ID HPT_CEREL Reviewed; 400 AA. AC B6D985; DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 1. DT 30-NOV-2016, entry version 33. DE RecName: Full=Haptoglobin; DE AltName: Full=Zonulin; DE Contains: DE RecName: Full=Haptoglobin alpha chain; DE Contains: DE RecName: Full=Haptoglobin beta chain; DE Flags: Precursor; GN Name=HP; OS Cervus elaphus (Red deer). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia; OC Pecora; Cervidae; Cervinae; Cervus. OX NCBI_TaxID=9860; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Rahman M.M.D., Lecchi C., Miranda-Ribera A., Ceciliani F., RA Sartorelli P.; RT "The acute phase proteins in Cervus elaphus."; RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: As a result of hemolysis, hemoglobin is found to CC accumulate in the kidney and is secreted in the urine. Haptoglobin CC captures, and combines with free plasma hemoglobin to allow CC hepatic recycling of heme iron and to prevent kidney damage. CC Haptoglobin also acts as an antioxidant, has antibacterial CC activity and plays a role in modulating many aspects of the acute CC phase response. Hemoglobin/haptoglobin complexes are rapidely CC cleared by the macrophage CD163 scavenger receptor expressed on CC the surface of liver Kupfer cells through an endocytic lysosomal CC degradation pathway (By similarity). {ECO:0000250}. CC -!- FUNCTION: Uncleaved haptoglogin, also known as zonulin, plays a CC role in intestinal permeability, allowing intercellular tight CC junction disassembly, and controlling the equilibrium between CC tolerance and immunity to non-self antigens. {ECO:0000250}. CC -!- SUBUNIT: Tetramer of two alpha and two beta chains; disufide- CC linked. The Hemoglobin/haptoglobin complex is composed of a CC haptoglobin dimer bound to two hemoglobin alpha-beta dimers. CC Interacts with CD163 (By similarity). {ECO:0000250}. 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 CC homodimeric interface. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- SIMILARITY: Contains 1 peptidase S1 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- SIMILARITY: Contains 2 Sushi (CCP/SCR) domains. CC {ECO:0000255|PROSITE-ProRule:PRU00302}. CC -!- CAUTION: Although homologous to serine proteases, it has lost all CC essential catalytic residues and has no enzymatic activity. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; EU884574; ACH73014.1; -; mRNA. DR PRIDE; B6D985; -. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW. DR GO; GO:0030492; F:hemoglobin binding; IEA:UniProtKB-KW. 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 CDD; cd00033; CCP; 1. DR CDD; cd00190; Tryp_SPc; 1. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR InterPro; IPR001254; Trypsin_dom. 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; Repeat; Secreted; KW Serine protease homolog; Signal; Sushi. FT SIGNAL 1 18 {ECO:0000250}. FT CHAIN 19 400 Haptoglobin. FT /FTId=PRO_0000367495. FT CHAIN 19 154 Haptoglobin alpha chain. {ECO:0000250}. FT /FTId=PRO_0000367496. FT CHAIN 156 400 Haptoglobin beta chain. {ECO:0000250}. FT /FTId=PRO_0000367497. FT DOMAIN 28 83 Sushi 1. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 84 141 Sushi 2. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 156 398 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT REGION 312 317 Interaction with CD163. {ECO:0000250}. FT CARBOHYD 285 285 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 309 309 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 315 315 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 30 30 Interchain. {ECO:0000250}. FT DISULFID 49 81 {ECO:0000250}. FT DISULFID 86 86 Interchain. {ECO:0000250}. FT DISULFID 105 139 {ECO:0000250}. FT DISULFID 143 260 Interchain (between alpha and beta FT chains). {ECO:0000255|PROSITE- FT ProRule:PRU00274, ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DISULFID 303 334 {ECO:0000250}. FT DISULFID 345 375 {ECO:0000250}. SQ SEQUENCE 400 AA; 44690 MW; 6E8281618AB2E448 CRC64; MSALPVVVTL LLCGQLLAVE ISSEATADSC PKAPEIANSH VEYSVRYQCD KYYKLRAGDG VYTFNNKQWI NKDIGQQLPE CEDASCPEPP KIENGYVEHS IRFQCKTYYK LRSAGDGVYT FNSKKQWINK NVGQQLPECE AVCGKPKHPV DQVQRIIGGS LDAKGSFPWQ AKMVSHHNLI SGATLINERW LLTTAKNLYL GHTSDKKAKD IAPTLRLYVG KNQPVEVEKV VLHPDRSKVD IGLIKLRQKV PVNEKVMPIC LPSKDYVAVG RVGYVSGWGR NANFNFTEHL KYIMLPVADQ DKCVEHYENS TVPENKTDKS PVGVQPILNK NTFCVGLSKY QEDTCYGDAG SAFVVHDQED DTWYAAGILS FDKSCAVAEY GVYVKVTSIL DWVRKTIADN //