Q7Z6J9 (SEN54_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
tRNA-splicing endonuclease subunit Sen54

Alternative name(s):
SEN54 homolog
Short name=HsSEN54
tRNA-intron endonuclease Sen54

Gene names

Name:	TSEN54
Synonyms:	SEN54

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

General annotation (Comments)

Function	Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3' end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3' end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Ref.4
Subunit structure	tRNA splicing endonuclease is a heterotetramer composed of SEN2, SEN15, SEN34/LENG5 and SEN54. tRNA splicing endonuclease complex also contains proteins of the Pre-mRNA 3' end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2. Also belongs to a complex containing isoform 2 of SEN2.
Subcellular location	Nucleus Probable. Nucleus › nucleolus Probable. Note: May be transiently localized in the nucleolus Probable.
Involvement in disease	Pontocerebellar hypoplasia 4 (PCH4) [MIM:225753]: A disorder characterized by an abnormally small cerebellum and brainstem, severe neonatal encephalopathy, microcephaly, myoclonus and muscular hypertonia. There is a severe inferior olivary and pontine neuronal loss and a diffuse white matter gliosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Pontocerebellar hypoplasia 2A (PCH2A) [MIM:277470]: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the SEN54 family.
Sequence caution	The sequence AAH53643.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	mRNA processing tRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Pontocerebellar hypoplasia
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW tRNA splicing, via endonucleolytic cleavage and ligation Inferred from direct assay PubMed 17495927. Source: UniProtKB
Cellular_component	nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q7Z6J9-1)

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: Q7Z6J9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     157-177: VFSHLKRLGYVVRRFQPSSVL → PPEEVGLCGSTIPTKLCPVPV
     178-526: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 526	526	tRNA-splicing endonuclease subunit Sen54		PRO_0000194029
Amino acid modifications
	Modified residue	178	1	Phosphoserine Ref.6
	Modified residue	267	1	Phosphoserine Ref.6
Natural variations
	Alternative sequence	157 – 177	21	VFSHL…PSSVL → PPEEVGLCGSTIPTKLCPVP V in isoform 2.		VSP_010988
	Alternative sequence	178 – 526	349	Missing in isoform 2.		VSP_010989
	Natural variant	4	1	E → D. Ref.1 Ref.3 Corresponds to variant rs7216673 [ dbSNP | Ensembl ].		VAR_019459
	Natural variant	38	1	H → Q. Corresponds to variant rs8079373 [ dbSNP | Ensembl ].		VAR_019461
	Natural variant	93	1	S → P in PCH4; associated with S-307 on the other allele. Ref.7		VAR_054812
	Natural variant	137	1	I → L. Corresponds to variant rs11559205 [ dbSNP | Ensembl ].		VAR_057721
	Natural variant	307	1	A → S in PCH2A and PCH4; associated with P-93 on the other allele. Ref.7		VAR_054813
	Natural variant	347	1	K → N. Ref.3 Corresponds to variant rs9911502 [ dbSNP | Ensembl ].		VAR_019462
	Natural variant	437	1	A → V. Ref.3 Corresponds to variant rs8064529 [ dbSNP | Ensembl ].		VAR_019463
	Natural variant	525	1	G → R. Corresponds to variant rs11870627 [ dbSNP | Ensembl ].		VAR_057722

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 857D95C8F7C39461	FASTA	526	58,819
	10 20 30 40 50 60 MEPEPEPAAV EVPAGRVLSA RELFAARSRS QKLPQRSHGP KDFLPDGSAA QAERLRRCRE 70 80 90 100 110 120 ELWQLLAEQR VERLGSLVAA EWRPEEGFVE LKSPAGKFWQ TMGFSEQGRQ RLHPEEALYL 130 140 150 160 170 180 LECGSIHLFH QDLPLSIQEA YQLLLTDHTV TFLQYQVFSH LKRLGYVVRR FQPSSVLSPY 190 200 210 220 230 240 ERQLNLDASV QHLEDGDGKR KRSSSSPRSI NKKAKALDNS LQPKSLAASS PPPCSQPSQC 250 260 270 280 290 300 PEEKPQESSP MKGPGGPFQL LGSLGPSPGP AREGVGCSWE SGRAENGVTG AGKRRWNFEQ 310 320 330 340 350 360 ISFPNMASDS RHTLLRAPAP ELLPANVAGR ETDAESWCQK LNQRKEKLSR REREHHAEAA 370 380 390 400 410 420 QFQEDVNADP EVQRCSSWRE YKELLQRRQV QRSQRRAPHL WGQPVTPLLS PGQASSPAVV 430 440 450 460 470 480 LQHISVLQTT HLPDGGARLL EKSGGLEIIF DVYQADAVAT FRKNNPGKPY ARMCISGFDE 490 500 510 520 PVPDLCSLKR LSYQSGDVPL IFALVDHGDI SFYSFRDFTL PQDVGH
	Isoform 2 [UniParc]. Checksum: 68B620EF98884157	FASTA	177	19,981
	10 20 30 40 50 60 MEPEPEPAAV EVPAGRVLSA RELFAARSRS QKLPQRSHGP KDFLPDGSAA QAERLRRCRE 70 80 90 100 110 120 ELWQLLAEQR VERLGSLVAA EWRPEEGFVE LKSPAGKFWQ TMGFSEQGRQ RLHPEEALYL 130 140 150 160 170 LECGSIHLFH QDLPLSIQEA YQLLLTDHTV TFLQYQPPEE VGLCGSTIPT KLCPVPV

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ASP-4. Tissue: Cerebellum.
[2]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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), VARIANTS ASP-4; ASN-347 AND VAL-437. Tissue: Blood and Uterus.
[4]	"Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3' end formation." Paushkin S.V., Patel M., Furia B.S., Peltz S.W., Trotta C.R. Cell 117:311-321(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COMPONENT OF A COMPLEX WITH SEN2; SEN15; SEN34 AND CLP1.
[5]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-178 AND SER-267, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia." Budde B.S., Namavar Y., Barth P.G., Poll-The B.T., Nuernberg G., Becker C., van Ruissen F., Weterman M.A.J., Fluiter K., te Beek E.T., Aronica E., van der Knaap M.S., Hoehne W., Toliat M.R., Crow Y.J., Steinling M., Voit T., Roelenso F. , Brussel W., Brockmann K., Kyllerman M., Boltshauser E., Hammersen G., Willemsen M., Basel-Vanagaite L., Kraegeloh-Mann I., de Vries L.S., Sztriha L., Muntoni F., Ferrie C.D., Battini R., Hennekam R.C.M., Grillo E., Beemer F.A., Stoets L.M.E., Wollnik B., Nuernberg P., Baas F. Nat. Genet. 40:1113-1118(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PCH2A SER-307, VARIANTS PCH4 PRO-93 AND SER-307.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK094466 mRNA. Translation: BAC04362.1. BC047793 mRNA. Translation: AAH47793.1. AC100787 Genomic DNA. No translation available. BC053643 mRNA. Translation: AAH53643.1. Different initiation.
IPI	IPI00329143. IPI00429119.
RefSeq	NP_997229.2. NM_207346.2.
UniGene	Hs.378501.
3D structure databases
ProteinModelPortal	Q7Z6J9.
SMR	Q7Z6J9. Positions 79-169, 445-519.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7Z6J9. 1 interaction.
STRING	9606.ENSP00000327487.
PTM databases
PhosphoSite	Q7Z6J9.
Polymorphism databases
DMDM	296452961.
Proteomic databases
PaxDb	Q7Z6J9.
PRIDE	Q7Z6J9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000333213; ENSP00000327487; ENSG00000182173.
GeneID	283989.
KEGG	hsa:283989.
UCSC	uc002joe.1. human. uc002jof.1. human.
Organism-specific databases
CTD	283989.
GeneCards	GC17P073512.
H-InvDB	HIX0022516.
HGNC	HGNC:27561. TSEN54.
HPA	HPA053097.
MIM	225753. phenotype. 277470. phenotype. 608755. gene.
neXtProt	NX_Q7Z6J9.
Orphanet	2524. Pontocerebellar hypoplasia type 2. 166063. Pontocerebellar hypoplasia type 4. 166068. Pontocerebellar hypoplasia type 5.
PharmGKB	PA142670692.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG327149.
HOGENOM	HOG000049169.
HOVERGEN	HBG061211.
InParanoid	Q7Z6J9.
KO	K15326.
OMA	QISFPNM.
OrthoDB	EOG4XKV79.
PhylomeDB	Q7Z6J9.
Gene expression databases
Bgee	Q7Z6J9.
CleanEx	HS_TSEN54.
Genevestigator	Q7Z6J9.
GermOnline	ENSG00000182173. Homo sapiens.
Family and domain databases
InterPro	IPR024337. tRNA_splic_suSen54. IPR024336. tRNA_splic_suSen54_N. [Graphical view]
PANTHER	PTHR21027. PTHR21027. 1 hit.
Pfam	PF12928. tRNA_int_end_N2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TSEN54. human.
GenomeRNAi	283989.
NextBio	94415.
SOURCE	Search...

Entry information

Entry name

SEN54_HUMAN

Accession

Primary (citable) accession number: Q7Z6J9
Secondary accession number(s): Q86WV3, Q86XE4, Q8N9H2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 82 of the entry and version 3 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.