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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

HHLA2 Gene

protein-coding   GIFtS: 46
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)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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. GO annotations related to this gene include molecular_function. An important paralog of this gene is ICOSLG.




(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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000003.11  NT_005612.16  NC_018914.2  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for HHLA2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: HHLA2_HUMAN, Q9UM44 (See protein sequence)
Recommended Name: HERV-H LTR-associating protein 2 precursor  
Size: 414 amino acids; 46850 Da
Subcellular location: Membrane; Single-pass type I membrane protein (By similarity)
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 

HHLA2 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

HHLA2 Protein Expression

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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Cloud-Clone Corp. Proteins for HHLA2 

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

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

HHLA2 for ontologies           About GeneDecksing



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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section
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,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

     Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    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:
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miRNA
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SwitchGear 3'UTR luciferase reporter plasmidHHLA2 3' UTR sequence
Inhib. RNA
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In Situ Assay
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Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HHLA2


(Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
About This Section



Interactions:

    Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for HHLA2

Gene Ontology (GO): 1 biological process term (GO ID links to tree view):    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 HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section
Browse Small Molecules at EMD Millipore
Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for HHLA2

Search CenterWatch for drugs/clinical trials and news about 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,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

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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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
Inhib. RNA
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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 

24/29 AceView cDNA sequences (see all 29):

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

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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

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


See HHLA2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for HHLA2

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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In Situ
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Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HHLA2

(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)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for HHLA2 gene from 2/5 species (see all 5)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
oppossum
(Monodelphis domestica)
Mammalia HHLA26
HERV-H LTR-associating 2
37(a)
1 ↔ 1
4(67986741-68023573)
chicken
(Gallus gallus)
Aves HHLA26
Uncharacterized protein
37(a)
1 ↔ 1
1(86867701-86874706)


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)
About This Section
Paralogs for HHLA2 gene
ICOSLG2  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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

10/1449 SNPs in HHLA2 are shown (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

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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.)
About This Section

HHLA2 for disorders           About MalaCards
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)
About This Section

PubMed articles for HHLA2 gene integrated from 9 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. (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. (2004)
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (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. (2013)
  5. Evolution of the B7 family: co-evolution of B7H6 and N Kp30, identification of a new B7 family member, B7H7, and of B7's historical rel ationship with the MHC. (PubMed id 22488247)1 Flajnik M.F....Ohta Y. (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. (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. (2002)
  8. Normalization and subtraction: two approaches to facilitate gene discovery. (PubMed id 8889548)1 Bonaldo M.F.... Soares M.B. (1996)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section
 ANDOR
Aliases
Free Text  

  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)
About This Section
Entrez Gene: 11148 HGNC: 4905 AceView: HHLA2 Ensembl:ENSG00000114455 euGenes: HUgn11148
ECgene: HHLA2 H-InvDB: HHLA2

(According to HUGE)
About This Section
  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section
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.)
About This Section
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, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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transforming growth factor, beta 1
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