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UniProtKB - P24394 (IL4RA_HUMAN)

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Protein

Interleukin-4 receptor subunit alpha

Gene

IL4R

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

Functioni

Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.1 Publication
Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei38Major IL4 binding determinant1
Sitei64Minor IL4 binding determinant1
Sitei66Minor IL4 binding determinant1
Sitei92Minor IL4 binding determinant1
Sitei94Minor IL4 binding determinant1
Sitei97Major IL4 binding determinant1
Sitei152Minor IL4 binding determinant1
Sitei208Major IL4 binding determinant1

GO - Molecular functioni

  • interleukin-4 receptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionReceptor
Biological processImmunity

Enzyme and pathway databases

ReactomeiR-HSA-6785807 Interleukin-4 and 13 signaling
SignaLinkiP24394
SIGNORiP24394

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-4 receptor subunit alpha
Short name:
IL-4 receptor subunit alpha
Short name:
IL-4R subunit alpha
Short name:
IL-4R-alpha
Short name:
IL-4RA
Alternative name(s):
CD_antigen: CD124
Cleaved into the following chain:
Soluble interleukin-4 receptor subunit alpha
Short name:
Soluble IL-4 receptor subunit alpha
Short name:
Soluble IL-4R-alpha
Short name:
sIL4Ralpha/prot
Alternative name(s):
IL-4-binding protein
Short name:
IL4-BP
Gene namesi
Name:IL4R
Synonyms:IL4RA
ORF Names:582J2.1
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 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000077238.13
HGNCiHGNC:6015 IL4R
MIMi147781 gene
neXtProtiNX_P24394

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 232ExtracellularSequence analysisAdd BLAST207
Transmembranei233 – 256HelicalSequence analysisAdd BLAST24
Topological domaini257 – 825CytoplasmicSequence analysisAdd BLAST569

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38Y → A: 700-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi38Y → F: 25-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi39M → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi40S → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi64L → A: 100-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi66F → A: 45-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi67L → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi68L → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi91D → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi92D → A: 50-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi93V → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi94V → A: 35-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi95S → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi97D → A or N: >150-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi98N → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi99Y → A: 10-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi116K → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi117P → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi118S → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi119E → A: No effect on IL4 binding. 1 Publication1
Mutagenesisi150D → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi151N → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi152Y → A: 40-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi152Y → F: No effect on IL4 binding. 1 Publication1
Mutagenesisi153L → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi154Y → A: Little effect on IL4 binding. 1 Publication1
Mutagenesisi208Y → A: 500-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi208Y → F: 200-fold reduction in IL4 binding. 1 Publication1
Mutagenesisi497Y → F: Abolishes IRS1 tyrosine phosphorylation. No cell proliferation. 1 Publication1
Mutagenesisi575Y → F: Loss of CD23 gene induction; when associated with F-603 and F-631. 2 Publications1
Mutagenesisi603Y → F: Loss of CD23 gene induction; when associated with F-575 and F-631. 1 Publication1
Mutagenesisi631Y → F: Loss of CD23 gene induction; when associated with F-575 and F-603. 1 Publication1
Mutagenesisi713Y → F: Increased IL4-induced cell proliferation and STAT6 activation. 1 Publication1

Organism-specific databases

DisGeNETi3566
MalaCardsiIL4R
OpenTargetsiENSG00000077238
PharmGKBiPA29832

Chemistry databases

ChEMBLiCHEMBL3580490
DrugBankiDB05078 AER001
GuidetoPHARMACOLOGYi1697

Polymorphism and mutation databases

BioMutaiIL4R
DMDMi124335

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25By similarityAdd BLAST25
ChainiPRO_000001088726 – 825Interleukin-4 receptor subunit alphaAdd BLAST800
ChainiPRO_000001088826 – ?Soluble interleukin-4 receptor subunit alpha

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 44By similarity
Glycosylationi53N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi74 ↔ 86By similarity
Glycosylationi98N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi134N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi176N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi209N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei497Phosphotyrosine1 Publication1
Modified residuei575Phosphotyrosine1 Publication1
Modified residuei603Phosphotyrosine1 Publication1
Modified residuei631Phosphotyrosine1 Publication1

Post-translational modificationi

On IL4 binding, phosphorylated on C-terminal tyrosine residues. Phosphorylation on any one of tyrosine residues, Tyr-575, Tyr-603 or Tyr-631, is required for STAT6-induced gene induction.1 Publication
The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP24394
PeptideAtlasiP24394
PRIDEiP24394
ProteomicsDBi54203
54204 [P24394-2]

PTM databases

iPTMnetiP24394
PhosphoSitePlusiP24394

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are highly expressed in activated T-cells.

Gene expression databases

BgeeiENSG00000077238
ExpressionAtlasiP24394 baseline and differential
GenevisibleiP24394 HS

Organism-specific databases

HPAiCAB004451
HPA050124

Interactioni

Subunit structurei

The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequent recruitment to the complex of the common gamma chain, in immune cells, creates a type I receptor and, in non-immune cells, of IL13RA1 forms a type II receptor. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor (PubMed:7775445, PubMed:8804422). Interacts with PIK3C3 (By similarity). Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP (PubMed:11714803). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5; inhibits IL4 signaling (By similarity). Interacts with JAK3 (PubMed:7538655). Interacts with CLM1 (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109780, 41 interactors
CORUMiP24394
DIPiDIP-3223N
ELMiP24394
IntActiP24394, 11 interactors
MINTiP24394
STRINGi9606.ENSP00000170630

Structurei

Secondary structure

1825
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 36Combined sources9
Beta strandi38 – 50Combined sources13
Helixi54 – 57Combined sources4
Beta strandi58 – 68Combined sources11
Beta strandi72 – 74Combined sources3
Beta strandi77 – 89Combined sources13
Beta strandi99 – 105Combined sources7
Beta strandi108 – 115Combined sources8
Helixi117 – 119Combined sources3
Beta strandi127 – 132Combined sources6
Turni135 – 137Combined sources3
Beta strandi139 – 144Combined sources6
Helixi154 – 156Combined sources3
Beta strandi158 – 168Combined sources11
Beta strandi172 – 177Combined sources6
Beta strandi179 – 181Combined sources3
Beta strandi183 – 186Combined sources4
Helixi188 – 190Combined sources3
Beta strandi193 – 195Combined sources3
Beta strandi197 – 204Combined sources8
Helixi206 – 208Combined sources3
Beta strandi219 – 221Combined sources3
Helixi495 – 497Combined sources3

3D structure databases

ProteinModelPortaliP24394
SMRiP24394
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24394

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini125 – 224Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni437 – 557Required for IRS1 activation and IL4-induced cell growthAdd BLAST121
Regioni558 – 657Required for IL4-induced gene expressionAdd BLAST100

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi212 – 216WSXWS motif5
Motifi262 – 270Box 1 motif9
Motifi711 – 716ITIM motif6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi370 – 380Poly-GluAdd BLAST11
Compositional biasi563 – 566Poly-Ala4
Compositional biasi789 – 794Poly-Ser6

Domaini

The extracellular domain represents the IL4 binding protein (IL4BP).
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Sequence similaritiesi

Belongs to the type I cytokine receptor family. Type 4 subfamily.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGBQ Eukaryota
ENOG41124QC LUCA
GeneTreeiENSGT00510000049182
HOVERGENiHBG052116
InParanoidiP24394
KOiK05071
OMAiASPCCGC
OrthoDBiEOG091G010H
PhylomeDBiP24394
TreeFamiTF337996

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR003531 Hempt_rcpt_S_F1_CS
IPR013783 Ig-like_fold
IPR015319 IL-4_rcpt-alpha_N
PfamiView protein in Pfam
PF09238 IL4Ra_N, 1 hit
SUPFAMiSSF49265 SSF49265, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01355 HEMATOPO_REC_S_F1, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P24394-1) [UniParc]FASTAAdd to basket
Also known as: Membrane-bound form

This isoform has been chosen as the 'canonical' 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
MGWLCSGLLF PVSCLVLLQV ASSGNMKVLQ EPTCVSDYMS ISTCEWKMNG 
        60         70         80         90        100
PTNCSTELRL LYQLVFLLSE AHTCIPENNG GAGCVCHLLM DDVVSADNYT 
       110        120        130        140        150
LDLWAGQQLL WKGSFKPSEH VKPRAPGNLT VHTNVSDTLL LTWSNPYPPD 
       160        170        180        190        200
NYLYNHLTYA VNIWSENDPA DFRIYNVTYL EPSLRIAAST LKSGISYRAR 
       210        220        230        240        250
VRAWAQCYNT TWSEWSPSTK WHNSYREPFE QHLLLGVSVS CIVILAVCLL 
       260        270        280        290        300
CYVSITKIKK EWWDQIPNPA RSRLVAIIIQ DAQGSQWEKR SRGQEPAKCP 
       310        320        330        340        350
HWKNCLTKLL PCFLEHNMKR DEDPHKAAKE MPFQGSGKSA WCPVEISKTV 
       360        370        380        390        400
LWPESISVVR CVELFEAPVE CEEEEEVEEE KGSFCASPES SRDDFQEGRE 
       410        420        430        440        450
GIVARLTESL FLDLLGEENG GFCQQDMGES CLLPPSGSTS AHMPWDEFPS 
       460        470        480        490        500
AGPKEAPPWG KEQPLHLEPS PPASPTQSPD NLTCTETPLV IAGNPAYRSF 
       510        520        530        540        550
SNSLSQSPCP RELGPDPLLA RHLEEVEPEM PCVPQLSEPT TVPQPEPETW 
       560        570        580        590        600
EQILRRNVLQ HGAAAAPVSA PTSGYQEFVH AVEQGGTQAS AVVGLGPPGE 
       610        620        630        640        650
AGYKAFSSLL ASSAVSPEKC GFGASSGEEG YKPFQDLIPG CPGDPAPVPV 
       660        670        680        690        700
PLFTFGLDRE PPRSPQSSHL PSSSPEHLGL EPGEKVEDMP KPPLPQEQAT 
       710        720        730        740        750
DPLVDSLGSG IVYSALTCHL CGHLKQCHGQ EDGGQTPVMA SPCCGCCCGD 
       760        770        780        790        800
RSSPPTTPLR APDPSPGGVP LEASLCPASL APSGISEKSK SSSSFHPAPG 
       810        820 
NAQSSSQTPK IVNFVSVGPT YMRVS
Length:825
Mass (Da):89,658
Last modified:March 1, 1992 - v1
Checksum:i9F886DF5612297F8
GO
Isoform 2 (identifier: P24394-2) [UniParc]FASTAAdd to basket
Also known as: Soluble form, sIL4Ralpha/splice

The sequence of this isoform differs from the canonical sequence as follows:
     225-227: YRE → NIC
     228-825: Missing.

Show »
Length:227
Mass (Da):25,553
Checksum:i9FE8FCC827717CC5
GO
Isoform 3 (identifier: P24394-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MGWLCSGLLFPVSCLVLLQVASS → MQKDARRE

Note: No experimental confirmation available.
Show »
Length:810
Mass (Da):88,267
Checksum:i234ADCAA655651CB
GO

Polymorphismi

Allelic variants in IL4RA are associated with a susceptibility to atopy, an immunological condition that can lead to clinical symptoms such as allergic rhinitis, sinusitis, asthma and eczema.
Allelic variants in IL4RA are associated with cedar pollen sensitization. Individuals develop Japanese cedar pollinosis with increased exposure to cedar pollen. Japanese cedar pollinosis is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05930275I → F. Corresponds to variant dbSNP:rs1805010EnsemblClinVar.1
Natural variantiVAR_05930375I → L. Corresponds to variant dbSNP:rs1805010EnsemblClinVar.1
Natural variantiVAR_00803475I → V Associated with atopic asthma and cedar pollen sensitization. 5 PublicationsCorresponds to variant dbSNP:rs1805010EnsemblClinVar.1
Natural variantiVAR_019999387S → L. Corresponds to variant dbSNP:rs6413500Ensembl.1
Natural variantiVAR_011657400E → A Associated with cedar pollen sensitization. 4 PublicationsCorresponds to variant dbSNP:rs1805011Ensembl.1
Natural variantiVAR_011658431C → R3 PublicationsCorresponds to variant dbSNP:rs1805012Ensembl.1
Natural variantiVAR_011659436S → L3 PublicationsCorresponds to variant dbSNP:rs1805013Ensembl.1
Natural variantiVAR_049164492A → T. Corresponds to variant dbSNP:rs35606110Ensembl.1
Natural variantiVAR_049165492A → V. Corresponds to variant dbSNP:rs34727572Ensembl.1
Natural variantiVAR_011660503S → P Lowered total IgE concentration. 3 PublicationsCorresponds to variant dbSNP:rs1805015EnsemblClinVar.1
Natural variantiVAR_008035576Q → R Associated with atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction. 6 PublicationsCorresponds to variant dbSNP:rs1801275EnsemblClinVar.1
Natural variantiVAR_011661579V → I2 PublicationsCorresponds to variant dbSNP:rs3024677Ensembl.1
Natural variantiVAR_020000675P → S1 PublicationCorresponds to variant dbSNP:rs3024678Ensembl.1
Natural variantiVAR_011662752S → A2 PublicationsCorresponds to variant dbSNP:rs1805016Ensembl.1
Natural variantiVAR_011663786S → P in 1.8% of the population. 2 PublicationsCorresponds to variant dbSNP:rs1805014Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0537381 – 23MGWLC…QVASS → MQKDARRE in isoform 3. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_011116225 – 227YRE → NIC in isoform 2. Curated3
Alternative sequenceiVSP_011117228 – 825Missing in isoform 2. CuratedAdd BLAST598

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52425 mRNA Translation: CAA36672.1
AC004525 Genomic DNA Translation: AAC23495.1
AF421855 Genomic DNA Translation: AAL12163.1
AJ293647 Genomic DNA Translation: CAC20445.1
AJ293648 Genomic DNA Translation: CAC20446.1
AJ293649 Genomic DNA Translation: CAC20447.1
AJ293650 Genomic DNA Translation: CAC20448.1
AJ293651 Genomic DNA Translation: CAC20449.1
AJ293652 Genomic DNA Translation: CAC20450.1
AJ293653 Genomic DNA Translation: CAC20451.1
AK303255 mRNA Translation: BAG64338.1
AC106739 Genomic DNA No translation available.
BC151131 mRNA Translation: AAI51132.1
AJ293654 Genomic DNA Translation: CAC20452.1
CCDSiCCDS10629.1 [P24394-1]
CCDS58441.1 [P24394-3]
PIRiA60386
RefSeqiNP_000409.1, NM_000418.3 [P24394-1]
NP_001244335.1, NM_001257406.1 [P24394-1]
NP_001244336.1, NM_001257407.1 [P24394-3]
XP_011544127.1, XM_011545825.1 [P24394-1]
XP_011544128.1, XM_011545826.2 [P24394-1]
XP_011544129.1, XM_011545827.2 [P24394-1]
UniGeneiHs.513457
Hs.742121

Genome annotation databases

EnsembliENST00000170630; ENSP00000170630; ENSG00000077238 [P24394-3]
ENST00000395762; ENSP00000379111; ENSG00000077238 [P24394-1]
ENST00000543915; ENSP00000441667; ENSG00000077238 [P24394-1]
GeneIDi3566
KEGGihsa:3566
UCSCiuc002don.5 human [P24394-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL4RA_HUMAN
AccessioniPrimary (citable) accession number: P24394
Secondary accession number(s): B4E076
, B9EKU8, H3BSY5, Q96P01, Q9H181, Q9H182, Q9H183, Q9H184, Q9H185, Q9H186, Q9H187, Q9H188
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: July 18, 2018
This is version 206 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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