P23276 (KELL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kell blood group glycoprotein
EC=3.4.24.-

Alternative name(s):
CD_antigen=CD238

Gene names

Name:

KEL

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	732 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Zinc endopeptidase with endothelin-3-converting enzyme activity. Cleaves EDN1, EDN2 and EDN3, with a marked preference for EDN3. Ref.10
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Heterodimer with XK; disulfide-linked. Ref.9
Subcellular location	Cell membrane; Single-pass type II membrane protein. Note: Spans the erythrocyte membrane, and is attached to the underlying cytoskeleton.
Tissue specificity	Expressed at high levels in erythrocytes and testis (in Sertoli cells), and, at lower levels, in skeletal muscle, tonsils (in follicular dendritic cells), lymph node, spleen and appendix (at protein level). Also expressed in many adult and fetal nonerythroid tissues, including brain, spleen, lymph nodes and bone marrow. Ref.11 Ref.12
Post-translational modification	N-glycosylated. Ref.12
Polymorphism	KEL is responsible for the Kell blood group system. The molecular basis of the K=KEL1/k=KEL2 blood group antigens is a single variation in position 193; Thr-193 corresponds to KEL2 and Met-193 to KEL1. The molecular basis of the Kpa=KEL3/Kpb=KEL4/Kpc=KEL21 blood group antigens is a single variation in position 281; Arg-281 corresponds to KEL4, Trp-281 to KEL3 and Gln-281 to KEL21. The molecular basis of the Jsa=KEL6/Jsb=KEL7 blood group antigens is a single variation in position 597; Leu-597 corresponds to KEL7 and Pro-597 to KEL6. The molecular basis of the KEL11/KEL17 blood group antigens is a single variation in position 302; Val-302 corresponds to KEL11 and Ala-302 to KEL17. The molecular basis of the KEL14/KEL24 blood group antigens is a single variation in position 180; Arg-180 corresponds to KEL14 and Pro-180 to KEL24.
Sequence similarities	Belongs to the peptidase M13 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Blood group antigen Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW vasoconstriction Traceable author statement PubMed 15769748. Source: HGNC
Cellular_component	integral to membrane Traceable author statement PubMed 9647734. Source: HGNC plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from direct assay PubMed 15769748. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 732	732	Kell blood group glycoprotein		PRO_0000078227
Regions
	Topological domain	1 – 47	47	Cytoplasmic Potential
	Transmembrane	48 – 67	20	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	68 – 732	665	Extracellular Potential
Sites
	Active site	582	1
	Active site	638	1	Proton donor By similarity
	Metal binding	581	1	Zinc; catalytic By similarity
	Metal binding	585	1	Zinc; catalytic By similarity
	Metal binding	634	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Glycosylation	115	1	N-linked (GlcNAc...) Potential
	Glycosylation	191	1	N-linked (GlcNAc...); in KEL2 antigen
	Glycosylation	345	1	N-linked (GlcNAc...) Potential
	Glycosylation	627	1	N-linked (GlcNAc...) Potential
	Disulfide bond	72		Interchain (with C-347 in XK) Ref.9
Natural variations
	Natural variant	163	1	A → T. Ref.3 Corresponds to variant rs8175974 [ dbSNP | Ensembl ].		VAR_016265
	Natural variant	180	1	R → P in KEL24 antigen.		VAR_006731
	Natural variant	193	1	T → M in KEL1/K antigen. Ref.3 Ref.13 Corresponds to variant rs8176058 [ dbSNP | Ensembl ].		VAR_006732
	Natural variant	248	1	R → Q in KEL25 antigen.		VAR_015120
	Natural variant	249	1	E → K in KEL27 antigen.		VAR_015121
	Natural variant	281	1	R → Q in KEL21/Kp(c) antigen.		VAR_006734
	Natural variant	281	1	R → W in KEL3/Kp(a) antigen. Ref.3 Corresponds to variant rs8176059 [ dbSNP | Ensembl ].		VAR_006733
	Natural variant	302	1	V → A in KEL17 antigen.		VAR_006735
	Natural variant	322	1	A → V in KEL22 antigen.		VAR_015122
	Natural variant	382	1	Q → R in KEL23 antigen.		VAR_015123
	Natural variant	406	1	R → Q in KEL26 antigen.		VAR_015124
	Natural variant	492	1	R → Q in KEL19 antigen.		VAR_015125
	Natural variant	494	1	E → V in KEL10/Ul(a) antigen.		VAR_006736
	Natural variant	548	1	H → R in KEL12 antigen.		VAR_015126
	Natural variant	597	1	L → P in KEL6/Js(a) antigen. Ref.3 Corresponds to variant rs8176038 [ dbSNP | Ensembl ].		VAR_006737
	Natural variant	726	1	S → A. Ref.3 Corresponds to variant rs8176048 [ dbSNP | Ensembl ].		VAR_016266
Experimental info
	Mutagenesis	72	1	C → S: Loss of Kell-XK complex. Ref.9
	Mutagenesis	319	1	C → S: No loss of Kell-XK complex. Ref.9
	Mutagenesis	582	1	E → G: Loss of catalytic activity. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P23276 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 604A168AD300EDB4	FASTA	732	82,824
	10 20 30 40 50 60 MEGGDQSEEE PRERSQAGGM GTLWSQESTP EERLPVEGSR PWAVARRVLT AILILGLLLC 70 80 90 100 110 120 FSVLLFYNFQ NCGPRPCETS VCLDLRDHYL ASGNTSVAPC TDFFSFACGR AKETNNSFQE 130 140 150 160 170 180 LATKNKNRLR RILEVQNSWH PGSGEEKAFQ FYNSCMDTLA IEAAGTGPLR QVIEELGGWR 190 200 210 220 230 240 ISGKWTSLNF NRTLRLLMSQ YGHFPFFRAY LGPHPASPHT PVIQIDQPEF DVPLKQDQEQ 250 260 270 280 290 300 KIYAQIFREY LTYLNQLGTL LGGDPSKVQE HSSLSISITS RLFQFLRPLE QRRAQGKLFQ 310 320 330 340 350 360 MVTIDQLKEM APAIDWLSCL QATFTPMSLS PSQSLVVHDV EYLKNMSQLV EEMLLKQRDF 370 380 390 400 410 420 LQSHMILGLV VTLSPALDSQ FQEARRKLSQ KLRELTEQPP MPARPRWMKC VEETGTFFEP 430 440 450 460 470 480 TLAALFVREA FGPSTRSAAM KLFTAIRDAL ITRLRNLPWM NEETQNMAQD KVAQLQVEMG 490 500 510 520 530 540 ASEWALKPEL ARQEYNDIQL GSSFLQSVLS CVRSLRARIV QSFLQPHPQH RWKVSPWDVN 550 560 570 580 590 600 AYYSVSDHVV VFPAGLLQPP FFHPGYPRAV NFGAAGSIMA HELLHIFYQL LLPGGCLACD 610 620 630 640 650 660 NHALQEAHLC LKRHYAAFPL PSRTSFNDSL TFLENAADVG GLAIALQAYS KRLLRHHGET 670 680 690 700 710 720 VLPSLDLSPQ QIFFRSYAQV MCRKPSPQDS HDTHSPPHLR VHGPLSSTPA FARYFRCARG 730 ALLNPSSRCQ LW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and primary structure of Kell blood group protein." Lee S., Zambas E.D., Marsh W.L., Redman C.M. Proc. Natl. Acad. Sci. U.S.A. 88:6353-6357(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Organization of the gene encoding the human Kell blood group protein." Lee S., Zambas E., Green E.D., Redman C.M. Blood 85:1364-1370(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	SeattleSNPs variation discovery resource Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-163; MET-193; TRP-281; PRO-597 AND ALA-726.
[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]. Tissue: Testis.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Skin.
[7]	"PCR amplification and sequencing of the human KEL gene." Denomme G.A., Matheson K.A. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 225-308.
[8]	"Molecular basis of the K:6,-7 [Js(a+b-)] phenotype in the Kell blood group system." Lee S., Wu X., Reid M.E., Redman C.M. Transfusion 35:822-825(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 569-647, VARIANT BLOOD GROUP KEL6/KEL7.
[9]	"Association of XK and Kell blood group proteins." Russo D., Redman C., Lee S. J. Biol. Chem. 273:13950-13956(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH XK, DISULFIDE BOND, MUTAGENESIS OF CYS-72 AND CYS-319.
[10]	"Proteolytic processing of big endothelin-3 by the kell blood group protein." Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C. Blood 94:1440-1450(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-582.
[11]	"Expression of Kell blood group protein in nonerythroid tissues." Russo D., Wu X., Redman C.M., Lee S. Blood 96:340-346(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH XK.
[12]	"Transcriptional regulation of the KEL gene and Kell protein expression in erythroid and non-erythroid cells." Camara-Clayette V., Rahuel C., Lopez C., Hattab C., Verkarre V., Bertrand O., Cartron J.P. Biochem. J. 356:171-180(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, GLYCOSYLATION.
[13]	"Molecular basis of the Kell (K1) phenotype." Lee S., Wu X., Reid M.E., Zelinski T., Redman C.M. Blood 85:912-916(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BLOOD GROUP KEL1/KEL2 MET-193.
[14]	"Point mutations characterize KEL10, the KEL3, KEL4, and KEL21 alleles, and the KEL17 and KEL11 alleles." Lee S., Wu X., Son S., Naime D., Reid M.E., Okubo Y., Sistonen P., Redman C.M. Transfusion 36:490-494(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BLOOD GROUP KEL3/KEL4/KEL21; KEL11/17 AND KEL10.
+	Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	M64934 mRNA. Translation: AAA03192.1. AF172627 , AF172609, AF172610, AF172611, AF172612, AF172613, AF172614, AF172615, AF172616, AF172617, AF172618, AF172619, AF172620, AF172621, AF172622, AF172623, AF172624, AF172625, AF172626 Genomic DNA. Translation: AAB33459.1. AY228336 Genomic DNA. Translation: AAO38053.1. AK314831 mRNA. Translation: BAG37351.1. CH471198 Genomic DNA. Translation: EAW51891.1. BC003135 mRNA. Translation: AAH03135.1. BC050639 mRNA. Translation: AAH50639.1. AF279657 Genomic DNA. Translation: AAK69488.1. S80081 Genomic DNA. Translation: AAB47018.1.
IPI	IPI00220459.
RefSeq	NP_000411.1. NM_000420.2.
UniGene	Hs.368588.
3D structure databases
ProteinModelPortal	P23276.
SMR	P23276. Positions 79-732.
ModBase	Search...
Protein-protein interaction databases
IntAct	P23276. 1 interaction.
MINT	MINT-1464824.
STRING	9606.ENSP00000347409.
Protein family/group databases
MEROPS	M13.090.
PTM databases
PhosphoSite	P23276.
Polymorphism databases
DMDM	1346376.
Proteomic databases
PaxDb	P23276.
PRIDE	P23276.
Protocols and materials databases
DNASU	3792.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355265; ENSP00000347409; ENSG00000197993. ENST00000561891; ENSP00000457677; ENSG00000260040.
GeneID	3792.
KEGG	hsa:3792.
UCSC	uc003wcb.3. human.
Organism-specific databases
CTD	3792.
GeneCards	GC07M142638.
HGNC	HGNC:6308. KEL.
HPA	HPA042391.
MIM	110900. phenotype. 613883. gene.
neXtProt	NX_P23276.
Orphanet	157938. Joker disease.
PharmGKB	PA30087.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3590.
HOGENOM	HOG000245574.
HOVERGEN	HBG002194.
InParanoid	P23276.
KO	K06577.
OMA	SYAQVMC.
OrthoDB	EOG47PX5G.
PhylomeDB	P23276.
Gene expression databases
ArrayExpress	P23276.
Bgee	P23276.
CleanEx	HS_KEL.
Genevestigator	P23276.
Family and domain databases
InterPro	IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view]
PANTHER	PTHR11733. PTHR11733. 1 hit.
Pfam	PF01431. Peptidase_M13. 1 hit. PF05649. Peptidase_M13_N. 1 hit. [Graphical view]
PRINTS	PR00786. NEPRILYSIN.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3792.
NextBio	14891.
SOURCE	Search...

Entry information

Entry name

KELL_HUMAN

Accession

Primary (citable) accession number: P23276
Secondary accession number(s): B2RBV4, Q96RS8, Q99885

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 138 of the entry and version 2 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.