FHR2_HUMAN
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 03-AUG-2022, entry version 180.
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=4; 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}.
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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 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; P36980; -.
DR PeptideAtlas; P36980; -.
DR PRIDE; P36980; -.
DR ProteomicsDB; 55252; -. [P36980-1]
DR ProteomicsDB; 55253; -. [P36980-2]
DR Antibodypedia; 34882; 173 antibodies from 19 providers.
DR DNASU; 3080; -.
DR Ensembl; ENST00000367415.8; ENSP00000356385.4; ENSG00000080910.13. [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 CTD; 3080; -.
DR DisGeNET; 3080; -.
DR GeneCards; CFHR2; -.
DR HGNC; HGNC:4890; CFHR2.
DR HPA; ENSG00000080910; Tissue enriched (liver).
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; 845963at2759; -.
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; 7 hits in 984 CRISPR screens.
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 112 other tissues.
DR ExpressionAtlas; P36980; baseline and differential.
DR Genevisible; P36980; 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; 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 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; 4.
DR PROSITE; PS50923; SUSHI; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Reference proteome; Repeat; Secreted; Signal;
KW 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
