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Q6ZN17 (LN28B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein lin-28 homolog B

Short name=Lin-28B
Gene names
Name:LIN28B
Synonyms:CSDD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length250 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. Mediates MYC-mediated let-7 repression. Isoform 1, when overexpressed, stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth. Ref.6 Ref.7 Ref.9

Subunit structure

Interacts with ZCCHC11/TUT4. Ref.9

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly cytoplasmic at G1 phase, accumulates in the nucleus in S and G2 phases. The frequency of nuclear localization in S and in G2 phases is 60% and 30%, respectively. Ref.6 Ref.7

Tissue specificity

High expression in testis, fetal liver, placenta and in hepatocellular carcinoma (HCC). Isoform 1 is only detected in moderately and poorly differentiated HCC tissues and placenta (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Ref.6

Induction

Might be negatively regulated by the microRNA let-7b. Ref.6

Domain

The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids. Ref.13

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6ZN17-1)

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: Q6ZN17-2)

Also known as: LIN28BS;

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 250250Protein lin-28 homolog B
PRO_0000253793

Regions

Domain29 – 10274CSD
Zinc finger127 – 14418CCHC-type 1
Zinc finger149 – 16618CCHC-type 2

Sites

Metal binding1291Zinc 1 By similarity
Metal binding1321Zinc 1 By similarity
Metal binding1371Zinc 1 By similarity
Metal binding1421Zinc 1 By similarity
Metal binding1511Zinc 2 By similarity
Metal binding1541Zinc 2 By similarity
Metal binding1591Zinc 2 By similarity
Metal binding1641Zinc 2 By similarity

Natural variations

Alternative sequence1 – 7070Missing in isoform 2.
VSP_027207

Secondary structure

............... 250
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: DEF2920C5F1D0BBD

FASTA25027,084
        10         20         30         40         50         60 
MAEGGASKGG GEEPGKLPEP AEEESQVLRG TGHCKWFNVR MGFGFISMIN REGSPLDIPV 

        70         80         90        100        110        120 
DVFVHQSKLF MEGFRSLKEG EPVEFTFKKS SKGLESIRVT GPGGSPCLGS ERRPKGKTLQ 

       130        140        150        160        170        180 
KRKPKGDRCY NCGGLDHHAK ECSLPPQPKK CHYCQSIMHM VANCPHKNVA QPPASSQGRQ 

       190        200        210        220        230        240 
EAESQPCTST LPREVGGGHG CTSPPFPQEA RAEISERSGR SPQEASSTKS SIAPEEQSKK 

       250 
GPSVQKRKKT 

« Hide

Isoform 2 (LIN28BS) [UniParc].

Checksum: 26526F59F88068F7
Show »

FASTA18019,511

References

« Hide 'large scale' references
[1]"Expression of Lin28A and Lin28B in post-implantation mouse embryos."
Moss E.G., Kemper K.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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. expand/collapse author list , 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 1).
Tissue: Teratocarcinoma.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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. expand/collapse author list , 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].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma."
Guo Y., Chen Y., Ito H., Watanabe A., Ge X., Kodama T., Aburatani H.
Gene 384:51-61(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, INTERACTION WITH ZCCHC11.
[10]"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. expand/collapse author list , Llovet J.M., Radich J., Mullighan C.G., Golub T.R., Sorensen P.H., Daley G.Q.
Nat. Genet. 41:843-848(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN CANCERS.
[11]"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].
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"The Lin28 cold-shock domain remodels pre-let-7 microRNA."
Mayr F., Schutz A., Doge N., Heinemann U.
Nucleic Acids Res. 40:7492-7506(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 24-111, ZINC KNUCKLE DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ127228 mRNA. Translation: AAZ38897.1.
AK131411 mRNA. Translation: BAD18558.1.
Z95329, AL135911 Genomic DNA. Translation: CAI21661.2.
AL135911, Z95329 Genomic DNA. Translation: CAI20969.2.
CH471051 Genomic DNA. Translation: EAW48434.1.
BC127712 mRNA. Translation: AAI27713.1.
BC127713 mRNA. Translation: AAI27714.1.
BC137526 mRNA. Translation: AAI37527.1.
BC137527 mRNA. Translation: AAI37528.1.
BC141960 mRNA. Translation: AAI41961.1.
CCDSCCDS34504.1. [Q6ZN17-1]
RefSeqNP_001004317.1. NM_001004317.3. [Q6ZN17-1]
UniGeneHs.23616.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4A4IX-ray1.95A/B24-111[»]
ProteinModelPortalQ6ZN17.
SMRQ6ZN17. Positions 26-167.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid133142. 4 interactions.
IntActQ6ZN17. 3 interactions.
STRING9606.ENSP00000344401.

PTM databases

PhosphoSiteQ6ZN17.

Polymorphism databases

DMDM74758701.

Proteomic databases

MaxQBQ6ZN17.
PaxDbQ6ZN17.
PeptideAtlasQ6ZN17.
PRIDEQ6ZN17.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000345080; ENSP00000344401; ENSG00000187772. [Q6ZN17-1]
GeneID389421.
KEGGhsa:389421.
UCSCuc003pqv.2. human. [Q6ZN17-1]

Organism-specific databases

CTD389421.
GeneCardsGC06P105404.
HGNCHGNC:32207. LIN28B.
HPAHPA036630.
HPA061745.
MIM611044. gene.
neXtProtNX_Q6ZN17.
Orphanet635. Neuroblastoma.
PharmGKBPA142671543.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1278.
HOGENOMHOG000047091.
HOVERGENHBG081922.
InParanoidQ6ZN17.
OMAGGGHGCT.
OrthoDBEOG72JWJ8.
PhylomeDBQ6ZN17.
TreeFamTF316240.

Enzyme and pathway databases

SignaLinkQ6ZN17.

Gene expression databases

BgeeQ6ZN17.
CleanExHS_LIN28B.
GenevestigatorQ6ZN17.

Family and domain databases

Gene3D2.40.50.140. 1 hit.
4.10.60.10. 1 hit.
InterProIPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR001878. Znf_CCHC.
[Graphical view]
PfamPF00313. CSD. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]
PRINTSPR00050. COLDSHOCK.
SMARTSM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMSSF50249. SSF50249. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEPS50158. ZF_CCHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi389421.
NextBio102860.
PROQ6ZN17.
SOURCESearch...

Entry information

Entry nameLN28B_HUMAN
AccessionPrimary (citable) accession number: Q6ZN17
Secondary accession number(s): A1L165, B2RPN6, Q5TCM4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM