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