAR_054025
	Natural variant	220	1	T → A. Corresponds to variant rs17711777 [ dbSNP | Ensembl ].		VAR_054026
	Natural variant	254	1	S → C. Ref.2 Corresponds to variant rs1078543 [ dbSNP | Ensembl ].		VAR_054027
	Natural variant	315	1	E → A. Corresponds to variant rs34656824 [ dbSNP | Ensembl ].		VAR_054028
Experimental info
	Mutagenesis	291	1	L → A: Abolishes interaction with TERF1. Ref.13
	Mutagenesis	293	1	P → A: Does not affect interaction with TERF1. Ref.13
	Sequence conflict	50	1	Q → H in AAH15479. Ref.9
	Sequence conflict	185 – 186	2	RM → PV in AAK31790. Ref.2
	Sequence conflict	204	1	E → V in CAC51436. Ref.3
	Sequence conflict	205	1	T → A in AAS19507. Ref.6
	Sequence conflict	259	1	E → K in AAK31790. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 20, 2002. Version 2. Checksum: A298B31AEA6D18E1	FASTA	328	37,035
	10 20 30 40 50 60 MSMLAERRRK QKWAVDPQNT AWSNDDSKFG QRMLEKMGWS KGKGLGAQEQ GATDHIKVQV 70 80 90 100 110 120 KNNHLGLGAT INNEDNWIAH QDDFNQLLAE LNTCHGQETT DSSDKKEKKS FSLEEKSKIS 130 140 150 160 170 180 KNRVHYMKFT KGKDLSSRSK TDLDCIFGKR QSKKTPEGDA SPSTPEENET TTTSAFTIQE 190 200 210 220 230 240 YFAKRMAALK NKPQVPVPGS DISETQVERK RGKKRNKEAT GKDVESYLQP KAKRHTEGKP 250 260 270 280 290 300 ERAEAQERVA KKKSAPAEEQ LRGPCWDQSS KASAQDAGDH VQPPEGRDFT LKPKKRRGKK 310 320 KLQKPVEIAE DATLEETLVK KKKKKDSK
	Isoform 2 (PINY1) [UniParc]. Checksum: C569D5959A04362C	FASTA	174	19,714
	10 20 30 40 50 60 MSMLAERRRK QKWAVDPQNT AWSNDDSKFG QRMLEKMGWS KGKGLGAQEQ GATDHIKVQV 70 80 90 100 110 120 KNNHLGLGAT INNEDNWIAH QDDFNQLLAE LNTCHGQETT DSSDKKEKKS FSLEEKSKIS 130 140 150 160 170 KNRVHYMKFT KGRCQSLHSR GERNHDNQRL HHPGVLCQAD GSTEEQAPGS SSRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the gene for a novel liver-related putative tumor suppressor at a high-frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma." Liao C., Zhao M., Song H., Uchida K., Yokoyama K.K., Li T.P. Hepatology 32:721-727(2000) [PubMed: 11003615] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[2]	"The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor." Zhou X.Z., Lu K.P. Cell 107:347-359(2001) [PubMed: 11701125] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CYS-254. Tissue: Cervix carcinoma.
[3]	Schmidt T. Thesis (2001), University of Goettingen, Germany Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Identification of the gene LPTL, encoding for a new isoform of human putative tumor suppressor LPTS." Liao C., Zhao M., Li T.P. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	Qiang F. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]	Fu Q., Cao Y., Zuo A., Liang D., Zhang Y., Wang B., Huang H., Wu Y., Zhu L., Wang P., Guo S., Guo G., Zhang J., Wang X. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]	"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 1), VARIANT ILE-215.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORM 1). Tissue: Uterus.
[10]	"Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length." Song H., Li Y., Chen G., Xing Z., Zhao J., Yokoyama K.K., Li T., Zhao M. Biochem. Biophys. Res. Commun. 316:1116-1123(2004) [PubMed: 15044100] [Abstract] Cited for: INTERACTION WITH MCRS1.
[11]	"Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR." Banik S.S.R., Counter C.M. J. Biol. Chem. 279:51745-51748(2004) [PubMed: 15381700] [Abstract] Cited for: FUNCTION, INTERACTION WITH TERT AND THE TELOMERASE RNA.
[12]	"Characterization of a novel effect of hPinX1 on hTERT nucleolar localization." Lin J., Jin R., Zhang B., Yang P.X., Chen H., Bai Y.X., Xie Y., Huang C., Huang J. Biochem. Biophys. Res. Commun. 353:946-952(2007) [PubMed: 17198684] [Abstract] Cited for: FUNCTION.
[13]	"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: 18202258] [Abstract] Cited for: INTERACTION WITH TERF1, DOMAIN TBM, MUTAGENESIS OF LEU-291 AND PRO-293.
[14]	"PinX1 is recruited to the mitotic chromosome periphery by nucleolin and facilitates chromosome congression." Li N., Yuan K., Yan F., Huo Y., Zhu T., Liu X., Guo Z., Yao X. Biochem. Biophys. Res. Commun. 384:76-81(2009) [PubMed: 19393617] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NCL/NUCLEOLIN.
[15]	"Silencing PinX1 compromises telomere length maintenance as well as tumorigenicity in telomerase-positive human cancer cells." Zhang B., Bai Y.X., Ma H.H., Feng F., Jin R., Wang Z.L., Lin J., Sun S.P., Yang P., Wang X.X., Huang P.T., Huang C.F., Peng Y., Chen Y.C., Kung H.F., Huang J.J. Cancer Res. 69:75-83(2009) [PubMed: 19117989] [Abstract] Cited for: FUNCTION.
[16]	"PinX1 is a novel microtubule-binding protein essential for accurate chromosome segregation." Yuan K., Li N., Jiang K., Zhu T., Huo Y., Wang C., Lu J., Shaw A., Thomas K., Zhang J., Mann D., Liao J., Jin C., Yao X. J. Biol. Chem. 284:23072-23082(2009) [PubMed: 19553660] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
[17]	"Human PinX1 mediates TRF1 accumulation in nucleolus and enhances TRF1 binding to telomeres." Yoo J.E., Oh B.-K., Park Y.N. J. Mol. Biol. 388:928-940(2009) [PubMed: 19265708] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF205718 mRNA. Translation: AAG18009.1. AY029161 mRNA. Translation: AAK31790.1. AJ344104 mRNA. Translation: CAC51436.1. AF418553 mRNA. Translation: AAN31333.1. AY238941 mRNA. Translation: AAP37006.1. AY523566 mRNA. Translation: AAS19507.1. AK000572 mRNA. Translation: BAA91263.1. AK313715 mRNA. Translation: BAG36458.1. CH471157 Genomic DNA. Translation: EAW65596.1. BC015479 mRNA. Translation: AAH15479.1. BC093762 mRNA. Translation: AAH93762.1.
IPI	IPI00297357. IPI00385561.
RefSeq	NP_060354.4. NM_017884.4.
UniGene	Hs.490991. Hs.583894.
3D structure databases
ProteinModelPortal	Q96BK5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96BK5. 6 interactions.
MINT	MINT-221403.
STRING	Q96BK5.
PTM databases
PhosphoSite	Q96BK5.
Polymorphism databases
DMDM	21542178.
Proteomic databases
PRIDE	Q96BK5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	54984.
KEGG	hsa:54984.
UCSC	uc003wth.2. human. uc003wti.2. human.
Organism-specific databases
CTD	54984.
GeneCards	GC08M010659.
H-InvDB	HIX0023045.
HGNC	HGNC:30046. PINX1.
HPA	HPA023139.
MIM	606505. gene.
neXtProt	NX_Q96BK5.
PharmGKB	PA165585852.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12019.
GeneTree	ENSGT00600000084237.
HOVERGEN	HBG061365.
InParanoid	Q96BK5.
Enzyme and pathway databases
Pathway_Interaction_DB	telomerasepathway. Regulation of Telomerase.
Gene expression databases
ArrayExpress	Q96BK5.
Bgee	Q96BK5.
Genevestigator	Q96BK5.
GermOnline	ENSG00000104637. Homo sapiens.
Family and domain databases
InterPro	IPR000467. G_patch. [Graphical view]
KO	K11135.
Pfam	PF01585. G-patch. 1 hit. [Graphical view]
SMART	SM00443. G_patch. 1 hit. [Graphical view]
PROSITE	PS50174. G_PATCH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	58258.
SOURCE	Search...

Entry information

Entry name

PINX1_HUMAN

Accession

Primary (citable) accession number: Q96BK5
Secondary accession number(s): B2R9B1 , Q548A5, Q6QWG9, Q7Z7J8, Q96QD7, Q9HBU7, Q9NWW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	June 20, 2002
Last modified:	January 25, 2012
This is version 92 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.