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   24-JAN-2024, entry version 188.
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   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; 190 antibodies from 19 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   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   Gene3D; 2.10.70.10; Complement Module, domain 1; 4.
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.
DR   Genevisible; P36980; HS.
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
//