Q96CB9 (NSUN4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-methylcytosine rRNA methyltransferase NSUN4
EC=2.1.1.-

Alternative name(s):
NOL1/NOP2/Sun domain family member 4

Gene names

Name:

NSUN4

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

General annotation (Comments)

Function	Involved in mitochondrial ribosome large subunit biogenesis.
Subunit structure	Heterodimer with MTERF4/MTERFD2.
Subcellular location	Mitochondrion Ref.7 Ref.8.
Sequence similarities	Belongs to the methyltransferase superfamily. RsmB/NOP family.

Ontologies

Keywords
Biological process	rRNA processing
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrial large ribosomal subunit Inferred from direct assay PubMed 21531335. Source: MGI
Molecular_function	methyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96CB9-1)

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: Q96CB9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     147-384: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q96CB9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-198: Missing.
     199-219: NLAANDLSPSRIARLQKILHS → MLPPCCLFWPSACSLGTSCLT

Note: No experimental confirmation available.

Isoform 4 (identifier: Q96CB9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 384

384

5-methylcytosine rRNA methyltransferase NSUN4

PRO_0000289234

Regions

Region

181 – 187

7

S-adenosyl-L-methionine binding

Sites

Active site

310

1

Nucleophile Ref.7

Binding site

237

1

S-adenosyl-L-methionine

Binding site

255

1

S-adenosyl-L-methionine

Natural variations

Alternative sequence

1 – 198

198

Missing in isoform 3.

VSP_025971

Alternative sequence

1 – 49

49

Missing in isoform 4.

VSP_045053

Alternative sequence

147 – 384

238

Missing in isoform 2.

VSP_025972

Alternative sequence

199 – 219

21

NLAAN…KILHS → MLPPCCLFWPSACSLGTSCL T in isoform 3.

VSP_025973

Natural variant

51

1

T → A. Ref.1 Ref.4
Corresponds to variant rs3737744 [ dbSNP | Ensembl ].

VAR_032606

Natural variant

128

1

N → K.
Corresponds to variant rs17102152 [ dbSNP | Ensembl ].

VAR_032607

Natural variant

325

1

I → T.
Corresponds to variant rs13374337 [ dbSNP | Ensembl ].

VAR_032608

Natural variant

365

1

I → V. Ref.1
Corresponds to variant rs9865 [ dbSNP | Ensembl ].

VAR_032609

Experimental info

Sequence conflict

282

1

Q → R in BAG51912. Ref.1

Secondary structure

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384

Helix Strand Turn

Details...

Helix

40 – 56

17

Helix

57 – 59

3

Helix

60 – 67

8

Beta strand

74 – 77

4

Helix

79 – 81

3

Helix

83 – 92

10

Helix

98 – 104

7

Turn

105 – 107

3

Helix

121 – 124

4

Beta strand

131 – 133

3

Beta strand

151 – 158

8

Helix

160 – 162

3

Helix

163 – 169

7

Beta strand

175 – 181

7

Helix

186 – 193

8

Beta strand

197 – 203

7

Helix

207 – 220

14

Turn

223 – 227

5

Beta strand

228 – 234

7

Helix

238 – 240

3

Helix

241 – 244

4

Beta strand

249 – 255

7

Helix

261 – 264

4

Helix

275 – 277

3

Helix

278 – 282

5

Helix

284 – 297

14

Beta strand

299 – 310

12

Turn

314 – 317

4

Helix

318 – 332

15

Beta strand

336 – 338

3

Helix

342 – 348

7

Turn

349 – 351

3

Beta strand

359 – 365

7

Beta strand

375 – 382

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: 4D83B6D55D65C27F	FASTA	384	43,089
	10 20 30 40 50 60 MAALTLRGVR ELLKRVDLAT VPRRHRYKKK WAATEPKFPA VRLALQNFDM TYSVQFGDLW 70 80 90 100 110 120 PSIRVSLLSE QKYGALVNNF AAWDHVSAKL EQLSAKDFVN EAISHWELQS EGGQSAAPSP 130 140 150 160 170 180 ASWACSPNLR CFTFDRGDIS RFPPARPGSL GVMEYYLMDA ASLLPVLALG LQPGDIVLDL 190 200 210 220 230 240 CAAPGGKTLA LLQTGCCRNL AANDLSPSRI ARLQKILHSY VPEEIRDGNQ VRVTSWDGRK 250 260 270 280 290 300 WGELEGDTYD RVLVDVPCTT DRHSLHEEEN NIFKRSRKKE RQILPVLQVQ LLAAGLLATK 310 320 330 340 350 360 PGGHVVYSTC SLSHLQNEYV VQGAIELLAN QYSIQVQVED LTHFRRVFMD TFCFFSSCQV 370 380 GELVIPNLMA NFGPMYFCKM RRLT
	Isoform 2 [UniParc]. Checksum: E49A839AA5937FB5	FASTA	146	16,507
	10 20 30 40 50 60 MAALTLRGVR ELLKRVDLAT VPRRHRYKKK WAATEPKFPA VRLALQNFDM TYSVQFGDLW 70 80 90 100 110 120 PSIRVSLLSE QKYGALVNNF AAWDHVSAKL EQLSAKDFVN EAISHWELQS EGGQSAAPSP 130 140 ASWACSPNLR CFTFDRGDIS RFPPAR
	Isoform 3 [UniParc]. Checksum: 4186007A46B086CD	FASTA	186	21,240
	10 20 30 40 50 60 MLPPCCLFWP SACSLGTSCL TYVPEEIRDG NQVRVTSWDG RKWGELEGDT YDRVLVDVPC 70 80 90 100 110 120 TTDRHSLHEE ENNIFKRSRK KERQILPVLQ VQLLAAGLLA TKPGGHVVYS TCSLSHLQNE 130 140 150 160 170 180 YVVQGAIELL ANQYSIQVQV EDLTHFRRVF MDTFCFFSSC QVGELVIPNL MANFGPMYFC KMRRLT
	Isoform 4 [UniParc]. Checksum: 85AACD29E9DDB7D7	FASTA	335	37,374
	10 20 30 40 50 60 MTYSVQFGDL WPSIRVSLLS EQKYGALVNN FAAWDHVSAK LEQLSAKDFV NEAISHWELQ 70 80 90 100 110 120 SEGGQSAAPS PASWACSPNL RCFTFDRGDI SRFPPARPGS LGVMEYYLMD AASLLPVLAL 130 140 150 160 170 180 GLQPGDIVLD LCAAPGGKTL ALLQTGCCRN LAANDLSPSR IARLQKILHS YVPEEIRDGN 190 200 210 220 230 240 QVRVTSWDGR KWGELEGDTY DRVLVDVPCT TDRHSLHEEE NNIFKRSRKK ERQILPVLQV 250 260 270 280 290 300 QLLAAGLLAT KPGGHVVYST CSLSHLQNEY VVQGAIELLA NQYSIQVQVE DLTHFRRVFM 310 320 330 DTFCFFSSCQ VGELVIPNLM ANFGPMYFCK MRRLT

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; 3 AND 4), VARIANTS ALA-51 AND VAL-365. Tissue: Brain, Embryo, Placenta and Testis.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton 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 (SEP-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] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 96-384 (ISOFORM 2), VARIANT ALA-51. Tissue: Colon and Duodenum.
[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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Structure of the human MTERF4-NSUN4 protein complex that regulates mitochondrial ribosome biogenesis." Spahr H., Habermann B., Gustafsson C.M., Larsson N.G., Hallberg B.M. Proc. Natl. Acad. Sci. U.S.A. 109:15253-15258(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-384 IN COMPLEX WITH MTERF4, ACTIVE SITE, SUBCELLULAR LOCATION.
[8]	"Structure of the essential MTERF4:NSUN4 protein complex reveals how an MTERF protein collaborates to facilitate rRNA modification." Yakubovskaya E., Guja K.E., Mejia E., Castano S., Hambardjieva E., Choi W.S., Garcia-Diaz M. Structure 20:1940-1947(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 26-384 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND MTERF4, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK021577 mRNA. Translation: BAB13847.1.
AK057420 mRNA. Translation: BAG51912.1.
AK291741 mRNA. Translation: BAF84430.1.
AK295003 mRNA. Translation: BAG58065.1.
AL122001 Genomic DNA. Translation: CAI21962.1.
CH471059 Genomic DNA. Translation: EAX06917.1.
BC014441 mRNA. Translation: AAH14441.1.
BC016907 mRNA. Translation: AAH16907.1.

IPI

IPI00303944.
IPI00847475.
IPI00847563.
IPI01012870.

RefSeq

NP_001243056.1. NM_001256127.1.
NP_001243057.1. NM_001256128.1.
NP_950245.2. NM_199044.3.

UniGene

Hs.163424.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4FP9	X-ray	2.90	A/C/D/F	26-384	[»]
4FZV	X-ray	2.00	A	26-384	[»]

ProteinModelPortal

Q96CB9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58104N.

IntAct

Q96CB9. 4 interactions.

MINT

MINT-1474456.

STRING

9606.ENSP00000419740.

PTM databases

PhosphoSite

Q96CB9.

Polymorphism databases

DMDM

152125805.

Proteomic databases

PaxDb

Q96CB9.

PRIDE

Q96CB9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000474844; ENSP00000419740; ENSG00000117481.
ENST00000536062; ENSP00000438912; ENSG00000117481.
ENST00000537428; ENSP00000437758; ENSG00000117481.

GeneID

387338.

KEGG

hsa:387338.

UCSC

uc001cpr.1. human.

Organism-specific databases

CTD

387338.

GeneCards

GC01P046805.

HGNC

HGNC:31802. NSUN4.

HPA

HPA027958.
HPA028489.

neXtProt

NX_Q96CB9.

PharmGKB

PA134953046.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0144.

HOGENOM

HOG000017426.

HOVERGEN

HBG106892.

InParanoid

Q96CB9.

OMA

EPKFPAT.

OrthoDB

EOG42V8GP.

PhylomeDB

Q96CB9.

Gene expression databases

ArrayExpress

Q96CB9.

Bgee

Q96CB9.

CleanEx

HS_NSUN4.

Genevestigator

Q96CB9.

Family and domain databases

InterPro

IPR001678. Fmu/NOL1/Nop2p.
IPR023267. RCMT.
[Graphical view]

Pfam

PF01189. Nol1_Nop2_Fmu. 1 hit.
[Graphical view]

PRINTS

PR02008. RCMTFAMILY.

PROSITE

PS01153. NOL1_NOP2_SUN. False negative.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

387338.

NextBio

101304.

Entry information

Entry name

NSUN4_HUMAN

Accession

Primary (citable) accession number: Q96CB9
Secondary accession number(s): A8K6S6 , B3KQ50, B4DHA4, Q5TDF7, Q96AN8, Q9HAJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 29, 2007
Last modified:	May 1, 2013
This is version 76 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.