Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
The new UniProt website is here! Take me to UniProt BETA

UniProtKB - O14654 (IRS4_HUMAN)

Entry version 179 (29 Sep 2021)
Sequence version 1 (01 Jan 1998)
Previous versions | rss
Add a publicationFeedback
Protein

Insulin receptor substrate 4

Gene

IRS4

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

Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.

5 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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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>Keywordsi

Molecular functionTransducer

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O14654

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-2428928, IRS-related events triggered by IGF1R

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

More...SignaLinki		O14654

SIGNOR Signaling Network Open Resource

More...SIGNORi		O14654

<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:
Insulin receptor substrate 4
Short name:
IRS-4
Alternative name(s):
160 kDa phosphotyrosine protein
Short name:
py160
Phosphoprotein of 160 kDa
Short name:
pp160
<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:IRS4
<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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<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 X

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6128, IRS4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		300904, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O14654

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000133124

<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

Keywords - Cellular componenti

Cell membrane, Membrane

<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

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Hypothyroidism, congenital, non-goitrous, 9 (CHNG9)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by thyrotropin of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG9 is a congenital, X-linked recessive form. Patients have a small thyroid gland with low free T4 levels and inappropriately normal levels of thyrotropin.
Related information in OMIM
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_083291215 – 1257Missing in CHNG9. 1 PublicationAdd BLAST1043

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>Mutagenesisi700Y → F: No effect. Reduces interaction with CRK by 50%; when associated with F-717. Abolishes interaction with CRK; when associated with F-717; F-743 and F-779. 1 Publication1
Mutagenesisi717Y → F: No effect. Reduces interaction with CRK by 50%; when associated with F-700. Abolishes interaction with CRK; when associated with F-700; F-743 and F-779. 1 Publication1
Mutagenesisi743Y → F: No effect. Reduces interaction with CRK by 50%; when associated with F-779. Abolishes interaction with CRK; when associated with F-700; F-717 and F-779. 1 Publication1
Mutagenesisi779Y → F: No effect. Reduces interaction with CRK by 50%; when associated with F-743. Abolishes interaction with CRK; when associated with F-700; F-717 and F-743. 1 Publication1

Keywords - Diseasei

Congenital hypothyroidism, Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		8471

MalaCards human disease database

More...MalaCardsi		IRS4
MIMi301035, phenotype

Open Targets

More...OpenTargetsi		ENSG00000133124

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA29923

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O14654, Tbio

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		IRS4

<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 or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00003146781 – 1257Insulin receptor substrate 4Add BLAST1257

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 residuei921Phosphotyrosine1 Publication1

<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 both insulin and IGF1 signaling. Phosphorylated on Tyr-921 in response to FGF2 signaling. Phosphorylation of Tyr-921 is required for GRB2, phospholipase C-gamma and phosphatidylinositol 3-kinase interaction.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O14654

MaxQB - The MaxQuant DataBase

More...MaxQBi		O14654

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

More...PaxDbi		O14654

PeptideAtlas

More...PeptideAtlasi		O14654

PRoteomics IDEntifications database

More...PRIDEi		O14654

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		48151

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		O14654, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O14654

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

More...PhosphoSitePlusi		O14654

<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

Expressed in myoblasts. Expressed in liver and hepatocellular carcinoma.2 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Down-regulated by PPP4C in a phosphatase activity-dependent manner.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000133124, Expressed in adenohypophysis and 33 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O14654, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000133124, Tissue enriched (pituitary)

<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

Interacts with SOCS6 in response to stimulation with either insulin or IGF1 (By similarity).

Interacts with CRK and CRKL. Interaction with CRK is stronger than with CRKL.

Interacts with CRK via the phosphorylated YXXM motifs.

Interacts with GRB2 and PIK3R1.

Interacts with PLC-gamma, SHC1, PTK6, PPP4C and NISCH.

By similarity8 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		114048, 173 interactors

Protein interaction database and analysis system

More...IntActi		O14654, 113 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000361202

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O14654, protein

<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

3D structure databases

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

More...SMRi		O14654

Database of comparative protein structure models

More...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>Domaini78 – 199PHPROSITE-ProRule annotationAdd BLAST122
Domaini231 – 335IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

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>Regioni406 – 653DisorderedSequence analysisAdd BLAST248
Regioni678 – 921DisorderedSequence analysisAdd BLAST244
Regioni678 – 800CRK-bindingAdd BLAST123
Regioni895 – 897GRB2-binding3
Regioni1179 – 1257DisorderedSequence analysisAdd BLAST79

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi487 – 490YXXM motif 14
Motifi700 – 703YXXM motif 24
Motifi717 – 720YXXM motif 34
Motifi743 – 746YXXM motif 44
Motifi779 – 782YXXM motif 54
Motifi828 – 831YXXM motif 64
Motifi921 – 924YXXM motif 74

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi454 – 470Polar residuesSequence analysisAdd BLAST17
Compositional biasi494 – 551Polar residuesSequence analysisAdd BLAST58
Compositional biasi625 – 642Pro residuesSequence analysisAdd BLAST18
Compositional biasi678 – 701Basic and acidic residuesSequence analysisAdd BLAST24
Compositional biasi716 – 730Polar residuesSequence analysisAdd BLAST15
Compositional biasi762 – 776Basic and acidic residuesSequence analysisAdd BLAST15
Compositional biasi794 – 825Polar residuesSequence analysisAdd BLAST32
Compositional biasi904 – 918Basic and acidic residuesSequence analysisAdd BLAST15
Compositional biasi1220 – 1257Basic and acidic residuesSequence analysisAdd BLAST38

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502SD84, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000160883

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_290952_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O14654

Identification of Orthologs from Complete Genome Data

More...OMAi		EDSRGYM

Database of Orthologous Groups

More...OrthoDBi		298675at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O14654

TreeFam database of animal gene trees

More...TreeFami		TF325994

Family and domain databases

Conserved Domains Database

More...CDDi		cd01204, PTB_IRS, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.30.29.30, 2 hits

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR039011, IRS
IPR002404, IRS_PTB
IPR011993, PH-like_dom_sf
IPR001849, PH_domain

The PANTHER Classification System

More...PANTHERi		PTHR10614, PTHR10614, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF02174, IRS, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00628, INSULINRSI

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00233, PH, 1 hit
SM00310, PTBI, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51064, IRS_PTB, 1 hit
PS50003, PH_DOMAIN, 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>Sequence (1+)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 has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O14654-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASCSFTRDQ ATRRLRGAAA AAAAALAAVV TTPLLSSGTP TALIGTGSSC 
        60         70         80         90        100
PGAMWLSTAT GSRSDSESEE EDLPVGEEVC KRGYLRKQKH GHRRYFVLKL 
       110        120        130        140        150
ETADAPARLE YYENARKFRH SVRAAAAAAA AAASGAAIPP LIPPRRVITL 
       160        170        180        190        200
YQCFSVSQRA DARYRHLIAL FTQDEYFAMV AENESEQESW YLLLSRLILE 
       210        220        230        240        250
SKRRRCGTLG AQPDGEPAAL AAAAAAEPPF YKDVWQVIVK PRGLGHRKEL 
       260        270        280        290        300
SGVFRLCLTD EEVVFVRLNT EVASVVVQLL SIRRCGHSEQ YFFLEVGRST 
       310        320        330        340        350
VIGPGELWMQ VDDCVVAQNM HELFLEKMRA LCADEYRARC RSYSISIGAH 
       360        370        380        390        400
LLTLLSARRH LGLVPLEPGG WLRRSRFEQF CHLRAIGDGE DEMLFTRRFV 
       410        420        430        440        450
TPSEPVAHSR RGRLHLPRGR RSRRAVSVPA SFFRRLAPSP ARPRHPAEAP 
       460        470        480        490        500
NNGARLSSEV SGSGSGNFGE EGNPQGKEDQ EGSGGDYMPM NNWGSGNGRG 
       510        520        530        540        550
SGGGQGSNGQ GSSSHSSGGN QCSGEGQGSR GGQGSNGQGS GGNQCSRDGQ 
       560        570        580        590        600
GTAGGHGSGG GQRPGGGHGS GGGQGPGDGH GSGGGKNSGG GKGSGSGKGS 
       610        620        630        640        650
DGDGERGKSL KKRSYFGKLT QSKQQQMPPP PPPPPPPPPA GGTGGKGKSG 
       660        670        680        690        700
GRFRLYFCVD RGATKECKEA KEVKDAEIPE GAARGPHRAR AFDEDEDDPY 
       710        720        730        740        750
VPMRPGVATP LVSSSDYMPM APQNVSASKK RHSRSPFEDS RGYMMMFPRV 
       760        770        780        790        800
SPPPAPSPPK APDTNKEDDS KDNDSESDYM FMAPGAGAIP KNPRNPQGGS 
       810        820        830        840        850
SSKSWSSYFS LPNPFRSSPL GQNDNSEYVP MLPGKFLGRG LDKEVSYNWD 
       860        870        880        890        900
PKDAASKPSG EGSFSKPGDG GSPSKPSDHE PPKNKAKRPN RLSFITKGYK 
       910        920        930        940        950
IKPKPQKPTH EQREADSSSD YVNMDFTKRE SNTPAPSTQG LPDSWGIIAE 
       960        970        980        990       1000
PRQSAFSNYV NVEFGVPFPN PANDLSDLLR AIPRANPLSL DSARWPLPPL 
      1010       1020       1030       1040       1050
PLSATGSNAI EEEGDYIEVI FNSAMTPAMA LADSAIRYDA ETGRIYVVDP 
      1060       1070       1080       1090       1100
FSECCMDISL SPSRCSEPPP VARLLQEEEQ ERRRPQSRSQ SFFAAARAAV 
      1110       1120       1130       1140       1150
SAFPTDSLER DLSPSSAPAV ASAAEPTLAL SQVVAAASAL AAAPGIGAAA 
      1160       1170       1180       1190       1200
AAAGFDSASA RWFQPVANAA DAEAVRGAQD VAGGSNPGAH NPSANLARGD 
      1210       1220       1230       1240       1250
NQAGGAAAAA AAPEPPPRSR RVPRPPERED SDNDDDTHVR MDFARRDNQF 

DSPKRGR
Length:1,257
Mass (Da):133,768
Last modified:January 1, 1998 - v1
<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:i4D512D65A7A80374
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 is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A804CF45A0A804CF45_HUMAN
Insulin receptor substrate 4
IRS4
1,256Annotation 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>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03804220A → V in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_05107834L → F. Corresponds to variant dbSNP:rs1801162Ensembl.1
Natural variantiVAR_083291215 – 1257Missing in CHNG9. 1 PublicationAdd BLAST1043
Natural variantiVAR_038043215G → E in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_051079508N → K. Corresponds to variant dbSNP:rs34287560Ensembl.1
Natural variantiVAR_038044557G → R in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_051080879H → D. Corresponds to variant dbSNP:rs1801164Ensembl.1
Natural variantiVAR_0616691230D → Y. Corresponds to variant dbSNP:rs28546943EnsemblClinVar.1

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
AF007567 mRNA Translation: AAC51738.1
AL035425 Genomic DNA No translation available.
CH471120 Genomic DNA Translation: EAX02682.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS14544.1

NCBI Reference Sequences

More...RefSeqi		NP_003595.1, NM_003604.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000564206; ENSP00000505547; ENSG00000133124

Database of genes from NCBI RefSeq genomes

More...GeneIDi		8471

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:8471

UCSC genome browser

More...UCSCi		uc004eoc.3, human

<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
AF007567 mRNA Translation: AAC51738.1
AL035425 Genomic DNA No translation available.
CH471120 Genomic DNA Translation: EAX02682.1
CCDSiCCDS14544.1
RefSeqiNP_003595.1, NM_003604.2

3D structure databases

SMRiO14654
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi114048, 173 interactors
IntActiO14654, 113 interactors
STRINGi9606.ENSP00000361202

PTM databases

GlyGeniO14654, 1 site, 1 O-linked glycan (1 site)
iPTMnetiO14654
PhosphoSitePlusiO14654

Genetic variation databases

BioMutaiIRS4

Proteomic databases

MassIVEiO14654
MaxQBiO14654
PaxDbiO14654
PeptideAtlasiO14654
PRIDEiO14654
ProteomicsDBi48151

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		15310, 168 antibodies

The DNASU plasmid repository

More...DNASUi		8471

Genome annotation databases

EnsembliENST00000564206; ENSP00000505547; ENSG00000133124
GeneIDi8471
KEGGihsa:8471
UCSCiuc004eoc.3, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		8471
DisGeNETi8471

GeneCards: human genes, protein and diseases

More...GeneCardsi		IRS4
HGNCiHGNC:6128, IRS4
HPAiENSG00000133124, Tissue enriched (pituitary)
MalaCardsiIRS4
MIMi300904, gene
301035, phenotype
neXtProtiNX_O14654
OpenTargetsiENSG00000133124
PharmGKBiPA29923
VEuPathDBiHostDB:ENSG00000133124

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiENOG502SD84, Eukaryota
GeneTreeiENSGT00940000160883
HOGENOMiCLU_290952_0_0_1
InParanoidiO14654
OMAiEDSRGYM
OrthoDBi298675at2759
PhylomeDBiO14654
TreeFamiTF325994

Enzyme and pathway databases

PathwayCommonsiO14654
ReactomeiR-HSA-2428928, IRS-related events triggered by IGF1R
SignaLinkiO14654
SIGNORiO14654

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		8471, 11 hits in 637 CRISPR screens

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		IRS4

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

More...GenomeRNAii		8471
PharosiO14654, Tbio

Protein Ontology

More...PROi		PR:O14654
RNActiO14654, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000133124, Expressed in adenohypophysis and 33 other tissues
GenevisibleiO14654, HS

Family and domain databases

CDDicd01204, PTB_IRS, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR039011, IRS
IPR002404, IRS_PTB
IPR011993, PH-like_dom_sf
IPR001849, PH_domain
PANTHERiPTHR10614, PTHR10614, 1 hit
PfamiView protein in Pfam
PF02174, IRS, 1 hit
PRINTSiPR00628, INSULINRSI
SMARTiView protein in SMART
SM00233, PH, 1 hit
SM00310, PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064, IRS_PTB, 1 hit
PS50003, PH_DOMAIN, 1 hit

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 nameiIRS4_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: O14654
<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: January 15, 2008
Last sequence update: January 1, 1998
Last modified: September 29, 2021
This is version 179 of the entry and version 1 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

Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again