ID   ITIH1_HUMAN             Reviewed;         911 AA.
AC   P19827; A8K9N5; B2RAH9; B7Z558; B7Z8C0; F5H165; F5H7Y8; P78455; Q01746;
AC   Q562G1;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 3.
DT   24-JAN-2024, entry version 210.
DE   RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H1;
DE            Short=ITI heavy chain H1;
DE            Short=ITI-HC1;
DE            Short=Inter-alpha-inhibitor heavy chain 1;
DE   AltName: Full=Inter-alpha-trypsin inhibitor complex component III;
DE   AltName: Full=Serum-derived hyaluronan-associated protein;
DE            Short=SHAP;
DE   Flags: Precursor;
GN   Name=ITIH1; Synonyms=IGHEP1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-263; VAL-585 AND
RP   ARG-595.
RC   TISSUE=Blood, and Liver;
RX   PubMed=1380832; DOI=10.1016/0167-4781(92)90065-8;
RA   Diarra-Mehrpour M., Bourguignon J., Bost F., Sesboue R., Muschio F.,
RA   Sarafan N., Martin J.-P.;
RT   "Human inter-alpha-trypsin inhibitor: full-length cDNA sequence of the
RT   heavy chain H1.";
RL   Biochim. Biophys. Acta 1132:114-118(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7505744; DOI=10.1111/j.1432-1033.1993.tb18376.x;
RA   Bost F., Bourguignon J., Martin J.-P., Sesboue R., Thiberville L.,
RA   Diarra-Mehrpour M.;
RT   "Isolation and characterization of the human inter-alpha-trypsin inhibitor
RT   heavy-chain H1 gene.";
RL   Eur. J. Biochem. 218:283-291(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS
RP   VAL-585 AND ARG-595.
RC   TISSUE=Liver, and Thymus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   PROTEIN SEQUENCE OF 30-34; 117-119; 126-137; 318-329; 342-355 AND 478-501.
RC   TISSUE=Plasma;
RX   PubMed=1384548; DOI=10.1515/bchm3.1992.373.2.1009;
RA   Malki N., Balduyck M., Maes P., Capon C., Mizon C., Han K.K., Tartar A.,
RA   Fournet B., Mizon J.;
RT   "The heavy chains of human plasma inter-alpha-trypsin inhibitor: their
RT   isolation, their identification by electrophoresis and partial sequencing.
RT   Differential reactivity with concanavalin A.";
RL   Biol. Chem. Hoppe-Seyler 373:1009-1018(1992).
RN   [8]
RP   PROTEIN SEQUENCE OF 35-54; 110-124; 333-347 AND 399-435, IDENTIFICATION IN
RP   INTER-ALPHA-INHIBITOR COMPLEX, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Plasma;
RX   PubMed=2476436; DOI=10.1016/s0021-9258(18)71575-5;
RA   Enghild J.J., Thoegersen I.B., Pizzo S.V., Salvesen G.;
RT   "Analysis of inter-alpha-trypsin inhibitor and a novel trypsin inhibitor,
RT   pre-alpha-trypsin inhibitor, from human plasma. Polypeptide chain
RT   stoichiometry and assembly by glycan.";
RL   J. Biol. Chem. 264:15975-15981(1989).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 75-911 (ISOFORM 1), AND PARTIAL PROTEIN
RP   SEQUENCE.
RC   TISSUE=Liver;
RX   PubMed=2471637; DOI=10.1111/j.1432-1033.1989.tb14762.x;
RA   Gebhard W., Schreitmueller T., Hochstrasser K., Wachter E.;
RT   "Two out of the three kinds of subunits of inter-alpha-trypsin inhibitor
RT   are structurally related.";
RL   Eur. J. Biochem. 181:571-576(1989).
RN   [10]
RP   PROTEIN SEQUENCE OF 177-211 AND 387-428, AND HYALURONAN BINDING.
RC   TISSUE=Serum;
RX   PubMed=7504674; DOI=10.1016/s0021-9258(19)74373-7;
RA   Huang L., Yoneda M., Kimata K.;
RT   "A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of
RT   the inter alpha-trypsin inhibitor.";
RL   J. Biol. Chem. 268:26725-26730(1993).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 399-723 (ISOFORM 1/2/3).
RX   PubMed=2446322; DOI=10.1073/pnas.84.23.8272;
RA   Salier J.-P., Diarra-Mehrpour M., Sesboue R., Bourguignon J., Benarous R.,
RA   Ohkubo I., Kurachi S., Kurachi K., Martin J.-P.;
RT   "Isolation and characterization of cDNAs encoding the heavy chain of human
RT   inter-alpha-trypsin inhibitor (I alpha TI): unambiguous evidence for
RT   multipolypeptide chain structure of I alpha TI.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:8272-8276(1987).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 535-685 (ISOFORM 1/2/3).
RX   PubMed=3663330; DOI=10.1515/bchm3.1987.368.2.963;
RA   Schreitmueller T., Hochstrasser K., Resinger P.W.M., Wachter E.,
RA   Gebhard W.;
RT   "cDNA cloning of human inter-alpha-trypsin inhibitor discloses three
RT   different proteins.";
RL   Biol. Chem. Hoppe-Seyler 368:963-970(1987).
RN   [13]
RP   PROTEIN SEQUENCE OF 669-672, AND COVALENT LINKAGE WITH CHONDROITIN SULFATE.
RC   TISSUE=Plasma;
RX   PubMed=7513643; DOI=10.1111/j.1432-1033.1994.tb18803.x;
RA   Morelle W., Capon C., Balduyck M., Sautiere P., Kouach M., Michalski C.,
RA   Fournet B., Mizon J.;
RT   "Chondroitin sulphate covalently cross-links the three polypeptide chains
RT   of inter-alpha-trypsin inhibitor.";
RL   Eur. J. Biochem. 221:881-888(1994).
RN   [14]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 870-911.
RX   PubMed=7522574; DOI=10.1016/0167-4781(94)90087-6;
RA   Diarra-Mehrpour M., Bourguignon J., Sarafan N., Bost F., Sesbouee R.,
RA   Muschio-Bonnet F., Martin J.-P.;
RT   "Tandem orientation of the inter-alpha-trypsin inhibitor heavy chain H1 and
RT   H3 genes.";
RL   Biochim. Biophys. Acta 1219:551-554(1994).
RN   [15]
RP   GLYCOSYLATION AT ASN-285 AND ASN-588, AND MASS SPECTROMETRY.
RX   PubMed=9677337; DOI=10.1042/bj3330749;
RA   Flahaut C., Capon C., Balduyck M., Ricart G., Sautiere P., Mizon J.;
RT   "Glycosylation pattern of human inter-alpha-inhibitor heavy chains.";
RL   Biochem. J. 333:749-756(1998).
RN   [16]
RP   GLYCOSYLATION AT CYS-60; ASN-285; ASN-588 AND THR-653, DISULFIDE BONDS, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=9425062; DOI=10.1021/bi971137d;
RA   Olsen E.H.N., Rahbek-Nielsen H., Thoegersen I.B., Roepstorff P.,
RA   Enghild J.J.;
RT   "Posttranslational modifications of human inter-alpha-inhibitor:
RT   identification of glycans and disulfide bridges in heavy chains 1 and 2.";
RL   Biochemistry 37:408-416(1998).
RN   [17]
RP   GLYCOSYLATION AT ASN-285.
RX   PubMed=12754519; DOI=10.1038/nbt827;
RA   Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT   "Identification and quantification of N-linked glycoproteins using
RT   hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL   Nat. Biotechnol. 21:660-666(2003).
RN   [18]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-588.
RC   TISSUE=Plasma;
RX   PubMed=14760718; DOI=10.1002/pmic.200300556;
RA   Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT   "Screening for N-glycosylated proteins by liquid chromatography mass
RT   spectrometry.";
RL   Proteomics 4:454-465(2004).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-402 AND THR-407, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [20]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-750.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [21]
RP   GLYCOSYLATION AT ASN-285.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [23]
RP   INTERACTION WITH ITIH1, AND MUTAGENESIS OF ASP-298.
RX   PubMed=26468290; DOI=10.1074/jbc.m115.669838;
RA   Briggs D.C., Birchenough H.L., Ali T., Rugg M.S., Waltho J.P., Ievoli E.,
RA   Jowitt T.A., Enghild J.J., Richter R.P., Salustri A., Milner C.M.,
RA   Day A.J.;
RT   "Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates
RT   Assembly of the Cumulus-Oocyte Matrix.";
RL   J. Biol. Chem. 290:28708-28723(2015).
RN   [24]
RP   VARIANTS VAL-585 AND ARG-595.
RX   PubMed=7535743; DOI=10.1007/bf00208970;
RA   Ding M., Umetsu K., Yuasa I., Sato M., Harada A., Suzuki T.;
RT   "Molecular basis of inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1)
RT   polymorphism.";
RL   Hum. Genet. 95:435-436(1995).
CC   -!- FUNCTION: May act as a carrier of hyaluronan in serum or as a binding
CC       protein between hyaluronan and other matrix protein, including those on
CC       cell surfaces in tissues to regulate the localization, synthesis and
CC       degradation of hyaluronan which are essential to cells undergoing
CC       biological processes.
CC   -!- FUNCTION: Contains a potential peptide which could stimulate a broad
CC       spectrum of phagocytotic cells.
CC   -!- SUBUNIT: I-alpha-I plasma protease inhibitors are assembled from one or
CC       two heavy chains (HC) and one light chain, bikunin. Inter-alpha-
CC       inhibitor (I-alpha-I) is composed of ITIH1/HC1, ITIH2/HC2 and bikunin
CC       (PubMed:2476436). Interacts with TNFAIP6 (via Link and CUB domains)
CC       (PubMed:26468290). {ECO:0000269|PubMed:2476436,
CC       ECO:0000269|PubMed:26468290}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P19827-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P19827-2; Sequence=VSP_045420;
CC       Name=3;
CC         IsoId=P19827-3; Sequence=VSP_045419;
CC   -!- PTM: Heavy chains are linked to bikunin via chondroitin 4-sulfate
CC       esterified to the alpha-carboxyl of the C-terminal aspartate after
CC       propeptide cleavage.
CC   -!- PTM: The S-linked glycan is composed of two 6-carbon sugars, possibly
CC       Glc or Gal. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718,
CC       ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
CC       ECO:0000269|PubMed:9425062, ECO:0000269|PubMed:9677337}.
CC   -!- MASS SPECTROMETRY: Mass=76258; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:9677337};
CC   -!- POLYMORPHISM: There are 3 common alleles; ITIH1*1 with Glu-585/Gln-595,
CC       ITIH1*2 with Val-585/Arg-595 and ITIH1*3 with Glu-585/Arg-595.
CC   -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X63652; CAA45188.1; -; mRNA.
DR   EMBL; X69532; CAA49279.1; -; Genomic_DNA.
DR   EMBL; X69533; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69534; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69535; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69536; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69537; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69538; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69539; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69540; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69541; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69542; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69543; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69544; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69545; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69546; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; X69547; CAA49279.1; JOINED; Genomic_DNA.
DR   EMBL; AK292750; BAF85439.1; -; mRNA.
DR   EMBL; AK298455; BAH12794.1; -; mRNA.
DR   EMBL; AK303156; BAH13906.1; -; mRNA.
DR   EMBL; AK314198; BAG36876.1; -; mRNA.
DR   EMBL; AC006254; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471055; EAW65259.1; -; Genomic_DNA.
DR   EMBL; BC069464; AAH69464.1; -; mRNA.
DR   EMBL; X16260; CAA34346.1; -; mRNA.
DR   EMBL; M18192; AAA60557.1; -; mRNA.
DR   EMBL; X75318; CAA53067.1; -; Genomic_DNA.
DR   CCDS; CCDS2864.1; -. [P19827-1]
DR   CCDS; CCDS54595.1; -. [P19827-3]
DR   PIR; S39527; A39967.
DR   RefSeq; NP_001159906.1; NM_001166434.2. [P19827-2]
DR   RefSeq; NP_001159907.1; NM_001166435.2. [P19827-3]
DR   RefSeq; NP_002206.2; NM_002215.3. [P19827-1]
DR   PDB; 6FPY; X-ray; 2.34 A; A/B=35-672.
DR   PDB; 6FPZ; X-ray; 2.20 A; A/B=35-672.
DR   PDBsum; 6FPY; -.
DR   PDBsum; 6FPZ; -.
DR   AlphaFoldDB; P19827; -.
DR   SMR; P19827; -.
DR   BioGRID; 109903; 23.
DR   IntAct; P19827; 4.
DR   STRING; 9606.ENSP00000273283; -.
DR   DrugBank; DB09338; Mersalyl.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   GlyConnect; 284; 17 N-Linked glycans (2 sites), 1 O-Linked glycan (1 site).
DR   GlyCosmos; P19827; 7 sites, 21 glycans.
DR   GlyGen; P19827; 8 sites, 27 N-linked glycans (3 sites), 3 O-linked glycans (3 sites).
DR   iPTMnet; P19827; -.
DR   PhosphoSitePlus; P19827; -.
DR   SwissPalm; P19827; -.
DR   BioMuta; ITIH1; -.
DR   EPD; P19827; -.
DR   jPOST; P19827; -.
DR   MassIVE; P19827; -.
DR   PaxDb; 9606-ENSP00000273283; -.
DR   PeptideAtlas; P19827; -.
DR   ProteomicsDB; 25555; -.
DR   ProteomicsDB; 27630; -.
DR   ProteomicsDB; 53691; -. [P19827-1]
DR   Antibodypedia; 31337; 298 antibodies from 24 providers.
DR   DNASU; 3697; -.
DR   Ensembl; ENST00000273283.7; ENSP00000273283.2; ENSG00000055957.11. [P19827-1]
DR   Ensembl; ENST00000537050.5; ENSP00000443847.1; ENSG00000055957.11. [P19827-3]
DR   GeneID; 3697; -.
DR   KEGG; hsa:3697; -.
DR   MANE-Select; ENST00000273283.7; ENSP00000273283.2; NM_002215.4; NP_002206.2.
DR   UCSC; uc003dfs.4; human. [P19827-1]
DR   AGR; HGNC:6166; -.
DR   CTD; 3697; -.
DR   DisGeNET; 3697; -.
DR   GeneCards; ITIH1; -.
DR   HGNC; HGNC:6166; ITIH1.
DR   HPA; ENSG00000055957; Tissue enriched (liver).
DR   MIM; 147270; gene.
DR   neXtProt; NX_P19827; -.
DR   OpenTargets; ENSG00000055957; -.
DR   PharmGKB; PA29964; -.
DR   VEuPathDB; HostDB:ENSG00000055957; -.
DR   eggNOG; ENOG502RXR2; Eukaryota.
DR   GeneTree; ENSGT00940000162180; -.
DR   HOGENOM; CLU_008101_0_0_1; -.
DR   InParanoid; P19827; -.
DR   OMA; QEFRTTC; -.
DR   OrthoDB; 608326at2759; -.
DR   PhylomeDB; P19827; -.
DR   TreeFam; TF328982; -.
DR   PathwayCommons; P19827; -.
DR   SignaLink; P19827; -.
DR   BioGRID-ORCS; 3697; 12 hits in 1148 CRISPR screens.
DR   ChiTaRS; ITIH1; human.
DR   GeneWiki; ITIH1; -.
DR   GenomeRNAi; 3697; -.
DR   Pharos; P19827; Tbio.
DR   PRO; PR:P19827; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; P19827; Protein.
DR   Bgee; ENSG00000055957; Expressed in right lobe of liver and 113 other cell types or tissues.
DR   ExpressionAtlas; P19827; baseline and differential.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR   GO; GO:0030246; F:carbohydrate binding; EXP:DisProt.
DR   GO; GO:0005540; F:hyaluronic acid binding; IDA:UniProtKB.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0030212; P:hyaluronan metabolic process; IEA:InterPro.
DR   CDD; cd01461; vWA_interalpha_trypsin_inhibitor; 1.
DR   Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR   InterPro; IPR010600; ITI_HC_C.
DR   InterPro; IPR013694; VIT.
DR   InterPro; IPR002035; VWF_A.
DR   InterPro; IPR036465; vWFA_dom_sf.
DR   PANTHER; PTHR10338; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN FAMILY MEMBER; 1.
DR   PANTHER; PTHR10338:SF106; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN H1; 1.
DR   Pfam; PF06668; ITI_HC_C; 1.
DR   Pfam; PF08487; VIT; 1.
DR   Pfam; PF00092; VWA; 1.
DR   SMART; SM00609; VIT; 1.
DR   SMART; SM00327; VWA; 1.
DR   SUPFAM; SSF53300; vWA-like; 1.
DR   PROSITE; PS51468; VIT; 1.
DR   PROSITE; PS50234; VWFA; 1.
DR   Genevisible; P19827; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Phosphoprotein; Protease inhibitor;
KW   Proteoglycan; Reference proteome; Secreted; Serine protease inhibitor;
KW   Signal.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   PROPEP          28..34
FT                   /evidence="ECO:0000269|PubMed:2476436"
FT                   /id="PRO_0000016506"
FT   CHAIN           35..672
FT                   /note="Inter-alpha-trypsin inhibitor heavy chain H1"
FT                   /id="PRO_0000016507"
FT   PROPEP          673..911
FT                   /id="PRO_0000016508"
FT   DOMAIN          37..166
FT                   /note="VIT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT   DOMAIN          290..450
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   REGION          387..911
FT                   /note="Hyaluronan-binding"
FT   MOTIF           181..184
FT                   /note="Phagocytosis uptake signal"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         129
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         402
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         407
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         672
FT                   /note="Aspartate 1-(chondroitin 4-sulfate)-ester"
FT   CARBOHYD        60
FT                   /note="S-linked (Hex...) cysteine"
FT                   /evidence="ECO:0000269|PubMed:9425062"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:12754519,
FT                   ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:9425062,
FT                   ECO:0000269|PubMed:9677337"
FT                   /id="CAR_000138"
FT   CARBOHYD        588
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:9425062, ECO:0000269|PubMed:9677337"
FT                   /id="CAR_000139"
FT   CARBOHYD        653
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:9425062"
FT                   /id="CAR_000213"
FT   CARBOHYD        750
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   DISULFID        244..247
FT                   /evidence="ECO:0000269|PubMed:9425062"
FT   DISULFID        268..540
FT                   /evidence="ECO:0000269|PubMed:9425062"
FT   VAR_SEQ         1..288
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045419"
FT   VAR_SEQ         1..142
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045420"
FT   VARIANT         263
FT                   /note="S -> T (in dbSNP:rs1042777)"
FT                   /evidence="ECO:0000269|PubMed:1380832"
FT                   /id="VAR_011873"
FT   VARIANT         585
FT                   /note="E -> V (in allele ITIH1*2; dbSNP:rs678)"
FT                   /evidence="ECO:0000269|PubMed:1380832,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:7535743"
FT                   /id="VAR_004019"
FT   VARIANT         595
FT                   /note="Q -> R (in allele ITIH1*2 and allele ITIH1*3;
FT                   dbSNP:rs1042779)"
FT                   /evidence="ECO:0000269|PubMed:1380832,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:7535743"
FT                   /id="VAR_004020"
FT   VARIANT         695
FT                   /note="G -> C (in dbSNP:rs1042904)"
FT                   /id="VAR_011874"
FT   VARIANT         844
FT                   /note="D -> E (in dbSNP:rs1042849)"
FT                   /id="VAR_011875"
FT   MUTAGEN         298
FT                   /note="D->A: Abolishes binding to CUB domain of TNFAIP6."
FT                   /evidence="ECO:0000269|PubMed:26468290"
FT   CONFLICT        51
FT                   /note="V -> T (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        54
FT                   /note="R -> A (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        266
FT                   /note="K -> E (in Ref. 1; CAA45188)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        539
FT                   /note="T -> A (in Ref. 3; BAH12794)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        798
FT                   /note="V -> A (in Ref. 3; BAH12794)"
FT                   /evidence="ECO:0000305"
FT   STRAND          51..63
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          66..77
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          79..81
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          83..92
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          96..104
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          107..115
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           116..119
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           121..123
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          124..128
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           130..133
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          135..138
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          140..152
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          156..167
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          172..181
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          187..197
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          202..209
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           214..220
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          221..226
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          229..234
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           238..241
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          242..244
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          248..250
FT                   /evidence="ECO:0007829|PDB:6FPY"
FT   STRAND          254..262
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          265..267
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          269..273
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          276..281
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          291..298
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           301..303
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           306..321
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          327..343
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           349..361
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           370..386
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           389..391
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          394..404
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           413..424
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          430..439
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           441..449
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   TURN            450..452
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          455..458
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           464..475
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          478..486
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   TURN            489..491
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          492..495
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          499..504
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          509..515
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          524..531
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          534..541
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           544..554
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           557..578
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   HELIX           583..600
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          607..611
FT                   /evidence="ECO:0007829|PDB:6FPZ"
FT   STRAND          643..645
FT                   /evidence="ECO:0007829|PDB:6FPZ"
SQ   SEQUENCE   911 AA;  101389 MW;  8FE715FF223FC917 CRC64;
     MDGAMGPRGL LLCMYLVSLL ILQAMPALGS ATGRSKSSEK RQAVDTAVDG VFIRSLKVNC
     KVTSRFAHYV VTSQVVNTAN EAREVAFDLE IPKTAFISDF AVTADGNAFI GDIKDKVTAW
     KQYRKAAISG ENAGLVRASG RTMEQFTIHL TVNPQSKVTF QLTYEEVLKR NHMQYEIVIK
     VKPKQLVHHF EIDVDIFEPQ GISKLDAQAS FLPKELAAQT IKKSFSGKKG HVLFRPTVSQ
     QQSCPTCSTS LLNGHFKVTY DVSRDKICDL LVANNHFAHF FAPQNLTNMN KNVVFVIDIS
     GSMRGQKVKQ TKEALLKILG DMQPGDYFDL VLFGTRVQSW KGSLVQASEA NLQAAQDFVR
     GFSLDEATNL NGGLLRGIEI LNQVQESLPE LSNHASILIM LTDGDPTEGV TDRSQILKNV
     RNAIRGRFPL YNLGFGHNVD FNFLEVMSME NNGRAQRIYE DHDATQQLQG FYSQVAKPLL
     VDVDLQYPQD AVLALTQNHH KQYYEGSEIV VAGRIADNKQ SSFKADVQAH GEGQEFSITC
     LVDEEEMKKL LRERGHMLEN HVERLWAYLT IQELLAKRMK VDREERANLS SQALQMSLDY
     GFVTPLTSMS IRGMADQDGL KPTIDKPSED SPPLEMLGPR RTFVLSALQP SPTHSSSNTQ
     RLPDRVTGVD TDPHFIIHVP QKEDTLCFNI NEEPGVILSL VQDPNTGFSV NGQLIGNKAR
     SPGQHDGTYF GRLGIANPAT DFQLEVTPQN ITLNPGFGGP VFSWRDQAVL RQDGVVVTIN
     KKRNLVVSVD DGGTFEVVLH RVWKGSSVHQ DFLGFYVLDS HRMSARTHGL LGQFFHPIGF
     EVSDIHPGSD PTKPDATMVV RNRRLTVTRG LQKDYSKDPW HGAEVSCWFI HNNGAGLIDG
     AYTDYIVPDI F
//