Reviewed, UniProtKB/Swiss-Prot Q9HB71 (CYBP_HUMAN)

Names and origin

Protein names

Recommended name:
    Calcyclin-binding protein
      Short name=CacyBP
      Short name=hCacyBP
Alternative name(s):
    Siah-interacting protein
    S100A6-binding protein

Gene names

Name:	CACYBP
Synonyms:	S100A6BP, SIP
ORF Names:	PNAS-107

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	228 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 be involved in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1).
Subunit structure	Interacts with protein of the S100 family S100A1, S100A6, S100B, S100P and S100A12 at physiological calcium concentrations By similarity. Component of some large E3 complex at least composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts directly with SIAH1, SIAH2 and SKP1.
Subcellular location	Nucleus. Cytoplasm. Note: Cytoplasmic at low calcium concentrations. In neuroblastoma cells, after a retinoic acid (RA) induction and calcium increase, it localizes in both the nucleus and cytoplasm. The nuclear fraction may be phosphorylated. Ref.10
Post-translational modification	Phosphorylated on serine residues. Phosphorylated upon induction by RA or at high calcium concentrations. Ref.10 Ref.11
Sequence similarities	Contains 1 CS domain. Contains 1 SGS domain.
Sequence caution	The sequence AAG23817.1 differs from that shown. Reason: Frameshift at position 203.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPB41	P11171	1	EBI-1047302,EBI-1050906
GH1	P01241	1	EBI-1047302,EBI-1026046

Alternative products

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

Isoform 1 (identifier: Q9HB71-1)

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: Q9HB71-2)

Also known as: SIP-S; S;

The sequence of this isoform differs from the canonical sequence as follows:
     73-80: VKISNYGW → DGISQISL
     81-228: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7 Ref.8

Chain

2 – 228

227

Calcyclin-binding protein

PRO_0000185389

Regions

Domain

73 – 167

95

CS

Domain

168 – 228

61

SGS

Region

2 – 80

79

Interaction with SIAH1

Region

73 – 228

156

Interaction with SKP1

Region

154 – 228

75

Interaction with S100A6 By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7 Ref.8

Modified residue

209

1

Phosphothreonine Ref.11

Natural variations

Alternative sequence

73 – 80

8

VKISNYGW → DGISQISL in isoform 2.

VSP_010171

Alternative sequence

81 – 228

148

Missing in isoform 2.

VSP_010172

Experimental info

Sequence conflict

44

1

M → V in AAG23817. Ref.4

Sequence conflict

177

1

E → K in AAG23817. Ref.4

Sequence conflict

183

1

T → P in AAG23817. Ref.4

Sequence conflict

226

1

T → P in AAG23817. Ref.4

Secondary structure

1

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228

Helix Strand Turn

Details...

Helix

3 – 19

17

Helix

23 – 46

24

Beta strand

61 – 64

4

Beta strand

79 – 83

5

Beta strand

86 – 92

7

Turn

94 – 98

5

Beta strand

103 – 108

6

Beta strand

110 – 117

8

Beta strand

121 – 123

3

Beta strand

125 – 130

6

Beta strand

132 – 134

3

Turn

138 – 140

3

Beta strand

142 – 146

5

Beta strand

149 – 155

7

Beta strand

157 – 160

4

Beta strand

164 – 167

4

Helix

168 – 174

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: 88C822FB14A7EF89	FASTA	228	26,210
	10 20 30 40 50 60 MASEELQKDL EEVKVLLEKA TRKRVRDALT AEKSKIETEI KNKMQQKSQK KAELLDNEKP 70 80 90 100 110 120 AAVVAPITTG YTVKISNYGW DQSDKFVKIY ITLTGVHQVP TENVQVHFTE RSFDLLVKNL 130 140 150 160 170 180 NGKSYSMIVN NLLKPISVEG SSKKVKTDTV LILCRKKVEN TRWDYLTQVE KECKEKEKPS 190 200 210 220 YDTETDPSEG LMNVLKKIYE DGDDDMKRTI NKAWVESREK QAKGDTEF
	Isoform 2 (SIP-S) (S). Checksum: 13A2FAC2429FA9FD	FASTA	80	8,956
	10 20 30 40 50 60 MASEELQKDL EEVKVLLEKA TRKRVRDALT AEKSKIETEI KNKMQQKSQK KAELLDNEKP 70 80 AAVVAPITTG YTDGISQISL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human calcyclin binding protein (hCacyBP) gene." Liu W.X., Wu J., Zhao Z., Zhou Y., Peng X.Z., Yuan J.G., Qiang B.Q. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 34:181-186(2002) [PubMed: 12006993] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Amplification and overexpression of the gene encoding the human calcyclin binding protein on chromosome 1q24-q25 in advanced lung carcinomas." Petersen S., Schluens K., Dietel M., Petersen I. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Rhodes S. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Human acute promyelocytic leukemia cell line NB4's apoptosis related genes." Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W., Yang H., Zhao Z.-L. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Promyelocytic leukemia.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Skin.
[7]	Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-14; 34-41; 112-118 AND 124-143, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Hepatoma.
[8]	Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-19 AND 112-118, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[9]	"Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses." Matsuzawa S., Reed J.C. Mol. Cell 7:915-926(2001) [PubMed: 11389839] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2), SUBUNIT OF A COMPLEX WITH UBE2D1; SIAH1; SKP1; APC AND TBL1X, INTERACTION WITH SIAH1; SIAH2 AND SKP1.
[10]	"Translocation and phosphorylation of calcyclin binding protein during retinoic acid-induced neuronal differentiation of neuroblastoma SH-SY5Y cells." Wu J., Tan X., Peng X.Z., Yuan J.G., Qiang B.Q. J. Biochem. Mol. Biol. 36:354-358(2003) [PubMed: 12895292] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[11]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-209, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"Solution structure of the core domain of calcyclin binding protein; SIAH-interacting protein (SIP)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 63-176.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF057356 mRNA. Translation: AAC21458.1.
AF314752 mRNA. Translation: AAG34170.1.
AL035305 mRNA. Translation: CAA22910.1.
AF275803 mRNA. Translation: AAG23817.1. Frameshift.
Z99127 Genomic DNA. Translation: CAQ52581.1.
BC005975 mRNA. Translation: AAH05975.1.
BC022352 mRNA. Translation: AAH22352.1.
BC078151 mRNA. Translation: AAH78151.1.

IPI

IPI00395627.
IPI00410678.

RefSeq

NP_055227.1.

UniGene

Hs.508524

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X5M	NMR	-	A	63-176	[»]
2A25	X-ray	2.20	B	58-70	[»]
2A26	X-ray	1.20	A/B/C	1-47	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9HB71. 18 interactions.

PTM databases

PhosphoSite

Q9HB71.

Proteomic databases

PRIDE

Q9HB71.

Genome annotation databases

Ensembl

ENSG00000116161. Homo sapiens. [Contig view]

GeneID

27101.

UCSC

uc001gkj.1. human.

Organism-specific databases

GeneCards

GC01P173235.

H-InvDB

HIX0001350.
HIX0057113.

HGNC

HGNC:30423. CACYBP.

MIM

606186. gene.

PharmGKB

PA134894213.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9HB71.

HOVERGEN

Q9HB71.

OMA

Q9HB71. YAWDQSD.

Gene expression databases

ArrayExpress

Q9HB71.

Bgee

Q9HB71.

CleanEx

HS_CACYBP.

GermOnline

ENSG00000116161. Homo sapiens.

Family and domain databases

InterPro

IPR017447. CS.
IPR007052. CS_domain.
IPR007699. SGS.
IPR015120. Siah-Interact_N.
[Graphical view]

Pfam

PF04969. CS. 1 hit.
PF05002. SGS. 1 hit.
PF09032. Siah-Interact_N. 1 hit.
[Graphical view]

PROSITE

PS51203. CS. 1 hit.
PS51048. SGS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

49757.

SOURCE

Search...

Entry information

Entry name

CYBP_HUMAN

Accession

Primary (citable) accession number: Q9HB71
Secondary accession number(s): B2ZWH2, O60666

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	July 7, 2009
This is version 71 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)