MFAP4_HUMAN
ID MFAP4_HUMAN Reviewed; 255 AA.
AC P55083; A8KAJ1; A8MVM2; B4E317; Q6P680;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Microfibril-associated glycoprotein 4;
DE Flags: Precursor;
GN Name=MFAP4;
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 1).
RC TISSUE=Placenta;
RX PubMed=7633408; DOI=10.1093/hmg/4.4.589;
RA Zhao Z., Lee C.-C., Jiralerspong S., Juyal R.C., Lu F., Baldini A.,
RA Greenberg F., Caskey C.T., Patel P.I.;
RT "The gene for a human microfibril-associated glycoprotein is commonly
RT deleted in Smith-Magenis syndrome patients.";
RL Hum. Mol. Genet. 4:589-597(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-173.
RC TISSUE=PNS;
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 [6]
RP PROTEIN SEQUENCE OF 22-36.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-137.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-87 AND ASN-137.
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 [9]
RP FUNCTION, SUBUNIT, INTERACTION WITH FBN1; FBN2; COL1A1; ELN AND LOX,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-203 AND PHE-241.
RX PubMed=26601954; DOI=10.1074/jbc.m115.681775;
RA Pilecki B., Holm A.T., Schlosser A., Moeller J.B., Wohl A.P., Zuk A.V.,
RA Heumueller S.E., Wallis R., Moestrup S.K., Sengle G., Holmskov U.,
RA Sorensen G.L.;
RT "Characterization of microfibrillar-associated protein 4 (MFAP4) as a
RT tropoelastin- and fibrillin-binding protein involved in elastic fiber
RT formation.";
RL J. Biol. Chem. 291:1103-1114(2016).
CC -!- FUNCTION: Could be involved in calcium-dependent cell adhesion or
CC intercellular interactions. May contribute to the elastic fiber
CC assembly and/or maintenance (PubMed:26601954).
CC {ECO:0000269|PubMed:26601954}.
CC -!- SUBUNIT: Homodimer. Can also form higher oligomers. Interacts with
CC FBN1, FBN2 and LOX. Interacts with COL1A1 in a Ca (2+)-dependent
CC manner. Interacts with ELN in a Ca (2+)-dependent manner; this
CC interaction promotes ELN self-assembly (PubMed:26601954).
CC {ECO:0000269|PubMed:26601954}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:26601954}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55083-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55083-2; Sequence=VSP_045831;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB00968.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG65329.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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; L38486; AAB00968.1; ALT_INIT; mRNA.
DR EMBL; AK293056; BAF85745.1; -; mRNA.
DR EMBL; AK304528; BAG65329.1; ALT_TERM; mRNA.
DR EMBL; AC124066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471212; EAW50888.1; -; Genomic_DNA.
DR EMBL; CH471212; EAW50889.1; -; Genomic_DNA.
DR EMBL; BC062415; AAH62415.1; -; mRNA.
DR CCDS; CCDS11208.1; -. [P55083-1]
DR CCDS; CCDS56023.1; -. [P55083-2]
DR RefSeq; NP_001185624.1; NM_001198695.1. [P55083-2]
DR RefSeq; NP_002395.1; NM_002404.2. [P55083-1]
DR AlphaFoldDB; P55083; -.
DR SMR; P55083; -.
DR BioGRID; 110397; 162.
DR IntAct; P55083; 6.
DR STRING; 9606.ENSP00000378957; -.
DR GlyConnect; 1512; 17 N-Linked glycans (2 sites).
DR GlyGen; P55083; 3 sites, 16 N-linked glycans (2 sites).
DR iPTMnet; P55083; -.
DR PhosphoSitePlus; P55083; -.
DR BioMuta; MFAP4; -.
DR DMDM; 2506403; -.
DR CPTAC; CPTAC-2226; -.
DR jPOST; P55083; -.
DR MassIVE; P55083; -.
DR PaxDb; P55083; -.
DR PeptideAtlas; P55083; -.
DR PRIDE; P55083; -.
DR ProteomicsDB; 2188; -.
DR ProteomicsDB; 56785; -. [P55083-1]
DR Antibodypedia; 25925; 254 antibodies from 28 providers.
DR DNASU; 4239; -.
DR Ensembl; ENST00000299610.5; ENSP00000299610.5; ENSG00000166482.12. [P55083-1]
DR Ensembl; ENST00000395592.6; ENSP00000378957.2; ENSG00000166482.12. [P55083-2]
DR GeneID; 4239; -.
DR KEGG; hsa:4239; -.
DR MANE-Select; ENST00000299610.5; ENSP00000299610.5; NM_002404.3; NP_002395.1.
DR UCSC; uc002gvs.4; human. [P55083-1]
DR CTD; 4239; -.
DR DisGeNET; 4239; -.
DR GeneCards; MFAP4; -.
DR HGNC; HGNC:7035; MFAP4.
DR HPA; ENSG00000166482; Low tissue specificity.
DR MIM; 600596; gene.
DR neXtProt; NX_P55083; -.
DR OpenTargets; ENSG00000166482; -.
DR PharmGKB; PA30771; -.
DR VEuPathDB; HostDB:ENSG00000166482; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000154615; -.
DR HOGENOM; CLU_038628_6_0_1; -.
DR InParanoid; P55083; -.
DR OMA; TAYAKYT; -.
DR PhylomeDB; P55083; -.
DR TreeFam; TF336658; -.
DR PathwayCommons; P55083; -.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR SignaLink; P55083; -.
DR BioGRID-ORCS; 4239; 11 hits in 1067 CRISPR screens.
DR ChiTaRS; MFAP4; human.
DR GenomeRNAi; 4239; -.
DR Pharos; P55083; Tbio.
DR PRO; PR:P55083; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P55083; protein.
DR Bgee; ENSG00000166482; Expressed in right coronary artery and 155 other tissues.
DR ExpressionAtlas; P55083; baseline and differential.
DR Genevisible; P55083; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0071953; C:elastic fiber; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0001527; C:microfibril; IDA:BHF-UCL.
DR GO; GO:0003823; F:antigen binding; IBA:GO_Central.
DR GO; GO:0097367; F:carbohydrate derivative binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0071493; P:cellular response to UV-B; IDA:BHF-UCL.
DR GO; GO:0001867; P:complement activation, lectin pathway; IBA:GO_Central.
DR GO; GO:0048251; P:elastic fiber assembly; IDA:BHF-UCL.
DR GO; GO:0010712; P:regulation of collagen metabolic process; IDA:BHF-UCL.
DR GO; GO:0097435; P:supramolecular fiber organization; IDA:BHF-UCL.
DR GO; GO:0009650; P:UV protection; IDA:BHF-UCL.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Direct protein sequencing;
KW Extracellular matrix; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..255
FT /note="Microfibril-associated glycoprotein 4"
FT /id="PRO_0000009134"
FT DOMAIN 32..255
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT MOTIF 26..28
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT VAR_SEQ 1..2
FT /note="MK -> MGELSPLQRPLATEGTMKAQGVLLKL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045831"
FT VARIANT 173
FT /note="A -> V (in dbSNP:rs17855749)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_069073"
FT MUTAGEN 203
FT /note="S->A: No effect on its interaction with COL1A1 and
FT ELN."
FT /evidence="ECO:0000269|PubMed:26601954"
FT MUTAGEN 203
FT /note="S->Y: Moderate reduction in its interaction with
FT COL1A1. Significant reduction in its interaction with ELN."
FT /evidence="ECO:0000269|PubMed:26601954"
FT MUTAGEN 241
FT /note="F->A: Significant reduction in its interaction with
FT COL1A1 and ELN."
FT /evidence="ECO:0000269|PubMed:26601954"
FT MUTAGEN 241
FT /note="F->W: Significant reduction in its interaction with
FT COL1A1 and ELN."
FT /evidence="ECO:0000269|PubMed:26601954"
FT CONFLICT 69
FT /note="F -> S (in Ref. 2; BAG65329)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 255 AA; 28648 MW; B8F0B47AC694435E CRC64;
MKALLALPLL LLLSTPPCAP QVSGIRGDAL ERFCLQQPLD CDDIYAQGYQ SDGVYLIYPS
GPSVPVPVFC DMTTEGGKWT VFQKRFNGSV SFFRGWNDYK LGFGRADGEY WLGLQNMHLL
TLKQKYELRV DLEDFENNTA YAKYADFSIS PNAVSAEEDG YTLFVAGFED GGAGDSLSYH
SGQKFSTFDR DQDLFVQNCA ALSSGAFWFR SCHFANLNGF YLGGSHLSYA NGINWAQWKG
FYYSLKRTEM KIRRA
