CFAH_BOVIN
ID CFAH_BOVIN Reviewed; 1236 AA.
AC Q28085; Q3MHF3; Q9TQZ7;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Complement factor H;
DE AltName: Full=H factor 1;
DE Flags: Precursor;
GN Name=CFH; Synonyms=HF1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 92-761, AND PROTEIN SEQUENCE OF 19-34.
RC TISSUE=Liver;
RX PubMed=8615824; DOI=10.1042/bj3150523;
RA Soames C.J., Day A.J., Sim R.B.;
RT "Prediction from sequence comparisons of residues of factor H involved in
RT the interaction with complement component C3b.";
RL Biochem. J. 315:523-531(1996).
CC -!- FUNCTION: Glycoprotein that plays an essential role in maintaining a
CC well-balanced immune response by modulating complement activation. Acts
CC as a soluble inhibitor of complement, where its binding to self markers
CC such as glycan structures prevents complement activation and
CC amplification on cell surfaces. Accelerates the decay of the complement
CC alternative pathway (AP) C3 convertase C3bBb, thus preventing local
CC formation of more C3b, the central player of the complement
CC amplification loop. As a cofactor of the serine protease factor I, CFH
CC also regulates proteolytic degradation of already-deposited C3b. In
CC addition, mediates several cellular responses through interaction with
CC specific receptors. For example, interacts with CR3/ITGAM receptor and
CC thereby mediates the adhesion of human neutrophils to different
CC pathogens. In turn, these pathogens are phagocytosed and destroyed.
CC {ECO:0000250|UniProtKB:P08603}.
CC -!- SUBUNIT: Homodimer. Forms also homooligomers. Interacts with complement
CC protein C3b; this interaction inhibits complement activation. Interacts
CC with complement protein C3d. Interacts with CR3/ITGAM; this interaction
CC mediates adhesion of neutrophils to pathogens leading to pathogen
CC clearance. {ECO:0000250|UniProtKB:P08603}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P08603}.
CC -!- TISSUE SPECIFICITY: CFH is one of the most abundant complement
CC components in blood where the liver is the major source of CFH protein
CC in vivo. in addition, CFH is secreted by additional cell types
CC including monocytes, fibroblasts, or endothelial cells.
CC {ECO:0000250|UniProtKB:P08603}.
CC -!- DOMAIN: Sushi 1-3 domain represents the minimal unit capable of
CC cofactor activity. The property to discriminate self surfaces from non-
CC self surfaces depends on the C-terminal region made of Sushis 19-20.
CC {ECO:0000250|UniProtKB:P08603}.
CC -!- PTM: Sulfated on tyrosine residues. {ECO:0000250|UniProtKB:P08603}.
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; BC105258; AAI05259.1; -; mRNA.
DR EMBL; X98697; CAA67257.1; -; mRNA.
DR PIR; S65551; S65551.
DR RefSeq; NP_001029108.1; NM_001033936.1.
DR PDB; 6XZ6; X-ray; 2.70 A; B/D=264-323.
DR PDBsum; 6XZ6; -.
DR AlphaFoldDB; Q28085; -.
DR SMR; Q28085; -.
DR PaxDb; Q28085; -.
DR PRIDE; Q28085; -.
DR GeneID; 280816; -.
DR KEGG; bta:280816; -.
DR CTD; 3075; -.
DR eggNOG; ENOG502QVSB; Eukaryota.
DR InParanoid; Q28085; -.
DR OrthoDB; 296899at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0006956; P:complement activation; IBA:GO_Central.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR CDD; cd00033; CCP; 16.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 18.
DR SMART; SM00032; CCP; 19.
DR SUPFAM; SSF57535; SSF57535; 19.
DR PROSITE; PS50923; SUSHI; 16.
PE 1: Evidence at protein level;
KW 3D-structure; Complement alternate pathway; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Reference proteome; Repeat; Secreted; Signal; Sulfation; Sushi.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:8615824"
FT CHAIN 19..1236
FT /note="Complement factor H"
FT /id="PRO_0000048516"
FT DOMAIN 19..82
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 83..143
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 144..207
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 208..264
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 265..322
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 325..383
FT /note="Sushi 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 385..442
FT /note="Sushi 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 444..505
FT /note="Sushi 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 507..562
FT /note="Sushi 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 565..623
FT /note="Sushi 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 627..685
FT /note="Sushi 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 688..745
FT /note="Sushi 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 750..804
FT /note="Sushi 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 809..866
FT /note="Sushi 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 868..936
FT /note="Sushi 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 937..994
FT /note="Sushi 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 995..1053
FT /note="Sushi 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1054..1111
FT /note="Sushi 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1114..1172
FT /note="Sushi 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1173..1235
FT /note="Sushi 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT MOD_RES 168
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 170
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 465
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 473
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 575
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 579
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 585
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT CARBOHYD 775
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 21..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 52..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 85..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 114..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 146..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 178..205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 210..251
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 237..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 267..309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 294..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 325..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 355..383
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 387..429
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 414..440
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 446..492
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 475..503
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 507..551
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 534..562
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 567..609
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 595..621
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 629..672
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 658..683
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 690..732
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 718..743
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 752..791
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 780..802
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 811..853
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 839..864
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 870..923
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 909..934
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 939..981
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 967..992
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 997..1040
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1026..1051
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1056..1098
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1084..1109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1116..1159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1145..1170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1174..1225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 1208..1235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CONFLICT 92..93
FT /note="PF -> VS (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="F -> P (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="T -> N (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="T -> P (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="A -> Q (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="I -> V (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="T -> A (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 397..399
FT /note="TPY -> NQH (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="R -> H (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 661
FT /note="R -> K (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 677
FT /note="W -> S (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 691..694
FT /note="GNIP -> EIS (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 708
FT /note="Y -> I (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT CONFLICT 759..761
FT /note="PPE -> FLL (in Ref. 2; CAA67257)"
FT /evidence="ECO:0000305"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:6XZ6"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:6XZ6"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:6XZ6"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:6XZ6"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:6XZ6"
SQ SEQUENCE 1236 AA; 140374 MW; 5F8B1AE1825B020E CRC64;
MRFPAKIVWL VLWTVCVAED CKEPPPRKET EILSGSWTEQ TYQEGTQATY KCRPGYRTLG
SIVMMCRGGK WVSLHPSRIC RKKPCAHPGD TPFGSFHLAE GTQFEYGAKV VYTCDEGYQM
VGEMNFRECD TNGWTNDIPI CEVVKCLPVT EPENGKIFSD ALEPDQEYTY GQVVQFECNS
GYMLDGPKQI HCSAGGVWSA ETPKCVEIFC KTPVILNGQA VLPKATYKAN ERVQYRCAAG
FEYGQRGDTI CTKSGWTPAP TCIEITCDPP RIPNGVYRPE LSKYRGQDKI TYECKKGFFP
EIRGTDATCT RDGWVPVPRC AWKPCSYPVI KHGRLYYSYR GYFPARVNQQ FVYSCDHHFV
PPSQRSWDHL TCTAEGWSPE EPCLRQCIFN YLENGHTPYR EEKYLQGETV RVRCYEGYSL
QNDQNTMTCT ESGWSPPPRC IRVKTCSKSN IRIENGFLSE STFTYPLNKQ TEYKCKPGYV
TADGKTSGLI TCLKNGWSAQ PVCIKSCDRP VFEKARVKSD GTWFRLNDRL DYECVDGYEN
RDGRTTGSIV CGQDGWSDKA ACYERECSIP EMDPYLNAYP RKETYKVGDV LKFSCSQGRI
MVGADSVQCY HFGWSPKLPT CKVKKVKSCA LPPELPNGKR KEIHKEEYAH NEVVEYACNP
RFLMKGSHKI QCVDGEWTAL PVCIEEERTC GNIPDLDHGD VKPSVPPYHH GDSVEFSCRE
AFTMIGPRFI TCISGEWTQP PQCIATDELR KCKGSTLFPP EGRQAHKIEY DHNTNKSYQC
RGKSEHKHSI CINGEWDPKV DCNEEAKIQL CPPPPQVPNA CDMTTTVNYQ DGEKISILCK
ENYLIQDAEE IVCKDGRWQS IPRCIEKIGC SQPPQIDHGT ISSSSSAEER REIHEQRLYA
HGTKLSYTCE EGFEISENNV IICHMGKWSS PPQCVGLPCG LPPYVQNGVV SHKKDRYQYG
EEVTYDCDEG FGTDGPASIR CLGGEWSRPQ DCISTNCVNL PTFEDAVLTD REKDFYRSGE
QVAFKCLSYY QLDGSNTIQC IKSKWIGRPA CRDVSCGNPP QVENAIIHNQ KSKYQSEERA
RYECIGNYDL FGEMEVVCLN GTWTEPPQCK DSQGKCGPPP PIDNGDITSL LQSVYPPGMI
VEYRCQAYYE LRGNKNVVCR NGEWSQLPKC LEACVISEET MRKHHIQLRW KHDKKIYSKT
EDTIEFMCQH GYRQLTPKHT FRATCREGKV VYPRCG
