LOCUS       NM_002216               3146 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens inter-alpha-trypsin inhibitor heavy chain 2 (ITIH2),
            mRNA.
ACCESSION   NM_002216
VERSION     NM_002216.3
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 3146)
  AUTHORS   Scavenius,C., Poulsen,E.C., Thogersen,I.B., Roebuck,M.,
            Frostick,S., Bou-Gharios,G., Yamamoto,K., Deleuran,B. and
            Enghild,J.J.
  TITLE     Matrix-degrading protease ADAMTS-5 cleaves inter-alpha-inhibitor
            and releases active heavy chain 2 in synovial fluids from arthritic
            patients
  JOURNAL   J Biol Chem 294 (42), 15495-15504 (2019)
   PUBMED   31484722
  REMARK    GeneRIF: Both IalphaI and the HC-hyaluronan complex are substrates
            for the extracellular matrix proteases ADAMTS-5 and matrix
            metalloprotease (MMP) -3, -7, and -13.
REFERENCE   2  (bases 1 to 3146)
  AUTHORS   Naba,A., Pearce,O.M.T., Del Rosario,A., Ma,D., Ding,H., Rajeeve,V.,
            Cutillas,P.R., Balkwill,F.R. and Hynes,R.O.
  TITLE     Characterization of the Extracellular Matrix of Normal and Diseased
            Tissues Using Proteomics
  JOURNAL   J Proteome Res 16 (8), 3083-3091 (2017)
   PUBMED   28675934
REFERENCE   3  (bases 1 to 3146)
  AUTHORS   Ragelle,H., Naba,A., Larson,B.L., Zhou,F., Prijic,M.,
            Whittaker,C.A., Del Rosario,A., Langer,R., Hynes,R.O. and
            Anderson,D.G.
  TITLE     Comprehensive proteomic characterization of stem cell-derived
            extracellular matrices
  JOURNAL   Biomaterials 128, 147-159 (2017)
   PUBMED   28327460
REFERENCE   4  (bases 1 to 3146)
  AUTHORS   Scavenius,C., Nikolajsen,C.L., Stenvang,M., Thogersen,I.B.,
            Wyrozemski,L., Wisniewski,H.G., Otzen,D.E., Sanggaard,K.W. and
            Enghild,J.J.
  TITLE     The Compact and Biologically Relevant Structure of
            Inter-alpha-inhibitor Is Maintained by the Chondroitin Sulfate
            Chain and Divalent Cations
  JOURNAL   J Biol Chem 291 (9), 4658-4670 (2016)
   PUBMED   26728454
  REMARK    GeneRIF: Data suggest that Mg2+ or Mn2+ (but not Ca2+) induce a
            conformational change in inter-alpha-inhibitor (ITIH1 and ITIH2)
            and a bikunin/chondroitin sulfate-dependent increase in
            thermodynamic stability; bikunin binds adjacent to the two heavy
            chains.
REFERENCE   5  (bases 1 to 3146)
  AUTHORS   Naba,A., Clauser,K.R., Whittaker,C.A., Carr,S.A., Tanabe,K.K. and
            Hynes,R.O.
  TITLE     Extracellular matrix signatures of human primary metastatic colon
            cancers and their metastases to liver
  JOURNAL   BMC Cancer 14, 518 (2014)
   PUBMED   25037231
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3146)
  AUTHORS   Malki,N., Balduyck,M., Maes,P., Capon,C., Mizon,C., Han,K.K.,
            Tartar,A., Fournet,B. and Mizon,J.
  TITLE     The heavy chains of human plasma inter-alpha-trypsin inhibitor:
            their isolation, their identification by electrophoresis and
            partial sequencing. Differential reactivity with concanavalin A
  JOURNAL   Biol Chem Hoppe Seyler 373 (10), 1009-1018 (1992)
   PUBMED   1384548
REFERENCE   7  (bases 1 to 3146)
  AUTHORS   Salier,J.P., Simon,D., Rouet,P., Raguenez,G., Muscatelli,F.,
            Gebhard,W., Guenet,J.L. and Mattei,M.G.
  TITLE     Homologous chromosomal locations of the four genes for
            inter-alpha-inhibitor and pre-alpha-inhibitor family in human and
            mouse: assignment of the ancestral gene for the lipocalin
            superfamily
  JOURNAL   Genomics 14 (1), 83-88 (1992)
   PUBMED   1385302
REFERENCE   8  (bases 1 to 3146)
  AUTHORS   Salier,J.P., Diarra-Mehrpour,M., Sesboue,R., Bourguignon,J. and
            Martin,J.P.
  TITLE     Human inter-alpha-trypsin inhibitor. Isolation and characterization
            of heavy (H) chain cDNA clones coding for a 383 amino-acid sequence
            of the H chain
  JOURNAL   Biol Chem Hoppe Seyler 369 Suppl, 15-18 (1988)
   PUBMED   2462430
REFERENCE   9  (bases 1 to 3146)
  AUTHORS   Gebhard,W., Schreitmuller,T., Hochstrasser,K. and Wachter,E.
  TITLE     Complementary DNA and derived amino acid sequence of the precursor
            of one of the three protein components of the inter-alpha-trypsin
            inhibitor complex
  JOURNAL   FEBS Lett 229 (1), 63-67 (1988)
   PUBMED   2450046
REFERENCE   10 (bases 1 to 3146)
  AUTHORS   Salier,J.P., Diarra-Mehrpour,M., Sesboue,R., Bourguignon,J.,
            Benarous,R., Ohkubo,I., Kurachi,S., Kurachi,K. and Martin,J.P.
  TITLE     Isolation and characterization of cDNAs encoding the heavy chain of
            human inter-alpha-trypsin inhibitor (I alpha TI): unambiguous
            evidence for multipolypeptide chain structure of I alpha TI
  JOURNAL   Proc Natl Acad Sci U S A 84 (23), 8272-8276 (1987)
   PUBMED   2446322
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BG617651.1, X07173.1, AL158044.17, CB154170.1 and AA406494.1.
            
            On Nov 23, 2018 this sequence version replaced NM_002216.2.
            
            Summary: The inter-alpha-trypsin inhibitors (ITI) are a family of
            structurally related plasma serine protease inhibitors involved in
            extracellular matrix stabilization and in prevention of tumor
            metastasis. The ITI family contains multiple proteins made up of a
            light chain (see MIM 176870) and a variable number of heavy chains
            (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004
            [PubMed 14744536]).[supplied by OMIM, Nov 2009].
            
            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 :: AK225329.1, SRR1660809.121555.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145122, SAMEA2145743
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000358415.9/ ENSP00000351190.4
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-151               BG617651.1         45-195
            152-905             X07173.1           96-849
            906-908             AL158044.17        105322-105324
            909-1205            X07173.1           853-1149
            1206-1766           CB154170.1         22-582
            1767-3144           X07173.1           1711-3088
            3145-3146           AA406494.1         10-11               c
FEATURES             Location/Qualifiers
     source          1..3146
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p14"
     gene            1..3146
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /note="inter-alpha-trypsin inhibitor heavy chain 2"
                     /db_xref="GeneID:3698"
                     /db_xref="HGNC:HGNC:6167"
                     /db_xref="MIM:146640"
     exon            1..203
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     CDS             120..2960
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /note="inter-alpha (globulin) inhibitor, H2 polypeptide;
                     ITI heavy chain H2; inter-alpha-inhibitor heavy chain 2;
                     inter-alpha-trypsin inhibitor complex component II;
                     serum-derived hyaluronan-associated protein;
                     inter-alpha-trypsin inhibitor heavy chain H2; inter-alpha
                     (globulin) inhibitor H2"
                     /codon_start=1
                     /product="inter-alpha-trypsin inhibitor heavy chain H2
                     precursor"
                     /protein_id="NP_002207.2"
                     /db_xref="CCDS:CCDS31141.1"
                     /db_xref="GeneID:3698"
                     /db_xref="HGNC:HGNC:6167"
                     /db_xref="MIM:146640"
                     /translation="MKRLTCFFICFFLSEVSGFEIPINGLSEFVDYEDLVELAPGKFQ
                     LVAENRRYQRSLPGESEEMMEEVDQVTLYSYKVQSTITSRMATTMIQSKVVNNSPQPQ
                     NVVFDVQIPKGAFISNFSMTVDGKTFRSSIKEKTVGRALYAQARAKGKTAGLVRSSAL
                     DMENFRTEVNVLPGAKVQFELHYQEVKWRKLGSYEHRIYLQPGRLAKHLEVDVWVIEP
                     QGLRFLHVPDTFEGHFDGVPVISKGQQKAHVSFKPTVAQQRICPNCRETAVDGELVVL
                     YDVKREEKAGELEVFNGYFVHFFAPDNLDPIPKNILFVIDVSGSMWGVKMKQTVEAMK
                     TILDDLRAEDHFSVIDFNQNIRTWRNDLISATKTQVADAKRYIEKIQPSGGTNINEAL
                     LRAIFILNEANNLGLLDPNSVSLIILVSDGDPTVGELKLSKIQKNVKENIQDNISLFS
                     LGMGFDVDYDFLKRLSNENHGIAQRIYGNQDTSSQLKKFYNQVSTPLLRNVQFNYPHT
                     SVTDVTQNNFHNYFGGSEIVVAGKFDPAKLDQIESVITATSANTQLVLETLAQMDDLQ
                     DFLSKDKHADPDFTRKLWAYLTINQLLAERSLAPTAAAKRRITRSILQMSLDHHIVTP
                     LTSLVIENEAGDERMLADAPPQDPSCCSGALYYGSKVVPDSTPSWANPSPTPVISMLA
                     QGSQVLESTPPPHVMRVENDPHFIIYLPKSQKNICFNIDSEPGKILNLVSDPESGIVV
                     NGQLVGAKKPNNGKLSTYFGKLGFYFQSEDIKIEISTETITLSHGSSTFSLSWSDTAQ
                     VTNQRVQISVKKEKVVTITLDKEMSFSVLLHRVWKKHPVNVDFLGIYIPPTNKFSPKA
                     HGLIGQFMQEPKIHIFNERPGKDPEKPEASMEVKGQKLIITRGLQKDYRTDLVFGTDV
                     TCWFVHNSGKGFIDGHYKDYFVPQLYSFLKRP"
     exon            204..278
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            279..311
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            312..481
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            482..586
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            587..749
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            750..857
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            858..986
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            987..1103
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1104..1272
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1273..1398
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1399..1580
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1581..1766
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1767..1906
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1907..2076
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2077..2214
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2215..2328
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2329..2527
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2528..2700
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2701..2812
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2813..3146
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3127..3132
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /note="hexamer: AATAAA"
     polyA_site      3146
                     /gene="ITIH2"
                     /gene_synonym="H2P; ITI-HC2; SHAP"
                     /note="major polyA site"
ORIGIN      
        1 cttctttctt aaagcgaact gtactcctct gctgttcctt tgaacttggt tcagtaggaa
       61 gaagtgatat cctccccaga ccatctgctt tggggagctt ggcaaaactg tccagcaaaa
      121 tgaaaagact cacgtgcttt ttcatctgct tctttctttc tgaagtatca ggcttcgaaa
      181 tccccataaa tggactttct gaatttgtag actatgaaga tcttgtggaa ctggccccag
      241 gcaaatttca attggtggca gagaaccgga gatatcagag aagccttcca ggagaatcgg
      301 aagaaatgat ggaagaggtt gatcaagtaa ctctttatag ctataaagtc cagtctacta
      361 ttacttctcg gatggccacc accatgatcc agagcaaagt ggtgaacaat tccccgcagc
      421 ctcagaatgt cgtgtttgat gttcagatcc ccaaaggagc attcatttcc aacttctcca
      481 tgactgtgga cggcaagaca tttaggagct ctattaagga gaaaactgtg ggccgagctc
      541 tttatgcaca ggccagagca aaaggcaaga cggctggctt ggtgaggagc agcgctcttg
      601 atatggaaaa cttcagaacg gaagtaaatg tcctcccagg agcaaaggtg cagttcgaac
      661 ttcactacca ggaggtgaag tggaggaagc tgggctccta tgagcacagg atctatctgc
      721 aacctggacg gctggccaaa cacttagagg tagatgtgtg ggttatcgaa ccacagggac
      781 tgagatttct tcatgttccc gacacatttg aaggccattt cgatggtgtt ccggtcattt
      841 ctaaaggaca acagaaggcg cacgtctcct tcaagcccac ggtagcacag cagagaatat
      901 gccctaactg ccgggagact gcggtagatg gggaactggt ggtgctgtat gacgtgaaaa
      961 gagaagagaa ggctggtgaa ctggaggtgt ttaatggata ttttgtccac ttctttgctc
     1021 ctgacaacct ggacccaatt cccaaaaaca tcctctttgt catcgatgtg agtggctcca
     1081 tgtggggagt taaaatgaaa caaactgtgg aagcaatgaa gaccatattg gatgacctca
     1141 gagcagaaga ccatttctct gtgattgatt tcaaccagaa cattcgaact tggagaaatg
     1201 atttaatttc agctacaaaa acacaggttg cagatgccaa gaggtatatt gagaaaatcc
     1261 agcccagtgg aggcacaaac atcaacgaag cactcctacg ggcaatcttc attttgaatg
     1321 aagccaataa cttgggactg ttagacccca actccgtctc gctgatcatt ttggtttctg
     1381 atggagatcc aacagtgggc gaactaaaac tgtcaaaaat tcagaaaaac gttaaggaga
     1441 acatccaaga caatatctcc ttgttcagtt tgggcatggg atttgatgtg gactatgatt
     1501 ttttgaagag actgtccaat gaaaaccatg gaattgcaca aaggatttat ggaaaccagg
     1561 acacgtcttc ccagcttaag aaattctaca accaggtctc cactccattg ctccggaatg
     1621 ttcagttcaa ctatccccat acatcagtca cggacgtcac tcaaaacaat ttccataact
     1681 actttggagg ctcagagatt gtggtggcag gaaaatttga ccctgctaaa ttggatcaaa
     1741 tagagagcgt tatcacggcg acttcggcta acacgcagtt agtcttggag accctggccc
     1801 agatggacga cttgcaggat tttctatcga aagacaagca tgcagatccc gatttcacca
     1861 ggaaactgtg ggcctatcta accatcaacc aactgctagc tgaacgaagc ctggctccta
     1921 cagctgccgc caagagaaga attacaagat cgatcctgca gatgtctcta gaccaccaca
     1981 ttgtgactcc gctgacctcg ctggtgatcg agaacgaggc tggggatgag cgcatgctgg
     2041 cggatgcccc accgcaggat ccctcctgct gctcaggggc cctgtattac ggcagcaaag
     2101 tggttccaga ttccaccccg tcttgggcca atccttcacc aacgcccgtg atctccatgc
     2161 tggcacaagg atctcaggtg ctagagtcca cgccaccccc acatgtgatg agagttgaaa
     2221 atgacccaca tttcatcatt tatctaccaa aaagccaaaa gaacatttgt ttcaatattg
     2281 actcagaacc tggaaaaatc ctcaacctgg tttctgaccc agaatcagga attgtagtca
     2341 acggtcagct tgttggtgcc aagaagccca acaatggaaa actaagcacc tattttggaa
     2401 aactgggatt ttatttccaa agtgaagaca taaaaataga aatcagcact gagaccatca
     2461 ccctgagcca tggttctagc acattctcct tgtcctggtc cgacacggct caagtcacga
     2521 atcagagggt gcagatctca gtgaagaaag aaaaagtggt aactatcacc ctggataaag
     2581 agatgtcctt ttctgtttta cttcatcgtg tttggaagaa gcatcccgtc aatgttgact
     2641 ttctgggaat ctacataccc cctacaaaca agttctcacc taaagcccac ggactaatag
     2701 gccagttcat gcaggaacca aagatacaca tcttcaatga gagaccagga aaggaccctg
     2761 agaagccaga ggccagcatg gaagtgaagg ggcagaagct gatcatcacc aggggcttac
     2821 agaaagacta cagaacggat ctagtgtttg gaacggacgt tacctgctgg tttgtgcaca
     2881 acagtggaaa aggattcatt gacgggcatt acaaggatta cttcgtgcct cagctctaca
     2941 gctttctcaa acggccttaa aggtttatag tttgggaaat tatatatatt aatatacatc
     3001 tttcccctgt cacttttgca gatattcttc ggtttgaata attaaaatga accagatatc
     3061 agggtggtta attaaaatga accagatatc agggtggttt ataaagcctg taaacacacc
     3121 taagaaaata aacattttac aaatga
//
