ID FHR2_HUMAN Reviewed; 270 AA. AC P36980; Q14310; Q5T9T1; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-NOV-2024, entry version 192. DE RecName: Full=Complement factor H-related protein 2; DE Short=FHR-2; DE AltName: Full=DDESK59; DE AltName: Full=H factor-like 3; DE AltName: Full=H factor-like protein 2; DE Flags: Precursor; GN Name=CFHR2; Synonyms=CFHL2, FHR2, HFL3; 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 LONG), PROTEIN SEQUENCE OF 19-37, AND RP GLYCOSYLATION AT ASN-126. RC TISSUE=Liver; RX PubMed=1533657; RA Skerka C., Timman C., Horstmann R.D., Zipfel P.E.; RT "Two additional human serum proteins structurally related to complement RT factor H. Evidence for a family of factor H-related genes."; RL J. Immunol. 148:3313-3318(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=7672821; DOI=10.1007/bf00176444; RA Skerka C., Moulds J.M., Taillon-Miller P., Hourcade D., Zipfel P.F.; RT "The human factor H-related gene 2 (FHR2): structure and linkage to the RT coagulation factor XIIIb gene."; RL Immunogenetics 42:268-274(1995). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 [5] 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 [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-126. 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). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 147-270, FUNCTION, SUBUNIT, AND RP DISULFIDE BONDS. 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). 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. Can associate with CC lipoproteins and may play a role in lipid metabolism. CC {ECO:0000269|PubMed:23487775}. CC -!- SUBUNIT: Head-to-tail homodimer and heterodimer with CFHR1 or CFHR5. CC {ECO:0000269|PubMed:23487775}. CC -!- INTERACTION: CC P36980; Q03591: CFHR1; NbExp=5; IntAct=EBI-21976709, EBI-3935840; CC P36980; P36980: CFHR2; NbExp=2; IntAct=EBI-21976709, EBI-21976709; CC PRO_0000005897; PRO_0000005913 [P01024]: C3; NbExp=2; IntAct=EBI-21988278, EBI-21988425; CC PRO_0000005897; PRO_0000005915 [P01024]: C3; NbExp=3; IntAct=EBI-21988278, EBI-6863106; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P36980-1; Sequence=Displayed; CC Name=Short; Synonyms=Truncated; CC IsoId=P36980-2; Sequence=VSP_001192; CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1533657, CC ECO:0000269|PubMed:19159218}. 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; X64877; CAA46096.1; -; mRNA. DR EMBL; X86564; CAA60375.1; -; Genomic_DNA. DR EMBL; X86565; CAA60375.1; JOINED; Genomic_DNA. DR EMBL; X86566; CAA60375.1; JOINED; Genomic_DNA. DR EMBL; X86567; CAA60375.1; JOINED; Genomic_DNA. DR EMBL; AL139418; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022283; AAH22283.1; -; mRNA. DR CCDS; CCDS30959.1; -. [P36980-1] DR PIR; I37278; I37278. DR RefSeq; NP_001299601.1; NM_001312672.1. DR RefSeq; NP_005657.1; NM_005666.3. [P36980-1] DR PDB; 3ZD1; X-ray; 2.00 A; A/B=147-270. DR PDB; 5EA0; X-ray; 2.00 A; P=150-162. DR PDBsum; 3ZD1; -. DR PDBsum; 5EA0; -. DR AlphaFoldDB; P36980; -. DR SMR; P36980; -. DR BioGRID; 109328; 6. DR IntAct; P36980; 3. DR STRING; 9606.ENSP00000356385; -. DR GlyConnect; 1153; 4 N-Linked glycans (1 site). DR GlyCosmos; P36980; 1 site, 5 glycans. DR GlyGen; P36980; 1 site, 5 N-linked glycans (1 site). DR iPTMnet; P36980; -. DR PhosphoSitePlus; P36980; -. DR BioMuta; CFHR2; -. DR DMDM; 543983; -. DR jPOST; P36980; -. DR MassIVE; P36980; -. DR PaxDb; 9606-ENSP00000356385; -. DR PeptideAtlas; P36980; -. DR ProteomicsDB; 55252; -. [P36980-1] DR ProteomicsDB; 55253; -. [P36980-2] DR Antibodypedia; 34882; 168 antibodies from 18 providers. DR DNASU; 3080; -. DR Ensembl; ENST00000367415.8; ENSP00000356385.4; ENSG00000080910.14. [P36980-1] DR Ensembl; ENST00000709546.1; ENSP00000517754.1; ENSG00000292003.1. [P36980-1] DR GeneID; 3080; -. DR KEGG; hsa:3080; -. DR MANE-Select; ENST00000367415.8; ENSP00000356385.4; NM_005666.4; NP_005657.1. DR UCSC; uc001gtq.2; human. [P36980-1] DR AGR; HGNC:4890; -. DR CTD; 3080; -. DR DisGeNET; 3080; -. DR GeneCards; CFHR2; -. DR HGNC; HGNC:4890; CFHR2. DR HPA; ENSG00000080910; Tissue enriched (liver). DR MalaCards; CFHR2; -. DR MIM; 600889; gene. DR neXtProt; NX_P36980; -. DR OpenTargets; ENSG00000080910; -. DR Orphanet; 329931; C3 glomerulonephritis. DR PharmGKB; PA29267; -. DR VEuPathDB; HostDB:ENSG00000080910; -. DR eggNOG; ENOG502RTVV; Eukaryota. DR GeneTree; ENSGT00940000163634; -. DR HOGENOM; CLU_020107_3_0_1; -. DR InParanoid; P36980; -. DR OMA; GKYFYYT; -. DR OrthoDB; 4851222at2759; -. DR PhylomeDB; P36980; -. DR TreeFam; TF326157; -. DR PathwayCommons; P36980; -. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P36980; -. DR BioGRID-ORCS; 3080; 9 hits in 1050 CRISPR screens. DR EvolutionaryTrace; P36980; -. DR GeneWiki; CFHR2; -. DR GenomeRNAi; 3080; -. DR Pharos; P36980; Tbio. DR PRO; PR:P36980; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P36980; protein. DR Bgee; ENSG00000080910; Expressed in right lobe of liver and 114 other cell types or tissues. DR ExpressionAtlas; P36980; baseline and differential. 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; IDA: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:0006956; P:complement activation; IBA:GO_Central. DR GO; GO:0051838; P:cytolysis by host of symbiont cells; IMP:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; IMP:UniProtKB. DR CDD; cd00033; CCP; 2. DR FunFam; 2.10.70.10:FF:000131; Complement factor H-related protein 1; 1. DR FunFam; 2.10.70.10:FF:000026; Complement inhibitory factor H; 1. DR FunFam; 2.10.70.10:FF:000054; Complement inhibitory factor H; 1. DR FunFam; 2.10.70.10:FF:000060; Complement inhibitory factor H; 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 4. DR InterPro; IPR051503; ComplSys_Reg/VirEntry_Med. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR PANTHER; PTHR45785:SF7; COMPLEMENT FACTOR H; 1. DR PANTHER; PTHR45785; COMPLEMENT FACTOR H-RELATED; 1. DR Pfam; PF00084; Sushi; 4. DR SMART; SM00032; CCP; 4. DR SUPFAM; SSF57535; Complement control module/SCR domain; 4. DR PROSITE; PS50923; SUSHI; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Proteomics identification; KW Reference proteome; Repeat; Secreted; Signal; Sushi. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:1533657" FT CHAIN 19..270 FT /note="Complement factor H-related protein 2" FT /id="PRO_0000005897" 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 147..205 FT /note="Sushi 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 206..268 FT /note="Sushi 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT CARBOHYD 126 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1533657, FT 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 149..192 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:23487775" FT DISULFID 178..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:23487775" FT DISULFID 207..257 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:23487775" FT DISULFID 241..267 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:23487775" FT VAR_SEQ 144..171 FT /note="ISAEKCGPPPPIDNGDITSFLLSVYAPG -> S (in isoform FT Short)" FT /evidence="ECO:0000305" FT /id="VSP_001192" FT CONFLICT 85 FT /note="R -> K (in Ref. 2; CAA60375)" FT /evidence="ECO:0000305" FT STRAND 158..162 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 173..178 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 183..186 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 188..193 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:3ZD1" FT HELIX 211..216 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 219..222 FT /evidence="ECO:0007829|PDB:3ZD1" FT TURN 224..226 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 229..231 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 236..241 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:3ZD1" FT STRAND 253..256 FT /evidence="ECO:0007829|PDB:3ZD1" SQ SEQUENCE 270 AA; 30651 MW; E1B2E9F139B217A8 CRC64; MWLLVSVILI SRISSVGGEA MFCDFPKINH GILYDEEKYK PFSQVPTGEV FYYSCEYNFV SPSKSFWTRI TCAEEGWSPT PKCLRLCFFP FVENGHSESS GQTHLEGDTV QIICNTGYRL QNNENNISCV ERGWSTPPKC RSTISAEKCG PPPPIDNGDI TSFLLSVYAP GSSVEYQCQN LYQLEGNNQI TCRNGQWSEP PKCLDPCVIS QEIMEKYNIK LKWTNQQKLY SRTGDIVEFV CKSGYHPTKS HSFRAMCQNG KLVYPSCEEK //