KCP_MOUSE
ID KCP_MOUSE Reviewed; 1550 AA.
AC Q3U492; E9QJU0; Q56NI8;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Kielin/chordin-like protein;
DE AltName: Full=Cysteine-rich BMP regulator 2;
DE AltName: Full=Cysteine-rich motor neuron 2 protein;
DE Short=CRIM-2;
DE AltName: Full=Kielin/chordin-like protein 1;
DE Short=KCP-1;
DE Flags: Precursor;
GN Name=Kcp; Synonyms=Crim2, Kcp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH BMP7,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND
RP INDUCTION BY RENAL STRESSES.
RC STRAIN=FVB/N;
RX PubMed=15793581; DOI=10.1038/nm1217;
RA Lin J., Patel S.R., Cheng X., Cho E.A., Levitan I., Ullenbruch M.,
RA Phan S.H., Park J.M., Dressler G.R.;
RT "Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates
RT renal fibrotic disease.";
RL Nat. Med. 11:387-393(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP INTERACTION WITH ACTIVIN A AND TGFB1.
RX PubMed=16738323; DOI=10.1128/mcb.02127-05;
RA Lin J., Patel S.R., Wang M., Dressler G.R.;
RT "The cysteine-rich domain protein KCP is a suppressor of transforming
RT growth factor beta/activin signaling in renal epithelia.";
RL Mol. Cell. Biol. 26:4577-4585(2006).
CC -!- FUNCTION: Enhances bone morphogenetic protein (BMP) signaling in a
CC paracrine manner. In contrast, it inhibits both the activin-A and
CC TGFB1-mediated signaling pathways. {ECO:0000269|PubMed:15793581}.
CC -!- SUBUNIT: Interacts with BMP7 and, by doing so, enhances binding to the
CC type I receptors that contains cytoplasmic serine-/threonine protein
CC kinase domains. Also able to interact with activin-A and TGFB1.
CC {ECO:0000269|PubMed:15793581, ECO:0000269|PubMed:16738323}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15793581}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3U492-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3U492-2; Sequence=VSP_031232, VSP_031233;
CC -!- TISSUE SPECIFICITY: Weakly expressed in embryonic kidney and brain. Not
CC expressed in adult tissues and several cell lines.
CC {ECO:0000269|PubMed:15793581}.
CC -!- DEVELOPMENTAL STAGE: Prominently expressed in two areas, the limb buds
CC and the developing kidney, with diffuse staining in the central nervous
CC system. At 9.5 dpc the limb bud mesenchyme is positive. Expression in
CC the kidney region could be detected as early as 9 dpc in the
CC intermediate mesoderm. By 10 dpc, the mesonephric tubules and nephric
CC ducts are clearly positive. At later stages, high levels are localized
CC to the developing tubules. At 18.5 dpc, it is localized to more mature
CC renal tubules located in the developing cortex with little expression
CC detected in the nephrogenic zone. {ECO:0000269|PubMed:15793581}.
CC -!- INDUCTION: By renal stresses. {ECO:0000269|PubMed:15793581}.
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DR EMBL; AY884211; AAX77677.1; -; mRNA.
DR EMBL; AK154369; BAE32541.1; -; mRNA.
DR EMBL; AC079276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS57415.1; -. [Q3U492-1]
DR RefSeq; NP_001025156.3; NM_001029985.4. [Q3U492-1]
DR AlphaFoldDB; Q3U492; -.
DR SMR; Q3U492; -.
DR BioGRID; 237147; 1.
DR STRING; 10090.ENSMUSP00000099135; -.
DR GlyGen; Q3U492; 1 site.
DR iPTMnet; Q3U492; -.
DR PhosphoSitePlus; Q3U492; -.
DR MaxQB; Q3U492; -.
DR PaxDb; Q3U492; -.
DR PRIDE; Q3U492; -.
DR ProteomicsDB; 263507; -. [Q3U492-1]
DR ProteomicsDB; 263508; -. [Q3U492-2]
DR Antibodypedia; 73205; 25 antibodies from 13 providers.
DR DNASU; 333088; -.
DR Ensembl; ENSMUST00000078112; ENSMUSP00000077251; ENSMUSG00000059022. [Q3U492-2]
DR Ensembl; ENSMUST00000101614; ENSMUSP00000099135; ENSMUSG00000059022. [Q3U492-1]
DR GeneID; 333088; -.
DR KEGG; mmu:333088; -.
DR UCSC; uc009bdt.2; mouse. [Q3U492-1]
DR CTD; 375616; -.
DR MGI; MGI:2141640; Kcp.
DR VEuPathDB; HostDB:ENSMUSG00000059022; -.
DR eggNOG; KOG1216; Eukaryota.
DR GeneTree; ENSGT00940000160243; -.
DR HOGENOM; CLU_000367_0_0_1; -.
DR InParanoid; Q3U492; -.
DR OMA; CQECVVE; -.
DR OrthoDB; 1104860at2759; -.
DR PhylomeDB; Q3U492; -.
DR TreeFam; TF106451; -.
DR BioGRID-ORCS; 333088; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Kcp; mouse.
DR PRO; PR:Q3U492; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3U492; protein.
DR Bgee; ENSMUSG00000059022; Expressed in internal carotid artery and 150 other tissues.
DR ExpressionAtlas; Q3U492; baseline and differential.
DR Genevisible; Q3U492; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR GO; GO:0070700; F:BMP receptor binding; IBA:GO_Central.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:MGI.
DR InterPro; IPR036084; Ser_inhib-like_sf.
DR InterPro; IPR014853; Unchr_dom_Cys-rich.
DR InterPro; IPR001007; VWF_dom.
DR InterPro; IPR001846; VWF_type-D.
DR Pfam; PF00093; VWC; 9.
DR Pfam; PF00094; VWD; 1.
DR SMART; SM00832; C8; 1.
DR SMART; SM00214; VWC; 17.
DR SMART; SM00215; VWC_out; 10.
DR SMART; SM00216; VWD; 1.
DR SUPFAM; SSF57567; SSF57567; 1.
DR PROSITE; PS01208; VWFC_1; 13.
DR PROSITE; PS50184; VWFC_2; 14.
DR PROSITE; PS51233; VWFD; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Disulfide bond; Glycoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1550
FT /note="Kielin/chordin-like protein"
FT /id="PRO_0000318587"
FT DOMAIN 134..191
FT /note="VWFC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 192..251
FT /note="VWFC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 253..312
FT /note="VWFC 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 313..370
FT /note="VWFC 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 371..425
FT /note="VWFC 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 426..485
FT /note="VWFC 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 486..544
FT /note="VWFC 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 545..602
FT /note="VWFC 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 603..661
FT /note="VWFC 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 665..724
FT /note="VWFC 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 725..781
FT /note="VWFC 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 782..840
FT /note="VWFC 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 841..902
FT /note="VWFC 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 903..958
FT /note="VWFC 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 959..1016
FT /note="VWFC 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1017..1084
FT /note="VWFC 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1085..1144
FT /note="VWFC 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1148..1208
FT /note="VWFC 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1212..1388
FT /note="VWFD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DOMAIN 1489..1542
FT /note="TIL"
FT REGION 31..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 60..92
FT /evidence="ECO:0000255"
FT COMPBIAS 34..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 1214..1346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DISULFID 1236..1387
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT VAR_SEQ 1250..1255
FT /note="SVHVTN -> RWTSTQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15793581"
FT /id="VSP_031232"
FT VAR_SEQ 1256..1550
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15793581"
FT /id="VSP_031233"
FT CONFLICT 385
FT /note="F -> L (in Ref. 1; AAX77677)"
FT /evidence="ECO:0000305"
FT CONFLICT 829
FT /note="L -> F (in Ref. 2; BAE32541)"
FT /evidence="ECO:0000305"
FT CONFLICT 1045
FT /note="Missing (in Ref. 1; AAX77677)"
FT /evidence="ECO:0000305"
FT CONFLICT 1147
FT /note="T -> N (in Ref. 2; BAE32541)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1550 AA; 166628 MW; 6E6630EDA239D744 CRC64;
MAGARAALLP LLLHLGSLAL AARGGEVSRE QPRLADAISQ QQAPSHSLVP GETHQQQWCP
LEERLERLEA EVTDLRKQNR ELQARVVQLE SCECWGPGHT CPEGARWEPD ACTACVCRDG
TAHCGPQPNL PHCRGCSHNG QSYGHGETFS PDACTTCRCL AGTVQCQGPS CSELNCLESF
IPPGECCPIC RPGCEYEGQL HQEGSSFLSS SNPCLQCSCL RSLVRCVPVK CQPSPCLNPV
PRLGHCCPVC QASGCTEGNS HRDHGQEWTT PGDPCRICQC LEGHIQCRQR ECASLCPYPA
RPLPGTCCPV CDGCFLNGRE HSSGEPVGSQ DPCSSCRCTN GSVQCEPLPC PPAPCRYPGR
IPGQCCPVCD GCKYQGHEYR SQETFTLQEN GRCLRCVCQA GEVSCEEQDC PVTPCVRSAS
GPQLCSACVL NGEEFAEGIQ WEPDDQPCTS CSCQDGVPVC RAVLCSPVPC QHPTQPPGAC
CPSCDSCTYH SLVYANGQNF TDVDSPCQTC YCEDGTVRCS LINCPFTTCA KPQNGPGQCC
PKCPDCILEA QVFVDGERFP HPRDPCQECW CQEGQAHCQL RACPSAPCVH PLPGTCCKND
CTGCAFGGKE YPNGADFPHP TDPCRLCRCL SGNVQCLARR CPPLSCPQPV LTPGDCCPQC
PDAPADCPQS GNMVPVRHQE HFFQPGDPCS RCLCLDGSVS CQRLTCPPAP CAHPRRDACC
PSCDGCLYQG KEFASGERFP SPNVACHVCL CWEGSVKCEP RTCAPAQCPF PTREDCCPAC
DSCDYLGVSY LSSQEFPDPR EACNLCTCLG GFVTCTRRPC EPPACSHPLI VPEHCCPTCQ
GCLYHGITAA LGETLPDPLD PTCSLCTCEE GSMRCQKKPC PPAPCAHPSP GPCFCPVCRS
CLSQGREHQD GEEFEGPEGS CERCRCLAGQ VSCTRLQCPS LPCLHQVTEP GTCCPRCTGC
LARGEEHPEG SSWVPADSPC SSCMCHKGII TCAQVQCVSA CIWPQEGPSD CCPQCSGCEH
GGRKYEPGES FQPGADPCEV CICKQKREGP PSLHCSRRQC PSLVGCPPSQ LLPPGPQHCC
PTCAQALSNC TEDLVGSELV PPDPCYTCQC QDLTWLCTHR ACPELSCPLW ERHTTPGSCC
PVCKDPTQSC MHQGRWVASG EQWAVDACTS CSCVAGTVHC QTQRCRKLAC SRDEVPALSP
GSCCLRCLPR PASCMAFGDP HYRTFDGRLL HFQGSCSYVL AKDCHGEDFS VHVTNDDRGR
RGVAWTQEVA VLLGTVAVRL LQGRTVMVDQ HTVTLPFLRE PLLYIELRGH TVILHAQPGL
QVLWDGQSQV EVRVPSSYRG QTCGLCGNFN GFAQDDLQGP DGRLLPTEAS FGNSWKVPKG
LGPGRPCSAG REVDPCRAAG YRARREANAR CGILKTSPFS HCHAVVPPEP FFAACVYDLC
ACGPGSSSDT CLCDALEAYA SHCRQAGVTP VWRGPTLCVV GCPVDRGFVF DECGPPCPRT
CFNRHIPLGE LAAHCVRPCV PGCQCPAGLV EHEGHCISPE VCPPVLLTGD
