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Immunoglobulin heavy variable 1-46



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


V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition (PubMed:24600447). 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).4 Publications

GO - Molecular functioni

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

GO - Biological processi


Biological processAdaptive 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-202733. Cell surface interactions at the vascular wall.
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-977606. Regulation of Complement cascade.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Protein family/group databases


Names & Taxonomyi

Protein namesi
Recommended name:
Immunoglobulin heavy variable 1-462 Publications
Alternative name(s):
Ig heavy chain V-I region DOT1 Publication
Ig heavy chain V-I region HG31 Publication
Ig heavy chain V-I region Mot1 Publication
Gene namesi
Name:IGHV1-462 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5554. IGHV1-46.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases


Polymorphism and mutation databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 192 PublicationsAdd BLAST19
ChainiPRO_000001524420 – 117Immunoglobulin heavy variable 1-462 PublicationsAdd BLAST98

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20Pyrrolidone carboxylic acidBy similarity1
Disulfide bondi41 ↔ 115PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid

Proteomic databases


PTM databases



Subunit structurei

Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked.1 Publication


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – ›117Ig-likePROSITE-ProRule annotationAdd BLAST›98

Keywords - Domaini

Immunoglobulin domain, Immunoglobulin V region, Signal

Phylogenomic databases


Family and domain databases

InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013106. Ig_V-set.
PfamiView protein in Pfam
PF07686. V-set. 1 hit.
SMARTiView protein in SMART
SM00406. IGv. 1 hit.
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 1 hit.


Sequence statusi: Complete.

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

P01743-1 [UniParc]FASTAAdd to basket

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Mass (Da):12,933
Last modified:October 5, 2016 - v2

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20Q → A AA sequence (PubMed:7737190).Curated1
Sequence conflicti28 – 32AEVKK → VERKV AA sequence (PubMed:7737190).Curated5
Sequence conflicti35A → S AA sequence (PubMed:3084950).Curated1
Sequence conflicti37 – 39VKV → ARL AA sequence (PubMed:3084950).Curated3
Sequence conflicti38 – 39KV → RI AA sequence (PubMed:7737190).Curated2
Sequence conflicti43A → V AA sequence (PubMed:3084950).Curated1
Sequence conflicti46 – 47YT → DD AA sequence (PubMed:3084950).Curated2
Sequence conflicti47 – 50TFTS → AFEN AA sequence (PubMed:7737190).Curated4
Sequence conflicti50S → T AA sequence (PubMed:3084950).Curated1
Sequence conflicti52 – 53YM → DI AA sequence (PubMed:3084950).Curated2
Sequence conflicti53M → I AA sequence (PubMed:7737190).Curated1
Sequence conflicti62Q → L AA sequence (PubMed:7737190).Curated1
Sequence conflicti62Q → R AA sequence (PubMed:3084950).Curated1
Sequence conflicti68 – 71GIIN → AVVH AA sequence (PubMed:3084950).Curated4
Sequence conflicti70I → F AA sequence (PubMed:7737190).Curated1
Sequence conflicti73 – 81SGGSTSYAQ → VAGAVSSE AA sequence (PubMed:7737190).Curated9
Sequence conflicti74 – 76GGS → DDR AA sequence (PubMed:3084950).Curated3
Sequence conflicti78S → T AA sequence (PubMed:3084950).Curated1
Sequence conflicti80 – 83AQKF → GPRS AA sequence (PubMed:3084950).Curated4
Sequence conflicti84 – 91QGRVTMTR → RDRLVMSS AA sequence (PubMed:7737190).Curated8
Sequence conflicti85G → A AA sequence (PubMed:3084950).Curated1
Sequence conflicti87V → F AA sequence (PubMed:3084950).Curated1
Sequence conflicti89M → V AA sequence (PubMed:3084950).Curated1
Sequence conflicti93T → S AA sequence (PubMed:3084950).Curated1
Sequence conflicti95 – 96TS → AN AA sequence (PubMed:7737190).Curated2
Sequence conflicti96S → T AA sequence (PubMed:3084950).Curated1
Sequence conflicti99 – 104YMELSS → SMQLRN AA sequence (PubMed:7737190).Curated6
Sequence conflicti103 – 104SS → TA AA sequence (PubMed:3084950).Curated2
Sequence conflicti106R → I AA sequence (PubMed:3084950).Curated1
Sequence conflicti108E → A AA sequence (PubMed:3084950).Curated1
Sequence conflicti108E → D AA sequence (PubMed:7737190).Curated1
Sequence conflicti111 – 114AVYY → GRYF AA sequence (PubMed:7737190).Curated4
Sequence conflicti112V → I AA sequence (PubMed:3084950).Curated1
Non-terminal residuei1171


There are several alleles. The sequence shown is that of IMGT allele IGHV1-46*01.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07671249T → N in IMGT allele IGHV1-46*02. 1

Sequence databases

Select the link destinations:
Links Updated
J00240 Genomic DNA. Translation: AAA52988.1.
AC244452 Genomic DNA. No translation available.
A02025. HVHUMO.

Genome annotation databases

EnsembliENST00000390622; ENSP00000375031; ENSG00000211962.
ENST00000632105; ENSP00000488713; ENSG00000282131.

Keywords - Coding sequence diversityi


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.

Entry informationi

Entry nameiHV146_HUMAN
AccessioniPrimary (citable) accession number: P01743
Secondary accession number(s): A0A0B4J1V4, P06326, P80421
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 5, 2016
Last modified: July 5, 2017
This is version 117 of the entry and version 2 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.



For examples of full length immunoglobulin heavy chains (of different isotypes) see AC P0DOX2, AC P0DOX3, AC P0DOX4, AC P0DOX5 and AC P0DOX6.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome


  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations