LOCUS       NM_001282556            2417 bp    mRNA    linear   PRI 15-JUL-2024
DEFINITION  Homo sapiens HHLA2 member of B7 family (HHLA2), transcript variant
            2, mRNA.
ACCESSION   NM_001282556 XM_005247081
VERSION     NM_001282556.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2417)
  AUTHORS   Wang,J., Yang,K., Yang,X., Jin,T., Tian,Y., Dai,C. and Xu,F.
  TITLE     HHLA2 promotes hepatoma cell proliferation, migration, and invasion
            via SPP1/PI3K/AKT signaling pathway
  JOURNAL   Mol Carcinog 63 (7), 1275-1287 (2024)
   PUBMED   38578157
  REMARK    GeneRIF: HHLA2 promotes hepatoma cell proliferation, migration, and
            invasion via SPP1/PI3K/AKT signaling pathway.
REFERENCE   2  (bases 1 to 2417)
  AUTHORS   Zhou,S., Wang,Z., Zhao,D., Fu,Y., Zhang,S., Wang,Z. and Zou,X.
  TITLE     HHLA2 deficiency inhibits pancreatic cancer progression and THP-1
            macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway
  JOURNAL   World J Surg Oncol 22 (1), 133 (2024)
   PUBMED   38762741
  REMARK    GeneRIF: HHLA2 deficiency inhibits pancreatic cancer progression
            and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT
            pathway.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2417)
  AUTHORS   Li,Y., Yang,Q., Yang,X., Ge,J., Xu,T. and Liu,H.
  TITLE     HHLA2 is more significantly associated with poor prognosis in TSCC
            than PD-L1
  JOURNAL   J Oral Pathol Med 53 (2), 159-168 (2024)
   PUBMED   38321252
  REMARK    GeneRIF: HHLA2 is more significantly associated with poor prognosis
            in TSCC than PD-L1.
REFERENCE   4  (bases 1 to 2417)
  AUTHORS   Shigemura,T., Perrot,N., Huang,Z., Bhatt,R.S., Sheshdeh,A.B.,
            Ahmar,N.E., Ghandour,F., Signoretti,S., McDermott,D.F.,
            Freeman,G.J. and Mahoney,K.M.
  TITLE     Regulation of HHLA2 expression in kidney cancer and myeloid cells
  JOURNAL   BMC Cancer 23 (1), 1039 (2023)
   PUBMED   37891555
  REMARK    GeneRIF: Regulation of HHLA2 expression in kidney cancer and
            myeloid cells.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2417)
  AUTHORS   Byers,J.T., Paniccia,A., Kaplan,J., Koenig,M., Kahn,N., Wilson,L.,
            Chen,L., Schulick,R.D., Edil,B.H. and Zhu,Y.
  TITLE     Expression of the Novel Costimulatory Molecule B7-H5 in Pancreatic
            Cancer
  JOURNAL   Ann Surg Oncol 22 Suppl 3, S1574-S1579 (2015)
   PUBMED   25519928
  REMARK    GeneRIF: Low B7-H5 expression is associated with pancreatic
            adenocarcinomas.
REFERENCE   6  (bases 1 to 2417)
  AUTHORS   Janakiram,M., Chinai,J.M., Fineberg,S., Fiser,A., Montagna,C.,
            Medavarapu,R., Castano,E., Jeon,H., Ohaegbulam,K.C., Zhao,R.,
            Zhao,A., Almo,S.C., Sparano,J.A. and Zang,X.
  TITLE     Expression, Clinical Significance, and Receptor Identification of
            the Newest B7 Family Member HHLA2 Protein
  JOURNAL   Clin Cancer Res 21 (10), 2359-2366 (2015)
   PUBMED   25549724
  REMARK    GeneRIF: The HHLA2 pathway represents a novel immunosuppressive
            mechanism within the tumor microenvironment.
REFERENCE   7  (bases 1 to 2417)
  AUTHORS   Zhao,R., Chinai,J.M., Buhl,S., Scandiuzzi,L., Ray,A., Jeon,H.,
            Ohaegbulam,K.C., Ghosh,K., Zhao,A., Scharff,M.D. and Zang,X.
  TITLE     HHLA2 is a member of the B7 family and inhibits human CD4 and CD8
            T-cell function
  JOURNAL   Proc Natl Acad Sci U S A 110 (24), 9879-9884 (2013)
   PUBMED   23716685
  REMARK    GeneRIF: Data indicate that HHLA2 protein was predominantly found
            on cell membranes with some in the cytoplasm.
REFERENCE   8  (bases 1 to 2417)
  AUTHORS   Zhu,Y., Yao,S., Iliopoulou,B.P., Han,X., Augustine,M.M., Xu,H.,
            Phennicie,R.T., Flies,S.J., Broadwater,M., Ruff,W., Taube,J.M.,
            Zheng,L., Luo,L., Zhu,G., Chen,J. and Chen,L.
  TITLE     B7-H5 costimulates human T cells via CD28H
  JOURNAL   Nat Commun 4, 2043 (2013)
   PUBMED   23784006
  REMARK    GeneRIF: B7 homologue 5 (B7-H5), was identified as a specific
            ligand for CD28H
REFERENCE   9  (bases 1 to 2417)
  AUTHORS   Flajnik,M.F., Tlapakova,T., Criscitiello,M.F., Krylov,V. and
            Ohta,Y.
  TITLE     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
  JOURNAL   Immunogenetics 64 (8), 571-590 (2012)
   PUBMED   22488247
  REMARK    Erratum:[Immunogenetics. 2013 Jul;65(7):559]
REFERENCE   10 (bases 1 to 2417)
  AUTHORS   Mager,D.L., Hunter,D.G., Schertzer,M. and Freeman,J.D.
  TITLE     Endogenous retroviruses provide the primary polyadenylation signal
            for two new human genes (HHLA2 and HHLA3)
  JOURNAL   Genomics 59 (3), 255-263 (1999)
   PUBMED   10444326
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BP293912.1, AK000692.1,
            AC078855.13, AC135308.2 and BM980981.1.
            
            On Aug 14, 2020 this sequence version replaced NM_001282556.1.
            
            Summary: 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].
            
            Transcript Variant: This variant (2) represents the use of an
            alternate promoter and differs in the 5' UTR, compared to variant
            1. Variants 1, 2 and 3 encode the same protein (isoform a).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK000692.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1970526
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000467761.6/ ENSP00000419207.1
            RefSeq Select criteria :: based on manual assertion
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-31                BP293912.1         59-89
            32-826              AK000692.1         16-810
            827-827             AC078855.13        167001-167001
            828-1511            AK000692.1         812-1495
            1512-1863           AC135308.2         3057-3408           c
            1864-2413           AK000692.1         1848-2397
            2414-2417           BM980981.1         14-17               c
FEATURES             Location/Qualifiers
     source          1..2417
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q13.13"
     gene            1..2417
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /note="HHLA2 member of B7 family"
                     /db_xref="GeneID:11148"
                     /db_xref="HGNC:HGNC:4905"
                     /db_xref="MIM:604371"
     exon            1..52
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            53..139
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            140..229
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     CDS             166..1410
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /note="isoform a precursor is encoded by transcript
                     variant 2; HERV-H LTR-associating protein 2; human
                     endogenous retrovirus-H long terminal repeat-associating
                     protein 2; HERV-H LTR-associating 2"
                     /codon_start=1
                     /product="HERV-H LTR-associating protein 2 isoform a
                     precursor"
                     /protein_id="NP_001269485.1"
                     /db_xref="CCDS:CCDS46883.1"
                     /db_xref="GeneID:11148"
                     /db_xref="HGNC:HGNC:4905"
                     /db_xref="MIM:604371"
                     /translation="MKAQTALSFFLILITSLSGSQGIFPLAFFIYVPMNEQIVIGRLD
                     EDIILPSSFERGSEVVIHWKYQDSYKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNG
                     NASLFFRRVSLLDEGIYTCYVGTAIQVITNKVVLKVGVFLTPVMKYEKRNTNSFLICS
                     VLSVYPRPIITWKMDNTPISENNMEETGSLDSFSINSPLNITGSNSSYECTIENSLLK
                     QTWTGRWTMKDGLHKMQSEHVSLSCQPVNDYFSPNQDFKVTWSRMKSGTFSVLAYYLS
                     SSQNTIINESRFSWNKELINQSDFSMNLMDLNLSDSGEYLCNISSDEYTLLTIHTVHV
                     EPSQETASHNKGLWILVPSAILAAFLLIWSVKCCRAQLEARRSRHPADGAQQERCCVP
                     PGERCPSAPDNGEENVPLSGKV"
     exon            230..583
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            584..850
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            851..1168
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            1169..1273
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            1274..1324
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            1325..1389
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     exon            1390..2417
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2391..2396
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /note="hexamer: AATAAA"
     polyA_site      2417
                     /gene="HHLA2"
                     /gene_synonym="B7-H5; B7-H7; B7H7; B7y"
                     /note="major polyA site"
ORIGIN      
        1 attcttatgg actacttagc atttgactag acggtatgaa tttctaagta agcacatata
       61 gaactggatg cccttgtggt acatctcaag gctgatttga aagcttgaga gaccatcaag
      121 aattggattt ggggaagagc atgactaata tgttctgcac aagacatgaa ggcacagaca
      181 gcactgtctt tcttcctcat tctcataaca tctctgagtg gatctcaagg catattccct
      241 ttggctttct tcatttatgt tcctatgaat gaacaaatcg tcattggaag acttgatgaa
      301 gatataattc tcccttcttc atttgagagg ggatccgaag tcgtaataca ctggaagtat
      361 caagatagct ataaggttca cagttactac aaaggcagtg accatttgga aagccaagat
      421 cccagatatg caaacaggac atcccttttc tataatgaga ttcaaaatgg gaatgcgtcg
      481 ctatttttca gaagagtaag ccttctggac gaaggaattt acacctgcta tgtaggaaca
      541 gcaattcaag tgattacaaa caaagtggtg ctaaaggtgg gagtttttct cacacccgtg
      601 atgaagtatg aaaagaggaa cacaaacagc ttcttaatat gcagcgtgtt aagtgtttat
      661 cctcgtccaa ttatcacgtg gaaaatggac aacacaccta tctctgaaaa caacatggaa
      721 gaaacagggt ctttggattc tttttctatt aacagcccac tgaatattac aggatcaaat
      781 tcatcttatg aatgtacaat tgaaaattca ctgctgaagc aaacatggac agggcgctgg
      841 acgatgaaag atggccttca taaaatgcaa agtgaacacg tttcactctc atgtcaacct
      901 gtaaatgatt atttttcacc aaaccaagac ttcaaagtta cttggtccag aatgaaaagt
      961 gggactttct ctgtcctggc ttactatctg agctcctcac aaaatacaat tatcaatgaa
     1021 tcccgattct catggaacaa agagctgata aaccagagtg acttctctat gaatttgatg
     1081 gatcttaatc tttcagacag tggggaatat ttatgcaata tttcttcgga tgaatatact
     1141 ttacttacca tccacacagt gcatgtagaa ccgagccaag aaacagcttc ccataacaaa
     1201 ggcttatgga ttttggtgcc ctctgcgatt ttggcagctt ttctgctgat ttggagcgta
     1261 aaatgttgca gagcccagct agaagccagg aggagcagac accctgctga tggagcccaa
     1321 caagaaagat gttgtgtccc tcctggtgag cgctgtccca gtgcacccga taatggcgaa
     1381 gaaaatgtgc ctctttcagg aaaagtatag gaaatgagag aagactgtga caactcatga
     1441 cctgcatcct taatatccag tgacttcatc tcccctttct tcaccacaat tccaggcaat
     1501 ggcctgtcgg agcagacaat tctaccactg caaagagttg taaccatttt ctggtatcac
     1561 atttattttt caagacatac ttttcaagac atcattcact gacccactac ctgcattgag
     1621 tataaatgcc tggatgttaa ggattccaat ttaactttga aaagaactgt ctcattcatt
     1681 tacatttctg ttacagtcag cccaggaggt tacagtgagc tctccactaa gaatctggaa
     1741 gaaatgcatc actaggggtt gattcccaat ctgatcaact gataatgggt gagagagcag
     1801 gtaagagcca aagtcacctt agtggaaagg ttaaaaacca gagcctggaa accaagatga
     1861 ttgatttgac aaggtatttt agtctagttt tatatgaacg gttgtatcag ggtaaccaac
     1921 tcgatttggg atgaatctta gggcaccaaa gactaagaca gtatctttaa gattgctagg
     1981 gaaaagggcc ctatgtgtca ggcctctgag cccaagccaa gcatcgcatc ccctgtgatt
     2041 tgcacgtata catccagatg gcctaaagta actgaagatc cacaaaagaa gtaaaaatag
     2101 ccttaactga tgacattcca ccattgtgat ttgttcctgc cccaccctaa ctgatcaatg
     2161 tactttgtaa tctcccccac ccttaagaag gtactttgta atcttcccca cccttaagaa
     2221 ggttctttgt aattctcccc acccttgaga atgtactttg tgagatccac cctgcccaca
     2281 aaacattgct cttaacttca ccgcctaacc caaaacctat aagaactaat gataatccat
     2341 cacccttcgc tgactctctt ttcggactca gcccacctgc acccaggtga aataaacagc
     2401 tttattgctc acacaaa
//
