ID   HPTR_HUMAN              Reviewed;         348 AA.
AC   P00739; Q7LE20; Q92658; Q92659; Q9ULB0;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   03-NOV-2009, sequence version 2.
DT   13-FEB-2019, entry version 171.
DE   RecName: Full=Haptoglobin-related protein;
GN   Name=HPR;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX   PubMed=4018023;
RA   Bensi G., Raugei G., Klefenz H., Cortese R.;
RT   "Structure and expression of the human haptoglobin locus.";
RL   EMBO J. 4:119-126(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX   PubMed=2987228;
RA   Maeda N.;
RT   "Nucleotide sequence of the haptoglobin and haptoglobin-related gene
RT   pair. The haptoglobin-related gene contains a retrovirus-like
RT   element.";
RL   J. Biol. Chem. 260:6698-6709(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX   PubMed=1478675; DOI=10.1016/S0888-7543(05)80116-8;
RA   Erickson L.M., Kim H.S., Maeda N.;
RT   "Junctions between genes in the haptoglobin gene cluster of
RT   primates.";
RL   Genomics 14:948-958(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA   Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA   Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA   Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA   Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA   Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA   Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA   Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA   Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA   Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA   Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA   Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA   Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA   Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA   Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA   Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA   Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA   Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA   Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA   Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA   Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=8945641; DOI=10.1089/dna.1996.15.1001;
RA   Tabak S., Lev A., Valansi C., Shalitin C.;
RT   "Transcriptionally active haptoglobin-related (Hpr) gene in Hepatoma
RT   G2 and leukamia molt-4 cells.";
RL   DNA Cell Biol. 15:1001-1007(1996).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 3-348.
RX   PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA   Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA   Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA   Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA   Harris P.C., Venter J.C., Adams M.D.;
RT   "Genome duplications and other features in 12 Mb of DNA sequence from
RT   human chromosome 16p and 16q.";
RL   Genomics 60:295-308(1999).
RN   [7]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16778136; DOI=10.1182/blood-2006-05-022327;
RA   Nielsen M.J., Petersen S.V., Jacobsen C., Oxvig C., Rees D.,
RA   Moller H.J., Moestrup S.K.;
RT   "Haptoglobin-related protein is a high-affinity hemoglobin-binding
RT   plasma protein.";
RL   Blood 108:2846-2849(2006).
RN   [8]
RP   SIGNAL SEQUENCE.
RX   PubMed=25037218; DOI=10.1074/jbc.M114.567578;
RA   Harrington J.M., Nishanova T., Pena S.R., Hess M., Scelsi C.L.,
RA   Widener J., Hajduk S.L.;
RT   "A retained secretory signal peptide mediates high density lipoprotein
RT   (HDL) assembly and function of haptoglobin-related protein.";
RL   J. Biol. Chem. 289:24811-24820(2014).
CC   -!- FUNCTION: Primate-specific plasma protein associated with
CC       apolipoprotein L-I (apoL-I)-containing high-density lipoprotein
CC       (HDL). This HDL particle, termed trypanosome lytic factor-1 (TLF-
CC       1), mediates human innate immune protection against many species
CC       of African trypanosomes. Binds hemoglobin with high affinity and
CC       may contribute to the clearance of cell-free hemoglobin to allow
CC       hepatic recycling of heme iron. {ECO:0000269|PubMed:16778136}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16778136}.
CC       Note=Secreted into blood plasma and associated with subtypes of
CC       high density lipoproteins (HDL). {ECO:0000269|PubMed:16778136}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P00739-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P00739-2; Sequence=VSP_014529;
CC   -!- TISSUE SPECIFICITY: In adult liver the amount of HPR mRNA is at
CC       the lower limit of detection, therefore the extent of its
CC       expression is at most less than 1000-fold that of the HP1F gene.
CC       No HPR mRNA can be detected in fetal liver. Expressed in Hep-G2
CC       and leukemia MOLT-4 cell lines. {ECO:0000269|PubMed:8945641}.
CC   -!- DOMAIN: The uncleaved signal sequence interacts with HDL fluid
CC       lipids and mediates incorporation into the HDL particle.
CC       {ECO:0000269|PubMed:25037218}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC       {ECO:0000255|PROSITE-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; X01794; CAA25927.1; -; Genomic_DNA.
DR   EMBL; X01787; CAA25927.1; JOINED; Genomic_DNA.
DR   EMBL; X01788; CAA25927.1; JOINED; Genomic_DNA.
DR   EMBL; X01790; CAA25927.1; JOINED; Genomic_DNA.
DR   EMBL; X01792; CAA25927.1; JOINED; Genomic_DNA.
DR   EMBL; K03431; AAA88081.1; -; Genomic_DNA.
DR   EMBL; M10935; AAA88081.1; JOINED; Genomic_DNA.
DR   EMBL; M69197; AAA88079.1; -; Genomic_DNA.
DR   EMBL; X89214; CAA61501.1; -; mRNA.
DR   EMBL; AC009087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC004682; AAC27433.1; -; Genomic_DNA.
DR   CCDS; CCDS42193.1; -. [P00739-1]
DR   PIR; A00919; HPHUR.
DR   RefSeq; NP_066275.3; NM_020995.3. [P00739-1]
DR   UniGene; Hs.655361; -.
DR   ProteinModelPortal; P00739; -.
DR   SMR; P00739; -.
DR   BioGrid; 109487; 3.
DR   CORUM; P00739; -.
DR   STRING; 9606.ENSP00000441828; -.
DR   MEROPS; S01.974; -.
DR   GlyConnect; 1293; -.
DR   iPTMnet; P00739; -.
DR   PhosphoSitePlus; P00739; -.
DR   BioMuta; HPR; -.
DR   DMDM; 262527547; -.
DR   DOSAC-COBS-2DPAGE; P00739; -.
DR   jPOST; P00739; -.
DR   MaxQB; P00739; -.
DR   PaxDb; P00739; -.
DR   PeptideAtlas; P00739; -.
DR   PRIDE; P00739; -.
DR   ProteomicsDB; 51272; -.
DR   ProteomicsDB; 51273; -. [P00739-2]
DR   DNASU; 3250; -.
DR   Ensembl; ENST00000540303; ENSP00000441828; ENSG00000261701. [P00739-1]
DR   GeneID; 3250; -.
DR   KEGG; hsa:3250; -.
DR   UCSC; uc002fby.4; human. [P00739-1]
DR   CTD; 3250; -.
DR   DisGeNET; 3250; -.
DR   EuPathDB; HostDB:ENSG00000261701.6; -.
DR   GeneCards; HPR; -.
DR   HGNC; HGNC:5156; HPR.
DR   HPA; HPA047750; -.
DR   MIM; 140210; gene.
DR   neXtProt; NX_P00739; -.
DR   OpenTargets; ENSG00000261701; -.
DR   PharmGKB; PA29426; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   eggNOG; COG5640; LUCA.
DR   GeneTree; ENSGT00940000159903; -.
DR   HOGENOM; HOG000112945; -.
DR   HOVERGEN; HBG005989; -.
DR   InParanoid; P00739; -.
DR   KO; K14477; -.
DR   OMA; SYLPWIH; -.
DR   OrthoDB; 798576at2759; -.
DR   PhylomeDB; P00739; -.
DR   TreeFam; TF334326; -.
DR   Reactome; R-HSA-2168880; Scavenging of heme from plasma.
DR   ChiTaRS; HPR; human.
DR   GeneWiki; HPR_(gene); -.
DR   GenomeRNAi; 3250; -.
DR   PRO; PR:P00739; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   Bgee; ENSG00000261701; Expressed in 125 organ(s), highest expression level in liver.
DR   ExpressionAtlas; P00739; baseline and differential.
DR   Genevisible; P00739; HS.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL.
DR   GO; GO:0030492; F:hemoglobin binding; NAS:UniProtKB.
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:0010942; P:positive regulation of cell death; IBA:GO_Central.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; TAS:Reactome.
DR   GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   InterPro; IPR008292; Haptoglobin.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR001254; Trypsin_dom.
DR   PANTHER; PTHR44686; PTHR44686; 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; PS50240; TRYPSIN_DOM; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Complete proteome; Disulfide bond;
KW   Hemoglobin-binding; Polymorphism; Reference proteome; Secreted;
KW   Serine protease homolog; Signal; Sushi.
FT   CHAIN         1    348       Haptoglobin-related protein.
FT                                /FTId=PRO_0000028486.
FT   SIGNAL        1     18       Not cleaved.
FT                                {ECO:0000269|PubMed:25037218}.
FT   DOMAIN       34     87       Sushi.
FT   DOMAIN      104    346       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   DISULFID    251    282       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   DISULFID    293    323       {ECO:0000255|PROSITE-ProRule:PRU00274}.
FT   VAR_SEQ       1      1       M -> MHVCVCVCVCVYMPVCVDACMCCEAGRPAFRSFLFS
FT                                LC (in isoform 2).
FT                                {ECO:0000303|PubMed:8945641}.
FT                                /FTId=VSP_014529.
FT   VARIANT      27     27       T -> M (in dbSNP:rs11642506).
FT                                /FTId=VAR_057161.
FT   VARIANT      42     42       N -> H (in dbSNP:rs152832).
FT                                /FTId=VAR_057162.
FT   VARIANT      58     58       R -> K (in dbSNP:rs152833).
FT                                /FTId=VAR_057163.
FT   VARIANT     156    156       A -> V (in dbSNP:rs1049933).
FT                                /FTId=VAR_059789.
FT   VARIANT     203    203       R -> K (in dbSNP:rs2021171).
FT                                /FTId=VAR_057164.
FT   VARIANT     283    283       V -> A (in dbSNP:rs1065360).
FT                                /FTId=VAR_057165.
FT   VARIANT     339    339       H -> D (in dbSNP:rs12646).
FT                                {ECO:0000269|PubMed:1478675,
FT                                ECO:0000269|PubMed:2987228,
FT                                ECO:0000269|PubMed:4018023}.
FT                                /FTId=VAR_014571.
FT   CONFLICT    191    191       L -> I (in Ref. 1; CAA25927).
FT                                {ECO:0000305}.
SQ   SEQUENCE   348 AA;  39030 MW;  CF9EC3352B8182FA CRC64;
     MSDLGAVISL LLWGRQLFAL YSGNDVTDIS DDRFPKPPEI ANGYVEHLFR YQCKNYYRLR
     TEGDGVYTLN DKKQWINKAV GDKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK
     MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA PTLTLYVGKK QLVEIEKVVL
     HPNYHQVDIG LIKLKQKVLV NERVMPICLP SKNYAEVGRV GYVSGWGQSD NFKLTDHLKY
     VMLPVADQYD CITHYEGSTC PKWKAPKSPV GVQPILNEHT FCVGMSKYQE DTCYGDAGSA
     FAVHDLEEDT WYAAGILSFD KSCAVAEYGV YVKVTSIQHW VQKTIAEN
//