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ITIH4_BOVIN
ID   ITIH4_BOVIN             Reviewed;         916 AA.
AC   Q3T052;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   25-MAY-2022, entry version 81.
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   Flags: Precursor;
GN   Name=ITIH4;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Testis;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 389-413, INDUCTION, SUBCELLULAR LOCATION, AND FUNCTION.
RX   PubMed=15213118; DOI=10.1128/iai.72.7.3777-3782.2004;
RA   Pineiro M., Andres M., Iturralde M., Carmona S., Hirvonen J., Pyorala S.,
RA   Heegaard P.M., Tjornehoj K., Lampreave F., Pineiro A., Alava M.A.;
RT   "ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase
RT   protein isolated from cattle during experimental infection.";
RL   Infect. Immun. 72:3777-3782(2004).
RN   [3]
RP   GLYCOSYLATION AT SER-683; THR-705; THR-706 AND THR-708, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RX   PubMed=19674964; DOI=10.1074/mcp.m900211-mcp200;
RA   Darula Z., Medzihradszky K.F.;
RT   "Affinity enrichment and characterization of mucin core-1 type
RT   glycopeptides from bovine serum.";
RL   Mol. Cell. Proteomics 8:2515-2526(2009).
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:15213118}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15213118}.
CC   -!- INDUCTION: Levels of ITIH4 in serum increase 3- to 12-fold on
CC       inoculation with various bacteria which induce mastitis. Peak levels
CC       are reached around 42h-72 h after infection.
CC       {ECO:0000269|PubMed:15213118}.
CC   -!- PTM: Appears to be both N- and O-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
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DR   EMBL; BC102561; AAI02562.1; -; mRNA.
DR   RefSeq; NP_001015590.2; NM_001015590.3.
DR   AlphaFoldDB; Q3T052; -.
DR   SMR; Q3T052; -.
DR   STRING; 9913.ENSBTAP00000010330; -.
DR   GlyConnect; 801; 2 O-Linked glycans (4 sites).
DR   iPTMnet; Q3T052; -.
DR   PaxDb; Q3T052; -.
DR   PeptideAtlas; Q3T052; -.
DR   PRIDE; Q3T052; -.
DR   GeneID; 513700; -.
DR   KEGG; bta:513700; -.
DR   CTD; 3700; -.
DR   eggNOG; ENOG502QPS2; Eukaryota.
DR   InParanoid; Q3T052; -.
DR   Proteomes; UP000009136; 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   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:0000255"
FT   CHAIN           28..916
FT                   /note="Inter-alpha-trypsin inhibitor heavy chain H4"
FT                   /id="PRO_0000285684"
FT   DOMAIN          28..149
FT                   /note="VIT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT   DOMAIN          275..458
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   REGION          597..616
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          678..701
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        208
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        518
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        683
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:19674964"
FT   CARBOHYD        705
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19674964"
FT   CARBOHYD        706
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19674964"
FT   CARBOHYD        708
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19674964"
FT   DISULFID        733..911
FT                   /evidence="ECO:0000250"
FT   CONFLICT        390
FT                   /note="T -> D (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        397
FT                   /note="L -> S (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        411..412
FT                   /note="HS -> QV (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   916 AA;  101513 MW;  FC1AEC0745DB7086 CRC64;
     MKTPAPGRIH SIVLVLLSLA VLQTSKAQKV QNDIDIYSLT VDSKVSSRFA HTVITSRVVN
     KADAVREATF QMELPKKAFI TNFSMVIDGV TYPGNIKEKA AAQEQYSAAV ARGESAGLVR
     ATGRKTEQFQ VSVSVAPAAK VTFELVYEEL LARHLGAYEL LLKVRPQQLV KHLQMDIHIF
     EPQGISFLET ESTFMTNKLA EALTTSQNKT KAHVRFKPTL SQQQKYPEKQ DTVIDGSFIV
     RYDVDRPLSG GSIQIENGYF VHYFAPDSLS TIPKNVIFVI DKSGSMMGRK IKQTREALIK
     ILDDLSPHDQ FDLISFSSEA TTWKPLLVPA STENVNEAKS YATGIQAQGG TNINDAMLMA
     VQLLEKANQE ELLPEGSITL IILLTDGDPT VGETNPLNIQ KNVRKAINGQ HSLFCLGFGF
     DVSYAFLEKM ALENGGLARR IYEDSDSALQ LQDFYQEVAN PLMTSVAFEY PSNAVESVTQ
     DTFRVFFKGS ELVVAGKLRE QSPDVLLAQI RGQLHRENIT YMMMSHVAEQ EEMFRSPKYI
     FHSFIERLWA YLTIQQLLEQ MVSALDAEKQ ALEARALSLS LSYSFVTPLT SMVITKPEGQ
     EQSQVAEKPV EDESRGSRVY LGPMRFGHSV GDRTSRKPGG GLKLLNGTPL FGPPGPPAAA
     SPFHRMTSRL VLPELMSPLA PASAPSPTSG PGGASHDTDF RIKGTTPTAL PFAPVQAPSV
     ILPLPGQSVD RLCVDLRRPQ ELVNLLSDPD QGVEVTGHFE TAKARFSWIE VTFENPQVQI
     HASPEHVVMT RNRRNSAYKW KETLYSVMPG LKVTMDKEGL LLLSRPDRVT IGLLFWDGPG
     KGLRLLLQNT DRFSSHVSGT LGQFYQDVLW GPLDTADDSK RTLKVQGRDY SATRELKLDY
     QESPPGKEIS CWSVEL
 
 
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