HPT_PIG
ID HPT_PIG Reviewed; 347 AA.
AC Q8SPS7;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 127.
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 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].
RC TISSUE=Liver;
RX PubMed=12139523; DOI=10.1046/j.1365-2052.2002.t01-10-00886.x;
RA Ponsuksili S., Schellander K., Wimmers K.;
RT "Isolation, polymorphism identification and linkage mapping of the porcine
RT haptoglobin locus.";
RL Anim. Genet. 33:324-325(2002).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH HEMOGLOBIN,
RP GLYCOSYLATION AT ASN-125; ASN-151; ASN-183 AND ASN-232, DISULFIDE BONDS,
RP SUBUNIT, AND INTERACTION WITH CD163.
RX PubMed=22922649; DOI=10.1038/nature11369;
RA Andersen C.B., Torvund-Jensen M., Nielsen M.J., de Oliveira C.L.,
RA Hersleth H.P., Andersen N.H., Pedersen J.S., Andersen G.R., Moestrup S.K.;
RT "Structure of the haptoglobin-haemoglobin complex.";
RL Nature 489:456-459(2012).
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
CC (PubMed:22922649). Interacts with CD163 (PubMed:22922649). Interacts
CC with ERGIC3 (By similarity). {ECO:0000250|UniProtKB:P00738,
CC ECO:0000269|PubMed:22922649}.
CC -!- SUBCELLULAR LOCATION: Secreted {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.
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; AF492467; AAM12554.1; -; mRNA.
DR RefSeq; NP_999165.1; NM_214000.2.
DR PDB; 4F4O; X-ray; 2.90 A; C/F/I/L=1-347.
DR PDBsum; 4F4O; -.
DR AlphaFoldDB; Q8SPS7; -.
DR SMR; Q8SPS7; -.
DR DIP; DIP-59911N; -.
DR IntAct; Q8SPS7; 1.
DR STRING; 9823.ENSSSCP00000002967; -.
DR MEROPS; S01.972; -.
DR iPTMnet; Q8SPS7; -.
DR PaxDb; Q8SPS7; -.
DR PeptideAtlas; Q8SPS7; -.
DR PRIDE; Q8SPS7; -.
DR Ensembl; ENSSSCT00005035691; ENSSSCP00005021746; ENSSSCG00005022282.
DR Ensembl; ENSSSCT00040059197; ENSSSCP00040024815; ENSSSCG00040043677.
DR Ensembl; ENSSSCT00045037657; ENSSSCP00045026174; ENSSSCG00045021880.
DR Ensembl; ENSSSCT00065044215; ENSSSCP00065018851; ENSSSCG00065032557.
DR Ensembl; ENSSSCT00070003326; ENSSSCP00070002755; ENSSSCG00070001777.
DR GeneID; 397061; -.
DR KEGG; ssc:397061; -.
DR CTD; 3240; -.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; Q8SPS7; -.
DR OrthoDB; 798576at2759; -.
DR TreeFam; TF334326; -.
DR Reactome; R-SSC-2168880; Scavenging of heme from plasma.
DR Reactome; R-SSC-6798695; Neutrophil degranulation.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 6.
DR Genevisible; Q8SPS7; SS.
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; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001137; Haptoglobin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS50923; SUSHI; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Antibiotic; Antimicrobial; Antioxidant;
KW Disulfide bond; Glycoprotein; Hemoglobin-binding; Immunity;
KW Reference proteome; Secreted; Serine protease homolog; Signal; Sushi.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..347
FT /note="Haptoglobin"
FT /id="PRO_0000028474"
FT CHAIN 19..101
FT /note="Haptoglobin alpha chain"
FT /id="PRO_0000028475"
FT CHAIN 103..347
FT /note="Haptoglobin beta chain"
FT /id="PRO_0000028476"
FT DOMAIN 31..88
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 103..345
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 259..264
FT /note="Interaction with CD163"
FT /evidence="ECO:0000269|PubMed:22922649"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22922649"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22922649"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22922649"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22922649"
FT DISULFID 33
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:22922649"
FT DISULFID 52..86
FT /evidence="ECO:0000269|PubMed:22922649"
FT DISULFID 90..207
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:22922649"
FT DISULFID 250..281
FT /evidence="ECO:0000269|PubMed:22922649"
FT DISULFID 292..322
FT /evidence="ECO:0000269|PubMed:22922649"
FT STRAND 42..52
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 219..224
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 247..254
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 309..318
FT /evidence="ECO:0007829|PDB:4F4O"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:4F4O"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:4F4O"
FT HELIX 333..344
FT /evidence="ECO:0007829|PDB:4F4O"
SQ SEQUENCE 347 AA; 38482 MW; 3341A3CA93FF9FEA CRC64;
MRALGAVVAL LLCGQLFAAE TGNEATDATD DSCPKPPEIP KGYVEHMVRY HCQTYYKLRT
AGDGVYTLDS NKQWTNKVTG EKLPECEAVC GKPKNPVDQV QRIMGGSLDA KGSFPWQAKM
ISHHNLTSGA TLINEQWLLT TAKNLRLGHK NDTKAKDIAP TLRLYVGKKQ EVEIEKVIFH
PDNSTVDIGL IKLKQKVPVN ERVMPICLPS KDYVNVGLVG YVSGWGRNAN LNFTEHLKYV
MLPVADQEKC VQYYEGSTVP EKKTPKSPVG VQPILNEHTF CAGLSKYQED TCYGDAGSAF
AVHDKDDDTW YAAGILSFDK SCRTAEYGVY VRVTSILDWI QTTIADN
