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ITIH4_PIG
ID   ITIH4_PIG               Reviewed;         921 AA.
AC   P79263;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   25-MAY-2022, entry version 107.
DE   RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H4;
DE            Short=ITI heavy chain H4;
DE            Short=ITI-HC4;
DE            Short=Inter-alpha-inhibitor heavy chain 4;
DE   AltName: Full=Inter-alpha-trypsin inhibitor family heavy chain-related protein;
DE            Short=IHRP;
DE   AltName: Full=Major acute phase protein;
DE            Short=MAP;
DE   Flags: Precursor;
GN   Name=ITIH4; Synonyms=IHRP;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING, AND PROTEIN SEQUENCE OF
RP   28-36; 695-703 AND 710-722.
RC   TISSUE=Liver;
RX   PubMed=8830057; DOI=10.1093/oxfordjournals.jbchem.a021281;
RA   Hashimoto K., Tobe T., Sumiya J., Sano Y., Choi-Miura N.-H., Ozawa A.,
RA   Yasue H., Tomita M.;
RT   "Primary structure of the pig homologue of human IHRP: inter-alpha-trypsin
RT   inhibitor family heavy chain-related protein.";
RL   J. Biochem. 119:577-584(1996).
RN   [2]
RP   PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 267-556, TISSUE SPECIFICITY, AND
RP   INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=1697703;
RA   Buchman T.G., Cabin D.E., Vickers S., Deutschman C.S., Delgado E.,
RA   Sussman M.M., Bulkley G.B.;
RT   "Molecular biology of circulatory shock. Part II. Expression of four groups
RT   of hepatic genes is enhanced after resuscitation from cardiogenic shock.";
RL   Surgery 108:559-566(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 28-54 AND 223-240.
RC   TISSUE=Serum;
RX   PubMed=7556597; DOI=10.1016/0014-5793(95)00882-a;
RA   Gonzalez-Ramon N., Alava M.A., Sarsa J.A., Pineiro M., Escartin A.,
RA   Garcia-Gil A., Lampreave F., Pineiro A.;
RT   "The major acute phase serum protein in pigs is homologous to human plasma
RT   kallikrein sensitive PK-120.";
RL   FEBS Lett. 371:227-230(1995).
RN   [4]
RP   FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=10712621; DOI=10.1046/j.1432-1327.2000.01195.x;
RA   Gonzalez-Ramon N., Hoebe K., Alava M.A., Van Leengoed L., Pineiro M.,
RA   Carmona S., Iturralde M., Lampreave F., Pineiro A.;
RT   "Pig MAP/ITIH4 and haptoglobin are interleukin-6-dependent acute-phase
RT   plasma proteins in porcine primary cultured hepatocytes.";
RL   Eur. J. Biochem. 267:1878-1885(2000).
CC   -!- FUNCTION: Type II acute-phase protein (APP) involved in inflammatory
CC       responses to trauma. May also play a role in liver development or
CC       regeneration. {ECO:0000269|PubMed:10712621}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10712621}.
CC   -!- TISSUE SPECIFICITY: Liver specific. {ECO:0000269|PubMed:1697703}.
CC   -!- INDUCTION: Levels increase significantly after cardiogenic shock.
CC       Specifically induced by the cytokine IL6 in hepatocytes.
CC       {ECO:0000269|PubMed:10712621, ECO:0000269|PubMed:1697703}.
CC   -!- PTM: Appears to be both N- and O-glycosylated. {ECO:0000250}.
CC   -!- PTM: Cleaved by plasma kallikrein to yield 55- and 25-kDa fragments.
CC   -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=M29507; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=M29507; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
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DR   EMBL; U43164; AAD00024.1; -; mRNA.
DR   EMBL; S82800; AAB46821.1; -; mRNA.
DR   EMBL; M29507; -; NOT_ANNOTATED_CDS; mRNA.
DR   PIR; JC4625; JC4625.
DR   RefSeq; NP_001001537.1; NM_001001537.1.
DR   AlphaFoldDB; P79263; -.
DR   SMR; P79263; -.
DR   STRING; 9823.ENSSSCP00000012206; -.
DR   PaxDb; P79263; -.
DR   PeptideAtlas; P79263; -.
DR   PRIDE; P79263; -.
DR   GeneID; 396799; -.
DR   KEGG; ssc:396799; -.
DR   CTD; 3700; -.
DR   eggNOG; ENOG502QPS2; Eukaryota.
DR   InParanoid; P79263; -.
DR   OrthoDB; 955432at2759; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
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:0006953; P:acute-phase response; IEP:UniProtKB.
DR   GO; GO:0030212; P:hyaluronan metabolic process; IEA:InterPro.
DR   GO; GO:0034097; P:response to cytokine; IEP:UniProtKB.
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   Acute phase; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Protease inhibitor; Reference proteome; Secreted;
KW   Serine protease inhibitor; Signal.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000269|PubMed:7556597,
FT                   ECO:0000269|PubMed:8830057"
FT   CHAIN           28..921
FT                   /note="Inter-alpha-trypsin inhibitor heavy chain H4"
FT                   /id="PRO_0000016544"
FT   DOMAIN          28..146
FT                   /note="VIT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT   DOMAIN          270..428
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   REGION          591..646
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        591..638
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        80
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        205
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        513
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        577
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        712
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3T052"
FT   DISULFID        738..916
FT                   /evidence="ECO:0000250"
FT   CONFLICT        49..50
FT                   /note="HT -> SK (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        703
FT                   /note="D -> H (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   921 AA;  102146 MW;  E2BF95925DE8D07C CRC64;
     MKTLSPTGYG LLLVLPLLLA VLQSTTAHKN DINIYSLTVD SKVSSRFAHT VVTSRVVNKG
     SAVQEATFQM ELPKKAFITN FSMIIDGVTY PGNIKEKAAA QEQYSAVARG ESAGLVRATG
     RKTEQFQVAV SVAPAAKVTF ELVYEELLAR HLGVYELLLK IQPQQLVKHL QMDIHIFEPQ
     GISFLETEST FMTNELAEAL TISQNKTKAH IRFKPTLSQQ QKSPEQQETV LDGNFIVRYD
     VNRTVTGGSI QIENGYFVHY FAPEVWSAIP KNVIFVIDTS GSMRGRKIQQ TREALIKILG
     DLGSRDQFNL VSFSGEAPRR RAVAASAENV EEAKSYAAEI HAQGGTNIND AMLMAVQLLE
     RANREELLPA RSVTFIILLT DGDPTVGETN PSKIQKNVRE AIDGQHSLFC LGFGFDVPYA
     FLEKMALENG GLARRIYEDS DSALQLEDFY QEVANPLLRL VAFEYPSNAV EEVTQDNFRL
     FFKGSELVVA GKLRDQSPDV LSAKVRGQLH MENVTFVMES RVAEQEAEFL SPKYIFHSFM
     ERLWAYLTIQ QLLAQTVSAS DAEKKALEAR ALSLSLNYSF VTPLTSMVIT KPEGQEQSQV
     AEKPVENGNR QGNTHSGHSS FQFHSVGDRT SRLTGGSSVD PVFSHRRGWK GQAQGFEKMS
     YLPPRLGPPG PLQPTRFSHP FSRITLDRVL PEVLSVPDET SHDMDSRIIG ATIPPPPARI
     QAPSVILPLP GQSVDQLCVD LKHSQGPVKL LSDPGQGVEV TGHYEREKAR FSWIEVTFKH
     PPLQVRASLE HIVVIRNRQS SAYKWKETLY SVMPGLKITM DKAGLLLLSS PNRVTIGLLS
     WDGPGKGLRL LLRDTDHFSS QISGTFGQFY QDVVWGPPAA ADDSKRTVTV QGHDHSATRE
     LKLDYQEGSP GKEISCWTVV L
 
 
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