Q9H9Z2 (LN28A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein lin-28 homolog A
Short name=Lin-28A

Alternative name(s):
Zinc finger CCHC domain-containing protein 1

Gene names

Name:	LIN28A
Synonyms:	CSDD1, LIN28, ZCCHC1

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

General annotation (Comments)

Function	Acts as a 'translational enhancer', driving specific mRNAs to polysomes and thus increasing the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in stabilizing the mRNAs. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression By similarity. Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let-7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Degradation of pre-let-7 in embryonic stem (ES) cells contributes to the maintenance of ES cells. In contrast, LIN28A down-regulation in neural stem cells by miR-125, allows the processing of pre-let-7. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation. Ref.12 Ref.13
Subunit structure	During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment. Directly interacts with EIF3S2. Interaction with NCL is RNA-dependent By similarity. Interacts with ZCCHC11/TUT4. Ref.13
Subcellular location	Cytoplasm. Nucleus › nucleolus. Note: Nucleolar localization observed in 10-15% of the nuclei in differentiated myotubes By similarity. Shuttles between the cytoplasm and the nucleus. Localizes to cytoplasmic processing bodies and stress granules. Ref.11 Ref.12
Tissue specificity	Expressed in embryonic stem cells (ES cells), placenta and testis. Ref.7 Ref.8 Ref.9
Developmental stage	Expressed in fetal liver. Expression decreases during differentiation of ES cells or upon induction of neuronal differentiation by retinoic acid. Ref.7 Ref.8 Ref.9
Induction	Can be negatively regulated by the interaction of microRNAs miR-125a and miR-125b with at least two miRNA responsive elements (miREs) in the 3'-UTR of this gene. These interactions may reduce both translation efficiency and mRNA abundance. Negatively regulated by retinoic acid. Ref.6 Ref.10
Domain	The CSD domain is required for function in muscle differentiation By similarity.
Miscellaneous	Overexpressed in primary tumors (overall frequency approximately 15%), overexpression being linked to repression of let-7 family miRNAs and derepression of let-7 targets. Facilitates cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types.
Sequence similarities	Belongs to the lin-28 family. Contains 2 CCHC-type zinc fingers. Contains 1 CSD (cold-shock) domain.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing
Cellular component	Cytoplasm Nucleus
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	RNA 3'-end processing Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB miRNA catabolic process Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB pre-miRNA processing Inferred from mutant phenotype Ref.12Ref.13. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro stem cell maintenance Inferred from mutant phenotype Ref.13. Source: UniProtKB
Cellular component	cytoplasmic mRNA processing body Inferred from direct assay Ref.11. Source: UniProtKB cytoplasmic stress granule Inferred from direct assay Ref.11. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 209

209

Protein lin-28 homolog A

PRO_0000253787

Regions

Domain

39 – 112

74

CSD

Zinc finger

137 – 154

18

CCHC-type 1

Zinc finger

159 – 176

18

CCHC-type 2

Sites

Metal binding

139

1

Zinc 1

Metal binding

142

1

Zinc 1

Metal binding

147

1

Zinc 1

Metal binding

152

1

Zinc 1

Metal binding

161

1

Zinc 2

Metal binding

164

1

Zinc 2

Metal binding

169

1

Zinc 2

Metal binding

174

1

Zinc 2

Experimental info

Mutagenesis

46

1

W → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-55 and A-73. Ref.11

Mutagenesis

55

1

F → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-46 and A-73. Ref.11

Mutagenesis

73

1

F → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-46 and A-55. Ref.11

Mutagenesis

147

1

H → A: Abolishes ability to suppress pre-let-7 biogenesis and localization to cytoplasmic processing bodies without affecting pre-let-7 binding; when associated with A-169. Ref.11 Ref.12

Mutagenesis

169

1

H → A: Abolishes ability to suppress pre-let-7 biogenesis and localization to cytoplasmic processing bodies without affecting pre-let-7 binding; when associated with A-147. Ref.11 Ref.12

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

209

Helix Strand Turn

Details...

Beta strand

140 – 142

3

Beta strand

145 – 147

3

Turn

149 – 151

3

Turn

162 – 164

3

Beta strand

167 – 169

3

Turn

171 – 173

3

Helix

176 – 178

3

Sequences

	Sequence		Length	Mass (Da)
	Q9H9Z2 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: FA5EF6DD33FABF54	FASTA	209	22,743
	10 20 30 40 50 60 MGSVSNQQFA GGCAKAAEEA PEEAPEDAAR AADEPQLLHG AGICKWFNVR MGFGFLSMTA 70 80 90 100 110 120 RAGVALDPPV DVFVHQSKLH MEGFRSLKEG EAVEFTFKKS AKGLESIRVT GPGGVFCIGS 130 140 150 160 170 180 ERRPKGKSMQ KRRSKGDRCY NCGGLDHHAK ECKLPPQPKK CHFCQSISHM VASCPLKAQQ 190 200 GPSAQGKPTY FREEEEEIHS PTLLPEAQN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites." Moss E.G., Tang L. Dev. Biol. 258:432-442(2003) [PubMed: 12798299] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Moss E.G., Tang L. Dev. Biol. 262:361-361(2003)
[3]	"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]. Tissue: Teratocarcinoma.
[4]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Placenta.
[6]	"Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation." Sempere L.F., Freemantle S., Pitha-Rowe I., Moss E.G., Dmitrovsky E., Ambros V. Genome Biol. 5:R13.1-R13.11(2004) [PubMed: 15003116] [Abstract] Cited for: INDUCTION.
[7]	"The transcriptome profile of human embryonic stem cells as defined by SAGE." Richards M., Tan S.-P., Tan J.-H., Chan W.-K., Bongso A. Stem Cells 22:51-64(2004) [PubMed: 14688391] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[8]	"Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cells." Gerecht-Nir S., Dazard J.-E., Golan-Mashiach M., Osenberg S., Botvinnik A., Amariglio N., Domany E., Rechavi G., Givol D., Itskovitz-Eldor J. Dev. Dyn. 232:487-497(2005) [PubMed: 15614775] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[9]	"Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation." Lee Y.S., Kim H.K., Chung S., Kim K.-S., Dutta A. J. Biol. Chem. 280:16635-16641(2005) [PubMed: 15722555] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[10]	"Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells." Wu L., Belasco J.G. Mol. Cell. Biol. 25:9198-9208(2005) [PubMed: 16227573] [Abstract] Cited for: INDUCTION.
[11]	"Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules." Balzer E., Moss E.G. RNA Biol. 4:16-25(2007) [PubMed: 17617744] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-46; PHE-55; PHE-73; HIS-147 AND HIS-169.
[12]	"Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA." Heo I., Joo C., Cho J., Ha M., Han J., Kim V.N. Mol. Cell 32:276-284(2008) [PubMed: 18951094] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, MUTAGENESIS OF HIS-147 AND HIS-169.
[13]	"TUT4 in concert with Lin28 suppresses MicroRNA biogenesis through pre-microRNA uridylation." Heo I., Joo C., Kim Y.-K., Ha M., Yoon M.-J., Cho J., Yeom K.-H., Han J., Kim V.N. Cell 138:696-708(2009) [PubMed: 19703396] [Abstract] Cited for: FUNCTION, RNA-BINDING, INTERACTION WITH ZCCHC11.
[14]	"Lin28 promotes transformation and is associated with advanced human malignancies." Viswanathan S.R., Powers J.T., Einhorn W., Hoshida Y., Ng T.L., Toffanin S., O'Sullivan M., Lu J., Phillips L.A., Lockhart V.L., Shah S.P., Tanwar P.S., Mermel C.H., Beroukhim R., Azam M., Teixeira J., Meyerson M., Hughes T.P. , Llovet J.M., Radich J., Mullighan C.G., Golub T.R., Sorensen P.H., Daley G.Q. Nat. Genet. 41:843-848(2009) [PubMed: 19483683] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN CANCERS.
[15]	"Solution structure of the zinc-finger domain in LIN-28." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 134-186, ZINC-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF521099 mRNA. Translation: AAM77751.1.
AK022519 mRNA. Translation: BAB14075.1.
AL513365 Genomic DNA. Translation: CAI21500.1.
BC028566 mRNA. Translation: AAH28566.1.

IPI

IPI00002948.

RefSeq

NP_078950.1. NM_024674.4.

UniGene

Hs.86154.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CQF	NMR	-	A	136-186	[»]

ProteinModelPortal

Q9H9Z2.

SMR

Q9H9Z2. Positions 39-111, 134-186.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H9Z2. 1 interaction.

STRING

Q9H9Z2.

PTM databases

PhosphoSite

Q9H9Z2.

Polymorphism databases

DMDM

74752750.

Proteomic databases

PRIDE

Q9H9Z2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254231; ENSP00000254231; ENSG00000131914.
ENST00000326279; ENSP00000363314; ENSG00000131914.

GeneID

79727.

KEGG

hsa:79727.

UCSC

uc001bmj.1. human.

Organism-specific databases

CTD

79727.

GeneCards

GC01P026737.

H-InvDB

HIX0199820.

HGNC

HGNC:15986. LIN28A.

HPA

CAB020785.

MIM

611043. gene.

neXtProt

NX_Q9H9Z2.

PharmGKB

PA134861411.
PA165751523.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06860.

GeneTree

ENSGT00390000001177.

HOGENOM

HBG717773.

HOVERGEN

HBG081922.

InParanoid

Q9H9Z2.

OMA

IHSPTLL.

OrthoDB

EOG4640D4.

PhylomeDB

Q9H9Z2.

Gene expression databases

ArrayExpress

Q9H9Z2.

Bgee

Q9H9Z2.

CleanEx

HS_LIN28.

Genevestigator

Q9H9Z2.

GermOnline

ENSG00000131914. Homo sapiens.

Family and domain databases

InterPro

IPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR016027. NA-bd_OB-fold-like.
IPR013084. Znf_CCH_retrovir.
IPR001878. Znf_CCHC.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
G3DSA:4.10.60.10. Znf_CCH_retrovir. 1 hit.

Pfam

PF00313. CSD. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]

PRINTS

PR00050. COLDSHOCK.

SMART

SM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]

SUPFAM

SSF50249. Nucleic_acid_OB. 1 hit.

PROSITE

PS50158. ZF_CCHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

69098.

SOURCE

Search...

Entry information

Entry name

LN28A_HUMAN

Accession

Primary (citable) accession number: Q9H9Z2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 91 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.