FHR5_HUMAN
ID FHR5_HUMAN Reviewed; 569 AA.
AC Q9BXR6; Q2NKK2;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Complement factor H-related protein 5;
DE Short=FHR-5;
DE Flags: Precursor;
GN Name=CFHR5; Synonyms=CFHL5, FHR5;
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], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=11058592; DOI=10.1074/jbc.m007495200;
RA McRae J.L., Cowan P.J., Power D.A., Mitchelhill K.I., Kemp B.E.,
RA Morgan B.P., Murphy B.F.;
RT "Human factor H-related protein 5 (FHR-5). A new complement-associated
RT protein.";
RL J. Biol. Chem. 276:6747-6754(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP INVOLVEMENT IN CFHR5D.
RX PubMed=20800271; DOI=10.1016/s0140-6736(10)60670-8;
RA Gale D.P., de Jorge E.G., Cook H.T., Martinez-Barricarte R.,
RA Hadjisavvas A., McLean A.G., Pusey C.D., Pierides A., Kyriacou K.,
RA Athanasiou Y., Voskarides K., Deltas C., Palmer A., Fremeaux-Bacchi V.,
RA de Cordoba S.R., Maxwell P.H., Pickering M.C.;
RT "Identification of a mutation in complement factor H-related protein 5 in
RT patients of Cypriot origin with glomerulonephritis.";
RL Lancet 376:794-801(2010).
RN [4]
RP INVOLVEMENT IN CFHR5D.
RX PubMed=22503529; DOI=10.1053/j.ajkd.2012.02.329;
RA Vernon K.A., Goicoechea de Jorge E., Hall A.E., Fremeaux-Bacchi V.,
RA Aitman T.J., Cook H.T., Hangartner R., Koziell A., Pickering M.C.;
RT "Acute presentation and persistent glomerulonephritis following
RT streptococcal infection in a patient with heterozygous complement factor H-
RT related protein 5 deficiency.";
RL Am. J. Kidney Dis. 60:121-125(2012).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23487775; DOI=10.1073/pnas.1219260110;
RA Goicoechea de Jorge E., Caesar J.J., Malik T.H., Patel M., Colledge M.,
RA Johnson S., Hakobyan S., Morgan B.P., Harris C.L., Pickering M.C.,
RA Lea S.M.;
RT "Dimerization of complement factor H-related proteins modulates complement
RT activation in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:4685-4690(2013).
RN [6]
RP VARIANT [LARGE SCALE ANALYSIS] SER-216.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [7]
RP VARIANTS ASN-277 AND LEU-379, AND POSSIBLE INVOLVEMENT IN ATYPICAL
RP HEMOLYTIC UREMIC SYNDROME.
RX PubMed=20513133; DOI=10.1002/humu.21256;
RA Maga T.K., Nishimura C.J., Weaver A.E., Frees K.L., Smith R.J.H.;
RT "Mutations in alternative pathway complement proteins in American patients
RT with atypical hemolytic uremic syndrome.";
RL Hum. Mutat. 31:E1445-E1460(2010).
RN [8]
RP VARIANTS ARG-105; THR-195 AND CYS-436, AND POSSIBLE INVOLVEMENT IN ATYPICAL
RP HEMOLYTIC UREMIC SYNDROME.
RX PubMed=22622361; DOI=10.1038/jhg.2012.57;
RA Westra D., Vernon K.A., Volokhina E.B., Pickering M.C., van de Kar N.C.,
RA van den Heuvel L.P.;
RT "Atypical hemolytic uremic syndrome and genetic aberrations in the
RT complement factor H-related 5 gene.";
RL J. Hum. Genet. 57:459-464(2012).
CC -!- FUNCTION: Involved in complement regulation. The dimerized forms have
CC avidity for tissue-bound complement fragments and efficiently compete
CC with the physiological complement inhibitor CFH.
CC {ECO:0000269|PubMed:23487775}.
CC -!- SUBUNIT: Head-to-tail homodimer and heterodimer with CFHR1 or CFHR2.
CC Binds C3b in vitro. {ECO:0000269|PubMed:23487775}.
CC -!- INTERACTION:
CC Q9BXR6; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-11579371, EBI-11343438;
CC Q9BXR6; Q03591: CFHR1; NbExp=3; IntAct=EBI-11579371, EBI-3935840;
CC Q9BXR6; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-11579371, EBI-1045797;
CC Q9BXR6; O43889-2: CREB3; NbExp=3; IntAct=EBI-11579371, EBI-625022;
CC Q9BXR6; Q96BA8: CREB3L1; NbExp=6; IntAct=EBI-11579371, EBI-6942903;
CC Q9BXR6; O00559: EBAG9; NbExp=3; IntAct=EBI-11579371, EBI-8787095;
CC Q9BXR6; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-11579371, EBI-781551;
CC Q9BXR6; O15552: FFAR2; NbExp=3; IntAct=EBI-11579371, EBI-2833872;
CC Q9BXR6; Q8TED1: GPX8; NbExp=3; IntAct=EBI-11579371, EBI-11721746;
CC Q9BXR6; Q9Y2U2-2: KCNK7; NbExp=3; IntAct=EBI-11579371, EBI-23647813;
CC Q9BXR6; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-11579371, EBI-373355;
CC Q9BXR6; Q96RD7: PANX1; NbExp=3; IntAct=EBI-11579371, EBI-7037612;
CC Q9BXR6; Q14973: SLC10A1; NbExp=3; IntAct=EBI-11579371, EBI-3923031;
CC Q9BXR6; Q05940: SLC18A2; NbExp=3; IntAct=EBI-11579371, EBI-18036244;
CC Q9BXR6; P02730: SLC4A1; NbExp=3; IntAct=EBI-11579371, EBI-7576138;
CC Q9BXR6; P27105: STOM; NbExp=3; IntAct=EBI-11579371, EBI-1211440;
CC Q9BXR6; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-11579371, EBI-8638294;
CC Q9BXR6; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-11579371, EBI-10982110;
CC Q9BXR6; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-11579371, EBI-12345267;
CC PRO_0000005900; P02741: CRP; NbExp=5; IntAct=EBI-22114654, EBI-1395983;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- DISEASE: Note=Defects in CFHR5 have been found in patients with
CC atypical hemolytic uremic syndrome and may contribute to the disease.
CC Atypical hemolytic uremic syndrome is a complex genetic disease
CC characterized by microangiopathic hemolytic anemia, thrombocytopenia,
CC renal failure and absence of episodes of enterocolitis and diarrhea. In
CC contrast to typical hemolytic uremic syndrome, atypical forms have a
CC poorer prognosis, with higher death rates and frequent progression to
CC end-stage renal disease. Susceptibility to the development of atypical
CC hemolytic uremic syndrome can be conferred by mutations in various
CC components of or regulatory factors in the complement cascade system.
CC Other genes may play a role in modifying the phenotype.
CC {ECO:0000269|PubMed:20513133, ECO:0000269|PubMed:22622361}.
CC -!- DISEASE: CFHR5 deficiency (CFHR5D) [MIM:614809]: A progressive disease
CC characterized by glomerulonephritis, hematuria, renal failure, end-
CC stage renal disease, subendothelial and mesangial glomerular C3
CC deposits, mesangial matrix expansion, increased glomerular cellularity,
CC and segmental capillary wall thickening. Hematuria may become apparent
CC after respiratory infections. {ECO:0000269|PubMed:20800271,
CC ECO:0000269|PubMed:22503529}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; AF295327; AAK15619.1; -; mRNA.
DR EMBL; BC111773; AAI11774.1; -; mRNA.
DR CCDS; CCDS1387.1; -.
DR RefSeq; NP_110414.1; NM_030787.3.
DR AlphaFoldDB; Q9BXR6; -.
DR SMR; Q9BXR6; -.
DR BioGRID; 123503; 21.
DR IntAct; Q9BXR6; 23.
DR STRING; 9606.ENSP00000256785; -.
DR GlyConnect; 1155; 3 N-Linked glycans (2 sites).
DR GlyGen; Q9BXR6; 3 sites, 3 N-linked glycans (2 sites), 2 O-linked glycans (1 site).
DR iPTMnet; Q9BXR6; -.
DR PhosphoSitePlus; Q9BXR6; -.
DR BioMuta; CFHR5; -.
DR DMDM; 23396597; -.
DR jPOST; Q9BXR6; -.
DR MassIVE; Q9BXR6; -.
DR PaxDb; Q9BXR6; -.
DR PeptideAtlas; Q9BXR6; -.
DR PRIDE; Q9BXR6; -.
DR ProteomicsDB; 79486; -.
DR Antibodypedia; 34475; 200 antibodies from 21 providers.
DR DNASU; 81494; -.
DR Ensembl; ENST00000256785.5; ENSP00000256785.4; ENSG00000134389.10.
DR GeneID; 81494; -.
DR KEGG; hsa:81494; -.
DR MANE-Select; ENST00000256785.5; ENSP00000256785.4; NM_030787.4; NP_110414.1.
DR UCSC; uc001gts.5; human.
DR CTD; 81494; -.
DR DisGeNET; 81494; -.
DR GeneCards; CFHR5; -.
DR GeneReviews; CFHR5; -.
DR HGNC; HGNC:24668; CFHR5.
DR HPA; ENSG00000134389; Tissue enriched (liver).
DR MalaCards; CFHR5; -.
DR MIM; 608593; gene.
DR MIM; 614809; phenotype.
DR neXtProt; NX_Q9BXR6; -.
DR OpenTargets; ENSG00000134389; -.
DR Orphanet; 93581; Atypical hemolytic uremic syndrome with anti-factor H antibodies.
DR Orphanet; 329931; C3 glomerulonephritis.
DR PharmGKB; PA134937417; -.
DR VEuPathDB; HostDB:ENSG00000134389; -.
DR eggNOG; ENOG502RTVY; Eukaryota.
DR GeneTree; ENSGT00940000154386; -.
DR HOGENOM; CLU_020107_6_0_1; -.
DR InParanoid; Q9BXR6; -.
DR OMA; CINGIWT; -.
DR OrthoDB; 296899at2759; -.
DR PhylomeDB; Q9BXR6; -.
DR TreeFam; TF326157; -.
DR PathwayCommons; Q9BXR6; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; Q9BXR6; -.
DR BioGRID-ORCS; 81494; 8 hits in 1059 CRISPR screens.
DR GeneWiki; CFHR5; -.
DR GenomeRNAi; 81494; -.
DR Pharos; Q9BXR6; Tbio.
DR PRO; PR:Q9BXR6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BXR6; protein.
DR Bgee; ENSG00000134389; Expressed in right lobe of liver and 12 other tissues.
DR Genevisible; Q9BXR6; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0001851; F:complement component C3b binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0006956; P:complement activation; IBA:GO_Central.
DR GO; GO:0006957; P:complement activation, alternative pathway; NAS:UniProtKB.
DR GO; GO:0051838; P:cytolysis by host of symbiont cells; IMP:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR CDD; cd00033; CCP; 6.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 7.
DR SMART; SM00032; CCP; 9.
DR SUPFAM; SSF57535; SSF57535; 8.
DR PROSITE; PS50923; SUSHI; 7.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disease variant; 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..569
FT /note="Complement factor H-related protein 5"
FT /id="PRO_0000005900"
FT DOMAIN 23..83
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 145..203
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 206..264
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 267..324
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 329..383
FT /note="Sushi 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 387..444
FT /note="Sushi 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 447..505
FT /note="Sushi 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 507..569
FT /note="Sushi 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 147..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 175..201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 208..251
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 237..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 269..311
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 297..322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 331..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 359..381
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 389..431
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 417..442
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 449..492
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 478..503
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 507..558
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 541..568
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VARIANT 46
FT /note="P -> S (in dbSNP:rs12097550)"
FT /id="VAR_048818"
FT VARIANT 105
FT /note="L -> R (found in patients with atypical hemolytic
FT uremic syndrome; dbSNP:rs318240754)"
FT /evidence="ECO:0000269|PubMed:22622361"
FT /id="VAR_069090"
FT VARIANT 195
FT /note="S -> T (found in patients with atypical hemolytic
FT uremic syndrome; dbSNP:rs318240755)"
FT /evidence="ECO:0000269|PubMed:22622361"
FT /id="VAR_069091"
FT VARIANT 216
FT /note="N -> S (in a breast cancer sample; somatic mutation;
FT dbSNP:rs147488267)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035827"
FT VARIANT 277
FT /note="Y -> N (found in a patient with atypical hemolytic
FT uremic syndrome; dbSNP:rs318240756)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063652"
FT VARIANT 356
FT /note="R -> H (in dbSNP:rs35662416)"
FT /id="VAR_048819"
FT VARIANT 379
FT /note="V -> L (found in patients with atypical hemolytic
FT uremic syndrome; dbSNP:rs111327589)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063653"
FT VARIANT 436
FT /note="W -> C (found in patients with atypical hemolytic
FT uremic syndrome; dbSNP:rs201265664)"
FT /evidence="ECO:0000269|PubMed:22622361"
FT /id="VAR_069092"
FT VARIANT 521
FT /note="L -> I (in dbSNP:rs35957013)"
FT /id="VAR_048820"
FT VARIANT 529
FT /note="L -> R (in dbSNP:rs16840956)"
FT /id="VAR_048821"
SQ SEQUENCE 569 AA; 64419 MW; 7FAAE31707B0C112 CRC64;
MLLLFSVILI SWVSTVGGEG TLCDFPKIHH GFLYDEEDYN PFSQVPTGEV FYYSCEYNFV
SPSKSFWTRI TCTEEGWSPT PKCLRMCSFP FVKNGHSESS GLIHLEGDTV QIICNTGYSL
QNNEKNISCV ERGWSTPPIC SFTKGECHVP ILEANVDAQP KKESYKVGDV LKFSCRKNLI
RVGSDSVQCY QFGWSPNFPT CKGQVRSCGP PPQLSNGEVK EIRKEEYGHN EVVEYDCNPN
FIINGPKKIQ CVDGEWTTLP TCVEQVKTCG YIPELEYGYV QPSVPPYQHG VSVEVNCRNE
YAMIGNNMIT CINGIWTELP MCVATHQLKR CKIAGVNIKT LLKLSGKEFN HNSRIRYRCS
DIFRYRHSVC INGKWNPEVD CTEKREQFCP PPPQIPNAQN MTTTVNYQDG EKVAVLCKEN
YLLPEAKEIV CKDGRWQSLP RCVESTAYCG PPPSINNGDT TSFPLSVYPP GSTVTYRCQS
FYKLQGSVTV TCRNKQWSEP PRCLDPCVVS EENMNKNNIQ LKWRNDGKLY AKTGDAVEFQ
CKFPHKAMIS SPPFRAICQE GKFEYPICE
