FIP1L1

Protein identityUniProt · HPA

UniProt accession

Q6UN15

Gene

FIP1L1

Ensembl

ENSG00000145216

Chromosome

4

Canonical length

594 aa

Protein class

Cancer-related genes, Disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a subunit of the CPSF (cleavage and polyadenylation specificity factor) complex that polyadenylates the 3' end of mRNA precursors. This gene, the homolog of yeast Fip1 (factor interacting with PAP), binds to U-rich sequences of pre-mRNA and stimulates poly(A) polymerase activity. Its N-terminus contains a PAP-binding site and its C-terminus an RNA-binding domain. An interstitial chromosomal deletion on 4q12 creates an in-frame fusion of human genes FIP1L1 and PDGFRA (platelet-derived growth factor receptor, alpha). The FIP1L1-PDGFRA fusion gene encodes a constitutively activated tyrosine kinase that joins the first 233 amino acids of FIP1L1 to the last 523 amino acids of PDGFRA. This gene fusion and chromosomal deletion is the cause of some forms of idiopathic hypereosinophilic syndrome (HES). This syndrome, recently reclassified as chronic eosinophilic leukemia (CEL), is responsive to treatment with tyrosine kinase inhibitors. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

594 residues, UniProt reviewed canonical sequence.

>Q6UN15|FIP1L1
     1  MSAGEVERLV SELSGGTGGD EEEEWLYGGP WDVHVHSDLA KDLDENEVER PEEENASANP
    61  PSGIEDETAE NGVPKPKVTE TEDDSDSDSD DDEDDVHVTI GDIKTGAPQY GSYGTAPVNL
   121  NIKTGGRVYG TTGTKVKGVD LDAPGSINGV PLLEVDLDSF EDKPWRKPGA DLSDYFNYGF
   181  NEDTWKAYCE KQKRIRMGLE VIPVTSTTNK ITAEDCTMEV TPGAEIQDGR FNLFKVQQGR
   241  TGNSEKETAL PSTKAEFTSP PSLFKTGLPP SRNSTSSQSQ TSTASRKANS SVGKWQDRYG
   301  RAESPDLRRL PGAIDVIGQT ITISRVEGRR RANENSNIQV LSERSATEVD NNFSKPPPFF
   361  PPGAPPTHLP PPPFLPPPPT VSTAPPLIPP PGFPPPPGAP PPSLIPTIES GHSSGYDSRS
   421  ARAFPYGNVA FPHLPGSAPS WPSLVDTSKQ WDYYARREKD RDRERDRDRE RDRDRDRERE
   481  RTRERERERD HSPTPSVFNS DEERYRYREY AERGYERHRA SREKEERHRE RRHREKEETR
   541  HKSSRSNSRR RHESEEGDSH RRHKHKKSKR SKEGKEAGSE PAPEQESTEA TPAE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FIP1L1 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)

0.66

Highest tissue expression

30 nTPM

Expression across tissuesHPA

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)

0.36

gnomAD pLI

0.79

gnomAD missense Z

3.07

DepMap mean gene effect

-1.05

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• mRNA processing

Molecular functions

• RNA binding

Cellular components

• cytosol
• mRNA cleavage and polyadenylation specificity factor complex
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Pre-mRNA polyadenylation factor Fip1 domain
• Pre-mRNA 3'-end-processing regulator
• Fip1 motif

KeywordsUniProt

• mRNA processing
• Nucleus
• Phosphoprotein
• RNA-binding

InteractionsUniProt · HPA

Protein binding partners of FIP1L1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AHCYL1
• CPSF1
• CPSF4
• CSTF2
• CSTF3
• PAPOLA
• NUDT21