Q9H6E5 (STPAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Speckle targeted PIP5K1A-regulated poly(A) polymerase
Short name=Star-PAP
EC=2.7.7.19

Alternative name(s):
RNA-binding motif protein 21
Short name=RNA-binding protein 21
U6 snRNA-specific terminal uridylyltransferase 1
Short name=U6-TUTase
EC=2.7.7.52

Gene names

Name:	TUT1
Synonyms:	RBM21

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

General annotation (Comments)

Function	Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs. Localizes to nuclear speckles together with PIP5K1A and mediates polyadenylation of a select set of mRNAs, such as HMOX1. In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs. In addition to adenylyltransferase activity, also has uridylyltransferase activity. However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase. Acts as a specific terminal uridylyltransferase for U6 snRNA in vitro: responsible for a controlled elongation reaction that results in the restoration of the four 3'-terminal UMP-residues found in newly transcribed U6 snRNA. Not involved in replication-dependent histone mRNA degradation. Ref.5 Ref.6 Ref.7 Ref.9
Catalytic activity	UTP + RNA(n) = diphosphate + RNA(n+1). Ref.7 ATP + RNA(n) = diphosphate + RNA(n+1). Ref.7
Cofactor	Magnesium or manganese By similarity.
Enzyme regulation	Adenylyltransferase activity is specifically phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Ref.7
Subunit structure	Associates with the cleavage and polyadenylation specificity factor (CPSF) complex. Interacts with CPSF1 and CPSF3; the interaction is direct. Interacts with PIP5K1A; interaction. Ref.7 Ref.9
Subcellular location	Nucleus › nucleolus. Nucleus speckle Ref.5 Ref.7 Ref.8.
Tissue specificity	Widely expressed. Ref.7
Post-translational modification	Phosphorylated by CK1 in the proline-rich (Pro-rich) region. Ref.8
Sequence similarities	Belongs to the DNA polymerase type-B-like family. Contains 1 C2H2-type zinc finger. Contains 1 PAP-associated domain. Contains 1 RRM (RNA recognition motif) domain.
Sequence caution	The sequence BAB15282.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	mRNA processing
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding RNA-binding Zinc
Molecular function	Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	mRNA cleavage Inferred from direct assay Ref.9. Source: UniProtKB mRNA polyadenylation Inferred from direct assay Ref.9. Source: UniProtKB snRNA processing Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	nuclear speck Inferred from direct assay Ref.7Ref.8. Source: UniProtKB nucleolus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA uridylyltransferase activity Inferred from direct assay Ref.5Ref.7. Source: UniProtKB mRNA 3'-UTR binding Inferred from direct assay Ref.9. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW polynucleotide adenylyltransferase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 874

874

Speckle targeted PIP5K1A-regulated poly(A) polymerase

PRO_0000254186

Regions

Domain

56 – 128

73

RRM

Domain

491 – 549

59

PAP-associated

Zinc finger

16 – 40

25

C2H2-type

Compositional bias

229 – 310

82

Pro-rich

Sites

Metal binding

216

1

Magnesium or manganese; catalytic By similarity

Metal binding

218

1

Magnesium or manganese; catalytic By similarity

Amino acid modifications

Modified residue

750

1

Phosphoserine By similarity

Natural variations

Natural variant

442

1

L → F.
Corresponds to variant rs3197865 [ dbSNP | Ensembl ].

VAR_028833

Experimental info

Mutagenesis

216

1

D → A: Abolishes adenylyltransferase activity; when associated with A-218. Ref.7

Mutagenesis

218

1

D → A: Abolishes adenylyltransferase activity; when associated with A-216. Ref.7

Sequence conflict

66

1

D → G in BAB15314. Ref.1

Sequence conflict

809

1

Q → R in BAF85299. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

874

Helix Strand Turn

Details...

Beta strand

57 – 61

5

Helix

69 – 75

7

Helix

76 – 78

3

Beta strand

82 – 87

6

Beta strand

89 – 91

3

Beta strand

94 – 101

8

Helix

102 – 109

8

Sequences

	Sequence		Length	Mass (Da)
	Q9H6E5 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 85A4117A040FC90D	FASTA	874	93,847
	10 20 30 40 50 60 MAAVDSDVES LPRGGFRCCL CHVTTANRPS LDAHLGGRKH RHLVELRAAR KAQGLRSVFV 70 80 90 100 110 120 SGFPRDVDSA QLSEYFLAFG PVASVVMDKD KGVFAIVEMG DVGAREAVLS QSQHSLGGHR 130 140 150 160 170 180 LRVRPREQKE FQSPASKSPK GAAPDSHQLA KALAEAADVG AQMIKLVGLR ELSEAERQLR 190 200 210 220 230 240 SLVVALMQEV FTEFFPGCVV HPFGSSINSF DVHGCDLDLF LDLGDLEEPQ PVPKAPESPS 250 260 270 280 290 300 LDSALASPLD PQALACTPAS PPDSQPPASP QDSEALDFET PSSSLAPQTP DSALASETLA 310 320 330 340 350 360 SPQSLPPASP LLEDREEGDL GKASELAETP KEEKAEGAAM LELVGSILRG CVPGVYRVQT 370 380 390 400 410 420 VPSARRPVVK FCHRPSGLHG DVSLSNRLAL HNSRFLSLCS ELDGRVRPLV YTLRCWAQGR 430 440 450 460 470 480 GLSGSGPLLS NYALTLLVIY FLQTRDPPVL PTVSQLTQKA GEGEQVEVDG WDCSFPRDAS 490 500 510 520 530 540 RLEPSINVEP LSSLLAQFFS CVSCWDLRGS LLSLREGQAL PVAGGLPSNL WEGLRLGPLN 550 560 570 580 590 600 LQDPFDLSHN VAANVTSRVA GRLQNCCRAA ANYCRSLQYQ RRSSRGRDWG LLPLLQPSSP 610 620 630 640 650 660 SSLLSATPIP LPLAPFTQLT AALVQVFREA LGCHIEQATK RTRSEGGGTG ESSQGGTSKR 670 680 690 700 710 720 LKVDGQKNCC EEGKEEQQGC AGDGGEDRVE EMVIEVGEMV QDWAMQSPGQ PGDLPLTTGK 730 740 750 760 770 780 HGAPGEEGQP SHAALAERGP KGHEAAQEWS QGEAGKGASL PSSASWRCAL WHRVWQGRRR 790 800 810 820 830 840 ARRRLQQQTK EGAGGGAGTR AGWLATEAQV TQELKGLSGG EERPETEPLL SFVASVSPAD 850 860 870 RMLTVTPLQD PQGLFPDLHH FLQVFLPQAI RHLK

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]. Tissue: Testis.
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"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]. Tissue: Colon and Eye.
[5]	"Identification, cloning, and functional analysis of the human U6 snRNA-specific terminal uridylyl transferase." Trippe R., Guschina E., Hossbach M., Urlaub H., Luehrmann R., Benecke B.-J. RNA 12:1494-1504(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION AS URIDYLYLTRANSFERASE, SUBCELLULAR LOCATION.
[6]	"Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'." Mullen T.E., Marzluff W.F. Genes Dev. 22:50-65(2008) [PubMed] [Europe PMC] [Abstract] Cited for: LACK OF FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY.
[7]	"A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs." Mellman D.L., Gonzales M.L., Song C., Barlow C.A., Wang P., Kendziorski C., Anderson R.A. Nature 451:1013-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ADENYLYLTRANSFERASE, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION, RNA-BINDING, INTERACTION WITH PIP5K1A, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-216 AND ASP-218.
[8]	"CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs." Gonzales M.L., Mellman D.L., Anderson R.A. J. Biol. Chem. 283:12665-12673(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION BY CK1.
[9]	"The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA." Laishram R.S., Anderson R.A. EMBO J. 29:4132-4145(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ADENYLYLTRANSFERASE, RNA-BINDING, INTERACTION WITH CPSF1 AND CPSF3.
[10]	"Solution structure of RNA binding domain in RNA binding motif protein 21." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 54-141.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK025920 mRNA. Translation: BAB15282.1. Different initiation.
AK026000 mRNA. Translation: BAB15314.1.
AK292610 mRNA. Translation: BAF85299.1.
AP002990 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74029.1.
BC005013 mRNA. Translation: AAH05013.2.
BC110910 mRNA. Translation: AAI10911.1.
BC128263 mRNA. Translation: AAI28264.1.

IPI

IPI01012096.

RefSeq

NP_073741.2. NM_022830.2.

UniGene

Hs.728983.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E5G	NMR	-	A	55-141	[»]

ProteinModelPortal

Q9H6E5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H6E5. 6 interactions.

MINT

MINT-7900460.

STRING

9606.ENSP00000278279.

Polymorphism databases

DMDM

126302611.

Proteomic databases

PaxDb

Q9H6E5.

PRIDE

Q9H6E5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000476907; ENSP00000419607; ENSG00000149016.

GeneID

64852.

KEGG

hsa:64852.

Organism-specific databases

CTD

64852.

GeneCards

GC11M062342.

HGNC

HGNC:26184. TUT1.

MIM

610641. gene.

neXtProt

NX_Q9H6E5.

PharmGKB

PA162407405.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5260.

HOGENOM

HOG000115998.

HOVERGEN

HBG079670.

InParanoid

Q9H6E5.

OrthoDB

EOG480HWB.

Gene expression databases

ArrayExpress

Q9H6E5.

Bgee

Q9H6E5.

CleanEx

HS_TUT1.

Genevestigator

Q9H6E5.

GermOnline

ENSG00000149016. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR002058. PAP_assoc.
IPR000504. RRM_dom.
IPR015880. Znf_C2H2-like.
[Graphical view]

Pfam

PF03828. PAP_assoc. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. False negative.
PS50157. ZINC_FINGER_C2H2_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9H6E5.

GenomeRNAi

64852.

NextBio

66977.

SOURCE

Search...

Entry information

Entry name

STPAP_HUMAN

Accession

Primary (citable) accession number: Q9H6E5
Secondary accession number(s): A1A527 , A8K995, Q2NL65, Q7L583, Q9H6H7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	February 20, 2007
Last modified:	May 29, 2013
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.