ITIH1_HUMAN
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 03-AUG-2022, entry version 202.
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}.
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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; 21.
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 GlyGen; P19827; 8 sites, 26 N-linked glycans (3 sites), 3 O-linked glycans (3 sites).
DR iPTMnet; P19827; -.
DR PhosphoSitePlus; P19827; -.
DR BioMuta; ITIH1; -.
DR EPD; P19827; -.
DR jPOST; P19827; -.
DR MassIVE; P19827; -.
DR PaxDb; P19827; -.
DR PeptideAtlas; P19827; -.
DR PRIDE; P19827; -.
DR ProteomicsDB; 25555; -.
DR ProteomicsDB; 27630; -.
DR ProteomicsDB; 53691; -. [P19827-1]
DR Antibodypedia; 31337; 280 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 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; FNFLEAM; -.
DR OrthoDB; 955432at2759; -.
DR PhylomeDB; P19827; -.
DR TreeFam; TF328982; -.
DR PathwayCommons; P19827; -.
DR SignaLink; P19827; -.
DR BioGRID-ORCS; 3697; 11 hits in 1070 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 111 other tissues.
DR ExpressionAtlas; P19827; baseline and differential.
DR Genevisible; P19827; HS.
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: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 Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR010600; ITI_HC_C.
DR InterPro; IPR013694; VIT.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
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; SSF53300; 1.
DR PROSITE; PS51468; VIT; 1.
DR PROSITE; PS50234; VWFA; 1.
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
