Format

Send to:

Choose Destination

RAF1 Raf-1 proto-oncogene, serine/threonine kinase [ Homo sapiens (human) ]

Gene ID: 5894, updated on 26-Oct-2020

Summary

Official Symbol
RAF1provided by HGNC
Official Full Name
Raf-1 proto-oncogene, serine/threonine kinaseprovided by HGNC
Primary source
HGNC:HGNC:9829
See related
Ensembl:ENSG00000132155 MIM:164760
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NS5; CRAF; Raf-1; c-Raf; CMD1NN
Summary
This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 34.4), heart (RPKM 32.5) and 25 other tissues See more
Orthologs

Genomic context

See RAF1 in Genome Data Viewer
Location:
3p25.2
Exon count:
22
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (12583601..12664117, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (12625100..12705700, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene tRNA splicing endonuclease subunit 2 Neighboring gene RNA, U6 small nuclear 377, pseudogene Neighboring gene MKRN2 opposite strand Neighboring gene makorin ring finger protein 2 Neighboring gene cysteine rich protein 1 pseudogene 1 Neighboring gene transmembrane protein 40

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Biological, clinical and population relevance of 95 loci for blood lipids.
GeneReviews: Not available
Cardiomyopathy, dilated, 1NN
MedGen: C4014656 OMIM: 615916 GeneReviews: Not available
Compare labs
Discovery and refinement of loci associated with lipid levels.
GeneReviews: Not available
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
GeneReviews: Not available
LEOPARD syndrome 2 Compare labs
Noonan syndrome 5
MedGen: C1969057 OMIM: 611553 GeneReviews: Noonan Syndrome
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2018-09-13)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2018-09-13)

ClinGen Genome Curation Page

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-induced release of IL-10 depends on the activation of Raf-1 along with NF-kappaB p65 in immature dentritic cells PubMed
env DC-SIGN-induced signaling by HIV-1 is essential for Raf-1-mediated phosphorylation of p65 NFkappaB at Ser276, which recruits pTEF-b to HIV-1 LTR to phosphorylate RNAPII at Ser2 PubMed
env Interaction of gp120 with DC-SIGN activates Raf-1 and phosphorylates Raf-1 at positions Ser338, Tyr340, and Tyr341 PubMed
env Binding of HIV-1 gp120 to CD4 molecules results in the association of Lck and Raf-1, which is abolished by preincubation of the virus with soluble CD4 PubMed
Nef nef A conserved acidic sequence motif in HIV-1 Nef at positions 174-179 binds to c-Raf1; the interaction of Nef with c-Raf1 leads to a downstream transduction of cell signaling through the c-Raf1-MAP kinase pathway in vivo PubMed
Tat tat HIV-1 Tat activates PRKCQ (PKC-theta) kinase activity, which leads to RELA (NFkB), NRAS, RAF1, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), and MAPK1 (ERK2) activation, in Jurkat T cells that stably express Tat PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
MAP kinase kinase kinase activity IEA
Inferred from Electronic Annotation
more info
 
adenylate cyclase activator activity IEA
Inferred from Electronic Annotation
more info
 
adenylate cyclase binding IEA
Inferred from Electronic Annotation
more info
 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
mitogen-activated protein kinase kinase binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
 
NOT small GTPase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
MAPK cascade TAS
Traceable Author Statement
more info
 
activation of MAPKK activity IDA
Inferred from Direct Assay
more info
PubMed 
activation of adenylate cyclase activity IDA
Inferred from Direct Assay
more info
PubMed 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
cell differentiation IEA
Inferred from Electronic Annotation
more info
 
death-inducing signaling complex assembly IEA
Inferred from Electronic Annotation
more info
 
face development IEA
Inferred from Electronic Annotation
more info
 
heart development IEA
Inferred from Electronic Annotation
more info
 
insulin secretion involved in cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
intermediate filament cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
 
ion transmembrane transport TAS
Traceable Author Statement
more info
 
negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
neurotrophin TRK receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
platelet activation TAS
Traceable Author Statement
more info
 
positive regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
protein phosphorylation TAS
Traceable Author Statement
more info
PubMed 
regulation of Rho protein signal transduction TAS
Traceable Author Statement
more info
PubMed 
regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
regulation of cell differentiation TAS
Traceable Author Statement
more info
PubMed 
regulation of cell motility TAS
Traceable Author Statement
more info
PubMed 
response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
response to muscle stretch IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
somatic stem cell population maintenance IEA
Inferred from Electronic Annotation
more info
 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
thymus development IEA
Inferred from Electronic Annotation
more info
 
thyroid gland development IEA
Inferred from Electronic Annotation
more info
 
wound healing TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IPI
Inferred from Physical Interaction
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
mitochondrial outer membrane TAS
Traceable Author Statement
more info
PubMed 
mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear speck IDA
Inferred from Direct Assay
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
pseudopodium IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
RAF proto-oncogene serine/threonine-protein kinase
Names
C-Raf proto-oncogene, serine/threonine kinase
Oncogene RAF1
proto-oncogene c-RAF
raf proto-oncogene serine/threonine protein kinase
v-raf-1 murine leukemia viral oncogene homolog 1
v-raf-1 murine leukemia viral oncogene-like protein 1
NP_001341618.1
NP_001341619.1
NP_001341620.1
NP_001341621.1
NP_001341622.1
NP_001341623.1
NP_001341624.1
NP_002871.1
XP_011532276.1
XP_016862455.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007467.1 RefSeqGene

    Range
    4979..85579
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_413

mRNA and Protein(s)

  1. NM_001354689.3NP_001341618.1  RAF proto-oncogene serine/threonine-protein kinase isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AC018500, AC026170
    Consensus CDS
    CCDS87047.1
    Related
    ENSP00000401888.2, ENST00000442415.7
    Conserved Domains (3) summary
    cd01816
    Location:57131
    Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
    cd14149
    Location:356638
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:139187
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  2. NM_001354690.3NP_001341619.1  RAF proto-oncogene serine/threonine-protein kinase isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variant 2, encodes isoform b.
    Source sequence(s)
    AC018500, AC026170
    Consensus CDS
    CCDS2612.1
    Conserved Domains (3) summary
    cd14149
    Location:336618
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17135
    Location:55131
    RBD_CRAF; Ras-binding domain (RBD) found in RAF proto-oncogene serine/threonine-protein kinase RAF1/CRAF
    pfam00130
    Location:139184
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  3. NM_001354691.3NP_001341620.1  RAF proto-oncogene serine/threonine-protein kinase isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variant 5, encodes isoform c.
    Source sequence(s)
    AC018500, AC026170
    Conserved Domains (2) summary
    cd14149
    Location:255537
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:58103
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  4. NM_001354692.3NP_001341621.1  RAF proto-oncogene serine/threonine-protein kinase isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variant 4, encodes isoform c.
    Source sequence(s)
    AC018500, AC026170
    Conserved Domains (2) summary
    cd14149
    Location:255537
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:58103
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  5. NM_001354693.3NP_001341622.1  RAF proto-oncogene serine/threonine-protein kinase isoform d

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170
    Conserved Domains (3) summary
    cd14149
    Location:303585
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17135
    Location:55131
    RBD_CRAF; Ras-binding domain (RBD) found in RAF proto-oncogene serine/threonine-protein kinase RAF1/CRAF
    pfam00130
    Location:139184
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  6. NM_001354694.3NP_001341623.1  RAF proto-oncogene serine/threonine-protein kinase isoform e

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170
    Conserved Domains (2) summary
    cd14149
    Location:275557
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:58106
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  7. NM_001354695.3NP_001341624.1  RAF proto-oncogene serine/threonine-protein kinase isoform f

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170
    Conserved Domains (2) summary
    cd14149
    Location:222504
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:58103
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  8. NM_002880.4NP_002871.1  RAF proto-oncogene serine/threonine-protein kinase isoform b

    See identical proteins and their annotated locations for NP_002871.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), as well as variant 3, encodes isoform b.
    Source sequence(s)
    BC018119, BU683389, DC342671
    Consensus CDS
    CCDS2612.1
    UniProtKB/Swiss-Prot
    P04049
    UniProtKB/TrEMBL
    L7RRS6
    Related
    ENSP00000251849.4, ENST00000251849.8
    Conserved Domains (3) summary
    cd14149
    Location:336618
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17135
    Location:55131
    RBD_CRAF; Ras-binding domain (RBD) found in RAF proto-oncogene serine/threonine-protein kinase RAF1/CRAF
    pfam00130
    Location:139184
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

RNA

  1. NR_148940.3 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170
  2. NR_148941.3 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170
  3. NR_148942.3 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC018500, AC026170

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

    Range
    12583601..12664117 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533974.3XP_011532276.1  RAF proto-oncogene serine/threonine-protein kinase isoform X1

    See identical proteins and their annotated locations for XP_011532276.1

    UniProtKB/Swiss-Prot
    P04049
    UniProtKB/TrEMBL
    L7RRS6
    Conserved Domains (3) summary
    cd14149
    Location:336618
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17135
    Location:55131
    RBD_CRAF; Ras-binding domain (RBD) found in RAF proto-oncogene serine/threonine-protein kinase RAF1/CRAF
    pfam00130
    Location:139184
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
  2. XM_017006966.1XP_016862455.1  RAF proto-oncogene serine/threonine-protein kinase isoform X2

    UniProtKB/TrEMBL
    A0A0S2Z4L5
    Related
    ENSP00000398591.2, ENST00000432427.2
    Conserved Domains (3) summary
    cd14149
    Location:303585
    STKc_C-Raf; Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17135
    Location:55131
    RBD_CRAF; Ras-binding domain (RBD) found in RAF proto-oncogene serine/threonine-protein kinase RAF1/CRAF
    pfam00130
    Location:139184
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

RNA

  1. XR_001740227.1 RNA Sequence

Support Center