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Entry version 188 (16 Oct 2019)
Sequence version 3 (20 Dec 2005)
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Protein

HLA class I histocompatibility antigen, C alpha chain

Gene

HLA-C

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

Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity (PubMed:20972337, PubMed:24091323, PubMed:20439706, PubMed:11172028, PubMed:20104487, PubMed:28649982, PubMed:29312307). In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells (PubMed:16141329). In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth (PubMed:20972337, PubMed:24091323). During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells (PubMed:20439706). Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection (PubMed:11172028, PubMed:20104487, PubMed:28649982). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (By similarity). Typically presents intracellular peptide antigens of 9 amino acids that arise from cytosolic proteolysis via proteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Preferentially displays peptides having a restricted repertoire of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val and Tyr) at the C-terminal anchor (PubMed:8265661, PubMed:25311805).By similarity10 Publications
ALLELE C*01:02: The peptide-bound form interacts with KIR2DL2 and KIR2DL3 inhibitory receptors on NK cells. The low affinity peptides compete with the high affinity peptides impeding KIR-mediated inhibition and favoring lysis of infected cells (PubMed:20439706). Presents to CD8-positive T cells a CMV epitope derived from UL83/pp65 (RCPEMISVL), an immediate-early antigen necessary for initiating viral replication (PubMed:12947002).2 Publications
ALLELE C*04:01: Presents a conserved HIV-1 epitope derived from env (SFNCGGEFF) to memory CD8-positive T cells, eliciting very strong IFNG responses (PubMed:20104487). Presents CMV epitope derived from UL83/pp65 (QYDPVAALF) to CD8-positive T cells, triggering T cell cytotoxic response (PubMed:12947002).2 Publications
ALLELE C*05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response.1 Publication
ALLELE C*06:02: In trophoblasts, interacts with KIR2DS2 on uterine NK cells and triggers NK cell activation, including secretion of cytokines such as GMCSF that enhances trophoblast migration.1 Publication
ALLELE C*07:02: Plays an important role in the control of chronic CMV infection. Presents immunodominant CMV epitopes derived from IE1 (LSEFCRVL and CRVLCCYVL) and UL28 (FRCPRRFCF), both antigens synthesized during immediate-early period of viral replication. Elicits a strong anti-viral CD8-positive T cell immune response that increases markedly with age.1 Publication
ALLELE C*08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response.2 Publications
ALLELE C*12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells.1 Publication
ALLELE C*15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei87Self- and pathogen-derived peptide antigen1 Publication1
Binding sitei94Self- and pathogen-derived peptide antigen1 Publication1
Binding sitei101Self- and pathogen-derived peptide antigen1 Publication1
Binding sitei183Self- and pathogen-derived peptide antigen1 Publication1
Binding sitei195Self- and pathogen-derived peptide antigen1 Publication1

<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

GO - Biological processi

<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

Biological processAdaptive immunity, Host-virus interaction, Immunity, Innate immunity

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1236974 ER-Phagosome pathway
R-HSA-1236977 Endosomal/Vacuolar pathway
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-6798695 Neutrophil degranulation
R-HSA-877300 Interferon gamma signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P10321

<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:
HLA class I histocompatibility antigen, C alpha chain
Short name:
HLA-C
Alternative name(s):
HLA-Cw
Human leukocyte antigen C
<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:HLA-CImported
Synonyms:HLAC
<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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<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 6

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:4933 HLA-C

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini25 – 308ExtracellularSequence analysisAdd BLAST284
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei309 – 333HelicalSequence analysisAdd BLAST25
Topological domaini334 – 366CytoplasmicSequence analysisAdd BLAST33

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane, MHC I

<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

Psoriasis 1 (PSORS1)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. Allele C*06:02 presents a melanocyte autoantigen ADAMTSL5 (VRSRRCLRL) to Valpha3S1/Vbeta13S1 TCR on CD8-positive T cells, and may trigger an autoimmune response against melanocytes.1 Publication
Disease descriptionA common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
Related information in OMIM

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>Mutagenesisi112S → G: Impairs N-linked glycosylation resulting in impaired interaction with CANX and CALR chaperones as well as TAPBPL. 1 Publication1

Organism-specific databases

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
177900 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000204525

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
99860 Precursor B-cell acute lymphoblastic leukemia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA35057

<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 denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 24Sequence analysisAdd BLAST24
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001886825 – 366HLA class I histocompatibility antigen, C alpha chainAdd BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi110N-linked (GlcNAc...) asparagine1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi125 ↔ 188PROSITE-ProRule annotation2 Publications
Disulfide bondi227 ↔ 283PROSITE-ProRule annotation2 Publications
<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 residuei357PhosphoserineBy similarity1
Modified residuei360PhosphoserineBy similarity1

<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

N-linked glycosylation at Asn-110 is required for efficient interaction with CANX and CALR chaperones and appropriate HLA-C-B2M folded conformers prior to peptide loading.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P10321

MaxQB - The MaxQuant DataBase

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MaxQBi
P10321

PeptideAtlas

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PeptideAtlasi
P10321

PRoteomics IDEntifications database

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PRIDEi
P10321

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
52599

PTM databases

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
P10321

<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

Ubiquitous. Highly expressed in fetal extravillous trophoblasts in the decidua basalis (at protein level).1 Publication

Gene expression databases

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P10321 baseline and differential

<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

Heterotrimer that consists of an alpha chain HLA-C, a beta chain B2M and a peptide (peptide-HLA-C-B2M) (PubMed:28649982, PubMed:10850706, PubMed:24990997). Early in biogenesis, HLA-C-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:18420581).

Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP1-TAP2 transporter (By similarity). Being very selective in the peptide binding, forms a stable interaction with TAP1-TAP2, often leading to the accumulation of free heavy chains in the ER (PubMed:18420581). Only optimally assembled peptide-HLA-C-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-C (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR3 domains) (By similarity). One HLA-C molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide-HLA-C-B2M recognition by CD8-positive T cells only (By similarity). The peptide-HLA-C-B2M complex also interacts with KIRs. HLA-C type 1 (C1, with Asn104), including HLA-C*2, C*4, C*5, C*6 and C*15, interact with KIR2DL1 and KIR2DS1, and HLA-C type 2 (C2, with Lys104), including HLA-C*1, C*3, C*7 and C*8, interact with KIR2DL2 and KIR2DL3 (PubMed:20972337, PubMed:24091323, PubMed:16141329, PubMed:20439706, PubMed:11323700, PubMed:10850706).

By similarity9 Publications

(Microbial infection) Interacts with HTLV-1 p12I accessory protein.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
KIR2DL3P436282EBI-9978491,EBI-8632435

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
109352, 121 interactors

Protein interaction database and analysis system

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IntActi
P10321, 48 interactors

Molecular INTeraction database

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MINTi
P10321

<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

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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SMRi
P10321

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
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>Domaini209 – 297Ig-like C1-typeAdd BLAST89

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>Regioni25 – 114Alpha-1Sequence analysisAdd BLAST90
Regioni115 – 206Alpha-2Sequence analysisAdd BLAST92
Regioni207 – 298Alpha-3Sequence analysisAdd BLAST92
Regioni299 – 308Connecting peptide10

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The alpha-1 domain is a structural part of the peptide-binding cleft.1 Publication
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:28649982, PubMed:10850706, PubMed:24990997). Mediates the interaction with TAP1-TAP2 complex.3 Publications
The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

KEGG Orthology (KO)

More...
KOi
K06751

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.10, 1 hit
3.30.500.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003597 Ig_C1-set
IPR011161 MHC_I-like_Ag-recog
IPR037055 MHC_I-like_Ag-recog_sf
IPR011162 MHC_I/II-like_Ag-recog
IPR001039 MHC_I_a_a1/a2
IPR010579 MHC_I_a_C

Pfam protein domain database

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Pfami
View protein in Pfam
PF07654 C1-set, 1 hit
PF00129 MHC_I, 1 hit
PF06623 MHC_I_C, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01638 MHCCLASSI

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00407 IGc1, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 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>Sequences (2+)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.

<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 in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 41 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P10321-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MRVMAPRALL LLLSGGLALT ETWACSHSMR YFDTAVSRPG RGEPRFISVG
60 70 80 90 100
YVDDTQFVRF DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQADRV
110 120 130 140 150
SLRNLRGYYN QSEDGSHTLQ RMSGCDLGPD GRLLRGYDQS AYDGKDYIAL
160 170 180 190 200
NEDLRSWTAA DTAAQITQRK LEAARAAEQL RAYLEGTCVE WLRRYLENGK
210 220 230 240 250
ETLQRAEPPK THVTHHPLSD HEATLRCWAL GFYPAEITLT WQRDGEDQTQ
260 270 280 290 300
DTELVETRPA GDGTFQKWAA VVVPSGQEQR YTCHMQHEGL QEPLTLSWEP
310 320 330 340 350
SSQPTIPIMG IVAGLAVLVV LAVLGAVVTA MMCRRKSSGG KGGSCSQAAC
360
SNSAQGSDES LITCKA
Length:366
Mass (Da):40,649
Last modified:December 20, 2005 - v3
<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:i59C23D95FD1D0BC8
GO
Isoform 2 (identifier: P10321-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-157: DLRSW → HLRSC
     297-338: SWEPSSQPTIPIMGIVAGLAVLVVLAVLGAVVTAMMCRRKSS → RW

Note: A transcript of allele C*16:01. This isoform lacks the transmembrane domain and is predicted to be a secreted protein.1 Publication
Show »
Length:326
Mass (Da):36,608
Checksum:i0A1E32B017AA2BC1
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 are 41 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JH50A0A0G2JH50_HUMAN
HLA class I histocompatibility anti...
HLA-C
372Annotation score:

Annotation score:2 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>
A0A140T9J9A0A140T9J9_HUMAN
HLA class I histocompatibility anti...
HLA-C
372Annotation score:

Annotation score:2 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>
O19617O19617_HUMAN
HLA class I antigen
HLA-C HLA-Cw
366Annotation score:

Annotation score:2 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>
A0A1W2PRU9A0A1W2PRU9_HUMAN
HLA class I histocompatibility anti...
HLA-C
244Annotation score:

Annotation score:2 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>
A2AEA2A2AEA2_HUMAN
HLA class I histocompatibility anti...
HLA-C
372Annotation score:

Annotation score:2 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>
A0A1W2PNZ7A0A1W2PNZ7_HUMAN
HLA class I histocompatibility anti...
HLA-C
244Annotation score:

Annotation score:2 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>
A0A1W2PP77A0A1W2PP77_HUMAN
HLA class I histocompatibility anti...
HLA-C
244Annotation score:

Annotation score:2 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>
A0A1W2PRX1A0A1W2PRX1_HUMAN
HLA class I histocompatibility anti...
HLA-C
244Annotation score:

Annotation score:2 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>
A0A1W2PS56A0A1W2PS56_HUMAN
HLA class I histocompatibility anti...
HLA-C
244Annotation score:

Annotation score:2 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>
A0A140T912A0A140T912_HUMAN
HLA class I histocompatibility anti...
HLA-C
372Annotation score:

Annotation score:2 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>
There are more potential isoformsShow all

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Displays lower polymorphism than HLA-A and HLA-B. Polymorphic residues encode for alpha-1 and alpha-2 domains of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The human population is estimated to have millions of HLA-C alleles. But only 14 common HLA-C alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: C*01:02; C*02:02; C*03:02; C*04:01; C*05:01; C*06:02; C*07:01; C*07:04; C*08:01; C*12:02; C*14:02; C*15:02; C*16:01 and C*17:01. Among these, C*01:02; C*02:02; C*03:02; C*08:01; C*12:02; C*14:02 and C*15:02, were likely passed by introgression from archaic to modern humans. Functional alleles of more recent origin (non-core) were derived by recombination (PubMed:28650991). The sequence shown is that of C*07:02. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of C*07:02.Curated1 Publication

Natural variant

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_0824087R → Q in allele C*17:01. 2 Publications1
Natural variantiVAR_0824098A → T in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02 and allele C*16:01. 13 Publications1
Natural variantiVAR_08241010L → I in allele C*01:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02 and allele C*16:01. 12 PublicationsCorresponds to variant dbSNP:rs2308527Ensembl.1
Natural variantiVAR_08241116G → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 15 Publications1
Natural variantiVAR_08241220T → I in allele C*17:01. 2 Publications1
Natural variantiVAR_08241325C → G in allele C*03:02, allele C*03:04, allele C*04:01 and allele C*17:01. 7 Publications1
Natural variantiVAR_08241430R → K in allele C*01:02. 1 Publication1
Natural variantiVAR_08241533D → F in allele C*01:02; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_08241633D → S in allele C*04:01 and allele C*14:02; requires 2 nucleotide substitutions. 4 Publications1
Natural variantiVAR_08241733D → Y in allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*12:02, allele C*15:02, allele C*16:01 and allele C*17:01. 13 Publications1
Natural variantiVAR_08241835A → S in allele C*01:02, allele C*04:01 and allele C*14:02. 5 Publications1
Natural variantiVAR_08241938R → W in allele C*04:01. 3 Publications1
Natural variantiVAR_08242040G → S in allele C*02:02. 1 Publication1
Natural variantiVAR_08242145R → H in allele C*02:02, allele C*03:02, allele C*03:04 and allele C*15:02. 4 Publications1
Natural variantiVAR_08242248S → A in allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 14 PublicationsCorresponds to variant dbSNP:rs707911Ensembl.1
Natural variantiVAR_08242359R → Q in allele C*05:01 and C*08:01. 3 Publications1
Natural variantiVAR_08242473A → E in allele C*04:01. 3 PublicationsCorresponds to variant dbSNP:rs1050409Ensembl.1
Natural variantiVAR_08242590K → N in allele C*07:01, C*15:02. 4 Publications1
Natural variantiVAR_08242697A → T in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*14:02, allele C*15:02 and allele C*16:01. 9 PublicationsCorresponds to variant dbSNP:rs41543814Ensembl.1
Natural variantiVAR_082427101S → N in allele C*02:02, allele C*04:01, allele C*05:01, allele C*06:02, allele C*15:02, allele C*17:01 and allele C*18:01. 11 Publications1
Natural variantiVAR_082428104N → K in allele C*02:02, allele C*04:01, allele C*05:01, allele C*06:02, allele C*15:02, allele C*17:01 and allele C*18:01. 11 Publications1
Natural variantiVAR_082429114D → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 12 Publications1
Natural variantiVAR_082430118T → I in allele C*03:02, allele C*03:04 and allele C*15:02. 4 Publications1
Natural variantiVAR_082431119L → F in allele C*07:04. 1 Publication1
Natural variantiVAR_082432119L → I in allele C*03:04, allele C*15:02 and allele C*17:01. 5 Publications1
Natural variantiVAR_082433121R → W in allele C*01:02, allele C*06:02, allele C*14:02 and allele C*16:01. 4 Publications1
Natural variantiVAR_082434123S → C in allele C*01:02. 1 Publication1
Natural variantiVAR_082435123S → F in allele C*04:01, allele C*14:02 and allele C*18:01. 5 Publications1
Natural variantiVAR_082436123S → Y in allele C*07:01, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*06:02, allele C*07:04, allele C*08:01, allele C*12:02, allele C*15:02, allele C*16:01 and allele C*17:01. 14 Publications1
Natural variantiVAR_082437127L → V in allele C*03:02 and allele C*03:04. 2 Publications1
Natural variantiVAR_082438137Y → H in allele C*15:02. 2 Publications1
Natural variantiVAR_082439138D → N in allele C*04:01, allele C*05:01, allele C*08:01, allele C*17:01 and allele C*18:01. 9 Publications1
Natural variantiVAR_082440140S → F in allele C*04:01, allele C*05:01, allele C*07:04, allele C*08:01, allele C*17:01 and allele C*18:01. 10 Publications1
Natural variantiVAR_082441140S → L in allele C*15:02. 2 Publications1
Natural variantiVAR_082442140S → Y in alleles C*01:02, C*03:04. 2 Publications1
Natural variantiVAR_082443162T → K in allele C*05:01. 2 Publications1
Natural variantiVAR_082444167T → S in allele C*17:01. 2 Publications1
Natural variantiVAR_082445171L → W in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications1
Natural variantiVAR_082446176A → E in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*12:02, allele C*14:02, allele C*15:02, allele C*17:01 and allele C*18:01. 15 Publications1
Natural variantiVAR_082447176A → T in allele C*08:01. 1 Publication1
Natural variantiVAR_082448180L → D in allele C*07:04; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_082449180L → Q in allele C*16:01. 1 Publication1
Natural variantiVAR_082450180L → R in allele C*01:02, allele C*04:01, allele C*05:01, allele C*14:02 and allele C*18:01. 8 Publications1
Natural variantiVAR_082451180L → W in allele C*02:02, allele C*06:02 and allele C*12:02. 4 Publications1
Natural variantiVAR_082452187T → E in alleles C*02:02 and allele C*17:01; requires 2 nucleotide substitutions. 3 Publications1
Natural variantiVAR_082453187T → L in allele C*03:02 and allele C*03:04; requires 2 nucleotide substitutions. 2 Publications1
Natural variantiVAR_082454194R → G in allele C*17:01. 2 Publications1
Natural variantiVAR_082455197E → K in allele C*03:02 and allele C*03:04. 2 Publications1
Natural variantiVAR_082456201E → K in allele C*05:01, allele C*07:04 and allele C*08:01. 4 Publications1
Natural variantiVAR_082457208P → H in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications1
Natural variantiVAR_082458208P → R in allele C*17:01. 2 Publications1
Natural variantiVAR_082459217P → L in allele C*16:01. 1 Publication1
Natural variantiVAR_082460218L → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications1
Natural variantiVAR_082461235A → T in allele C*02:02. 1 Publication1
Natural variantiVAR_082462243R → W in alleles C*01:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*14:02 and allele C*18:01. 7 Publications1
Natural variantiVAR_082463272V → M in allele C*01:02. Combined sources1 PublicationCorresponds to variant dbSNP:rs1050276Ensembl.1
Natural variantiVAR_082464277Q → E in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications1
Natural variantiVAR_082465285M → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications1
Natural variantiVAR_082466291Q → P in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications1
Natural variantiVAR_082467294L → C in allele C*17:01; requires 2 nucleotide substitutions. 2 Publications1
Natural variantiVAR_082468297S → R in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications1
Natural variantiVAR_082469299E → G in alleles C*05:01 and allele C*08:01. 3 Publications1
Natural variantiVAR_082470299E → K in allele C*04:01, allele C*17:01 and allele C*18:01. 6 Publications1
Natural variantiVAR_082471308 – 319IMGIV…LAVLV → NLGIVSGPAVLAVLAVLA in allele C*17:01. 2 PublicationsAdd BLAST12
Natural variantiVAR_082472309M → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications1
Natural variantiVAR_082473319V → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02 and allele C*16:01. 13 Publications1
Natural variantiVAR_082474327V → M in allele C*04:01. 3 Publications1
Natural variantiVAR_082475328V → M in allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02 and allele C*15:02. 7 Publications1
Natural variantiVAR_082476329T → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications1
Natural variantiVAR_082477330A → V in allele C*02:02, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 13 Publications1
Natural variantiVAR_082478331M → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications