Q9BQ65 (USB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
U6 snRNA phosphodiesterase
Short name=hUsb1
EC=3.1.4.-

Gene names

Name:	USB1
Synonyms:	C16orf57

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

General annotation (Comments)

Function	Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. Ref.6 Ref.7
Subcellular location	Nucleus Ref.6.
Involvement in disease	Poikiloderma with neutropenia (PN) [MIM:604173]: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5
Sequence similarities	Belongs to the USB1 family.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Inferred from mutant phenotype Ref.6. Source: UniProtKB U6 snRNA 3'-end processing Inferred from mutant phenotype Ref.6. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	3'-5'-exoribonuclease activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9BQ65-1)

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: Q9BQ65-2)

The sequence of this isoform differs from the canonical sequence as follows:
     150-167: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9BQ65-3)

The sequence of this isoform differs from the canonical sequence as follows:
     150-265: RFFFTANQVK...GNKFFSMPLK → SPHPGPHCLI...LRQEPGSQTR

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 265

265

U6 snRNA phosphodiesterase HAMAP-Rule MF_03040

PRO_0000274391

Sites

Active site

120

1

Proton donor/acceptor Probable

Active site

208

1

Proton donor/acceptor Probable

Natural variations

Alternative sequence

150 – 265

116

RFFFT…SMPLK → SPHPGPHCLIGTKDAPVTQE IPKDLGALRQEPGSQTR in isoform 3.

VSP_042936

Alternative sequence

150 – 167

18

Missing in isoform 2.

VSP_042878

Natural variant

115

1

R → K.
Corresponds to variant rs35025252 [ dbSNP | Ensembl ].

VAR_053822

Natural variant

250

1

Q → E.
Corresponds to variant rs16959641 [ dbSNP | Ensembl ].

VAR_030277

Experimental info

Mutagenesis

120

1

H → A: Abolishes exoribonuclease activity. Ref.7

Mutagenesis

208

1

H → A: Abolishes exoribonuclease activity. No rescue of the molecular phenotype caused by USB1 depletion. Ref.6 Ref.7

Sequence conflict

89

1

Y → C in AAH10099. Ref.3

Sequence conflict

209

1

L → P in BAB14469. Ref.1

Secondary structure

1

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265

Helix Strand Turn

Details...

Beta strand

80 – 89

10

Helix

93 – 107

15

Beta strand

117 – 122

6

Beta strand

127 – 130

4

Helix

131 – 133

3

Helix

134 – 145

12

Beta strand

155 – 162

8

Beta strand

166 – 175

10

Helix

179 – 195

17

Beta strand

208 – 216

9

Helix

219 – 222

4

Helix

225 – 235

11

Helix

241 – 244

4

Beta strand

250 – 255

6

Beta strand

258 – 263

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 75D8BF51DF8D353D	FASTA	265	30,268
	10 20 30 40 50 60 MSAAPLVGYS SSGSEDESED GMRTRPGDGS HRRGQSPLPR QRFPVPDSVL NMFPGTEEGP 70 80 90 100 110 120 EDDSTKHGGR VRTFPHERGN WATHVYVPYE AKEEFLDLLD VLLPHAQTYV PRLVRMKVFH 130 140 150 160 170 180 LSLSQSVVLR HHWILPFVQA LKARMTSFHR FFFTANQVKI YTNQEKTRTF IGLEVTSGHA 190 200 210 220 230 240 QFLDLVSEVD RVMEEFNLTT FYQDPSFHLS LAWCVGDARL QLEGQCLQEL QAIVDGFEDA 250 260 EVLLRVHTEQ VRCKSGNKFF SMPLK
	Isoform 2 [UniParc]. Checksum: E2A5B443D8385DF4	FASTA	247	28,051
	10 20 30 40 50 60 MSAAPLVGYS SSGSEDESED GMRTRPGDGS HRRGQSPLPR QRFPVPDSVL NMFPGTEEGP 70 80 90 100 110 120 EDDSTKHGGR VRTFPHERGN WATHVYVPYE AKEEFLDLLD VLLPHAQTYV PRLVRMKVFH 130 140 150 160 170 180 LSLSQSVVLR HHWILPFVQA LKARMTSFHR TFIGLEVTSG HAQFLDLVSE VDRVMEEFNL 190 200 210 220 230 240 TTFYQDPSFH LSLAWCVGDA RLQLEGQCLQ ELQAIVDGFE DAEVLLRVHT EQVRCKSGNK FFSMPLK
	Isoform 3 [UniParc]. Checksum: B319207B0717EF30	FASTA	186	20,802
	10 20 30 40 50 60 MSAAPLVGYS SSGSEDESED GMRTRPGDGS HRRGQSPLPR QRFPVPDSVL NMFPGTEEGP 70 80 90 100 110 120 EDDSTKHGGR VRTFPHERGN WATHVYVPYE AKEEFLDLLD VLLPHAQTYV PRLVRMKVFH 130 140 150 160 170 180 LSLSQSVVLR HHWILPFVQA LKARMTSFHS PHPGPHCLIG TKDAPVTQEI PKDLGALRQE PGSQTR

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] (ISOFORMS 1; 2 AND 3). Tissue: Synovium and Thymus.
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [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). Tissue: Kidney, Pancreas, Placenta, Skin and Uterus.
[4]	"Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene." Volpi L., Roversi G., Colombo E.A., Leijsten N., Concolino D., Calabria A., Mencarelli M.A., Fimiani M., Macciardi F., Pfundt R., Schoenmakers E.F., Larizza L. Am. J. Hum. Genet. 86:72-76(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PN.
[5]	"Identification of a homozygous deletion mutation in C16orf57 in a family with Clericuzio-type poikiloderma with neutropenia." Tanaka A., Morice-Picard F., Lacombe D., Nagy N., Hide M., Taieb A., McGrath J. Am. J. Med. Genet. A 152:1347-1348(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PN.
[6]	"C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3' end modification." Mroczek S., Krwawicz J., Kutner J., Lazniewski M., Kucinski I., Ginalski K., Dziembowski A. Genes Dev. 26:1911-1925(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF HIS-208.
[7]	"Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia." Hilcenko C., Simpson P.J., Finch A.J., Bowler F.R., Churcher M.J., Jin L., Packman L.C., Shlien A., Campbell P., Kirwan M., Dokal I., Warren A.J. Blood 121:1028-1038(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 73-265, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, MUTAGENESIS OF HIS-120 AND HIS-208.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK023216 mRNA. Translation: BAB14469.1.
AK301494 mRNA. Translation: BAG63005.1.
AK303121 mRNA. Translation: BAG64227.1.
AC010543 Genomic DNA. No translation available.
AC012182 Genomic DNA. No translation available.
BC004415 mRNA. Translation: AAH04415.1.
BC006291 mRNA. Translation: AAH06291.1.
BC007774 mRNA. Translation: AAH07774.1.
BC010099 mRNA. Translation: AAH10099.1.
BC021554 mRNA. Translation: AAH21554.1.

IPI

IPI00304431.
IPI00641878.
IPI01008741.

RefSeq

NP_001182231.1. NM_001195302.1.
NP_001191840.1. NM_001204911.1.
NP_078874.2. NM_024598.3.

UniGene

Hs.408702.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4H7W	X-ray	1.10	A	73-265	[»]

ProteinModelPortal

Q9BQ65.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BQ65. 1 interaction.

MINT

MINT-1184765.

STRING

9606.ENSP00000219281.

PTM databases

PhosphoSite

Q9BQ65.

Polymorphism databases

DMDM

74732815.

Proteomic databases

PaxDb

Q9BQ65.

PRIDE

Q9BQ65.

Protocols and materials databases

DNASU

79650.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219281; ENSP00000219281; ENSG00000103005.
ENST00000423271; ENSP00000409792; ENSG00000103005.
ENST00000539737; ENSP00000446143; ENSG00000103005.

GeneID

79650.

KEGG

hsa:79650.

UCSC

uc002emz.3. human.

Organism-specific databases

CTD

79650.

GeneCards

GC16P058033.

H-InvDB

HIX0019615.

HGNC

HGNC:25792. USB1.

HPA

HPA041791.

MIM

604173. phenotype.
613276. gene.

neXtProt

NX_Q9BQ65.

Orphanet

1775. Dyskeratosis congenita.
221046. Poikiloderma with neutropenia.

PharmGKB

PA143485394.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG251744.

HOGENOM

HOG000213585.

HOVERGEN

HBG081315.

InParanoid

Q9BQ65.

OMA

FHLSLAW.

OrthoDB

EOG4CVG84.

PhylomeDB

Q9BQ65.

Gene expression databases

ArrayExpress

Q9BQ65.

Bgee

Q9BQ65.

CleanEx

HS_C16orf57.

Genevestigator

Q9BQ65.

Family and domain databases

HAMAP

MF_03040. USB1.

InterPro

IPR019146. UPF0406.
[Graphical view]

PANTHER

PTHR13522. PTHR13522. 1 hit.

Pfam

PF09749. HVSL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

C16orf57. human.

GenomeRNAi

79650.

NextBio

68808.

SOURCE

Search...

Entry information

Entry name

USB1_HUMAN

Accession

Primary (citable) accession number: Q9BQ65
Secondary accession number(s): B4DWE3 , B4DZW5, Q96FZ9, Q9H8X8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 6, 2007
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 81 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.