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UniProtKB - O14654 (IRS4_HUMAN)

Protein

Insulin receptor substrate 4

Gene

IRS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

GO - Molecular functioni

  • insulin receptor binding Source: GO_Central
  • phosphatidylinositol 3-kinase binding Source: GO_Central
  • SH3/SH2 adaptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionTransducer

Enzyme and pathway databases

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

Names & Taxonomyi

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
Gene namesi
Name:IRS4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000133124.11
HGNCiHGNC:6128 IRS4
MIMi300904 gene
neXtProtiNX_O14654

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

Organism-specific databases

DisGeNETi8471
OpenTargetsiENSG00000133124
PharmGKBiPA29923

Polymorphism and mutation databases

BioMutaiIRS4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003146781 – 1257Insulin receptor substrate 4Add BLAST1257

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei921Phosphotyrosine1 Publication1

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

EPDiO14654
MaxQBiO14654
PaxDbiO14654
PeptideAtlasiO14654
PRIDEiO14654
ProteomicsDBi48151

PTM databases

iPTMnetiO14654
PhosphoSitePlusiO14654

Expressioni

Tissue specificityi

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

Inductioni

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

Gene expression databases

BgeeiENSG00000133124 Expressed in 23 organ(s), highest expression level in adenohypophysis
CleanExiHS_IRS4
GenevisibleiO14654 HS

Organism-specific databases

HPAiHPA017372

Interactioni

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

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114048, 111 interactors
IntActiO14654, 99 interactors
MINTiO14654
STRINGi9606.ENSP00000361202

Structurei

3D structure databases

ProteinModelPortaliO14654
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini78 – 199PHPROSITE-ProRule annotationAdd BLAST122
Domaini231 – 335IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni678 – 800CRK-bindingAdd BLAST123
Regioni895 – 897GRB2-binding3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Compositional biasi18 – 28Poly-AlaAdd BLAST11
Compositional biasi124 – 137Ala-richAdd BLAST14
Compositional biasi218 – 226Poly-Ala9
Compositional biasi628 – 639Pro-richAdd BLAST12
Compositional biasi1094 – 1212Ala-richAdd BLAST119

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IXEK Eukaryota
ENOG410Z9EP LUCA
GeneTreeiENSGT00530000063420
HOGENOMiHOG000113104
HOVERGENiHBG107140
InParanoidiO14654
KOiK17446
OMAiMFMAPGA
OrthoDBiEOG091G02EF
PhylomeDBiO14654
TreeFamiTF325994

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

Sequencei

Sequence statusi: Complete.

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
Checksum:i4D512D65A7A80374
GO

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_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:rs28546943Ensembl.1

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
UniGeneiHs.407141
Hs.460872

Genome annotation databases

EnsembliENST00000372129; ENSP00000361202; ENSG00000133124
GeneIDi8471
KEGGihsa:8471
UCSCiuc004eoc.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
UniGeneiHs.407141
Hs.460872

3D structure databases

ProteinModelPortaliO14654
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114048, 111 interactors
IntActiO14654, 99 interactors
MINTiO14654
STRINGi9606.ENSP00000361202

PTM databases

iPTMnetiO14654
PhosphoSitePlusiO14654

Polymorphism and mutation databases

BioMutaiIRS4

Proteomic databases

EPDiO14654
MaxQBiO14654
PaxDbiO14654
PeptideAtlasiO14654
PRIDEiO14654
ProteomicsDBi48151

Protocols and materials databases

DNASUi8471
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372129; ENSP00000361202; ENSG00000133124
GeneIDi8471
KEGGihsa:8471
UCSCiuc004eoc.3 human

Organism-specific databases

CTDi8471
DisGeNETi8471
EuPathDBiHostDB:ENSG00000133124.11
GeneCardsiIRS4
HGNCiHGNC:6128 IRS4
HPAiHPA017372
MIMi300904 gene
neXtProtiNX_O14654
OpenTargetsiENSG00000133124
PharmGKBiPA29923
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IXEK Eukaryota
ENOG410Z9EP LUCA
GeneTreeiENSGT00530000063420
HOGENOMiHOG000113104
HOVERGENiHBG107140
InParanoidiO14654
KOiK17446
OMAiMFMAPGA
OrthoDBiEOG091G02EF
PhylomeDBiO14654
TreeFamiTF325994

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiIRS4
GenomeRNAii8471
PROiPR:O14654
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133124 Expressed in 23 organ(s), highest expression level in adenohypophysis
CleanExiHS_IRS4
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
ProtoNetiSearch...

Entry informationi

Entry nameiIRS4_HUMAN
AccessioniPrimary (citable) accession number: O14654
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 159 of the entry and version 1 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
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