ID   HPT_BOVIN               Reviewed;         401 AA.
AC   Q2TBU0;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 1.
DT   25-MAY-2022, entry version 101.
DE   RecName: Full=Haptoglobin;
DE   Contains:
DE     RecName: Full=Haptoglobin alpha chain;
DE   Contains:
DE     RecName: Full=Haptoglobin beta chain;
DE   Flags: Precursor;
GN   Name=HP;
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=Crossbred X Angus; TISSUE=Liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: As a result of hemolysis, hemoglobin is found to accumulate
CC       in the kidney and is secreted in the urine. Haptoglobin captures, and
CC       combines with free plasma hemoglobin to allow hepatic recycling of heme
CC       iron and to prevent kidney damage. Haptoglobin also acts as an
CC       antioxidant, has antibacterial activity and plays a role in modulating
CC       many aspects of the acute phase response. Hemoglobin/haptoglobin
CC       complexes are rapidly cleared by the macrophage CD163 scavenger
CC       receptor expressed on the surface of liver Kupfer cells through an
CC       endocytic lysosomal degradation pathway (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Tetramer of two alpha and two beta chains; disulfide-linked
CC       (By similarity). The hemoglobin/haptoglobin complex is composed of a
CC       haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By
CC       similarity). Interacts with CD163 (By similarity). Interacts with
CC       ERGIC3 (By similarity). {ECO:0000250|UniProtKB:P00738,
CC       ECO:0000250|UniProtKB:Q8SPS7}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC   -!- DOMAIN: The beta chain mediates most of the interactions with both
CC       subunits of hemoglobin, while the alpha chain forms the homodimeric
CC       interface. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
CC   -!- CAUTION: Although homologous to serine proteases, it has lost all
CC       essential catalytic residues and has no enzymatic activity.
CC       {ECO:0000305}.
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DR   EMBL; BC109668; AAI09669.1; -; mRNA.
DR   RefSeq; NP_001035560.1; NM_001040470.2.
DR   AlphaFoldDB; Q2TBU0; -.
DR   SMR; Q2TBU0; -.
DR   STRING; 9913.ENSBTAP00000008335; -.
DR   MEROPS; S01.972; -.
DR   PaxDb; Q2TBU0; -.
DR   PeptideAtlas; Q2TBU0; -.
DR   PRIDE; Q2TBU0; -.
DR   GeneID; 280692; -.
DR   KEGG; bta:280692; -.
DR   CTD; 3240; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   InParanoid; Q2TBU0; -.
DR   OrthoDB; 798576at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0072562; C:blood microparticle; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR   GO; GO:0030492; F:hemoglobin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0002526; P:acute inflammatory response; IBA:GO_Central.
DR   GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR   GO; GO:0010942; P:positive regulation of cell death; IBA:GO_Central.
DR   GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
DR   CDD; cd00033; CCP; 1.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; -; 2.
DR   InterPro; IPR008292; Haptoglobin.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR   InterPro; IPR001254; Trypsin_dom.
DR   PANTHER; PTHR24255:SF27; PTHR24255:SF27; 2.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF57535; SSF57535; 2.
DR   PROSITE; PS50923; SUSHI; 2.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
PE   2: Evidence at transcript level;
KW   Acute phase; Antibiotic; Antimicrobial; Antioxidant; Disulfide bond;
KW   Glycoprotein; Hemoglobin-binding; Immunity; Reference proteome; Repeat;
KW   Secreted; Serine protease homolog; Signal; Sushi.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000250"
FT   CHAIN           19..401
FT                   /note="Haptoglobin"
FT                   /id="PRO_0000367489"
FT   CHAIN           19..155
FT                   /note="Haptoglobin alpha chain"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000367490"
FT   CHAIN           157..401
FT                   /note="Haptoglobin beta chain"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000367491"
FT   DOMAIN          28..83
FT                   /note="Sushi 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          85..142
FT                   /note="Sushi 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          157..399
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   REGION          313..318
FT                   /note="Interaction with CD163"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        316
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        30
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   DISULFID        49..81
FT                   /evidence="ECO:0000250"
FT   DISULFID        87
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   DISULFID        106..140
FT                   /evidence="ECO:0000250"
FT   DISULFID        144..261
FT                   /note="Interchain (between alpha and beta chains)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT                   ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DISULFID        304..335
FT                   /evidence="ECO:0000250"
FT   DISULFID        346..376
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   401 AA;  44859 MW;  91F83C9164FF55E3 CRC64;
     MSALQAVVTL LLCGQLLAVE TGSEATADSC PKAPEIANSH VEYSVRYQCD KYYKLHAGNG
     VYTFNNKQWI NKDIGQQLPE CEEDDSCPEP PKIENGYVEY LVRYQCKPYY TLRTCGDGVY
     TFNSKKQWIN KNIGQKLPEC EAVCGKPKHP VDQVQRIIGG SLDAKGSFPW QAKMVSQHNL
     ISGATLINER WLLTTAKNLY LGHSSDKKAK DITPTLRLYV GKNQLVEVEK VVLHPDHSKV
     DIGLIKLRQK VPVNDKVMPI CLPSKDYVKV GRVGYVSGWG RNENFNFTEH LKYVMLPVAD
     QDKCVKHYEG VDAPKNKTAK SPVGVQPILN ENTFCVGLSK YQDDTCYGDA GSAFVVHDKE
     DDTWYAAGIL SFDKSCAVAE YGVYVKVTSI LDWVRKTIAN N