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Entry version 151 (31 Jul 2019)
Sequence version 3 (30 Nov 2010)
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Protein

SH2B adapter protein 1

Gene

SH2B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis (By similarity).By similarity7 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1170546 Prolactin receptor signaling
R-HSA-2586552 Signaling by Leptin
R-HSA-982772 Growth hormone receptor signaling
R-HSA-983231 Factors involved in megakaryocyte development and platelet production

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q9NRF2

SIGNOR Signaling Network Open Resource

More...
SIGNORi
Q9NRF2

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
SH2B adapter protein 1
Alternative name(s):
Pro-rich, PH and SH2 domain-containing signaling mediator
Short name:
PSM
SH2 domain-containing protein 1B
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SH2B1
Synonyms:KIAA1299, SH2B
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 16

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:30417 SH2B1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
608937 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9NRF2

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi29F → R: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi34A → D: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi38A → D: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi41F → A: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi42A → D: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi48Y → A: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi68F → A: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi72F → A: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1
Mutagenesisi555R → A: Abolishes self-association and interaction with INSR and IGF1R. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
25970

MalaCards human disease database

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MalaCardsi
SH2B1

Open Targets

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OpenTargetsi
ENSG00000178188

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
261222 Distal 16p11.2 microdeletion syndrome
261197 Proximal 16p11.2 microdeletion syndrome
329249 Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA145148084

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
SH2B1

Domain mapping of disease mutations (DMDM)

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DMDMi
313104186

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00003235931 – 756SH2B adapter protein 1Add BLAST756

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei88PhosphoserineBy similarity1
Modified residuei96PhosphoserineCombined sources1
Modified residuei270Omega-N-methylarginineCombined sources1
Modified residuei417PhosphoserineBy similarity1
Modified residuei420PhosphoserineBy similarity1
Modified residuei439Phosphotyrosine; by JAK1, JAK2 and PDGFRBy similarity1
Modified residuei494Phosphotyrosine; by JAK1, JAK2By similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated on tyrosine residues in response to receptor kinase stimulation. Phosphorylated by RET.3 Publications

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9NRF2

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9NRF2

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9NRF2

PeptideAtlas

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PeptideAtlasi
Q9NRF2

PRoteomics IDEntifications database

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PRIDEi
Q9NRF2

ProteomicsDB human proteome resource

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ProteomicsDBi
82346 [Q9NRF2-1]
82347 [Q9NRF2-2]
82348 [Q9NRF2-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q9NRF2

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q9NRF2

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed with highest levels in skeletal muscle and ovary.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000178188 Expressed in 203 organ(s), highest expression level in right hemisphere of cerebellum

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9NRF2 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9NRF2 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA076175

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Self-associates. Homopentamer (By similarity).

Forms a heteromultimeric complex with SH2B2 (By similarity).

Interacts with SH2B2. Isoform 1 interacts via its SH2 domain with JAK2. Isoform 2 interacts via its SH2 domain and its N-terminus with JAK2; the SH2 domain is required for the major interaction with JAK2 phosphorylated on tyrosine residues; the N-terminus provides a low-affinity binding to JAK2 independent of JAK2 phosphorylation. Isoform 3 interacts via its SH2 domain with JAK2. Isoform 1 interacts via its SH2 domain with INSR; the interaction requires receptor activation. Isoform 3 interacts via its SH2 domain with INSR; the interaction requires receptor activation and requires INSR phosphorylation at 'Tyr-1185'. Isoform 1 interacts with IGF1R; the interaction requires receptor activation. Isoform 2 interacts with PRKAR1A/RET (PTC2) fusion protein; the interaction requires RET 'Tyr-905' and Tyr-981'. Isoform 2 interacts via its SH2 domain with FGFR3; the interaction requires FGFR3 'Tyr-724' and 'Tyr-760'. Isoform 2 interacts with RET; the interaction requires RET kinase activity and RET 'Tyr-981'. Isoform 2 interacts with RAC1. Isoform 2 interacts with PDGFRA and/or PDGFRB; the interaction requires receptor activation.

Interacts with ISR1 and ISR2. Isoform 3 is probably part of a complex consisting of INSR, ISR1 and SH2B1. Probably part of a ternary complex consisting of SH2B1, JAK2 and ISR1 or ISR2. May interact with FCER1G (By similarity).

Interacts (via SH2 domain) with NTRK1 (phosphorylated) (By similarity).

By similarity

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
117455, 19 interactors

Protein interaction database and analysis system

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IntActi
Q9NRF2, 15 interactors

Molecular INTeraction database

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MINTi
Q9NRF2

STRING: functional protein association networks

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STRINGi
9606.ENSP00000321221

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1756
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9NRF2

Database of comparative protein structure models

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ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini267 – 376PHAdd BLAST110
Domaini527 – 625SH2PROSITE-ProRule annotationAdd BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 555Interaction with JAK2 (low-affinity binding; independent of JAK2 phosphorylation)By similarityAdd BLAST555
Regioni24 – 85Required for self-associationAdd BLAST62
Regioni85 – 196Interaction with RAC1By similarityAdd BLAST112
Regioni100 – 243Required for NGF signalingBy similarityAdd BLAST144
Regioni224 – 233Required for nuclear localizationBy similarity10

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the SH2B adapter family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IMWK Eukaryota
ENOG41102PH LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00950000183191

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9NRF2

KEGG Orthology (KO)

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KOi
K12459

Identification of Orthologs from Complete Genome Data

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OMAi
GDRWTHR

Database of Orthologous Groups

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OrthoDBi
556279at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9NRF2

TreeFam database of animal gene trees

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TreeFami
TF323184

Family and domain databases

Conserved Domains Database

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CDDi
cd10346 SH2_SH2B_family, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.30.29.30, 1 hit
3.30.505.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015012 Phe_ZIP
IPR036290 Phe_ZIP_sf
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR030523 SH2B
IPR030521 SH2B1
IPR035057 SH2B1_SH2

The PANTHER Classification System

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PANTHERi
PTHR10872 PTHR10872, 1 hit
PTHR10872:SF3 PTHR10872:SF3, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00169 PH, 1 hit
PF08916 Phe_ZIP, 1 hit
PF00017 SH2, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00401 SH2DOMAIN

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00233 PH, 1 hit
SM00252 SH2, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF109805 SSF109805, 1 hit
SSF55550 SSF55550, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50001 SH2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NRF2-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MNGAPSPEDG ASPSSPPLPP PPPPSWREFC ESHARAAALD FARRFRLYLA
60 70 80 90 100
SHPQYAGPGA EAAFSRRFAE LFLQHFEAEV ARASGSLSPP ILAPLSPGAE
110 120 130 140 150
ISPHDLSLES CRVGGPLAVL GPSRSSEDLA GPLPSSVSSS STTSSKPKLK
160 170 180 190 200
KRFSLRSVGR SVRGSVRGIL QWRGTVDPPS SAGPLETSSG PPVLGGNSNS
210 220 230 240 250
NSSGGAGTVG RGLVSDGTSP GERWTHRFER LRLSRGGGAL KDGAGMVQRE
260 270 280 290 300
ELLSFMGAEE AAPDPAGVGR GGGVAGPPSG GGGQPQWQKC RLLLRSEGEG
310 320 330 340 350
GGGSRLEFFV PPKASRPRLS IPCSSITDVR TTTALEMPDR ENTFVVKVEG
360 370 380 390 400
PSEYIMETVD AQHVKAWVSD IQECLSPGPC PATSPRPMTL PLAPGTSFLT
410 420 430 440 450
RENTDSLELS CLNHSESLPS QDLLLGPSES NDRLSQGAYG GLSDRPSASI
460 470 480 490 500
SPSSASIAAS HFDSMELLPP ELPPRIPIEE GPPTGTVHPL SAPYPPLDTP
510 520 530 540 550
ETATGSFLFQ GEPEGGEGDQ PLSGYPWFHG MLSRLKAAQL VLTGGTGSHG
560 570 580 590 600
VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM
610 620 630 640 650
LEHFRVHPIP LESGGSSDVV LVSYVPSSQR QQEPTTSHDP PQPPEPPSWT
660 670 680 690 700
DPPQPGAEEA SRAPEVAAAA AAAAKERQEK EKAGGGGVPE ELVPVVELVP
710 720 730 740 750
VVELEEAIAP GSEAQGAGSG GDAGVPPMVQ LQQSPLGGDG EEGGHPRAIN

NQYSFV
Length:756
Mass (Da):79,366
Last modified:November 30, 2010 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iCF680B57114CB1D3
GO
Isoform 2 (identifier: Q9NRF2-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     633-756: EPTTSHDPPQ...RAINNQYSFV → GREQAGSHAG...ASDCVTDHLP

Show »
Length:671
Mass (Da):70,781
Checksum:i3EAD9A95F370FD94
GO
Isoform 3 (identifier: Q9NRF2-3) [UniParc]FASTAAdd to basket
Also known as: Gamma

The sequence of this isoform differs from the canonical sequence as follows:
     633-756: EPTTSHDPPQ...RAINNQYSFV → GEQSRSAGEE...PSCPSERVTV

Show »
Length:683
Mass (Da):72,188
Checksum:i353155178527B5A7
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BUN7H3BUN7_HUMAN
SH2B adapter protein 1
SH2B1
200Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
B4DLN5B4DLN5_HUMAN
SH2B adapter protein 1
SH2B1
335Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5GXU7F5GXU7_HUMAN
SH2B adapter protein 1
SH2B1
373Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BPZ4H3BPZ4_HUMAN
SH2B adapter protein 1
SH2B1
182Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BVF6H3BVF6_HUMAN
SH2B adapter protein 1
SH2B1
63Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BMY3H3BMY3_HUMAN
SH2B adapter protein 1
SH2B1
122Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BTK4H3BTK4_HUMAN
SH2B adapter protein 1
SH2B1
56Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BTT2H3BTT2_HUMAN
SH2B adapter protein 1
SH2B1
114Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BPB4H3BPB4_HUMAN
SH2B adapter protein 1
SH2B1
18Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAH10704 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA92537 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB55148 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti197N → D in BAF83021 (PubMed:14702039).Curated1
Sequence conflicti519D → G in BAF83021 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_039550484T → A2 PublicationsCorresponds to variant dbSNP:rs7498665Ensembl.1
Natural variantiVAR_039551541V → A1 PublicationCorresponds to variant dbSNP:rs17850682Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_032027633 – 756EPTTS…QYSFV → GREQAGSHAGVCEGDGCHPD ASCTLMPFGASDCVTDHLP in isoform 2. 5 PublicationsAdd BLAST124
Alternative sequenceiVSP_032028633 – 756EPTTS…QYSFV → GEQSRSAGEEVPVHPRSEAG SRLGAMRGCAREMDATPMPP APSCPSERVTV in isoform 3. 2 PublicationsAdd BLAST124

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF227967 mRNA Translation: AAF73912.1
AF227968 mRNA Translation: AAF73913.1
AF227969 mRNA Translation: AAF73914.1
AB037720 mRNA Translation: BAA92537.1 Different initiation.
AK027488 mRNA Translation: BAB55148.1 Different initiation.
AK290332 mRNA Translation: BAF83021.1
AL049924 mRNA Translation: CAB43208.1
AL713760 mRNA Translation: CAD28530.1
AC133550 Genomic DNA No translation available.
BC010704 mRNA Translation: AAH10704.1 Different initiation.

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS32424.1 [Q9NRF2-2]
CCDS53996.1 [Q9NRF2-1]
CCDS53997.1 [Q9NRF2-3]

Protein sequence database of the Protein Information Resource

More...
PIRi
T08662

NCBI Reference Sequences

More...
RefSeqi
NP_001139267.1, NM_001145795.1 [Q9NRF2-1]
NP_001139268.1, NM_001145796.1 [Q9NRF2-2]
NP_001139269.1, NM_001145797.1 [Q9NRF2-3]
NP_001139284.1, NM_001145812.1 [Q9NRF2-2]
NP_001295222.1, NM_001308293.1 [Q9NRF2-1]
NP_001295223.1, NM_001308294.1
NP_056318.2, NM_015503.2 [Q9NRF2-2]
XP_016878603.1, XM_017023114.1 [Q9NRF2-1]
XP_016878604.1, XM_017023115.1 [Q9NRF2-1]
XP_016878605.1, XM_017023116.1 [Q9NRF2-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000322610; ENSP00000321221; ENSG00000178188 [Q9NRF2-1]
ENST00000337120; ENSP00000337163; ENSG00000178188 [Q9NRF2-2]
ENST00000359285; ENSP00000352232; ENSG00000178188 [Q9NRF2-3]
ENST00000395532; ENSP00000378903; ENSG00000178188 [Q9NRF2-2]
ENST00000618521; ENSP00000481709; ENSG00000178188 [Q9NRF2-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
25970

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:25970

UCSC genome browser

More...
UCSCi
uc002dri.4 human [Q9NRF2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF227967 mRNA Translation: AAF73912.1
AF227968 mRNA Translation: AAF73913.1
AF227969 mRNA Translation: AAF73914.1
AB037720 mRNA Translation: BAA92537.1 Different initiation.
AK027488 mRNA Translation: BAB55148.1 Different initiation.
AK290332 mRNA Translation: BAF83021.1
AL049924 mRNA Translation: CAB43208.1
AL713760 mRNA Translation: CAD28530.1
AC133550 Genomic DNA No translation available.
BC010704 mRNA Translation: AAH10704.1 Different initiation.
CCDSiCCDS32424.1 [Q9NRF2-2]
CCDS53996.1 [Q9NRF2-1]
CCDS53997.1 [Q9NRF2-3]
PIRiT08662
RefSeqiNP_001139267.1, NM_001145795.1 [Q9NRF2-1]
NP_001139268.1, NM_001145796.1 [Q9NRF2-2]
NP_001139269.1, NM_001145797.1 [Q9NRF2-3]
NP_001139284.1, NM_001145812.1 [Q9NRF2-2]
NP_001295222.1, NM_001308293.1 [Q9NRF2-1]
NP_001295223.1, NM_001308294.1
NP_056318.2, NM_015503.2 [Q9NRF2-2]
XP_016878603.1, XM_017023114.1 [Q9NRF2-1]
XP_016878604.1, XM_017023115.1 [Q9NRF2-1]
XP_016878605.1, XM_017023116.1 [Q9NRF2-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5W3RX-ray1.39A519-628[»]
SMRiQ9NRF2
ModBaseiSearch...

Protein-protein interaction databases

BioGridi117455, 19 interactors
IntActiQ9NRF2, 15 interactors
MINTiQ9NRF2
STRINGi9606.ENSP00000321221

PTM databases

iPTMnetiQ9NRF2
PhosphoSitePlusiQ9NRF2

Polymorphism and mutation databases

BioMutaiSH2B1
DMDMi313104186

Proteomic databases

jPOSTiQ9NRF2
MaxQBiQ9NRF2
PaxDbiQ9NRF2
PeptideAtlasiQ9NRF2
PRIDEiQ9NRF2
ProteomicsDBi82346 [Q9NRF2-1]
82347 [Q9NRF2-2]
82348 [Q9NRF2-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322610; ENSP00000321221; ENSG00000178188 [Q9NRF2-1]
ENST00000337120; ENSP00000337163; ENSG00000178188 [Q9NRF2-2]
ENST00000359285; ENSP00000352232; ENSG00000178188 [Q9NRF2-3]
ENST00000395532; ENSP00000378903; ENSG00000178188 [Q9NRF2-2]
ENST00000618521; ENSP00000481709; ENSG00000178188 [Q9NRF2-1]
GeneIDi25970
KEGGihsa:25970
UCSCiuc002dri.4 human [Q9NRF2-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
25970
DisGeNETi25970

GeneCards: human genes, protein and diseases

More...
GeneCardsi
SH2B1
HGNCiHGNC:30417 SH2B1
HPAiHPA076175
MalaCardsiSH2B1
MIMi608937 gene
neXtProtiNX_Q9NRF2
OpenTargetsiENSG00000178188
Orphaneti261222 Distal 16p11.2 microdeletion syndrome
261197 Proximal 16p11.2 microdeletion syndrome
329249 Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency
PharmGKBiPA145148084

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IMWK Eukaryota
ENOG41102PH LUCA
GeneTreeiENSGT00950000183191
InParanoidiQ9NRF2
KOiK12459
OMAiGDRWTHR
OrthoDBi556279at2759
PhylomeDBiQ9NRF2
TreeFamiTF323184

Enzyme and pathway databases

ReactomeiR-HSA-1170546 Prolactin receptor signaling
R-HSA-2586552 Signaling by Leptin
R-HSA-982772 Growth hormone receptor signaling
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkiQ9NRF2
SIGNORiQ9NRF2

Miscellaneous databases

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
SH2B1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
25970

Protein Ontology

More...
PROi
PR:Q9NRF2

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000178188 Expressed in 203 organ(s), highest expression level in right hemisphere of cerebellum
ExpressionAtlasiQ9NRF2 baseline and differential
GenevisibleiQ9NRF2 HS

Family and domain databases

CDDicd10346 SH2_SH2B_family, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015012 Phe_ZIP
IPR036290 Phe_ZIP_sf
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR030523 SH2B
IPR030521 SH2B1
IPR035057 SH2B1_SH2
PANTHERiPTHR10872 PTHR10872, 1 hit
PTHR10872:SF3 PTHR10872:SF3, 1 hit
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF08916 Phe_ZIP, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF109805 SSF109805, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSH2B1_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9NRF2
Secondary accession number(s): A8K2R7
, Q96FK3, Q96SX3, Q9NRF1, Q9NRF3, Q9P2P7, Q9Y3Y3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: November 30, 2010
Last modified: July 31, 2019
This is version 151 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
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