HPT_RAT
ID HPT_RAT Reviewed; 347 AA.
AC P06866; Q5EBB4; Q7TP23;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Haptoglobin;
DE AltName: Full=Liver regeneration-related protein LRRG173;
DE Contains:
DE RecName: Full=Haptoglobin alpha chain;
DE Contains:
DE RecName: Full=Haptoglobin beta chain;
DE Flags: Precursor;
GN Name=Hp; ORFNames=Ba1-647;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2320005; DOI=10.1128/mcb.10.4.1573-1583.1990;
RA Marinkovic S., Baumann H.;
RT "Structure, hormonal regulation, and identification of the interleukin-
RT 6- and dexamethasone-responsive element of the rat haptoglobin gene.";
RL Mol. Cell. Biol. 10:1573-1583(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Xu C.S., Li W.Q., Li Y.C., Ma H., Wang L., Wang S.F., Han H.P., Wang G.P.,
RA Chai L.Q., Yuan J.Y., Yang K.J., Yan H.M., Chang C.F., Zhao L.F., Shi J.B.,
RA Rahman S., Wang Q.N., Zhang J.B.;
RT "Liver regeneration after PH.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-347 (ISOFORM 1).
RX PubMed=6204979; DOI=10.1016/s0021-9258(17)47287-5;
RA Goldstein L.A., Heath E.C.;
RT "Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha
RT beta-subunit junction region of prohaptoglobin.";
RL J. Biol. Chem. 259:9212-9217(1984).
RN [5]
RP PROTEIN SEQUENCE OF 19-43 AND 103-127.
RX PubMed=6863267; DOI=10.1016/s0021-9258(18)32258-0;
RA Hanley J.M., Haugen T.H., Heath E.C.;
RT "Biosynthesis and processing of rat haptoglobin.";
RL J. Biol. Chem. 258:7858-7869(1983).
RN [6]
RP PROTEIN SEQUENCE OF 103-142.
RX PubMed=975782; DOI=10.1016/0305-0491(76)90320-5;
RA Kurosky A., Kim H.H., Touchstone B.;
RT "Comparative sequence analysis of the N-terminal region of rat, rabbit, and
RT dog haptoglobin beta-chains.";
RL Comp. Biochem. Physiol. 55B:453-459(1976).
RN [7]
RP PROTEIN SEQUENCE OF 321-332, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (DEC-2006) to UniProtKB.
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.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06866-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06866-2; Sequence=VSP_022571;
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; M34232; AAA41348.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M34230; AAA41348.1; JOINED; Genomic_DNA.
DR EMBL; M34231; AAA41348.1; JOINED; Genomic_DNA.
DR EMBL; AY325231; AAP92632.1; -; mRNA.
DR EMBL; BC089816; AAH89816.1; -; mRNA.
DR EMBL; K01933; AAA41349.1; -; mRNA.
DR PIR; A34784; HPRT.
DR RefSeq; NP_036714.2; NM_012582.2. [P06866-1]
DR AlphaFoldDB; P06866; -.
DR SMR; P06866; -.
DR IntAct; P06866; 6.
DR STRING; 10116.ENSRNOP00000049003; -.
DR MEROPS; S01.972; -.
DR GlyGen; P06866; 2 sites.
DR iPTMnet; P06866; -.
DR PhosphoSitePlus; P06866; -.
DR jPOST; P06866; -.
DR PRIDE; P06866; -.
DR Ensembl; ENSRNOT00000118054; ENSRNOP00000085960; ENSRNOG00000014964. [P06866-1]
DR GeneID; 24464; -.
DR KEGG; rno:24464; -.
DR UCSC; RGD:2825; rat. [P06866-1]
DR CTD; 3240; -.
DR RGD; 2825; Hp.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159903; -.
DR HOGENOM; CLU_006842_0_0_1; -.
DR InParanoid; P06866; -.
DR OrthoDB; 798576at2759; -.
DR PhylomeDB; P06866; -.
DR TreeFam; TF334326; -.
DR Reactome; R-RNO-2168880; Scavenging of heme from plasma.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P06866; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Genevisible; P06866; RN.
DR GO; GO:0072562; C:blood microparticle; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0031838; C:haptoglobin-hemoglobin complex; ISO:RGD.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0030492; F:hemoglobin binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
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:0001889; P:liver development; IDA:RGD.
DR GO; GO:2000296; P:negative regulation of hydrogen peroxide catabolic process; ISO:RGD.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0033590; P:response to cobalamin; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0010165; P:response to X-ray; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
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 Acute phase; Alternative splicing; Antibiotic; Antimicrobial; Antioxidant;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemoglobin-binding; Immunity; Reference proteome; Secreted;
KW Serine protease homolog; Signal; Sushi.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..347
FT /note="Haptoglobin"
FT /id="PRO_0000028483"
FT CHAIN 19..101
FT /note="Haptoglobin alpha chain"
FT /id="PRO_0000028484"
FT CHAIN 103..347
FT /note="Haptoglobin beta chain"
FT /id="PRO_0000028485"
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:0000250"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 52..86
FT /evidence="ECO:0000250"
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 DISULFID 250..281
FT /evidence="ECO:0000250"
FT DISULFID 292..322
FT /evidence="ECO:0000250"
FT VAR_SEQ 89
FT /note="V -> GPTLSKNEMYTAFRSVIDFQRIVECVCVMTITYVL (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_022571"
FT CONFLICT 25
FT /note="A -> D (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 267
FT /note="S -> T (in Ref. 1; AAA41348 and 4; AAA41349)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="R -> K (in Ref. 1; AAA41348)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 347 AA; 38563 MW; 9DF52389AFD755D6 CRC64;
MRALGAVVTL LLWGQLFAVE LGNDATDIED DSCPKPPEIA NGYVEHLVRY RCRQFYKLQT
EGDGIYTLNS EKQWVNPAAG DKLPKCEAVC GKPKHPVDQV QRIIGGSMDA KGSFPWQAKM
ISRHGLTTGA TLISDQWLLT TAQNLFLNHS ENATAKDIAP TLTLYVGKNQ LVEIEKVVLH
PERSVVDIGL IKLKQKVLVT EKVMPICLPS KDYVAPGRMG YVSGWGRNVN FRFTERLKYV
MLPVADQEKC ELHYEKSTVP EKKGAVSPVG VQPILNKHTF CAGLTKYEED TCYGDAGSAF
AVHDTEEDTW YAAGILSFDK SCAVAEYGVY VRATDLKDWV QETMAKN
