FHR4_HUMAN
ID FHR4_HUMAN Reviewed; 578 AA.
AC Q92496; A8K9N7; B1ALQ9; C9J7J7; Q5DVJ7; Q9UJY6;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Complement factor H-related protein 4;
DE Short=FHR-4;
DE Flags: Precursor;
GN Name=CFHR4; Synonyms=CFHL4, FHR4;
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 3), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=9038172; DOI=10.1074/jbc.272.9.5627;
RA Skerka C., Hellwage J., Weber W., Tilkorn A., Buck F., Marti T., Kampen E.,
RA Beisiegel U., Zipfel P.F.;
RT "The human factor H-related protein 4 (FHR-4). A novel short consensus
RT repeat-containing protein is associated with human triglyceride-rich
RT lipoproteins.";
RL J. Biol. Chem. 272:5627-5634(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUSHI DOMAINS, ALTERNATIVE
RP SPLICING, AND VARIANT ASP-125.
RC TISSUE=Liver;
RX PubMed=15562282; DOI=10.1038/sj.ejhg.5201324;
RA Jozsi M., Richter H., Loschmann I., Skerka C., Buck F., Beisiegel U.,
RA Erdei A., Zipfel P.F.;
RT "FHR-4A: a new factor H-related protein is encoded by the human FHR-4
RT gene.";
RL Eur. J. Hum. Genet. 13:321-329(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT SER-210.
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
RA Male D.A., Ormsby R.J., Giannakis E., Gordon D.L.;
RT "Promoter region of complement factor H-related 4 (fHR-4) gene.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP CHARACTERIZATION.
RX PubMed=9476126; DOI=10.1016/s0162-3109(97)00075-1;
RA Hellwage J., Skerka C., Zipfel P.F.;
RT "Biochemical and functional characterization of the factor-H-related
RT protein 4 (FHR-4).";
RL Immunopharmacology 38:149-157(1997).
CC -!- FUNCTION: Involved in complement regulation. Can associate with
CC lipoproteins and may play a role in lipid metabolism.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC Q92496-1; P01024: C3; NbExp=5; IntAct=EBI-22033617, EBI-905851;
CC Q92496-1; P00751: CFB; NbExp=2; IntAct=EBI-22033617, EBI-1223668;
CC Q92496-1; P27918: CFP; NbExp=2; IntAct=EBI-22033617, EBI-9038570;
CC Q92496-1; P02741: CRP; NbExp=23; IntAct=EBI-22033617, EBI-1395983;
CC Q92496-3; PRO_0000005911 [P01024]: C3; NbExp=3; IntAct=EBI-22033638, EBI-12735725;
CC Q92496-3; P00751: CFB; NbExp=2; IntAct=EBI-22033638, EBI-1223668;
CC Q92496-3; P27918: CFP; NbExp=2; IntAct=EBI-22033638, EBI-9038570;
CC Q92496-3; P02741: CRP; NbExp=5; IntAct=EBI-22033638, EBI-1395983;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=FHR-4A;
CC IsoId=Q92496-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92496-2; Sequence=VSP_046418;
CC Name=3; Synonyms=FHR-4B;
CC IsoId=Q92496-3; Sequence=VSP_053528;
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- PTM: Glycosylated.
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; X98337; CAA66980.1; -; mRNA.
DR EMBL; AJ640130; CAG26679.2; -; mRNA.
DR EMBL; AK292752; BAF85441.1; -; mRNA.
DR EMBL; AL139418; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX248415; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91266.1; -; Genomic_DNA.
DR EMBL; BC074957; AAH74957.1; -; mRNA.
DR EMBL; AF190816; AAF05951.1; -; Genomic_DNA.
DR CCDS; CCDS41451.1; -. [Q92496-3]
DR CCDS; CCDS55671.1; -. [Q92496-2]
DR RefSeq; NP_001188479.1; NM_001201550.2. [Q92496-1]
DR RefSeq; NP_001188480.1; NM_001201551.1. [Q92496-2]
DR RefSeq; NP_006675.2; NM_006684.4. [Q92496-3]
DR AlphaFoldDB; Q92496; -.
DR SMR; Q92496; -.
DR BioGRID; 116085; 3.
DR IntAct; Q92496; 11.
DR MINT; Q92496; -.
DR STRING; 9606.ENSP00000356386; -.
DR GlyConnect; 1928; 8 N-Linked glycans (1 site).
DR GlyGen; Q92496; 7 sites, 8 N-linked glycans (1 site).
DR iPTMnet; Q92496; -.
DR PhosphoSitePlus; Q92496; -.
DR BioMuta; CFHR4; -.
DR DMDM; 212276433; -.
DR MassIVE; Q92496; -.
DR PaxDb; Q92496; -.
DR PeptideAtlas; Q92496; -.
DR PRIDE; Q92496; -.
DR ProteomicsDB; 75268; -. [Q92496-1]
DR ProteomicsDB; 8914; -.
DR Antibodypedia; 55923; 80 antibodies from 11 providers.
DR DNASU; 10877; -.
DR Ensembl; ENST00000251424.8; ENSP00000251424.4; ENSG00000134365.14. [Q92496-3]
DR Ensembl; ENST00000367416.6; ENSP00000356386.2; ENSG00000134365.14. [Q92496-2]
DR Ensembl; ENST00000608469.6; ENSP00000477162.2; ENSG00000134365.14. [Q92496-1]
DR GeneID; 10877; -.
DR KEGG; hsa:10877; -.
DR MANE-Select; ENST00000608469.6; ENSP00000477162.2; NM_001201550.3; NP_001188479.1.
DR UCSC; uc001gto.4; human. [Q92496-1]
DR CTD; 10877; -.
DR DisGeNET; 10877; -.
DR GeneCards; CFHR4; -.
DR GeneReviews; CFHR4; -.
DR HGNC; HGNC:16979; CFHR4.
DR HPA; ENSG00000134365; Tissue enriched (liver).
DR MalaCards; CFHR4; -.
DR MIM; 605337; gene.
DR neXtProt; NX_Q92496; -.
DR OpenTargets; ENSG00000134365; -.
DR Orphanet; 93581; Atypical hemolytic uremic syndrome with anti-factor H antibodies.
DR PharmGKB; PA134960382; -.
DR VEuPathDB; HostDB:ENSG00000134365; -.
DR eggNOG; ENOG502SM0B; Eukaryota.
DR GeneTree; ENSGT00940000154386; -.
DR HOGENOM; CLU_020107_6_0_1; -.
DR InParanoid; Q92496; -.
DR OMA; PRCRLMK; -.
DR OrthoDB; 296899at2759; -.
DR TreeFam; TF326157; -.
DR PathwayCommons; Q92496; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; Q92496; -.
DR BioGRID-ORCS; 10877; 14 hits in 1064 CRISPR screens.
DR GeneWiki; CFHR4; -.
DR GenomeRNAi; 10877; -.
DR Pharos; Q92496; Tbio.
DR PRO; PR:Q92496; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q92496; protein.
DR Bgee; ENSG00000134365; Expressed in right lobe of liver and 59 other tissues.
DR ExpressionAtlas; Q92496; baseline and differential.
DR Genevisible; Q92496; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0005319; F:lipid transporter activity; TAS:ProtInc.
DR GO; GO:0006956; P:complement activation; IBA:GO_Central.
DR CDD; cd00033; CCP; 4.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 8.
DR SMART; SM00032; CCP; 8.
DR SUPFAM; SSF57535; SSF57535; 8.
DR PROSITE; PS50923; SUSHI; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Reference proteome; Repeat; Secreted; Signal; Sushi.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..578
FT /note="Complement factor H-related protein 4"
FT /id="PRO_5000072607"
FT DOMAIN 20..85
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 86..147
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 148..206
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 209..267
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 268..332
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 333..394
FT /note="Sushi 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 395..453
FT /note="Sushi 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 456..514
FT /note="Sushi 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 515..578
FT /note="Sushi 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 88..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 117..145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 149..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 176..204
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 211..254
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 240..265
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 271..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 303..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 335..381
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 364..392
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 396..440
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 423..451
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 458..501
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 487..512
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 516..567
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 550..577
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 20
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046418"
FT VAR_SEQ 80..326
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9038172"
FT /id="VSP_053528"
FT VARIANT 125
FT /note="E -> D (in dbSNP:rs10801578)"
FT /evidence="ECO:0000269|PubMed:15562282"
FT /id="VAR_070195"
FT VARIANT 210
FT /note="N -> S (in dbSNP:rs7417769)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_070196"
FT VARIANT 553
FT /note="G -> E (in dbSNP:rs10494745)"
FT /id="VAR_047151"
FT CONFLICT 79
FT /note="S -> L (in Ref. 1; CAA66980 and 6; AAH74957)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 65351 MW; CB80749443932B3F CRC64;
MLLLINVILT LWVSCANGQE VKPCDFPEIQ HGGLYYKSLR RLYFPAAAGQ SYSYYCDQNF
VTPSGSYWDY IHCTQDGWSP TVPCLRTCSK SDVEIENGFI SESSSIYILN EETQYNCKPG
YATAEGNSSG SITCLQNGWS TQPICIKFCD MPVFENSRAK SNGMWFKLHD TLDYECYDGY
ESSYGNTTDS IVCGEDGWSH LPTCYNSSEN CGPPPPISNG DTTSFPQKVY LPWSRVEYQC
QSYYELQGSK YVTCSNGDWS EPPRCISMKP CEFPEIQHGH LYYENTRRPY FPVATGQSYS
YYCDQNFVTP SGSYWDYIHC TQDGWLPTVP CLRTCSKSDI EIENGFISES SSIYILNKEI
QYKCKPGYAT ADGNSSGSIT CLQNGWSAQP ICIKFCDMPV FENSRAKSNG MRFKLHDTLD
YECYDGYEIS YGNTTGSIVC GEDGWSHFPT CYNSSEKCGP PPPISNGDTT SFLLKVYVPQ
SRVEYQCQSY YELQGSNYVT CSNGEWSEPP RCIHPCIITE ENMNKNNIQL KGKSDIKYYA
KTGDTIEFMC KLGYNANTSV LSFQAVCREG IVEYPRCE
