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Protein

Immunoglobulin heavy variable 4-59

Gene

IGHV4-59

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).3 Publications

GO - Molecular functioni

  • antigen binding Source: UniProtKB
  • serine-type endopeptidase activity Source: Reactome

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-166663. Initial triggering of complement.
R-HSA-173623. Classical antibody-mediated complement activation.
R-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2029481. FCGR activation.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-2029485. Role of phospholipids in phagocytosis.
R-HSA-2168880. Scavenging of heme from plasma.
R-HSA-2454202. Fc epsilon receptor (FCERI) signaling.
R-HSA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-5690714. CD22 mediated BCR regulation.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Names & Taxonomyi

Protein namesi
Recommended name:
Immunoglobulin heavy variable 4-592 Publications
Alternative name(s):
Ig heavy chain V-II region NEWM1 Publication
Gene namesi
Name:IGHV4-592 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5654. IGHV4-59.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000224373.
ENSG00000282691.

Polymorphism and mutation databases

DMDMi123828.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
ChainiPRO_000005991320 – 116Immunoglobulin heavy variable 4-591 PublicationAdd BLAST97

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20Pyrrolidone carboxylic acid1 Publication1
Disulfide bondi41 ↔ 114PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid

Proteomic databases

PeptideAtlasiP01825.
PRIDEiP01825.

Interactioni

Subunit structurei

Immunoglobulins are composed of two identical heavy chains and two identical light chains, linked by disulfide bonds.1 Publication

Structurei

Secondary structure

1116
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 26Combined sources5
Beta strandi29 – 31Combined sources3
Beta strandi37 – 46Combined sources10
Beta strandi51 – 58Combined sources8
Beta strandi65 – 70Combined sources6
Beta strandi76 – 78Combined sources3
Helixi80 – 82Combined sources3
Turni83 – 85Combined sources3
Beta strandi86 – 91Combined sources6
Turni92 – 95Combined sources4
Beta strandi96 – 101Combined sources6
Helixi106 – 108Combined sources3
Beta strandi110 – 116Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
7FABX-ray2.00H21-116[»]
ProteinModelPortaliP01825.
SMRiP01825.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01825.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – ›116Ig-likePROSITE-ProRule annotationAdd BLAST›97

Sequence similaritiesi

Contains 1 Ig-like (immunoglobulin-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Immunoglobulin V region, Signal

Phylogenomic databases

GeneTreeiENSGT00760000118987.
HOVERGENiHBG018013.
OMAiFILRCAV.
PhylomeDBiP01825.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P01825-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKHLWFFLLL VAAPRWVLSQ VQLQESGPGL VKPSETLSLT CTVSGGSISS
60 70 80 90 100
YYWSWIRQPP GKGLEWIGYI YYSGSTNYNP SLKSRVTISV DTSKNQFSLK
110
LSSVTAADTA VYYCAR
Length:116
Mass (Da):12,936
Last modified:October 5, 2016 - v2
Checksum:i09C37EE35E4918D5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24 – 25QE → EQ AA sequence (PubMed:407927).Curated2
Sequence conflicti32K → R AA sequence (PubMed:407927).Curated1
Sequence conflicti35E → Q AA sequence (PubMed:407927).Curated1
Sequence conflicti46 – 56GSISSYYWSWI → STFSNDYYTWV AA sequence (PubMed:407927).CuratedAdd BLAST11
Sequence conflicti62K → R AA sequence (PubMed:407927).Curated1
Sequence conflicti70 – 83IYYSG…NPSLK → VFYHGTSDDTTPLR AA sequence (PubMed:407927).CuratedAdd BLAST14
Sequence conflicti88 – 89IS → ML AA sequence (PubMed:407927).Curated2
Sequence conflicti100K → R AA sequence (PubMed:407927).Curated1
Non-terminal residuei1161

Polymorphismi

There are several alleles. The sequence shown is that of IMGT allele IGHV4-59*01.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC244452 Genomic DNA. No translation available.
PIRiA90404. G1HUNM.

Genome annotation databases

EnsembliENST00000390629; ENSP00000375038; ENSG00000224373.
ENST00000619078; ENSP00000484250; ENSG00000282691.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

IMGT/GENE-DB

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC244452 Genomic DNA. No translation available.
PIRiA90404. G1HUNM.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
7FABX-ray2.00H21-116[»]
ProteinModelPortaliP01825.
SMRiP01825.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

IMGTiSearch...

Polymorphism and mutation databases

DMDMi123828.

Proteomic databases

PeptideAtlasiP01825.
PRIDEiP01825.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000390629; ENSP00000375038; ENSG00000224373.
ENST00000619078; ENSP00000484250; ENSG00000282691.

Organism-specific databases

HGNCiHGNC:5654. IGHV4-59.
OpenTargetsiENSG00000224373.
ENSG00000282691.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000118987.
HOVERGENiHBG018013.
OMAiFILRCAV.
PhylomeDBiP01825.

Enzyme and pathway databases

ReactomeiR-HSA-166663. Initial triggering of complement.
R-HSA-173623. Classical antibody-mediated complement activation.
R-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2029481. FCGR activation.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-2029485. Role of phospholipids in phagocytosis.
R-HSA-2168880. Scavenging of heme from plasma.
R-HSA-2454202. Fc epsilon receptor (FCERI) signaling.
R-HSA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-5690714. CD22 mediated BCR regulation.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

EvolutionaryTraceiP01825.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHV459_HUMAN
AccessioniPrimary (citable) accession number: P01825
Secondary accession number(s): A0A0C4DH40, A0A0G2JPU1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 5, 2016
Last modified: November 30, 2016
This is version 105 of the entry and version 2 of the sequence. [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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.