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   27-MAR-2024, entry version 158.
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; 2.
DR   DIP; DIP-47327N; -.
DR   IntAct; Q8N8U9; 1.
DR   MINT; Q8N8U9; -.
DR   STRING; 9606.ENSP00000497748; -.
DR   GlyCosmos; Q8N8U9; 5 sites, No reported glycans.
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; 9606-ENSP00000297161; -.
DR   PeptideAtlas; Q8N8U9; -.
DR   ProteomicsDB; 72462; -.
DR   Antibodypedia; 12854; 201 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   AGR; HGNC:24154; -.
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; 2906064at2759; -.
DR   PhylomeDB; Q8N8U9; -.
DR   TreeFam; TF343473; -.
DR   PathwayCommons; Q8N8U9; -.
DR   SignaLink; Q8N8U9; -.
DR   BioGRID-ORCS; 168667; 7 hits in 1138 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 105 other cell types or tissues.
DR   ExpressionAtlas; Q8N8U9; baseline and differential.
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: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; IEA:Ensembl.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR   GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; 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:0032880; P:regulation of protein localization; IEA:Ensembl.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR   GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR   CDD; cd19941; TIL; 1.
DR   Gene3D; 6.20.200.20; -; 3.
DR   Gene3D; 2.10.70.10; Complement Module, domain 1; 2.
DR   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR036084; Ser_inhib-like_sf.
DR   InterPro; IPR002919; TIL_dom.
DR   InterPro; IPR014853; VWF/SSPO/ZAN-like_Cys-rich_dom.
DR   InterPro; IPR001007; VWF_dom.
DR   InterPro; IPR001846; VWF_type-D.
DR   PANTHER; PTHR46698; CROSSVEINLESS 2; 1.
DR   PANTHER; PTHR46698:SF4; CROSSVEINLESS 2; 1.
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; SSF57603; FnI-like domain; 5.
DR   SUPFAM; SSF57567; Serine protease inhibitors; 1.
DR   PROSITE; PS01208; VWFC_1; 3.
DR   PROSITE; PS50184; VWFC_2; 2.
DR   PROSITE; PS51233; VWFD; 1.
DR   Genevisible; Q8N8U9; HS.
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
//