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HHLA2 Gene

protein-coding   GIFtS: 48
GCID: GC03P108015

HERV-H LTR-Associating 2

  Search for HHLA2
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
HERV-H LTR-Associating 21 2
Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 22 3
B7H72
HERV-H LTR-Associating Protein 22

External Ids:    HGNC: 49051   Entrez Gene: 111482   Ensembl: ENSG000001144557   OMIM: 6043715   UniProtKB: Q9UM443   

Export aliases for HHLA2 gene to outside databases

Previous GC identifers: GC03P104824 GC03U900035 GC03P109351 GC03P109342 GC03P109498 GC03P105394


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for HHLA2 Gene:
This gene encodes a protein ligand found on the surface of monocytes. The encoded protein is thought to regulate
cell-mediated immunity by binding to a receptor on T lymphocytes and inhibiting the proliferation of these cells.
Alternate splicing results in multiple transcript variants. (provided by RefSeq, Sep 2013)

GeneCards Summary for HHLA2 Gene:
HHLA2 (HERV-H LTR-associating 2) is a protein-coding gene. An important paralog of this gene is VTCN1.




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000003.12  NT_005612.17  NC_018914.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the HHLA2 gene promoter:
         HFH-3   RFX1   HNF-3beta   NF-AT   FOXI1   NF-AT4   NF-AT2   NF-AT3   IRF-7A   NF-AT1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHHLA2 promoter sequence
   Search Chromatin IP Primers for HHLA2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HHLA2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3q13.13   Ensembl cytogenetic band:  3q13.13   HGNC cytogenetic band: 3q13.13

HHLA2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HHLA2 gene location

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P108015:  view genomic region     (about GC identifiers)

Start:
108,015,376 bp from pter      End:
108,097,132 bp from pter
Size:
81,757 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: HHLA2_HUMAN, Q9UM44 (See protein sequence)
Recommended Name: HERV-H LTR-associating protein 2 precursor  
Size: 414 amino acids; 46850 Da
Sequence caution: Sequence=BAA91323.1; Type=Erroneous termination; Positions=221; Note=Translated as Trp;
Secondary accessions: D3DN60 Q9NWQ6

Explore the universe of human proteins at neXtProt for HHLA2: NX_Q9UM44

Explore proteomics data for HHLA2 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn90, Asn103, Asn318

  • See HHLA2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_001269485.1  NP_001269486.1  NP_001269487.1  NP_001269488.1  NP_009003.1  

    ENSEMBL proteins: 
     ENSP00000420622   ENSP00000419940   ENSP00000418284   ENSP00000418345   ENSP00000418174  
     ENSP00000419911   ENSP00000350402   ENSP00000419207   ENSP00000417856   ENSP00000418797  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    C1SET: Immunoglobulin superfamily / C1-set domain containing
    VSET: Immunoglobulin superfamily / V-set domain containing

    5 InterPro protein domains:
     IPR013783 Ig-like_fold
     IPR013106 Ig_V-set
     IPR003597 Ig_C1-set
     IPR007110 Ig-like_dom
     IPR003599 Ig_sub

    Graphical View of Domain Structure for InterPro Entry Q9UM44

    ProtoNet protein and cluster: Q9UM44

    1 Blocks protein domain: IPB013106 Immunoglobulin V-set

    UniProtKB/Swiss-Prot: HHLA2_HUMAN, Q9UM44
    Similarity: Contains 1 Ig-like C1-type (immunoglobulin-like) domain
    Similarity: Contains 2 Ig-like V-type (immunoglobulin-like) domains


    HHLA2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003674molecular_function ND--
    GO:0005515protein binding ----
         
    HHLA2 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for HHLA2:
     Increased gamma-H2AX phosphory 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HHLA2
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    hsa-miR-548a-3p hsa-miR-3673 hsa-miR-224 hsa-miR-3185 hsa-miR-143 hsa-miR-548e hsa-miR-4276 hsa-miR-500a
    SwitchGear 3'UTR luciferase reporter plasmidHHLA2 3' UTR sequence
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HHLA2_HUMAN, Q9UM44: Membrane; Single-pass type I membrane protein (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular3
    plasma membrane3
    cytosol1
    lysosome1
    peroxisome1

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005575cellular_component ND--
    GO:0016021integral component of membrane IEA--

    HHLA2 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for HHLA2
    Interactions:

        Search GeneGlobe Interaction Network for HHLA2

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0008150biological_process ND--

    HHLA2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for HHLA2



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for HHLA2 gene (5 alternative transcripts): 
    NM_001282556.1  NM_001282557.1  NM_001282558.1  NM_001282559.1  NM_007072.3  

    Unigene Cluster for HHLA2:

    HERV-H LTR-associating 2
    Hs.252351  [show with all ESTs]
    Unigene Representative Sequence: NM_007072
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000467282 ENST00000463019 ENST00000491820 ENST00000467562 ENST00000482430
    ENST00000462629 ENST00000357759(uc003dwz.3) ENST00000467761(uc011bhl.2 uc010hpu.3 uc003dwy.4)
    ENST00000489514 ENST00000482099
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate HHLA2 (see all 9):
    hsa-miR-548a-3p hsa-miR-3673 hsa-miR-224 hsa-miR-3185 hsa-miR-143 hsa-miR-548e hsa-miR-4276 hsa-miR-500a
    SwitchGear 3'UTR luciferase reporter plasmidHHLA2 3' UTR sequence
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    Additional mRNA sequence: 

    AF126162.1 AK000692.1 AK027132.1 AK296644.1 AK315109.1 BC035971.1 

    6 DOTS entries:

    DT.91791338  DT.91728725  DT.120841668  DT.100749399  DT.100749400  DT.100749398 

    Selected AceView cDNA sequences (see all 29):

    AA135407 BX483882 AF126162 BM983361 BC035971 AK000692 BQ083573 AA554037 
    AK027132 BG431193 AA917390 BX483821 BG283385 BM980757 BM823273 BM970569 
    BG426959 BP383085 BM980981 BM969731 AI261331 AI343844 NM_007072 BM769580 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for HHLA2    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12
    SP1:                                                                                                
    SP2:                    -                                                                           
    SP3:                    -           -                                                               
    SP4:                          -                                                                     
    SP5:                                                                                                


    ECgene alternative splicing isoforms for HHLA2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HHLA2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACCTGCATCC
    HHLA2 Expression
    About this image

    HHLA2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HHLA2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.252351

    UniProtKB/Swiss-Prot: HHLA2_HUMAN, Q9UM44
    Tissue specificity: Expressed in colon, small intestine, lung and kidney

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for HHLA2 gene from Selected species (see all 7)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    oppossum
    (Monodelphis domestica)
    Mammalia HHLA26
    HERV-H LTR-associating 2
    35(a)
    1 ↔ 1
    4(67986741-68023573)
    chicken
    (Gallus gallus)
    Aves HHLA26
    HERV-H LTR-associating 2
    37(a)
    1 ↔ 1
    1(86867701-86874706)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia hhla21 HERV-H LTR-associating 2 47.45(n)
    36.3(a)
      734131  NM_001128644.1  NP_001122116.1 
    zebrafish
    (Danio rerio)
    Actinopterygii HHLA2 (3 of 4)6
    HHLA2 (1 of 4)6
    (see all 4)
    HERV-H LTR-associating 2
    (see all 4)
    19(a)
    18(a)
    (see all 4)
    1 ↔ many
    1 ↔ many
    (see all 4)
    24(25844329-25852586) ENSDARG00000086254
    10(36463390-36475629) ENSDARG00000004763


    ENSEMBL Gene Tree for HHLA2 (if available)
    TreeFam Gene Tree for HHLA2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HHLA2 gene
    VTCN12  CD2762  
    1 SIMAP similar gene for HHLA2 using alignment to 8 protein entries:     HHLA2_HUMAN (see all proteins):
    CD276

    HHLA2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for HHLA2 (see all 1449)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs354854371,2
    C--105425768(+) AAAAA-/A/AA  
      
    /AAAAA
    TTAAT
    1 -- int11NA 2
    rs759949661,2
    C,F--107986754(+) GAAAAG/ACATGG 1 -- int13Minor allele frequency- A:0.12WA NA EA 358
    rs1890164221,2
    C--107986960(+) ACATAC/TGTCCT 1 -- int10--------
    rs1438949591,2
    C--107986962(+) TACGT-/CCCTGG 1 -- int10--------
    rs1168321901,2
    F--107987035(+) TCTAAG/ACCAGT 1 -- int11Minor allele frequency- A:0.03WA 118
    rs1148773751,2
    F--107987080(+) TCTAAA/GTTCCC 1 -- int11Minor allele frequency- G:0.01WA 118
    rs1820490541,2
    --107987113(+) TGTCAC/TATTTA 1 -- int10--------
    rs1871689731,2
    --107987184(+) TTTACA/GTTTAG 1 -- int10--------
    rs1894679731,2
    --107987218(+) CATAGC/GAGTAC 1 -- int10--------
    rs1423821711,2
    --107987380(+) CCTAGG/TCCCTC 1 -- int10--------

    HapMap Linkage Disequilibrium report for HHLA2 (108015376 - 108097132 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for HHLA2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv273465CNV Insertion20981092
    nsv829656CNV Loss17160897
    nsv829657CNV Gain17160897
    nsv526190CNV Gain19592680

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604371    OMIM disorders: --


    HHLA2 for disorders           About GeneDecksing

    Genetic Association Database (GAD): HHLA2

    Export disorders for HHLA2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HHLA2 gene integrated from 10 sources:
    (articles sorted by number of sources associating them with HHLA2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3). (PubMed id 10444326)1, 2, 3, 9 Mager D.L.... Freeman J.D. (Genomics 1999)
    2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    4. HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function. (PubMed id 23716685)1 Zhao R....Zang X. (Proc. Natl. Acad. Sci. U.S.A. 2013)
    5. Evolution of the B7 family: co-evolution of B7H6 and NKp30, identification of a new B7 family member, B7H7, and of B7's historical relationship with the MHC. (PubMed id 22488247)1 Flajnik M.F....Ohta Y. (Immunogenetics 2012)
    6. Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. (PubMed id 15342556)1 Suzuki Y.... Sugano S. (Genome Res. 2004)
    7. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    8. Normalization and subtraction: two approaches to facilitate gene discovery. (PubMed id 8889548)1 Bonaldo M.F.... Soares M.B. (Genome Res. 1996)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
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      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 11148 HGNC: 4905 AceView: HHLA2 Ensembl:ENSG00000114455 euGenes: HUgn11148
    ECgene: HHLA2 H-InvDB: HHLA2

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for HHLA2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for HHLA2 gene:
    Search GeneIP for patents involving HHLA2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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