ITIH2_MOUSE
ID ITIH2_MOUSE Reviewed; 946 AA.
AC Q61703; A2AKU6; Q3UZM0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 153.
DE RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H2;
DE Short=ITI heavy chain H2;
DE Short=ITI-HC2;
DE Short=Inter-alpha-inhibitor heavy chain 2;
DE Flags: Precursor;
GN Name=Itih2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6N; TISSUE=Liver;
RX PubMed=7534067; DOI=10.1042/bj3060505;
RA Chan P., Risler J.-L., Raguenez G., Salier J.-P.;
RT "The three heavy-chain precursors for the inter-alpha-inhibitor family in
RT mouse: new members of the multicopper oxidase protein group with
RT differential transcription in liver and brain.";
RL Biochem. J. 306:505-512(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000250}.
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 {ECO:0000250|UniProtKB:P19823}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in both liver and brain.
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. {ECO:0000250}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P19823}.
CC -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE21837.1; Type=Erroneous initiation; Evidence={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; X70392; CAA49842.1; -; mRNA.
DR EMBL; AK133782; BAE21837.1; ALT_INIT; mRNA.
DR EMBL; AL772367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS15677.2; -.
DR PIR; S54354; S54354.
DR RefSeq; NP_034712.2; NM_010582.3.
DR AlphaFoldDB; Q61703; -.
DR SMR; Q61703; -.
DR BioGRID; 200837; 1.
DR IntAct; Q61703; 1.
DR STRING; 10090.ENSMUSP00000046530; -.
DR GlyGen; Q61703; 3 sites.
DR iPTMnet; Q61703; -.
DR PhosphoSitePlus; Q61703; -.
DR CPTAC; non-CPTAC-5611; -.
DR jPOST; Q61703; -.
DR MaxQB; Q61703; -.
DR PaxDb; Q61703; -.
DR PRIDE; Q61703; -.
DR ProteomicsDB; 269414; -.
DR DNASU; 16425; -.
DR GeneID; 16425; -.
DR KEGG; mmu:16425; -.
DR CTD; 3698; -.
DR MGI; MGI:96619; Itih2.
DR eggNOG; ENOG502QPS2; Eukaryota.
DR InParanoid; Q61703; -.
DR OrthoDB; 955432at2759; -.
DR PhylomeDB; Q61703; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 16425; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Itih2; mouse.
DR PRO; PR:Q61703; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61703; protein.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005540; F:hyaluronic acid binding; ISO:MGI.
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 Gamma-carboxyglutamic acid; Glycoprotein; Phosphoprotein;
KW Protease inhibitor; Proteoglycan; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..54
FT /evidence="ECO:0000250"
FT /id="PRO_0000016520"
FT CHAIN 55..702
FT /note="Inter-alpha-trypsin inhibitor heavy chain H2"
FT /id="PRO_0000016521"
FT PROPEP 703..946
FT /evidence="ECO:0000250"
FT /id="PRO_0000016522"
FT DOMAIN 56..185
FT /note="VIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT DOMAIN 308..468
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"
FT MOD_RES 282
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P19823"
FT MOD_RES 283
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P19823"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19823"
FT MOD_RES 702
FT /note="Aspartate 1-(chondroitin 4-sulfate)-ester"
FT /evidence="ECO:0000250"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19823"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 833
FT /note="R -> G (in Ref. 2; BAE21837)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 946 AA; 105928 MW; 40DB6716433ED9DC CRC64;
MQRPVCLLIW LFLLEAQAFE IPINGNSEFA EYSDLVELAP DKLPFVQENG RHQRSLPEES
GEETDTVDPV TLYSYKVQST ITSRVATTTI QSKLVNNSPL PQSVVFDVQI PKGAFISNFT
MTVNGMTFTS SIKEKTVGRA LYSQARAKGK TAGWVRSRTL DMENFNTEVN IPPGAKVQFE
LHYQEVKWRK LGSYEHKIHL QPGKLAKHLE VNVWIIEPQG MRFLHVPDTF EGHFQGVPVI
SKGQQKAHVS FKPTVAQQRK CPNCTETAVN GELVVMYDVN REEKAGELEV FNGYFVHFFA
PENLDPIPKN ILFVIDVSGS MWGIKMKQTV EAMKTILDDL RTDDQFSVVD FNHNVRTWRN
DLVSATKTQI ADAKRYIEKI QPSGGTNINE ALLRAIFILN EASNMGLLNP DSVSLIILVS
DGDPTVGELK LSKIQKNVKQ SIQDNISLFS LGIGFDVDYD FLKRLSNENR GIAQRIYGNQ
DTSSQLKKFY NQVSTPLLRN VQFNYPQASV TDVTQNNFHN YFGGSEIVVA GKFDPSKLTE
VQSIITATSA NTELVLETLS QMDDLEEFLS KDKHADPDFT KKLWAYLTIN QLLAERSLAP
TAAIKRKITK TILQMSLDHH IVTPLTAMVI ENDAGDERML ADSPPQDHSC CSGALYYGTK
VASGPIPSWA NPSPTPMSAM LAVGAKPLES TPPTHLNQVE NDPHFIIYLP KSKRNICFNI
DSEPGKILSL VSDPESGIVV NGQLIGAKRA ENGKLSTYFG KLGFYFQKEG MKIEISTETI
TLSSGSSTSR LSWSDTAHLG NSRVLISVKK EKSVTLTLNK ELFFSVLLHR VWRKHPVNVD
FLGIYAPPID KFSPRVHGLL GQFMQEPAIH IFNERPGKEP GKPEASMEVK GHKLTVTRGL
QKDYRTDIVF GTDVPCWFVH NSGKGFIDGH YKDYFVPQLY SFLKRP
