Q96HD1 (CREL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cysteine-rich with EGF-like domain protein 1

Gene names

Name:	CRELD1
Synonyms:	CIRRIN
ORF Names:	UNQ188/PRO214

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	420 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)

Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Highly expressed in fetal lung, liver, kidney, adult heart, brain and skeletal muscle. Weakly expressed in placenta, fetal brain, and adult lung, liver, kidney and pancreas. Ref.1
Involvement in disease	Atrioventricular septal defect 2 (AVSD2) [MIM:606217]: A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8 Ref.9
Sequence similarities	Belongs to the CRELD family. Contains 2 EGF-like domains. Contains 2 FU (furin-like) repeats.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac septum development Traceable author statement PubMed 18076106. Source: BHF-UCL endocardial cushion development Traceable author statement PubMed 18076106. Source: BHF-UCL
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q96HD1-1)

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: Q96HD1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     350-420: ESAGFFSEMT...RVLEGFIKGR → GAFPILTDLT...IHSQQASSQR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 420	391	Cysteine-rich with EGF-like domain protein 1		PRO_0000042781
Regions
	Topological domain	30 – 362	333	Extracellular Potential
	Transmembrane	363 – 383	21	Helical; Potential
	Topological domain	384	1	Cytoplasmic Potential
	Transmembrane	385 – 405	21	Helical; Potential
	Topological domain	406 – 420	15	Extracellular Potential
	Domain	153 – 193	41	EGF-like 1
	Repeat	208 – 256	49	FU 1
	Repeat	268 – 315	48	FU 2
	Domain	305 – 344	40	EGF-like 2; calcium-binding Potential
	Compositional bias	3 – 45	43	Pro-rich
Amino acid modifications
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Potential
	Disulfide bond	155 ↔ 169		By similarity
	Disulfide bond	163 ↔ 181		By similarity
	Disulfide bond	183 ↔ 192		By similarity
	Disulfide bond	309 ↔ 321		By similarity
	Disulfide bond	314 ↔ 330		By similarity
	Disulfide bond	332 ↔ 343		By similarity
Natural variations
	Alternative sequence	350 – 420	71	ESAGF…FIKGR → GAFPILTDLTPETTRRWKLG SHPHSTYVKMKMQRDEATFP GLYGKQVAKLGSQSRQSDRG TRLIHSQQASSQR in isoform 2.		VSP_016091
	Natural variant	13	1	M → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Corresponds to variant rs279552 [ dbSNP | Ensembl ].		VAR_046653
	Natural variant	107	1	R → H in AVSD2 susceptibility; with heterotaxy syndrome. Ref.8 Corresponds to variant rs28941780 [ dbSNP | Ensembl ].		VAR_023764
	Natural variant	128	1	P → R. Corresponds to variant rs2302787 [ dbSNP | Ensembl ].		VAR_046654
	Natural variant	162	1	P → A in AVSD2 susceptibility. Ref.9		VAR_023765
	Natural variant	311	1	T → I in AVSD2 susceptibility. Ref.8 Corresponds to variant rs28942092 [ dbSNP | Ensembl ].		VAR_023766
	Natural variant	329	1	R → C in AVSD2 susceptibility. Ref.8 Corresponds to variant rs28942091 [ dbSNP | Ensembl ].		VAR_023767
Experimental info
	Sequence conflict	126	1	E → G in CAB43376. Ref.2
	Sequence conflict	153	1	L → P in CAG33661. Ref.5
	Sequence conflict	186	1	G → S in BAG36806. Ref.4
	Sequence conflict	229	1	C → R in CAG33661. Ref.5
	Sequence conflict	336	1	Y → C in CAB43376. Ref.2
	Sequence conflict	348	1	I → V in BAG36806. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 14, 2008. Version 3. Checksum: EEAAD0D143A0D35A	FASTA	420	45,440
	10 20 30 40 50 60 MAPWPPKGLV PAMLWGLSLF LNLPGPIWLQ PSPPPQSSPP PQPHPCHTCR GLVDSFNKGL 70 80 90 100 110 120 ERTIRDNFGG GNTAWEEENL SKYKDSETRL VEVLEGVCSK SDFECHRLLE LSEELVESWW 130 140 150 160 170 180 FHKQQEAPDL FQWLCSDSLK LCCPAGTFGP SCLPCPGGTE RPCGGYGQCE GEGTRGGSGH 190 200 210 220 230 240 CDCQAGYGGE ACGQCGLGYF EAERNASHLV CSACFGPCAR CSGPEESNCL QCKKGWALHH 250 260 270 280 290 300 LKCVDIDECG TEGANCGADQ FCVNTEGSYE CRDCAKACLG CMGAGPGRCK KCSPGYQQVG 310 320 330 340 350 360 SKCLDVDECE TEVCPGENKQ CENTEGGYRC ICAEGYKQME GICVKEQIPE SAGFFSEMTE 370 380 390 400 410 420 DELVVLQQMF FGIIICALAT LAAKGDLVFT AIFIGAVAAM TGYWLSERSD RVLEGFIKGR
	Isoform 2 [UniParc]. Checksum: 3FC9B9BC52BE6DA1	FASTA	422	45,942
	10 20 30 40 50 60 MAPWPPKGLV PAMLWGLSLF LNLPGPIWLQ PSPPPQSSPP PQPHPCHTCR GLVDSFNKGL 70 80 90 100 110 120 ERTIRDNFGG GNTAWEEENL SKYKDSETRL VEVLEGVCSK SDFECHRLLE LSEELVESWW 130 140 150 160 170 180 FHKQQEAPDL FQWLCSDSLK LCCPAGTFGP SCLPCPGGTE RPCGGYGQCE GEGTRGGSGH 190 200 210 220 230 240 CDCQAGYGGE ACGQCGLGYF EAERNASHLV CSACFGPCAR CSGPEESNCL QCKKGWALHH 250 260 270 280 290 300 LKCVDIDECG TEGANCGADQ FCVNTEGSYE CRDCAKACLG CMGAGPGRCK KCSPGYQQVG 310 320 330 340 350 360 SKCLDVDECE TEVCPGENKQ CENTEGGYRC ICAEGYKQME GICVKEQIPG AFPILTDLTP 370 380 390 400 410 420 ETTRRWKLGS HPHSTYVKMK MQRDEATFPG LYGKQVAKLG SQSRQSDRGT RLIHSQQASS QR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification, genomic organization and mRNA expression of CRELD1, the founding member of a unique family of matricellular proteins." Rupp P.A., Fouad G.T., Egelston C.A., Reifsteck C.A., Olson S.B., Knosp W.M., Glanville R.W., Thornburg K.L., Robinson S.W., Maslen C.L. Gene 293:47-57(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT VAL-13. Tissue: Fibroblast.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-13. Tissue: Kidney.
[3]	"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 1), VARIANT VAL-13.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-13. Tissue: Amygdala.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT VAL-13.
[6]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 2), VARIANT VAL-13. Tissue: Lung.
[8]	"Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects." Robinson S.W., Morris C.D., Goldmuntz E., Reller M.D., Jones M.A., Steiner R.D., Maslen C.L. Am. J. Hum. Genet. 72:1047-1052(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AVSD2 SUSCEPTIBILITY HIS-107; ILE-311 AND CYS-329.
[9]	"Analysis of CRELD1 as a candidate 3p25 atrioventicular septal defect locus (AVSD2)." Zatyka M., Priestley M., Ladusans E.J., Fryer A.E., Mason J., Latif F., Maher E.R. Clin. Genet. 67:526-528(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AVSD2 SUSCEPTIBILITY ALA-162.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF452623 mRNA. Translation: AAM75206.1. AL050275 mRNA. Translation: CAB43376.1. AY358363 mRNA. Translation: AAQ88729.1. AK314113 mRNA. Translation: BAG36806.1. CR457380 mRNA. Translation: CAG33661.1. AC018809 Genomic DNA. No translation available. BC008720 mRNA. Translation: AAH08720.1.
IPI	IPI00101608. IPI00168896.
PIR	T08724.
RefSeq	NP_001026887.1. NM_001031717.3. NP_001070883.1. NM_001077415.2. NP_056328.2. NM_015513.4.
UniGene	Hs.9383.
3D structure databases
ProteinModelPortal	Q96HD1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96HD1. 10 interactions.
MINT	MINT-1375344.
STRING	9606.ENSP00000295982.
Polymorphism databases
DMDM	209572751.
Proteomic databases
PaxDb	Q96HD1.
PRIDE	Q96HD1.
Protocols and materials databases
DNASU	78987.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000326434; ENSP00000321856; ENSG00000163703. ENST00000383811; ENSP00000373322; ENSG00000163703. ENST00000397170; ENSP00000380355; ENSG00000163703. ENST00000452070; ENSP00000393643; ENSG00000163703.
GeneID	78987.
KEGG	hsa:78987.
UCSC	uc003buf.3. human. uc003bug.3. human.
Organism-specific databases
CTD	78987.
GeneCards	GC03P009975.
H-InvDB	HIX0200522.
HGNC	HGNC:14630. CRELD1.
HPA	HPA026964.
MIM	606217. phenotype. 607170. gene.
neXtProt	NX_Q96HD1.
Orphanet	1329. Complete atrioventricular canal. 1330. Partial atrioventricular canal.
PharmGKB	PA26870.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315654.
HOGENOM	HOG000004778.
HOVERGEN	HBG081344.
OMA	EPHPCHT.
OrthoDB	EOG480HWV.
Gene expression databases
ArrayExpress	Q96HD1.
Bgee	Q96HD1.
CleanEx	HS_CRELD1.
Genevestigator	Q96HD1.
GermOnline	ENSG00000163703. Homo sapiens.
Family and domain databases
InterPro	IPR021852. DUF3456. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR002049. EGF_laminin. IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt. [Graphical view]
Pfam	PF11938. DUF3456. 2 hits. PF07645. EGF_CA. 2 hits. [Graphical view]
SMART	SM00181. EGF. 1 hit. SM00179. EGF_CA. 1 hit. SM00261. FU. 2 hits. [Graphical view]
SUPFAM	SSF57184. Grow_fac_recept. 1 hit.
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. 1 hit. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 2 hits. PS01187. EGF_CA. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	78987.
NextBio	67556.
SOURCE	Search...

Entry information

Entry name

CREL1_HUMAN

Accession

Primary (citable) accession number: Q96HD1
Secondary accession number(s): A8MX90 , B2RAA9, Q6I9X5, Q8NFT4, Q9Y409

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 102 of the entry and version 3 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.