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Protein

Protein lin-28 homolog B

Gene

LIN28B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA (PubMed:22118463). Does not act on pri-miR21 (PubMed:22118463). The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation (PubMed:19703396). This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463). Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity). When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi129Zinc 1By similarity1
Metal bindingi132Zinc 1By similarity1
Metal bindingi137Zinc 1By similarity1
Metal bindingi142Zinc 1By similarity1
Metal bindingi151Zinc 2By similarity1
Metal bindingi154Zinc 2By similarity1
Metal bindingi159Zinc 2By similarity1
Metal bindingi164Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri127 – 144CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri149 – 166CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

  • DNA binding Source: InterPro
  • poly(A) RNA binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • miRNA catabolic process Source: UniProtKB
  • pre-miRNA processing Source: UniProtKB
  • regulation of transcription, DNA-templated Source: InterPro
  • RNA 3'-end processing Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

RNA-mediated gene silencing

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:G66-31153-MONOMER.
SignaLinkiQ6ZN17.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein lin-28 homolog B
Short name:
Lin-28B
Gene namesi
Name:LIN28B
Synonyms:CSDD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:32207. LIN28B.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi389421.
MalaCardsiLIN28B.
OpenTargetsiENSG00000187772.
Orphaneti635. Neuroblastoma.
PharmGKBiPA142671543.

Polymorphism and mutation databases

BioMutaiLIN28B.
DMDMi74758701.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002537931 – 250Protein lin-28 homolog BAdd BLAST250

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei54PhosphoserineCombined sources1
Modified residuei96PhosphoserineCombined sources1
Modified residuei105PhosphoserineCombined sources1
Modified residuei110PhosphoserineCombined sources1
Modified residuei203PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6ZN17.
MaxQBiQ6ZN17.
PaxDbiQ6ZN17.
PeptideAtlasiQ6ZN17.
PRIDEiQ6ZN17.

PTM databases

iPTMnetiQ6ZN17.
PhosphoSitePlusiQ6ZN17.

Expressioni

Tissue specificityi

Expressed at high levels in the placenta and, at mucher lower, in testis and fetal liver (PubMed:16971064). Isoform 1 is only detected in placenta and in moderately and poorly differentiated hepatocellular carcinoma cells (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Tends to be up-regulated in triple-negative (ER-,PR-,HER2-) breast tumors, as well as in liver, ovarian, and thyroid carcinomas (PubMed:22118463).2 Publications

Inductioni

Might be negatively regulated by the microRNA let-7b.1 Publication

Gene expression databases

BgeeiENSG00000187772.
CleanExiHS_LIN28B.
GenevisibleiQ6ZN17. HS.

Organism-specific databases

HPAiHPA036630.
HPA061745.

Interactioni

Protein-protein interaction databases

BioGridi133142. 35 interactors.
IntActiQ6ZN17. 3 interactors.
STRINGi9606.ENSP00000344401.

Structurei

Secondary structure

1250
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 38Combined sources11
Turni39 – 42Combined sources4
Beta strandi43 – 51Combined sources9
Beta strandi54 – 65Combined sources12
Helixi66 – 68Combined sources3
Beta strandi71 – 74Combined sources4
Beta strandi82 – 88Combined sources7
Beta strandi95 – 101Combined sources7
Helixi102 – 104Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A4IX-ray1.95A/B24-111[»]
ProteinModelPortaliQ6ZN17.
SMRiQ6ZN17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 102CSDAdd BLAST74

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi112 – 125Bipartite nuclear localization signal1 PublicationAdd BLAST14
Motifi239 – 250Nucleolar localization signal1 PublicationAdd BLAST12

Domaini

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.

Sequence similaritiesi

Belongs to the lin-28 family.Curated
Contains 2 CCHC-type zinc fingers.PROSITE-ProRule annotation
Contains 1 CSD (cold-shock) domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri127 – 144CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri149 – 166CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3070. Eukaryota.
COG1278. LUCA.
GeneTreeiENSGT00860000133704.
HOGENOMiHOG000047091.
HOVERGENiHBG081922.
InParanoidiQ6ZN17.
KOiK18754.
OMAiSETSEWA.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ6ZN17.
TreeFamiTF316240.

Family and domain databases

CDDicd04458. CSP_CDS. 1 hit.
Gene3Di4.10.60.10. 1 hit.
InterProiIPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00313. CSD. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]
PRINTSiPR00050. COLDSHOCK.
SMARTiSM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6ZN17-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEGGASKGG GEEPGKLPEP AEEESQVLRG TGHCKWFNVR MGFGFISMIN
60 70 80 90 100
REGSPLDIPV DVFVHQSKLF MEGFRSLKEG EPVEFTFKKS SKGLESIRVT
110 120 130 140 150
GPGGSPCLGS ERRPKGKTLQ KRKPKGDRCY NCGGLDHHAK ECSLPPQPKK
160 170 180 190 200
CHYCQSIMHM VANCPHKNVA QPPASSQGRQ EAESQPCTST LPREVGGGHG
210 220 230 240 250
CTSPPFPQEA RAEISERSGR SPQEASSTKS SIAPEEQSKK GPSVQKRKKT
Length:250
Mass (Da):27,084
Last modified:July 5, 2004 - v1
Checksum:iDEF2920C5F1D0BBD
GO
Isoform 2 (identifier: Q6ZN17-2) [UniParc]FASTAAdd to basket
Also known as: LIN28BS

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Note: No experimental confirmation available.
Show »
Length:180
Mass (Da):19,511
Checksum:i26526F59F88068F7
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0272071 – 70Missing in isoform 2. CuratedAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34504.1. [Q6ZN17-1]
RefSeqiNP_001004317.1. NM_001004317.3. [Q6ZN17-1]
UniGeneiHs.23616.

Genome annotation databases

EnsembliENST00000345080; ENSP00000344401; ENSG00000187772. [Q6ZN17-1]
GeneIDi389421.
KEGGihsa:389421.
UCSCiuc003pqv.2. human. [Q6ZN17-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34504.1. [Q6ZN17-1]
RefSeqiNP_001004317.1. NM_001004317.3. [Q6ZN17-1]
UniGeneiHs.23616.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A4IX-ray1.95A/B24-111[»]
ProteinModelPortaliQ6ZN17.
SMRiQ6ZN17.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi133142. 35 interactors.
IntActiQ6ZN17. 3 interactors.
STRINGi9606.ENSP00000344401.

PTM databases

iPTMnetiQ6ZN17.
PhosphoSitePlusiQ6ZN17.

Polymorphism and mutation databases

BioMutaiLIN28B.
DMDMi74758701.

Proteomic databases

EPDiQ6ZN17.
MaxQBiQ6ZN17.
PaxDbiQ6ZN17.
PeptideAtlasiQ6ZN17.
PRIDEiQ6ZN17.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345080; ENSP00000344401; ENSG00000187772. [Q6ZN17-1]
GeneIDi389421.
KEGGihsa:389421.
UCSCiuc003pqv.2. human. [Q6ZN17-1]

Organism-specific databases

CTDi389421.
DisGeNETi389421.
GeneCardsiLIN28B.
HGNCiHGNC:32207. LIN28B.
HPAiHPA036630.
HPA061745.
MalaCardsiLIN28B.
MIMi611044. gene.
neXtProtiNX_Q6ZN17.
OpenTargetsiENSG00000187772.
Orphaneti635. Neuroblastoma.
PharmGKBiPA142671543.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3070. Eukaryota.
COG1278. LUCA.
GeneTreeiENSGT00860000133704.
HOGENOMiHOG000047091.
HOVERGENiHBG081922.
InParanoidiQ6ZN17.
KOiK18754.
OMAiSETSEWA.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ6ZN17.
TreeFamiTF316240.

Enzyme and pathway databases

BioCyciZFISH:G66-31153-MONOMER.
SignaLinkiQ6ZN17.

Miscellaneous databases

GenomeRNAii389421.
PROiQ6ZN17.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187772.
CleanExiHS_LIN28B.
GenevisibleiQ6ZN17. HS.

Family and domain databases

CDDicd04458. CSP_CDS. 1 hit.
Gene3Di4.10.60.10. 1 hit.
InterProiIPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00313. CSD. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]
PRINTSiPR00050. COLDSHOCK.
SMARTiSM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLN28B_HUMAN
AccessioniPrimary (citable) accession number: Q6ZN17
Secondary accession number(s): A1L165, B2RPN6, Q5TCM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.