BMPER_HUMAN
ID BMPER_HUMAN Reviewed; 685 AA.
AC Q8N8U9; A8K1P8; Q8TF36;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=BMP-binding endothelial regulator protein;
DE AltName: Full=Bone morphogenetic protein-binding endothelial cell precursor-derived regulator;
DE AltName: Full=Protein crossveinless-2;
DE Short=hCV2;
DE Flags: Precursor;
GN Name=BMPER; Synonyms=KIAA1965;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14766204; DOI=10.1016/j.bbrc.2004.01.048;
RA Binnerts M.E., Wen X., Cante-Barrett K., Bright J., Chen H.-T., Asundi V.,
RA Sattari P., Tang T., Boyle B., Funk W., Rupp F.;
RT "Human Crossveinless-2 is a novel inhibitor of bone morphogenetic
RT proteins.";
RL Biochem. Biophys. Res. Commun. 315:272-280(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 MRNA].
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 121-685.
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [5]
RP VARIANT DSD LEU-370.
RX PubMed=20869035; DOI=10.1016/j.ajhg.2010.08.015;
RA Funari V.A., Krakow D., Nevarez L., Chen Z., Funari T.L., Vatanavicharn N.,
RA Wilcox W.R., Rimoin D.L., Nelson S.F., Cohn D.H.;
RT "BMPER mutation in diaphanospondylodysostosis identified by ancestral
RT autozygosity mapping and targeted high-throughput sequencing.";
RL Am. J. Hum. Genet. 87:532-537(2010).
CC -!- FUNCTION: Inhibitor of bone morphogenetic protein (BMP) function, it
CC may regulate BMP responsiveness of osteoblasts and chondrocytes.
CC {ECO:0000269|PubMed:14766204}.
CC -!- SUBUNIT: Interacts with BMP4. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14766204}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, and brain and also in
CC primary chondrocytes. {ECO:0000269|PubMed:14766204}.
CC -!- DISEASE: Diaphanospondylodysostosis (DSD) [MIM:608022]: A rare,
CC recessively inherited, perinatal lethal skeletal disorder. The primary
CC skeletal characteristics of the phenotype include a small chest,
CC abnormal vertebral segmentation, and posterior rib gaps containing
CC incompletely differentiated mesenchymal tissue. Consistent craniofacial
CC features include ocular hypertelorism, epicanthal folds, a depressed
CC nasal bridge with a short nose, and low-set ears. The most commonly
CC described extraskeletal finding is nephroblastomatosis with cystic
CC kidneys, but other visceral findings have been described in some cases.
CC {ECO:0000269|PubMed:20869035}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AY324650; AAP89012.1; -; mRNA.
DR EMBL; AK096150; BAC04712.1; -; mRNA.
DR EMBL; AK289963; BAF82652.1; -; mRNA.
DR EMBL; BC060868; AAH60868.1; -; mRNA.
DR EMBL; AB075845; BAB85551.1; -; mRNA.
DR CCDS; CCDS5442.1; -.
DR RefSeq; NP_597725.1; NM_133468.4.
DR AlphaFoldDB; Q8N8U9; -.
DR SMR; Q8N8U9; -.
DR BioGRID; 127971; 1.
DR DIP; DIP-47327N; -.
DR IntAct; Q8N8U9; 1.
DR MINT; Q8N8U9; -.
DR STRING; 9606.ENSP00000297161; -.
DR GlyGen; Q8N8U9; 5 sites.
DR iPTMnet; Q8N8U9; -.
DR PhosphoSitePlus; Q8N8U9; -.
DR BioMuta; BMPER; -.
DR DMDM; 116241270; -.
DR jPOST; Q8N8U9; -.
DR MassIVE; Q8N8U9; -.
DR PaxDb; Q8N8U9; -.
DR PeptideAtlas; Q8N8U9; -.
DR PRIDE; Q8N8U9; -.
DR ProteomicsDB; 72462; -.
DR Antibodypedia; 12854; 179 antibodies from 24 providers.
DR DNASU; 168667; -.
DR Ensembl; ENST00000297161.6; ENSP00000297161.2; ENSG00000164619.10.
DR Ensembl; ENST00000649409.2; ENSP00000497748.1; ENSG00000164619.10.
DR GeneID; 168667; -.
DR KEGG; hsa:168667; -.
DR MANE-Select; ENST00000649409.2; ENSP00000497748.1; NM_001365308.1; NP_001352237.1.
DR UCSC; uc011kap.2; human.
DR CTD; 168667; -.
DR DisGeNET; 168667; -.
DR GeneCards; BMPER; -.
DR HGNC; HGNC:24154; BMPER.
DR HPA; ENSG00000164619; Low tissue specificity.
DR MalaCards; BMPER; -.
DR MIM; 608022; phenotype.
DR MIM; 608699; gene.
DR neXtProt; NX_Q8N8U9; -.
DR OpenTargets; ENSG00000164619; -.
DR Orphanet; 66637; Diaphanospondylodysostosis.
DR Orphanet; 85200; Ischiovertebral syndrome.
DR PharmGKB; PA142672557; -.
DR VEuPathDB; HostDB:ENSG00000164619; -.
DR eggNOG; KOG1216; Eukaryota.
DR GeneTree; ENSGT00940000156485; -.
DR HOGENOM; CLU_018024_2_0_1; -.
DR InParanoid; Q8N8U9; -.
DR OMA; WHFANSW; -.
DR OrthoDB; 1104860at2759; -.
DR PhylomeDB; Q8N8U9; -.
DR TreeFam; TF343473; -.
DR PathwayCommons; Q8N8U9; -.
DR SignaLink; Q8N8U9; -.
DR BioGRID-ORCS; 168667; 7 hits in 1062 CRISPR screens.
DR ChiTaRS; BMPER; human.
DR GeneWiki; BMPER; -.
DR GenomeRNAi; 168667; -.
DR Pharos; Q8N8U9; Tbio.
DR PRO; PR:Q8N8U9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8N8U9; protein.
DR Bgee; ENSG00000164619; Expressed in upper lobe of left lung and 104 other tissues.
DR ExpressionAtlas; Q8N8U9; baseline and differential.
DR Genevisible; Q8N8U9; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; IEA:Ensembl.
DR GO; GO:0042118; P:endothelial cell activation; IDA:BHF-UCL.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; TAS:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IGI:BHF-UCL.
DR GO; GO:0045765; P:regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0010594; P:regulation of endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0060393; P:regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR InterPro; IPR036084; Ser_inhib-like_sf.
DR InterPro; IPR002919; TIL_dom.
DR InterPro; IPR014853; Unchr_dom_Cys-rich.
DR InterPro; IPR001007; VWF_dom.
DR InterPro; IPR001846; VWF_type-D.
DR Pfam; PF08742; C8; 1.
DR Pfam; PF01826; TIL; 1.
DR Pfam; PF00093; VWC; 2.
DR Pfam; PF00094; VWD; 1.
DR SMART; SM00832; C8; 1.
DR SMART; SM00214; VWC; 5.
DR SMART; SM00216; VWD; 1.
DR SUPFAM; SSF57567; SSF57567; 1.
DR PROSITE; PS01208; VWFC_1; 3.
DR PROSITE; PS50184; VWFC_2; 2.
DR PROSITE; PS51233; VWFD; 1.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Glycoprotein; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..685
FT /note="BMP-binding endothelial regulator protein"
FT /id="PRO_0000020820"
FT DOMAIN 50..105
FT /note="VWFC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 108..163
FT /note="VWFC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 164..225
FT /note="VWFC 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 238..289
FT /note="VWFC 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 299..358
FT /note="VWFC 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 362..535
FT /note="VWFD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DOMAIN 629..682
FT /note="TIL"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 364..497
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DISULFID 386..534
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT VARIANT 370
FT /note="P -> L (in DSD; dbSNP:rs387906993)"
FT /evidence="ECO:0000269|PubMed:20869035"
FT /id="VAR_065823"
FT VARIANT 555
FT /note="R -> W (in dbSNP:rs10249320)"
FT /id="VAR_028166"
FT CONFLICT 79
FT /note="C -> R (in Ref. 2; BAC04712 and 3; AAH60868)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 685 AA; 75997 MW; A5048AADEBF04AB0 CRC64;
MLWFSGVGAL AERYCRRSPG ITCCVLLLLN CSGVPMSLAS SFLTGSVAKC ENEGEVLQIP
FITDNPCIMC VCLNKEVTCK REKCPVLSRD CALAIKQRGA CCEQCKGCTY EGNTYNSSFK
WQSPAEPCVL RQCQEGVVTE SGVRCVVHCK NPLEHLGMCC PTCPGCVFEG VQYQEGEEFQ
PEGSKCTKCS CTGGRTQCVR EVCPILSCPQ HLSHIPPGQC CPKCLGQRKV FDLPFGSCLF
RSDVYDNGSS FLYDNCTACT CRDSTVVCKR KCSHPGGCDQ GQEGCCEECL LRVPPEDIKV
CKFGNKIFQD GEMWSSINCT ICACVKGRTE CRNKQCIPIS SCPQGKILNR KGCCPICTEK
PGVCTVFGDP HYNTFDGRTF NFQGTCQYVL TKDCSSPASP FQVLVKNDAR RTRSFSWTKS
VELVLGESRV SLQQHLTVRW NGSRIALPCR APHFHIDLDG YLLKVTTKAG LEISWDGDSF
VEVMAAPHLK GKLCGLCGNY NGHKRDDLIG GDGNFKFDVD DFAESWRVES NEFCNRPQRK
PVPELCQGTV KVKLRAHREC QKLKSWEFQT CHSTVDYATF YRSCVTDMCE CPVHKNCYCE
SFLAYTRACQ REGIKVHWEP QQNCAATQCK HGAVYDTCGP GCIKTCDNWN EIGPCNKPCV
AGCHCPANLV LHKGRCIKPV LCPQR
