FHR3_HUMAN
ID FHR3_HUMAN Reviewed; 330 AA.
AC Q02985; B4DPR0; Q9UJ16;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Complement factor H-related protein 3;
DE Short=FHR-3;
DE AltName: Full=DOWN16;
DE AltName: Full=H factor-like protein 3;
DE Flags: Precursor;
GN Name=CFHR3; Synonyms=CFHL3, FHR3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8428964; DOI=10.1016/s0021-9258(18)53859-x;
RA Skerka C., Kuehn S., Guenther K., Lingelbach K., Zipfel P.F.;
RT "A novel short consensus repeat-containing molecule is related to human
RT complement factor H.";
RL J. Biol. Chem. 268:2904-2908(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10781834; DOI=10.1016/s0161-5890(00)00024-9;
RA Male D.A., Ormsby R.J., Ranganathan S., Giannakis E., Gordon D.L.;
RT "Complement factor H: sequence analysis of 221 kb of human genomic DNA
RT containing the entire fH, fHR-1 and fHR-3 genes.";
RL Mol. Immunol. 37:41-52(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 [6]
RP REVIEW.
RX PubMed=8172644; DOI=10.1016/0167-5699(94)90155-4;
RA Zipfel P.F., Skerka C.;
RT "Complement factor H and related proteins: an expanding family of
RT complement-regulatory proteins?";
RL Immunol. Today 15:121-126(1994).
RN [7]
RP INVOLVEMENT IN AHUS1.
RX PubMed=17367211; DOI=10.1371/journal.pgen.0030041;
RA Zipfel P.F., Edey M., Heinen S., Jozsi M., Richter H., Misselwitz J.,
RA Hoppe B., Routledge D., Strain L., Hughes A.E., Goodship J.A., Licht C.,
RA Goodship T.H., Skerka C.;
RT "Deletion of complement factor H-related genes CFHR1 and CFHR3 is
RT associated with atypical hemolytic uremic syndrome.";
RL PLoS Genet. 3:E41-E41(2007).
RN [8]
RP INVOLVEMENT IN AHUS1.
RX PubMed=18006700; DOI=10.1182/blood-2007-09-109876;
RA Jozsi M., Licht C., Strobel S., Zipfel S.L., Richter H., Heinen S.,
RA Zipfel P.F., Skerka C.;
RT "Factor H autoantibodies in atypical hemolytic uremic syndrome correlate
RT with CFHR1/CFHR3 deficiency.";
RL Blood 111:1512-1514(2008).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108; ASN-205 AND ASN-309.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Might be involved in complement regulation.
CC -!- INTERACTION:
CC Q02985; P02741: CRP; NbExp=2; IntAct=EBI-3941903, EBI-1395983;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q02985-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02985-2; Sequence=VSP_043041;
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- DISEASE: Hemolytic uremic syndrome atypical 1 (AHUS1) [MIM:235400]: An
CC atypical form of hemolytic uremic syndrome. It is a complex genetic
CC disease characterized by microangiopathic hemolytic anemia,
CC thrombocytopenia, renal failure and absence of episodes of
CC enterocolitis and diarrhea. In contrast to typical hemolytic uremic
CC syndrome, atypical forms have a poorer prognosis, with higher death
CC rates and frequent progression to end-stage renal disease.
CC {ECO:0000269|PubMed:17367211}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC A deletion encompassing CFHR1 and CFHR3 is associated with an increased
CC risk of atypical hemolytic uremic syndrome, likely due to a defective
CC regulation of complement activation (PubMed:17367211). Some patients
CC carrying the deletion have serum anti-CFH autoantibodies
CC (PubMed:18006700). {ECO:0000269|PubMed:17367211,
CC ECO:0000269|PubMed:18006700}.
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DR EMBL; X68679; CAA48639.1; -; mRNA.
DR EMBL; AK298459; BAG60672.1; -; mRNA.
DR EMBL; AL049741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058009; AAH58009.1; -; mRNA.
DR CCDS; CCDS30958.1; -. [Q02985-1]
DR CCDS; CCDS53453.1; -. [Q02985-2]
DR PIR; A45222; A45222.
DR RefSeq; NP_001160096.1; NM_001166624.1. [Q02985-2]
DR RefSeq; NP_066303.2; NM_021023.5. [Q02985-1]
DR AlphaFoldDB; Q02985; -.
DR SMR; Q02985; -.
DR BioGRID; 116086; 5.
DR IntAct; Q02985; 4.
DR STRING; 9606.ENSP00000356395; -.
DR GlyConnect; 1154; 9 N-Linked glycans (2 sites).
DR GlyGen; Q02985; 4 sites, 10 N-linked glycans (2 sites).
DR iPTMnet; Q02985; -.
DR PhosphoSitePlus; Q02985; -.
DR BioMuta; CFHR3; -.
DR DMDM; 13124752; -.
DR jPOST; Q02985; -.
DR MassIVE; Q02985; -.
DR PaxDb; Q02985; -.
DR PeptideAtlas; Q02985; -.
DR PRIDE; Q02985; -.
DR ProteomicsDB; 58149; -. [Q02985-1]
DR ProteomicsDB; 58150; -. [Q02985-2]
DR Antibodypedia; 47092; 75 antibodies from 18 providers.
DR DNASU; 10878; -.
DR Ensembl; ENST00000367425.9; ENSP00000356395.5; ENSG00000116785.15. [Q02985-1]
DR Ensembl; ENST00000391985.7; ENSP00000375845.3; ENSG00000116785.15. [Q02985-2]
DR GeneID; 10878; -.
DR KEGG; hsa:10878; -.
DR MANE-Select; ENST00000367425.9; ENSP00000356395.5; NM_021023.6; NP_066303.2.
DR UCSC; uc001gtl.4; human. [Q02985-1]
DR CTD; 10878; -.
DR DisGeNET; 10878; -.
DR GeneCards; CFHR3; -.
DR GeneReviews; CFHR3; -.
DR HGNC; HGNC:16980; CFHR3.
DR HPA; ENSG00000116785; Tissue enriched (liver).
DR MalaCards; CFHR3; -.
DR MIM; 235400; phenotype.
DR MIM; 605336; gene.
DR neXtProt; NX_Q02985; -.
DR OpenTargets; ENSG00000116785; -.
DR Orphanet; 93581; Atypical hemolytic uremic syndrome with anti-factor H antibodies.
DR Orphanet; 329931; C3 glomerulonephritis.
DR PharmGKB; PA134909646; -.
DR VEuPathDB; HostDB:ENSG00000116785; -.
DR eggNOG; ENOG502SM0B; Eukaryota.
DR GeneTree; ENSGT00940000163274; -.
DR HOGENOM; CLU_020107_3_0_1; -.
DR InParanoid; Q02985; -.
DR OMA; CIRVNST; -.
DR OrthoDB; 296899at2759; -.
DR PhylomeDB; Q02985; -.
DR TreeFam; TF326157; -.
DR PathwayCommons; Q02985; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; Q02985; -.
DR BioGRID-ORCS; 10878; 22 hits in 987 CRISPR screens.
DR ChiTaRS; CFHR3; human.
DR GeneWiki; CFHR3; -.
DR GenomeRNAi; 10878; -.
DR Pharos; Q02985; Tbio.
DR PRO; PR:Q02985; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q02985; protein.
DR Bgee; ENSG00000116785; Expressed in right lobe of liver and 88 other tissues.
DR ExpressionAtlas; Q02985; baseline and differential.
DR Genevisible; Q02985; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0001851; F:complement component C3b binding; IBA:GO_Central.
DR GO; GO:0006956; P:complement activation; IBA:GO_Central.
DR CDD; cd00033; CCP; 3.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 4.
DR SMART; SM00032; CCP; 4.
DR SUPFAM; SSF57535; SSF57535; 5.
DR PROSITE; PS50923; SUSHI; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein;
KW Hemolytic uremic syndrome; Reference proteome; Repeat; Secreted; Signal;
KW Sushi.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..330
FT /note="Complement factor H-related protein 3"
FT /id="PRO_0000005898"
FT DOMAIN 22..84
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 144..205
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 208..266
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 267..330
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 23..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 55..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 87..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 114..140
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 146..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 175..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 210..253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 239..264
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 268..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 302..329
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 144..204
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043041"
FT VARIANT 71
FT /note="H -> Y (in dbSNP:rs17575274)"
FT /id="VAR_048817"
FT CONFLICT 123
FT /note="A -> VR (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="K -> N (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="V -> D (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="Q -> R (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="P -> S (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="E -> A (in Ref. 1; CAA48639)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37323 MW; 67B64121D71CD65F CRC64;
MLLLINVILT LWVSCANGQV KPCDFPDIKH GGLFHENMRR PYFPVAVGKY YSYYCDEHFE
TPSGSYWDYI HCTQNGWSPA VPCLRKCYFP YLENGYNQNY GRKFVQGNST EVACHPGYGL
PKAQTTVTCT EKGWSPTPRC IRVRTCSKSD IEIENGFISE SSSIYILNKE IQYKCKPGYA
TADGNSSGSI TCLQNGWSAQ PICINSSEKC GPPPPISNGD TTSFLLKVYV PQSRVEYQCQ
PYYELQGSNY VTCSNGEWSE PPRCIHPCII TEENMNKNNI KLKGRSDRKY YAKTGDTIEF
MCKLGYNANT SILSFQAVCR EGIVEYPRCE
