ITIH3_MOUSE
ID ITIH3_MOUSE Reviewed; 889 AA.
AC Q61704; E9QME9; Q91WG9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H3;
DE Short=ITI heavy chain H3;
DE Short=ITI-HC3;
DE Short=Inter-alpha-inhibitor heavy chain 3;
DE Flags: Precursor;
GN Name=Itih3;
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 [LARGE SCALE MRNA].
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-889.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-889.
RC STRAIN=FVB/N; TISSUE=Liver;
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 [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-580.
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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. Pre-alpha-inhibitor
CC (P-alpha-I) is composed of ITIH3/HC3 and bikunin.
CC {ECO:0000250|UniProtKB:Q06033}.
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 -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15276.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA49843.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK146700; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CT025528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X70393; CAA49843.1; ALT_INIT; mRNA.
DR EMBL; BC015276; AAH15276.1; ALT_INIT; mRNA.
DR CCDS; CCDS49434.1; -.
DR PIR; S54355; S54355.
DR RefSeq; NP_032433.2; NM_008407.2.
DR AlphaFoldDB; Q61704; -.
DR SMR; Q61704; -.
DR BioGRID; 200838; 1.
DR IntAct; Q61704; 1.
DR MINT; Q61704; -.
DR STRING; 10090.ENSMUSP00000006697; -.
DR CarbonylDB; Q61704; -.
DR GlyConnect; 776; 1 N-Linked glycan (1 site).
DR GlyGen; Q61704; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q61704; -.
DR PhosphoSitePlus; Q61704; -.
DR CPTAC; non-CPTAC-3354; -.
DR MaxQB; Q61704; -.
DR PaxDb; Q61704; -.
DR PeptideAtlas; Q61704; -.
DR PRIDE; Q61704; -.
DR ProteomicsDB; 269107; -.
DR Antibodypedia; 7471; 109 antibodies from 23 providers.
DR DNASU; 16426; -.
DR Ensembl; ENSMUST00000006697; ENSMUSP00000006697; ENSMUSG00000006522.
DR GeneID; 16426; -.
DR KEGG; mmu:16426; -.
DR UCSC; uc033goy.1; mouse.
DR CTD; 3699; -.
DR MGI; MGI:96620; Itih3.
DR VEuPathDB; HostDB:ENSMUSG00000006522; -.
DR eggNOG; ENOG502QPS2; Eukaryota.
DR GeneTree; ENSGT00940000154554; -.
DR InParanoid; Q61704; -.
DR OMA; HPIHQDF; -.
DR OrthoDB; 955432at2759; -.
DR PhylomeDB; Q61704; -.
DR TreeFam; TF328982; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 16426; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q61704; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q61704; protein.
DR Bgee; ENSMUSG00000006522; Expressed in ventromedial nucleus of hypothalamus and 110 other tissues.
DR ExpressionAtlas; Q61704; baseline and differential.
DR Genevisible; Q61704; MM.
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: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 Cleavage on pair of basic residues; Glycoprotein; Protease inhibitor;
KW Proteoglycan; Reference proteome; Secreted; Serine protease inhibitor;
KW Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..33
FT /evidence="ECO:0000250"
FT /id="PRO_0000016535"
FT CHAIN 34..649
FT /note="Inter-alpha-trypsin inhibitor heavy chain H3"
FT /id="PRO_0000016536"
FT PROPEP 650..889
FT /evidence="ECO:0000250"
FT /id="PRO_0000016537"
FT DOMAIN 29..158
FT /note="VIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT DOMAIN 284..467
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT MOD_RES 649
FT /note="Aspartate 1-(chondroitin 4-sulfate)-ester"
FT /evidence="ECO:0000250"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 580
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CONFLICT 3
FT /note="T -> A (in Ref. 3; CAA49843)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="Q -> R (in Ref. 3; CAA49843 and 4; AAH15276)"
FT /evidence="ECO:0000305"
FT CONFLICT 618..619
FT /note="KP -> NA (in Ref. 3; CAA49843)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="I -> F (in Ref. 3; CAA49843)"
FT /evidence="ECO:0000305"
FT CONFLICT 746
FT /note="I -> V (in Ref. 3; CAA49843 and 4; AAH15276)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 889 AA; 99358 MW; CB3FF5F5062A27B9 CRC64;
MRTMWWPCLV LALLSGLETS GFPRSPLQLL GKRSLPEGVV DGIEVYSTKI SCKVTSRFAH
NVVTTRAVNR ADTAKEVSFD VELPKTAFIT NFTLTIDGVT YPGNVKEKEV AQKQYEKAVS
QGKTAGLVKA SGRKLEKFTV SVNVAAGSKV TFELTYEELL KRNKGKYEMY LKVQPKQLVR
HFEIDAHIFE PQGISMLDAE ASFITNDLLG SALTKSFSGK KGHVSFKPSL DQQRSCPTCT
DSLLNGDFTI VYDVNRESPG NVQIVNGYFV HFFAPQGLPV VPKNIVFVID VSGSMSGRKI
QQTREALLKI LDDVKEDDYL NFILFSTDVT TWKDHLVQAT PANLKEAKTF VKNIHDQSMT
NINDGLLKGI EMLNKAREDH TVPERSTSII IMLTDGDANT GESRPEKIQE NVRNAIGGKF
PLYNLGFGNN LNYNFLETLA LENHGLARRI YEDSDANLQL QGFYEEVANP LLTNVEVEYP
ENAILDLTRN SYPHFYDGSE IVVAGRLVDR NMDNFKADVK GHGALNDLTF TEEVDMEEMD
AALKEQGYIF GDYIERLWAY LTIEQLLEKR KNAKGDEKEN ITAEALDLSL KYHFVTPLTS
MVVTKPEDNE DQTSIADKPG EEAIAETTTM SFLTTQQSSQ SPYYYVDGDP HFIIQIPGKN
DSICFNIDEK PGTVLRLIQD PVTGITVTGQ IIGDKRSNAS SRTGKTYFGK LGITNAWMDF
RVEVTTEKII LGTGAELSTF SWLDTITVTQ TGLSVTINRK KNMVVSFGDG ISFVIILHQV
WKKHPVHQDF LGFYVVDSHR MSAQTHGLLG QFFQPFDFKV FGIRPGSDPT KPDATMVVKN
HRLTVTRGSQ KDYRKDASVG TKVICWFVHN NGEGLIDGVH TDYIVPSLF
