Q6WN34 (CRDL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chordin-like protein 2

Alternative name(s):
Breast tumor novel factor 1
Short name=BNF-1
Chordin-related protein 2

Gene names

Name:	CHRDL2
Synonyms:	BNF1, CHL2
ORF Names:	UNQ765/PRO1557

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	429 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May inhibit BMPs activity by blocking their interaction with their receptors. Has a negative regulator effect on the cartilage formation/regeneration from immature mesenchymal cells, by preventing or reducing the rate of matrix accumulation By similarity. Implicated in tumor angiogenesis. May play a role during myoblast and osteoblast differentiation, and maturation. Ref.1 Ref.2
Subunit structure	Interacts with GDF5 By similarity. May interact with BMP2, BMP4, BMP5, BMP6, BMP7 and INHBA. Ref.2 Ref.3
Subcellular location	Isoform 1: Secreted Potential Ref.2. Isoform 2: Secreted Potential Ref.2. Isoform 3: Cytoplasm Potential Ref.2. Isoform 4: Cytoplasm Potential Ref.2. Isoform 5: Cytoplasm Potential Ref.2.
Tissue specificity	Highly expressed in uterus. Moderately expressed in heart, liver, prostate, testis and ovary. Weakly expressed in skeletal muscle, kidney, spleen, small intestine and colon. Expressed in the secretory epithelial cells of uterine endometrium, fallopian tubes, endocervical glands, bladder and prostate, as well as the transitional epithelium of the urinary bladder, and in bone osteoblasts (at protein level). In normal cartilage, expression was confined in a few chondrocytes in the superficial zone as well as in the middle zone. In diseased cartilage coming from osteoarthritic patients, expression was limited to the middle zone of chondrocytes. Isoform 1 and isoform 2 are expressed in fetal cerebellum and heart, while only isoform 2 is detected in fetal spleen. Isoform 2 present in plasma. Ref.1 Ref.2 Ref.3
Induction	Up-regulated in breast tumors but also in lung and colon tumors. Ref.1
Post-translational modification	Phosphorylation sites are present in the extracellular medium. Isoform 2 is phosphorylated on Ser-402.
Sequence similarities	Contains 3 VWFC domains.
Caution	According to Ref.3, interacts with BMP2, BMP4, BMP5, BMP6, BMP7 but not INHBA. According to Ref.2, interacts with INHBA but not BMP2, BMP4 and BMP6.

Ontologies

Keywords
Biological process	Chondrogenesis Differentiation Osteogenesis
Cellular component	Cytoplasm Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Molecular function	Developmental protein
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cartilage development Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW ossification Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay. Source: HPA
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Five additional mRNAs also exist. Differential expression of isoforms was observed during myoblast and osteoblast differentiation and maturation.

Isoform 1 (identifier: Q6WN34-1)

Also known as: I;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6WN34-2)

Also known as: II;

The sequence of this isoform differs from the canonical sequence as follows:
     374-426: GIFHLTQIKK...LKVTASPDKV → DEETEAQRGE...GQSRQSDQDI

Isoform 3 (identifier: Q6WN34-3)

Also known as: VII;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     66-162: GAHVSCYRLH...TTCPEPGCPA → NLTLPLDSGP...KRTVCSRSMG
     163-429: Missing.

Isoform 4 (identifier: Q6WN34-4)

Also known as: VIII;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     145-162: EGQIYCGLTTCPEPGCPA → MRQVSNRMKRTVCSRSMG
     163-429: Missing.

Isoform 5 (identifier: Q6WN34-5)

Also known as: IX;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     66-113: GAHVSCYRLH...LRAPPKSCQH → NLTLPLDSGP...PTSVSSAAAQ
     114-429: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Ref.6
	Chain	26 – 429	404	Chordin-like protein 2		PRO_0000005371
Regions
	Domain	31 – 96	66	VWFC 1
	Domain	109 – 175	67	VWFC 2
	Domain	250 – 315	66	VWFC 3
Amino acid modifications
	Glycosylation	114	1	N-linked (GlcNAc...) Ref.7
Natural variations
	Alternative sequence	1 – 20	20	Missing in isoform 3, isoform 4 and isoform 5.		VSP_013512
	Alternative sequence	21 – 28	8	LDSHARAR → MALVGLPG in isoform 3, isoform 4 and isoform 5.		VSP_013513
	Alternative sequence	66 – 162	97	GAHVS…PGCPA → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQRARSTAASQPAP NQAAQHPSRCQTPAAKPAKM RQVSNRMKRTVCSRSMG in isoform 3.		VSP_013514
	Alternative sequence	66 – 113	48	GAHVS…KSCQH → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQ in isoform 5.		VSP_013515
	Alternative sequence	114 – 429	316	Missing in isoform 5.		VSP_013516
	Alternative sequence	145 – 162	18	EGQIY…PGCPA → MRQVSNRMKRTVCSRSMG in isoform 4.		VSP_013517
	Alternative sequence	163 – 429	267	Missing in isoform 3 and isoform 4.		VSP_013518
	Alternative sequence	374 – 426	53	GIFHL…SPDKV → DEETEAQRGEVPGPRPHSQN LPLDSDQESQEARLPERGTA LPTARWPPRRSLERLPSPDP GAEGHGQSRQSDQDI in isoform 2.		VSP_013519
	Natural variant	335	1	P → L. Corresponds to variant rs35903991 [ dbSNP | Ensembl ].		VAR_055651
Experimental info
	Sequence conflict	187	1	S → R in AX140199. Ref.2
	Sequence conflict	231	1	R → I in AX140199. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (I) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: A8111F26B2EF96A4	FASTA	429	47,495
	10 20 30 40 50 60 MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR 70 80 90 100 110 120 CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH 130 140 150 160 170 180 GEIFSAHELF PSRLPNQCVL CSCTEGQIYC GLTTCPEPGC PAPLPLPDSC CQACKDEASE 190 200 210 220 230 240 QSDEEDSVQS LHGVRHPQDP CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV 250 260 270 280 290 300 KIVLKEKHKK ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC 310 320 330 340 350 360 RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN LRRFALEHEA 370 380 390 400 410 420 SDLVEIYLWK LVKGIFHLTQ IKKVRKQDFQ KEAQHFRLLA GPHEGHWNVF LAQTLELKVT ASPDKVTKT
	Isoform 2 (II) [UniParc]. Checksum: CFBF0BFA7D58CFE3	FASTA	451	49,675
	10 20 30 40 50 60 MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR 70 80 90 100 110 120 CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH 130 140 150 160 170 180 GEIFSAHELF PSRLPNQCVL CSCTEGQIYC GLTTCPEPGC PAPLPLPDSC CQACKDEASE 190 200 210 220 230 240 QSDEEDSVQS LHGVRHPQDP CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV 250 260 270 280 290 300 KIVLKEKHKK ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC 310 320 330 340 350 360 RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN LRRFALEHEA 370 380 390 400 410 420 SDLVEIYLWK LVKDEETEAQ RGEVPGPRPH SQNLPLDSDQ ESQEARLPER GTALPTARWP 430 440 450 PRRSLERLPS PDPGAEGHGQ SRQSDQDITK T
	Isoform 3 (VII) [UniParc]. Checksum: 66564AA513E1D2E7	FASTA	142	15,136
	10 20 30 40 50 60 MALVGLPGPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR CTCSENLTLP LDSGPHQSPA 70 80 90 100 110 120 STTGPCTNTE RSSVPMSCSP PACPTSVSSA AAQRARSTAA SQPAPNQAAQ HPSRCQTPAA 130 140 KPAKMRQVSN RMKRTVCSRS MG
	Isoform 4 (VIII) [UniParc]. Checksum: 577245066155CBC1	FASTA	142	15,922
	10 20 30 40 50 60 MALVGLPGPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR CTCSEGAHVS CYRLHCPPVH 70 80 90 100 110 120 CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH GEIFSAHELF PSRLPNQCVL 130 140 CSCTMRQVSN RMKRTVCSRS MG
	Isoform 5 (IX) [UniParc]. Checksum: 9DFEC54E7C1EF6CE	FASTA	93	9,846
	10 20 30 40 50 60 MALVGLPGPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR CTCSENLTLP LDSGPHQSPA 70 80 90 STTGPCTNTE RSSVPMSCSP PACPTSVSSA AAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BNF-1, a novel gene encoding a putative extracellular matrix protein, is overexpressed in tumor tissues." Wu I., Moses M.A. Gene 311:105-110(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[2]	"hCHL2, a novel chordin-related gene, displays differential expression and complex alternative splicing in human tissues and during myoblast and osteoblast maturation." Oren A., Toporik A., Biton S., Almogy N., Eshel D., Bernstein J., Savitsky K., Rotman G. Gene 331:17-31(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), FUNCTION, INTERACTION WITH BMPS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
[3]	"A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage." Nakayama N., Han C.-Y.E., Cam L., Lee J.I., Pretorius J., Fisher S., Rosenfeld R., Scully S., Nishinakamura R., Duryea D., Van G., Bolon B., Yokota T., Zhang K. Development 131:229-240(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH BMPS.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40.
[7]	"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry." Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F. Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-114, MASS SPECTROMETRY. Tissue: Milk.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY163868 mRNA. Translation: AAO31809.1. AY279090 mRNA. Translation: AAQ19179.1. AY279092 mRNA. Translation: AAQ19181.1. AY279093 mRNA. Translation: AAQ19182.1. AY279094 mRNA. Translation: AAQ19183.1. AX140199 mRNA. No translation available. AY358522 mRNA. Translation: AAQ88886.1. BC142623 mRNA. Translation: AAI42624.1.
IPI	IPI00307781. IPI00449238. IPI00449239. IPI00449244. IPI00983254.
RefSeq	NP_056239.3. NM_015424.3.
UniGene	Hs.432379.
3D structure databases
ProteinModelPortal	Q6WN34.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000263671.
PTM databases
PhosphoSite	Q6WN34.
Polymorphism databases
DMDM	62900089.
Proteomic databases
PaxDb	Q6WN34.
PRIDE	Q6WN34.
Protocols and materials databases
DNASU	25884.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263671; ENSP00000263671; ENSG00000054938. ENST00000376332; ENSP00000365510; ENSG00000054938. ENST00000528471; ENSP00000434589; ENSG00000054938. ENST00000534276; ENSP00000432055; ENSG00000054938.
GeneID	25884.
KEGG	hsa:25884.
UCSC	uc001ovg.3. human. uc001ovh.3. human.
Organism-specific databases
CTD	25884.
GeneCards	GC11M074407.
HGNC	HGNC:24168. CHRDL2.
HPA	HPA021771.
MIM	613127. gene.
neXtProt	NX_Q6WN34.
PharmGKB	PA134883081.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG147797.
HOGENOM	HOG000049211.
HOVERGEN	HBG051113.
OMA	ADPGHSE.
Gene expression databases
ArrayExpress	Q6WN34.
Bgee	Q6WN34.
CleanEx	HS_CHRDL2.
Genevestigator	Q6WN34.
GermOnline	ENSG00000054938. Homo sapiens.
Family and domain databases
InterPro	IPR001007. VWF_C. [Graphical view]
Pfam	PF00093. VWC. 3 hits. [Graphical view]
SMART	SM00214. VWC. 3 hits. [Graphical view]
PROSITE	PS01208. VWFC_1. 3 hits. PS50184. VWFC_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	25884.
NextBio	47300.
SOURCE	Search...

Entry information

Entry name

CRDL2_HUMAN

Accession

Primary (citable) accession number: Q6WN34
Secondary accession number(s): A5PKU9 , Q6WN30, Q6WN31, Q6WN32, Q7Z5J3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.