NCL

Protein identityUniProt · HPA

UniProt accession

P19338

Gene

NCL

Ensembl

ENSG00000115053

Chromosome

2

Canonical length

710 aa

Protein class

Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli,Nucleoli rim,Mitotic chromosome

OverviewNCBI Gene

Nucleolin (NCL), a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. It is located mainly in dense fibrillar regions of the nucleolus. Human NCL gene consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

710 residues, UniProt reviewed canonical sequence.

>P19338|NCL
     1  MVKLAKAGKN QGDPKKMAPP PKEVEEDSED EEMSEDEEDD SSGEEVVIPQ KKGKKAAATS
    61  AKKVVVSPTK KVAVATPAKK AAVTPGKKAA ATPAKKTVTP AKAVTTPGKK GATPGKALVA
   121  TPGKKGAAIP AKGAKNGKNA KKEDSDEEED DDSEEDEEDD EDEDEDEDEI EPAAMKAAAA
   181  APASEDEDDE DDEDDEDDDD DEEDDSEEEA METTPAKGKK AAKVVPVKAK NVAEDEDEEE
   241  DDEDEDDDDD EDDEDDDDED DEEEEEEEEE EPVKEAPGKR KKEMAKQKAA PEAKKQKVEG
   301  TEPTTAFNLF VGNLNFNKSA PELKTGISDV FAKNDLAVVD VRIGMTRKFG YVDFESAEDL
   361  EKALELTGLK VFGNEIKLEK PKGKDSKKER DARTLLAKNL PYKVTQDELK EVFEDAAEIR
   421  LVSKDGKSKG IAYIEFKTEA DAEKTFEEKQ GTEIDGRSIS LYYTGEKGQN QDYRGGKNST
   481  WSGESKTLVL SNLSYSATEE TLQEVFEKAT FIKVPQNQNG KSKGYAFIEF ASFEDAKEAL
   541  NSCNKREIEG RAIRLELQGP RGSPNARSQP SKTLFVKGLS EDTTEETLKE SFDGSVRARI
   601  VTDRETGSSK GFGFVDFNSE EDAKAAKEAM EDGEIDGNKV TLDWAKPKGE GGFGGRGGGR
   661  GGFGGRGGGR GGRGGFGGRG RGGFGGRGGF RGGRGGGGDH KPQGKKTKFE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NCL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.54

Highest tissue expression

348 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for NCL from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

0.85

DepMap mean gene effect

-0.94

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• cellular response to epidermal growth factor stimulus
• cellular response to leukemia inhibitory factor
• negative regulation of insulin receptor signaling pathway
• negative regulation of translation
• positive regulation of mRNA splicing, via spliceosome
• positive regulation of transcription by RNA polymerase II
• positive regulation of transcription of nucleolar large rRNA by RNA polymerase I

Molecular functions

• DNA topoisomerase binding
• identical protein binding
• insulin receptor substrate binding
• mRNA 5'-UTR binding
• PH domain binding
• RNA binding
• telomeric DNA binding

Cellular components

• cell cortex
• chromosome
• cornified envelope
• cytoplasmic ribonucleoprotein granule
• extracellular exosome
• macropinosome membrane
• membrane
• nucleolus
• nucleoplasm
• nucleus
• plasma membrane
• ribonucleoprotein complex
• spliceosomal complex

Protein domainsUniProt · Pfam · InterPro

• RNA recognition motif domain
• RNA recognition motif domain, eukaryotic-type
• Nucleotide-binding alpha-beta plait domain superfamily
• RNA-binding domain superfamily
• RNA recognition motif
• Nucleolin, RNA recognition motif 1
• Nucleolin, RNA recognition motif 2
• Nucleolin, RNA recognition motif 3
• Nucleolin, RNA recognition motif 4

KeywordsUniProt

• Acetylation
• Cytoplasm
• DNA-binding
• Isopeptide bond
• Methylation
• Nucleus
• Phosphoprotein
• Repeat
• RNA-binding
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of NCL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AICDA
• ALKBH2
• APTX
• C1QBP
• DDX24
• ERBB4
• GZF1
• HDGF
• HNRNPU
• IGFBP5
• LRRC34
• MDK
• NSUN2
• NVL
• RIOK1
• RRP1B
• WDR46
• ZBTB7B
• ZFP36
• DGCR8
• SETX
• YBX1
• RNF146
• FMR1
• ARFGEF1
• LIN28A
• TERT
• ARRB1
• ARRB2
• CAPZB
• CSNK2A1
• CSNK2A2
• CTCF
• H1-5
• LARP7
• MDM2
• NOP56
• NPM1
• NPM3
• PA2G4